colistin and Acinetobacter-Infections

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a difficult-to-treat nosocomial pathogen responsible for significant morbidity and mortality. Sulbactam-durlobactam (SUL-DUR), formerly ETX2514SUL, is a novel β-lactam-β-lactamase inhibitor designed specifically for the treatment of CRAB infections. The United States Food and Drug Administration (FDA) fast-track approval of SUL-DUR for the treatment of CRAB infections is currently pending after completion of the phase III ATTACK trial, which compared SUL-DUR to colistin, both in combination with imipenem-cilastatin (IMI) for patients with CRAB-associated hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. The results of this trial demonstrated that SUL-DUR was non-inferior to colistin for CRAB while also possessing a much more favorable safety profile. SUL-DUR was well-tolerated with the most common side effects being headache, nausea, and injection-site phlebitis. With the current landscape of limited effective treatment options for CRAB infections, SUL-DUR represents a promising therapeutic option for the treatment of these severe infections. This review will discuss the pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical studies, safety, dosing, administration, as well as the potential role in therapy for SUL-DUR.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Colistin; Humans; Lactams; United States

Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) is one of the top-priority pathogens for new antibiotic development. Unlike other antibiotic-resistant threats, none of the available therapies have been shown to consistently reduce mortality or improve patient outcomes in clinical trials. Antibiotic combination therapy is routinely used in clinical practice; however, the preferred combination has not been defined. This narrative review focuses on evidence-based solutions for the treatment of invasive CRAB infections. We dissect the promise and perils of traditional agents used in combination, such as colistin, sulbactam, and the tetracyclines, and offer clinical pearls based on our interpretation of the available data. Next, we investigate the merits of newly developed β-lactam agents like cefiderocol and sulbactam-durlobactam, which have demonstrated contrasting results in recent randomized clinical trials. The review concludes with the authors' perspective on the evolving treatment landscape for CRAB infections, which is complicated by limited clinical data, imperfect treatment options, and a need for future clinical trials. We propose that effective treatment for CRAB infections requires a personalized approach that incorporates host factors, the site of infection, pharmacokinetic-pharmacodynamic principles, local molecular epidemiology of CRAB isolates, and careful interpretation of antibiotic susceptibility testing results. In most clinical scenarios, a dose-optimized, sulbactam-based regimen is recommended with the addition of at least one other in vitro active agent. Should sulbactam-durlobactam receive regulatory approval, recommendations will need to be re-evaluated with the most recent evidence.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Microbial Sensitivity Tests; Sulbactam

Acinetobacter baumannii is responsible for a variety of infections, such as nosocomial infections. In recent years, this pathogen has gained resistance to many antibiotics, and thus, carbapenems were used to treat infections with MDR A. baumannii strains in clinical settings. However, as carbapenem-resistant isolates are becoming increasingly prevalent, Colistin is now used as the last line of defense against resistant A. baumannii strains. Unfortunately, reports are increasing on the presence of Colistin-resistant phenotypes in infections caused by A. baumannii, creating an urgent need to find a substitute way to combat these resistant isolates. Quorum sensing inhibition, also known as quorum quenching, is an efficient alternative way of reversing resistance in different Gram-negative bacteria. Quorum sensing is a mechanism used by bacteria to communicate with each other by secreting signal molecules. When the population of bacteria increases and the concentration of signal molecules reaches a certain threshold, bacteria can implement mechanisms to adapt to a hostile environment, such as biofilm formation. Biofilms have many advantages for pathogens, such as antibiotic resistance. Different studies have revealed that disrupting the biofilm of A. baumannii makes it more susceptible to antibiotics. Although very few studies have been conducted on the biofilm disruption through quorum quenching in Colistin-resistant A. baumannii, these studies and similar studies bring hope in finding an alternative way of treating the Colistin-resistant isolates. In conclusion, quorum quenching has the potential to be used against Colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Quorum Sensing

The aim of this study was to discuss the potential clinical significance of heteroresistance in nonfermenting Gram-negative bacilli (GNB).. Recently, heteroresistance has been considered potentially responsible for clinical failure in Acinetobacter baumannii infections. This raised a scientific debate, still open, about the potential clinical significance of heteroresistance in nonfermenting GNB.. We reviewed the literature of last 20 years and found a limited number of studies evaluating the relationship between heteroresistance and clinical outcome in nonfermenting GNB. Unlike Gram-positive bacteria, heteroresistance is reported in a significant proportion of nonfermenting GNB with some studies describing it in all tested strains and for several antibiotics (including tigecycline, carbapenems, levofloxacin, cefiderocol, colistin). One important issue is the need for validated detection method since the population analysis profile test, that is considered the gold standard, requires high costs and time. Studies evaluating the correlation between heteroresistance and clinical outcome are contrasting and have several limitations. Although in-vitro detection of heteroresistance in nonfermenting GNB has not been associated with in-vivo treatment failure, its presence may suggest to prefer combination regimens instead monotherapy when treating infections by nonfermenters. Further studies are needed to clarify the clinical significance of heteroresistance.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Clinical Relevance; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

Carbapenem-resistant Acinetobacter baumannii has been classified as a top priority for the development of new therapies due to its resistance to most antibiotics. Drug repurposing may be a fast and inexpensive strategy for treating this pathogen. This review aims to critically evaluate repurposed drugs for the treatment of infections caused by carbapenem-resistant A. baumannii, correlating their antimicrobial activity with data available for toxicity and side effects. Some drugs have been suggested as promising candidates for repurposing; however, in some cases, high toxicity and low plasma concentrations reduce applicability in clinical practice. The most favorable applicability is offered by fusidic acid and colistin, possibly combined with a third agent, promising to be well tolerated and achieving satisfactory plasma concentrations.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

The potential of

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Calcium-Transporting ATPases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Lipopolysaccharides; Membrane Transport Proteins; Microbial Sensitivity Tests; Prospective Studies; Tigecycline

This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections.. We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity.. The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity.. Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Network Meta-Analysis; Pharmaceutical Preparations; Sulbactam

Acinetobacter baumannii antimicrobial resistance is a public health concern in developing and developed countries, especially in the hospital setting. Understanding the antibiotic resistance profile can help to provide better guidelines for the prescription of appropriate antibiotics, reduction of antibiotic resistance, and introducing new and effective treatment options.. Using the PRISMA guidelines, databases of PubMed, Embase, and Cochrane Library were searched systematically from January 1, 2000, to January 1, 2018. All statistical analyses were carried out via Comprehensive Meta-Analysis Software Version 2.0 (Biostat, Englewood, NJ). Depending on the heterogeneity test, either random or fix effect models were used for determining the pooled prevalence of drug resistance.. A total of 150 studies were included from 41 countries of six different WHO regional offices worldwide. The highest and the lowest rate of resistance were observed for cefotaxime (99%, 95% CI: 95-99.9) in Africa and colistin (1.1%, 95% CI: 0.3-4.5) in Western Pacific, respectively. Lebanon (17.5%, 95% CI: 16-19) and China (12%, 95% CI: 3.5-32.5) had the highest and Germany (0.2%, 95% CI: 0-2.5) had the lowest rate of resistance for colistin.. Our analysis showed that prevalence and rate of increased colistin resistance in South-East Asia and Eastern Mediterranean countries are higher than other regions of the world. Therefore, the establishment of appropriate antibiotic usage guidelines should be essential in these countries.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Global Health; History, 21st Century; Humans; Prevalence

Colistin is one of the few remaining options for carbapenem-resistant Acinetobacter baumannii (A. baumannii); however, emergence of resistance from heteroresistant populations is possible. This review aimed to systematically search and consolidate the literature on the prevalence, mechanisms and therapeutic implications of colistin heteroresistance in Acinetobacter spp.. A systematic search was conducted in PubMed and Scopus. The pooled prevalence of colistin heteroresistance was calculated using meta-analysis of proportions with the Freeman-Tukey transformation and the random-effects (DerSimonian and Laird) method.. Colistin heteroresistance was common but highly variable between studies. The impact of colistin heteroresistance (frequency of emergent resistance during treatment and correlation with treatment outcomes) requires further study.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Colistin; Drug Resistance, Bacterial; Humans

This review comprehensively assessed the safety and efficacy of colistin alone or in combination in adults with Acinetobacter baumannii infection. PubMed, Embase and the Cochrane Library were searched from inception to March 2018 for studies evaluating colistin monotherapy compared with other antibiotic therapy or colistin-based combination therapy for the treatment of A. baumannii infection in adults. Efficacy outcomes were clinical response and microbiological cure. Safety outcomes were mortality and nephrotoxic adverse events. A total of 4 randomised controlled trials (RCTs) and 14 observational studies were identified, including 7 reporting colistin versus other antibiotics and 12 reporting colistin monotherapy versus colistin-based combination therapy. Overall clinical response, microbiological response and mortality did not differ significantly between colistin monotherapy versus other antibiotics. However, the incidence of nephrotoxicity was significantly higher in colistin monotherapy (OR = 2.50, 95% CI 1.05-5.98; P = 0.04). No significant differences were detected in clinical response and >28-day mortality between colistin monotherapy and combination therapy. However, colistin-based combination therapy showed an increased microbiological response (OR = 0.49, 95% CI 0.32-0.74; P = 0.0009) and decreased incidence of nephrotoxicity (OR = 1.66, 95% CI 0.99-2.78; P =0.05). In conclusion, colistin alone is as effective as other antibiotics for the treatment of A. baumannii infection but has a higher risk of nephrotoxicity. Colistin-based combination therapy demonstrated a microbiological benefit and no higher risk of nephrotoxicity compared with monotherapy. High-quality RCTs are still needed to confirm the beneficial role of colistin-based combination therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Humans; Treatment Outcome

The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns.. In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections.. Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Child; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Infant, Newborn; Polymyxin B; Polymyxins

Acinetobacter baumannii is an important opportunistic pathogen due to its capabilities for developing mechanisms of resistance to a wide range of antimicrobial agents including carbapenems. This review described the risk factors, antimicrobial susceptibility and mechanisms of carbapenem resistance of A. baumannii from different geographical regions of Saudi Arabia. Several factors including complexity of intensive care unit (ICU) environments, increased numbers of patients with serious diseases, wide spread gastrointestinal colonization and extensive use of antimicrobial drugs led to a wide prevalence of A. baumannii infections in hospitals in Saudi Arabia. A. baumannii has been noted to be less susceptible to antimicrobials agents, including carbapenems, over time, resulting in the evolution of multidrug-resistant (MDR) strains. Dissemination of MDR A. baumannii is attributed to the extreme use of wide-spectrum antimicrobial drugs in hospitals, cross infection between inpatients, invasive ICU procedures, and hospitalized patients with diabetic and cancer those are under frequent invasive diagnostic and therapeutic interventions. Although an increasing prevalence of colistin and tigecycline resistance has been reported in many hospitals, combinations of these agents with carbapenems or other antibiotics remain the best therapeutic choice and reasonably safe to treat patients with MDR A. baumannii infections. The wide distribution of carbapenem resistant A. baumannii (CRAB) due to several mechanisms with diverse genetic determinants has been documented. Although OXA-23 β-lactamase and OXA-51 β-lactamase are the most common genes responsible for CRAB, other novel genes such as blaVIM, PER-1-like and GES-5 have been discovered in carbapenem resistant strains. The high rates of MDR A. baumannii in Saudi hospitals indicate that extensive investigation into the molecular basis of MDR and developing new therapies of CRAB is needed. Moreover, the development of a local antibiogram database coupled with a nationwide antimicrobial stewardship and infection prevention program might help to improve our knowledge of the resistance patterns of A. baumannii, and in developing a treatment protocol for decreasing the infection burden in Saudi Arabia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Hospitals; Humans; Microbial Sensitivity Tests; Prevalence; Risk Factors; Saudi Arabia

Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs).. Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018).. Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%-38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%-21.5%).. While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units, Pediatric; Male

Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.. To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin-only susceptible Gram-negative bacteria.. PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.. Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% - 43.6%), clinical success was 70.4% (58.5% - 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% - 83.2%) of cases.. Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Sulbactam; Tigecycline; Treatment Outcome

To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes.. PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed.. Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81-1.02, I. Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae

OBJECTIVE Neurosurgical infections due to multidrug-resistant organisms have become a nightmare that neurosurgeons are facing in the 21st century. This is the dawn of the so-called postantibiotic era. There is an urgent need to review and evaluate ways to reduce the high mortality rates due to these infections. The present study evaluates the efficacy of combined intravenous plus intrathecal or intraventricular (IV + IT) therapy versus only intravenous (IV) therapy in treating postneurosurgical Acinetobacter baumannii infections. METHODS The authors performed a meta-analysis of all peer-reviewed studies from the PubMed, Cochrane Library database, ScienceDirect, and EMBASE in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Five studies were finally included in the present analysis: 126 patients were studied who had postneurosurgical A. baumannii infection. The Cochrane collaboration tool was used to evaluate risk of bias, and a test of heterogeneity was performed. The I

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Female; Humans; Injections, Intraventricular; Male; Middle Aged; Treatment Outcome; Young Adult

Treatment of Acinetobacter baumannii has become a medical challenge because of the increasing incidence of multiresistant strains and a lack of viable treatment alternatives. This systematic review attempts to investigate the changes in resistance of A. baumannii to different classes of antibiotics in Iran, with emphasis on the antimicrobial activity of polymyxin B (PMB) and colistin (COL). Biomedical databases were searched for English-published articles evaluating microbiological activity of various antimicrobial agents, including PMB and COL. Then, the available data were extracted and analyzed. Thirty-one studies, published from 2009 to 2015, were identified which contain data for 3,018 A. baumannii clinical isolates. With the exception of polymyxins and tigecycline (TIG), there was a high rate of resistance to various groups of antibiotics, including carbapenems. The minimum inhibitory concentration (MIC) ranges for PMB and COL on A. baumannii isolates tested were 0.12-64 μg/ml and 0.001-128 μg/ml, respectively. Polymyxins showed adequate activity with no significant trends in the resistance rate during most of the study period. The incidence of resistance to TIG was estimated low from 2% to 38.4% among the majority of A. baumannii. The present systematic review of the published literatures revealed that multidrug-resistant (including carbapenem-resistant) strains of A. baumannii have increased in Iran. In these circumstances, the older antibiotics, such as COL or PMB, preferably in combination with other antimicrobials (rifampicin, meropenem), could be considered as the therapeutic solution against the healthcare-associated infections. Designing rational dosage regimens for patients to maximize the antimicrobial activity and minimize the emergence and prevalence of resistance is recommended.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Iran; Meropenem; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Rifampin; Thienamycins; Tigecycline

Central Nervous System (CNS) infections related to external ventricular derivation are a major complication of patients undergoing neurosurgical procedures. Antimicrobial treatment of CNS infections should be based not only on the susceptibility of the isolated microorganism, but also on the treatment's pharmacokinetic properties demonstrating the passage of the molecule through the blood-brain barrier. When CNS infections are caused by multi-drug resistant Gram-negative bacteria, intrathecal colistin is considered an effective and safe option. We review the literature of intrathecal/intraventricular use of colistin, comprehensive of both pharmacokinetic data and clinical experiences.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Central Nervous System Infections; Cerebrospinal Fluid Shunts; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Injections, Intraventricular; Injections, Spinal; Treatment Outcome

To review recent clinical pharmacokinetic and pharmacodynamic data to optimize dosing regimens for polymyxin B and colistin for treatment of infections due to A. baumannii.. A literature search was performed using the search terms Acinetobacter, polymyxin, colistin, polymyxin B on MEDLINE. Additional references were identified from the resulting citations.. Increasing the dose of polymyxin B or colistin and using either in combination with other antibiotic agents demonstrates improved antimicrobial activity against Acinetobacter spp. Polymyxin B, unlike colistin, is available as an active drug and appears to be relatively unaffected by renal function. This is advantageous both for patients with renal impairment and for those with intact renal function. Achieving therapeutic serum concentrations of colistin may be difficult for those with intact renal function due to rapid clearance of the prodrug, colistimethate sodium (CMS). Clinical data are still lacking for polymyxin B, and it remains to be seen whether advantages demonstrated in PK/PD analyses will persist in the larger scale of patient care and safety.. The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Polymyxin B

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cerebral Ventriculitis; Coinfection; Colistin; Drug Resistance, Multiple; Humans; Male; Middle Aged; Treatment Outcome

Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing problem worldwide. CRAB bacteremia is associated with a high fatality rate and its optimal treatment has not been established. Early institution of appropriate therapy is shown to improve survival of patients with CRAB bloodstream infection. Regrettably, treatment options are limited. Little information exists about the efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and tigecycline possess good in vitro activity and represent in many cases the only therapeutic options although clinical data are scarce. The need for a loading dose of colistin has been recently demonstrated to rapidly achieve therapeutic levels. The use of combination therapy is also a matter of debate but current evidence do not support its routine use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulbactam; Tigecycline

Multidrug resistant among Acinetobacter baumannii infection is associated with a high mortality rate and limits the therapeutic options. The aim of this study was to assess the safety and efficacy of colistin monotherapy vs. other single antibiotic therapy AND colistin-based combination therapy (with other antibiotics) vs. colistin alone for the treatment of Acinetobacter baumannii infection. Online electronic database were searched for studies evaluating colistin with or without other antibiotics in treatment of patients with drug-resistant Acinetobacter baumannii infection. Totally, twelve studies met the inclusion criteria. For colistin-based combination therapy, six articles including 668 patients were included. Our results showed that the overall clinical response did not differ significantly between colistin-based combination therapy and monotherapy (OR = 1.37, 95% CI = 0.86-2.19, P = 0.18). This insignificance was also detected in ICU mortality, length of stay and nephrotoxicity (P > 0.05). However, the colistin-based combination therapy was shown increasing the microbiological response (OR = 2.14, 95% CI = 1.48-3.07, P < 0.0001). For colistin monotherapy, six studies involving 491 patients were analyzed. The results were in concordance with the findings of the colistin-based combination therapy group. Our results suggest that colistin may be a promising therapy as safe and efficacious as standard antibiotics for the treatment of drug-resistant Acinetobacter baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Length of Stay; Treatment Outcome

The multiresistant Acinetobacter species bacteria are frequently involved in urinary or respiratory tract infections, and one of the most effective drugs, colistine, is associated with significant nephrotoxicity and neurotoxicity. Given that very high concentrations of colistine into biological fluids are safe for the human organism, attempts have been made at delivering the drug topically, by aerosol, or, occasionally, intratechally or intraventricularly for meningitis. These topical treatments could eradicate the Pseudomonas sp. from the lung of patients with cystic fibrosis or bronchiectasis and the Acinetobacter baumannii from lung and meninges. However, only one case of colistin topic treatment in urinary tract infection is described. We report a case series of three patients successfully undergone colistin bladder instillations for multi drug resistant Acinetobacter urinary tract infection, and we review the literature about colistin topic treatment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravesical; Aged; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Treatment Outcome; Urinary Tract Infections

To evaluate the available evidence regarding the efficacy and safety of rifampicin, as adjunct to colistin, in the treatment of multidrug resistant Acinetobacter baumannii (MDR-AB).. We searched MEDLINE (1966 to January 2014) using the following search terms: A baumannii, drug resistance, treatment, colistin, and rifampicin and combinations. In addition, the bibliographies of relevant articles were searched for additional citations.. The search was limited to English-language references and adults. Studies in which colistin was not administered intravenously were excluded. In addition, we excluded meeting abstracts and single case reports.. The search strategy identified 5 observational studies and 2 randomized controlled trials that evaluated the combination of intravenous colistin and rifampicin for the treatment of MDR-AB. All observational studies included a small sample size, and the microbiological clearance associated with the combination therapy ranged from 60% to 100%. The randomized controlled trials reported reduced time to microbiological clearance and higher microbiological eradication rate in the colistin/rifampicin group compared with colistin alone. However, there was no difference between both groups in the overall mortality, infection-related mortality, and the length of stay. Furthermore, rifampicin was associated with a higher incidence of hepatotoxicity.. Studies evaluating the combination of rifampicin and colistin in the treatment of MDR-AB are limited. The currently available evidence does not support the addition of rifampicin to colistin because of the lack of improved clinical outcomes with the combination therapy and the risk of rifampicin-induced hepatotoxicity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Rifampin

Acinetobacter baumannii ventriculitis/meningitis due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has become a clinical entity of considerable importance in recent years. A review of the available literature regarding intraventricular (IVT) or intrathecal (ITH) administration of colistin in MDR and XDR A. baumannii ventriculitis/meningitis was conducted and a total of 83 episodes in 81 patients were identified (71 cases in adults and 10 in children and neonates). Colistin was administered via the IVT and ITH route in 52 and 22 cases, respectively, whilst in 7 cases the exact route was not identified. The median dose of local colistin was 125000 IU (10mg) with a range of 20000 IU (1.6 mg) to 500000 IU (40 mg) in adults, whilst a dose of 2000 IU/kg (0.16 mg/kg) up to 125000 IU (10mg) was used in the paediatric population. The median duration of treatment of IVT/ITH polymyxin E was 18.5 days, whilst the median time to achieve sterilisation of cerebrospinal fluid was 4 days. The rate of successful outcome was 89%, and toxicity related to treatment mainly manifested as reversible chemical ventriculitis/meningitis was reported in nine cases (11%). Nowadays, IVT and ITH colistin represents the last resort treatment of MDR and XDR A. baumannii ventriculitis/meningitis, offering a unique, rather safe and successful mode of therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Injections, Intraventricular; Injections, Spinal; Meningitis, Bacterial; Time Factors; Treatment Outcome

Carbapenem-resistant Acinetobacter baumannii pose a significant threat to hospitalized patients, as therapeutic options are scarse. Alarmingly, rates of carbapenem-resistance in A. baumannii are on the rise and are slowly becoming a routine phenotype for this organism. This review focuses on infection control strategies for identification and control of A. baumannii, as well the available therapeutic options.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Disease Management; Disease Outbreaks; Epidemiological Monitoring; Humans; Minocycline; Tigecycline

Acinetobacter baumannii, recognized as a serious threat in healthcare facilities, has the ability to develop resistance to antibiotics quite easily. This resistance is related to either gene acquisition (horizontal gene transfer) or mutations in the genome, leading to gene disruption, over- or down-expression of genes. The clinically relevant antibiotic resistances in A. baumannii include resistance to aminoglycosides, broad-spectrum cephalosporins, carbapenems, tigecycline and colistin, which are the last resort antibiotics. The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance. The most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are also highlighted. The implementation of early detection and identification of multidrug-resistant A. baumannii is crucial to control their spread.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression; Gene Transfer, Horizontal; Humans; Minocycline; Mutation; Tigecycline

Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negative bacteria, including the fluoroquinolones and the cephalosporins. Some members of the species have accumulated these resistance genes in large resistance islands, located in a "hot-spot" within the bacterial chromosome. The only conventional remaining treatment options were the carbapenems. However, A. baumannii possesses an inherent class D β-lactamase gene (blaOXA-51-like) that can have the ability to confer carbapenem resistance. Additionally, mechanisms of carbapenem resistance have emerged that derive from the importation of the distantly related class D β-lactamase genes blaOXA-23 and blaOXA-58. Although not inducible, the expression of these genes is controlled by mobile promoters carried on ISAba elements. It has also been found that other resistance genes including the chromosomal class C β-lactamase genes conferring cephalosporin resistance are controlled in the same manner. Colistin is now considered to be the final drug capable of treating infections caused by carbapenem-resistant A. baumannii; however, strains are now being isolated that are resistant to this antibiotic as well. The increasing inability to treat infections caused by A. baumannii ensures that this pathogen more than ranks with MRSA or Clostridium difficile as a threat to modern medicine.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation; Humans; Immunocompromised Host

Despite having a reputation of low virulence, Acinetobacter baumannii is an emerging multidrug-resistant (MDR) pathogen responsible for community- and hospital-acquired infections that are difficult to control and treat. Interest in this pathogen emerged about one decade ago because of its natural MDR phenotype, its capability of acquiring new mechanisms of resistance and the existence of nosocomial outbreaks. Recent advances in molecular biology, including full genome sequencing of several A. baumannii isolates, has led to the discovery of the extraordinary plasticity of their genomes, which is linked to their great propensity to adapt to any environment, including hospitals. In this context, as well as the increasing antimicrobial resistance amongst A. baumannii isolates to the last-line antibiotics carbapenems and colistin, therapeutic options are very limited or absent in some cases of infections with pandrug-resistant bacteria. However, a large proportion of patients may be colonised by such MDR bacteria without any sign of infection, leading to a recurrent question for clinicians as to whether antibiotic treatment should be given and will be effective in the presence of resistance mechanisms. The worldwide emergence of A. baumannii strains resistant to colistin is worrying and the increasing use of colistin to treat infections caused by MDR bacteria will inevitably increase the recovery rate of colistin-resistant isolates in the future. Current knowledge about A. baumannii, including biological and epidemiological aspects as well as resistance to antibiotics and antibiotic therapy, are reviewed in this article, in addition to therapeutic recommendations.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Carrier State; Colistin; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Europe; Gene Transfer, Horizontal; Humans

Lower respiratory tract infections, due to Pseudomonas aeruginosa or Acinetobacter baumannii, are frequently encountered in patients with cystic fibrosis (CF) or in patients developing nosocomial pneumonias. Both of these conditions bear a high mortality risk and aggressive antibiotic therapy is necessary. Inhaled antibiotics might represent an effective therapeutic approach for these diseases as it has demonstrated good bactericidal efficacy and safety in both preclinical and clinical studies. This colistin formulation might be useful particularly in patients with respiratory tract infections due to multidrug-resistant Gram-negative bacteria. Its main advantages are a better safety profile with a minimal or absent risk of nephrotoxicity.. This paper discusses the available systemic formulations of colistin, with pharmacokinetic and safety profiles, followed by an overview of inhaled antibiotics in lower respiratory tract infections.. Inhaled colistin should be used selectively as monotherapy in chronic infections with P. aeruginosa in CF patients, whereas in patients with hospital/ventilator-acquired pneumonia (HAP/VAP), it should be used in a combined regimen with systemic antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Animals; Anti-Bacterial Agents; Bronchiectasis; Colistin; Cross Infection; Cystic Fibrosis; Drug Synergism; Drug Therapy, Combination; Humans; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Colistin is the last resort for treatment of multidrug-resistant Acinetobacter baumannii. Unfortunately, resistance to colistin has been reported all over the world. The highest resistance rate was reported in Asia, followed by Europe. The heteroresistance rate of A. baumannii to colistin is generally higher than the resistance rate. The mechanism of resistance might be loss of lipopolysaccharide or/and the PmrAB two-component system. Pharmacokinetic/pharmacodynamic studies revealed that colistin monotherapy is unable to prevent resistance, and combination therapy might be the best antimicrobial strategy against colistin-resistant A. baumannii. Colistin/rifampicin and colistin/carbapenem are the most studied combinations that showed promising results in vitro, in vivo and in the clinic. New peptides showing good activity against colistin-resistant A. baumannii are also being investigated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Asia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Europe; Humans; Prevalence

'Old' colistin and polymyxin B are increasingly used as last-line therapy against multidrug-resistant Gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. For intravenous administration, colistin is dosed as its inactive prodrug colistin methanesulfonate (sodium), while polymyxin B is used as its sulfate (active antibacterial). Over the last decade, significant progress has been made in understanding their chemistry, pharmacokinetics (PK), and pharmacodynamics (PD). The first scientifically based dosing suggestions are now available for colistin methanesulfonate to generate a desired target steady-state plasma concentration of formed colistin in various categories of critically ill patients. As simply increasing polymyxin dosage regimens is not an option for optimizing their PK/PD due to nephrotoxicity, combination therapy with other antibiotics has great potential to maximize the efficacy of polymyxins while minimizing emergence of resistance. We must pursue rational approaches to the use of polymyxins and other existing antibiotics through the application of PK/PD principles.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Humans; Klebsiella Infections; Polymyxin B; Polymyxins; Pseudomonas Infections

The emergence of multidrug-resistant Gram-negative bacteria that cause nosocomial infections is a growing problem worldwide. Colistin was first introduced in 1952 and was used until the early 1980s for the treatment of infections caused by Gram-negative bacilli. In vitro, colistin has demonstrated excellent activity against various Gram-negative rod-shaped bacteria, including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Recent clinical findings regarding colistin activity, pharmacokinetic properties, clinical uses, emerging resistance, toxicities and combination therapy have been reviewed. Recent approaches to the use of colistin in combination with other antibiotics hold promise for increased antibacterial efficacy. It is probable that colistin will be the 'last-line' therapeutic drug against multidrug-resistant Gram-negative pathogens in the 21st century.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cell Membrane; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Acinetobacter baumannii is an opportunistic Gram-negative pathogen with increasing relevance in a variety of hospital-acquired infections especially among intensive care unit patients. Resistance to antimicrobial agents is the main reason for A. baumannii spread. A. baumannii outbreaks described worldwide are caused by a limited number of genotypic clusters of multidrug-resistant strains that successfully spread among hospitals of different cities and countries. In this article, we will focus on the mechanisms responsible for resistance to antimicrobials and disinfectants in A. baumannii and the epidemiology of drug-resistant A. baumannii in healthcare facilities. We will also discuss the therapeutic and infection control strategies for management of drug-resistant A. baumannii epidemics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; DNA Fingerprinting; DNA, Ribosomal Spacer; Drug Resistance, Multiple, Bacterial; Humans; Infection Control; Molecular Epidemiology; RNA, Ribosomal, 16S; Sulbactam

Treatment limitations exist for drug-resistant Acinetobacter baumannii central nervous system (CNS) infection. We conducted a retrospective study and systematic literature review to identify patients with drug-resistant A. baumannii CNS infection who received primary or adjunct intrathecal or intraventricular (IT/IVT) colistin. In a case series of seven Thai patients and 17 patients identified in the literature, clinical and microbiological cure rates with IT/IVT colistin therapy were 83% and 92%, respectively. Three patients (13%) developed chemical ventriculitis and one (4%) experienced treatment-associated seizures. Death was associated with delayed IT/IVT colistin therapy compared to survival (mean time from diagnosis to IT/IVT colistin, 7 vs. 2 days; p 0.01). The only independent predictor of mortality was the severity of illness (APACHE II score > 19, adjusted odds ratio 49.5; 95% CI 1.7-1428.6; p 0.02). This case series suggests that administration of primary or adjunctive IT/IVT colistin therapy was effective for drug-resistant A. baumannii CNS infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; APACHE; Central Nervous System Bacterial Infections; Central Nervous System Infections; Child; Child, Preschool; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Intraventricular; Injections, Spinal; Male; Middle Aged; Risk Factors; Thailand; Treatment Outcome

Post-neurosurgical nosocomial meningitis has become an important subgroup of bacterial meningitis in the hospital setting. The increase in meningitis caused by multidrug-resistant (MDR) Acinetobacter baumannii has resulted in a significant reduction in available treatment options.. We report the case of a 36-year-old man with a complex craniofacial trauma, who developed a nosocomial meningitis due to MDR A. baumannii that was cured by intrathecal colistin. The case is contextualized among all the published cases of Acinetobacter meningitis treated with topical colistin found through a MEDLINE search of the literature. To date, including the present case, eight reported cases of Acinetobacter meningitis have been treated with colistin administered by an intrathecal route and 24 by an intraventricular route. The daily dose of colistin used ranged from 1.6 mg every 24 h to 20 mg every 24 h in adult patients. The median time necessary to obtain cerebrospinal fluid sterilization was 4.1 days, and treatment was always successful even if in two cases Acinetobacter meningitis relapsed. Toxicity probably or possibly related to the topical administration of colistin was noted in five out of the 32 patients.. Topical colistin can be an effective and safe treatment for MDR Acinetobacter meningitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Craniocerebral Trauma; Drug Resistance, Multiple, Bacterial; Humans; Injections, Spinal; Male; Meningitis, Bacterial; Postoperative Complications; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Arizona; Centers for Disease Control and Prevention, U.S.; Colistin; Communicable Diseases, Emerging; Critical Care; Disease Outbreaks; Disease Reservoirs; Drug Resistance, Multiple, Bacterial; Environmental Microbiology; Equipment Contamination; Genes, Bacterial; Genes, MDR; Humans; Infection Control; Minocycline; Nursing Staff, Hospital; Risk Factors; Tigecycline; Total Quality Management; United States

Acinetobacter baumannii is an important cause of nosocomial infections, mainly in patients in intensive care units. This microorganism, although with slight differences depending on the country, presents resistance to multiple antimicrobial agents, occasionally including resistance to colistin: hence, it can be considered the paradigm of nosocomial multiresistant bacteria. This review analyzes the evolution of antimicrobial resistance and the molecular bases associated with the increase in antimicrobial resistance, as well as the current treatment of Acinetobacter infections. Although controversy remains, the pooled data suggest that infections by A. baumannii may be associated with considerable attributable mortality. Moreover, in cases of pneumonia and bacteraemia, inappropriate treatment is associated with, among other factors, mortality. Therefore, treatment should be carefully considered.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Minocycline; Patient Selection; Rifampin; Sulbactam; Tigecycline; Treatment Outcome

The spectrum of available therapeutic options has become drastically narrowed in recent years, particularly for nosocomial multidrug-resistant gram-negative pathogens. This therapeutic void has created a resurgence of interest in colistin. In 5 published series since 1999, clinical response rates for pneumonia due to Pseudomonas aeruginosa or Acinetobacter baumannii treated with intravenous colistin have ranged from 25% to 62%, despite high severity of illness at baseline. De novo nephrotoxicity was observed in 8%-36% of patients, despite close attention to both appropriate dosing and duration of treatment. Neurotoxicity, which was commonly described in the old colistin era, has been exceedingly rare in recent experience. Aerosolized therapy as an adjunct to systemic treatment appears promising, but the current published data are much too limited to allow determination of the incremental benefit of the addition of aerosolized treatment to systemic treatment. Colistin is a reasonably safe last-line therapeutic alternative for pneumonia due to multi- or panresistant P. aeruginosa or A. baumannii.

Topics: Acinetobacter; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Infusions, Parenteral; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome; Ventilators, Mechanical

Intrathecal colistin (Polymxin E) is becoming an important option for the treatment of post-neurosurgical meningitis caused by multidrug resistant (MDR) Acinetobacter baumannii. We report a case of 28-year-old man who developed meningitis due to MDR A. baumannii associated with an external ventricular drain. The patient was cured using a 4-week course of intrathecal colistin 3.2 mg via external ventricular drain (EVD) daily without any serious side effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Craniocerebral Trauma; Drug Resistance, Multiple, Bacterial; Humans; Injections, Spinal; Male; Meningitis, Bacterial; Postoperative Complications

To review and evaluate clinically relevant epidemiology, microbiology, and clinical studies regarding the treatment of multidrug-resistant Acinetobacter infections.. Pertinent literature was identified by a MEDLINE search (1966-September 2003) and through secondary bibliographies of pertinent articles.. All English-language articles identified from data sources were evaluated for clinical relevance.. Acinetobacter baumannii has emerged as a worldwide problem as a nosocomial pathogen in hospitalized patients. Acinetobacter spp. can cause a multitude of infections including pneumonia, bacteremia, meningitis, urinary tract infections, and skin and soft tissue infections, and the mortality associated with these infections is high. Isolates resistant to almost all commercially available antimicrobials have been identified, thus limiting treatment options. The development of new agents and reappraisal of older compounds (ie, polymyxins, ampicillin/sulbactam) are necessary as we consider the optimal treatment of these multidrug-resistant organisms.. There is no simple answer to the treatment of Acinetobacter infections. Eradication of Acinetobacter spp. requires adherence to good infection control practices and prudent antibiotic use, as well as effective antimicrobial therapy. Alternative therapies such as colistin, ampicillin/sulbactam, and tetracycline are potential options, but prospective, randomized, controlled trials are still lacking.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Randomized Controlled Trials as Topic; Risk Factors; Sulbactam; Tetracyclines

There is a crucial need for novel antibiotics to stem the tide of antimicrobial resistance, particularly against difficult to treat gram-negative pathogens like Acinetobacter baumannii-calcoaceticus complex (ABC). An innovative approach to addressing antimicrobial resistance may be pathogen-targeted development programs. Sulbactam-durlobactam (SUL-DUR) is a β-lactam/β-lactamase inhibitor combination antibiotic that is being developed to specifically target drug-resistant ABC. The development of SUL-DUR culminated with the Acinetobacter Treatment Trial Against Colistin (ATTACK) trial, a global, randomized, active-controlled phase 3 clinical trial that compared SUL-DUR with colistin for treating serious infections due to carbapenem-resistant ABC. SUL-DUR met the primary noninferiority endpoint of 28-day all-cause mortality. Furthermore, SUL-DUR had a favorable safety profile with a statistically significant lower incidence of nephrotoxicity compared with colistin. If approved, SUL-DUR could be an important treatment option for infections caused by ABC, including carbapenem-resistant and multidrug-resistant strains. The development program and the ATTACK trial highlight the potential for pathogen-targeted development programs to address the challenge of antimicrobial resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Sulbactam

The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.. This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.. The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.. La forma más eficaz de controlar la gravedad y la tasa de mortalidad de la enfermedad del nuevo coronavirus (COVID-19) es mediante enfoques de diagnóstico sensibles y un protocolo de tratamiento adecuado. Nuestro objetivo fue identificar el efecto de agregar corticosteroides y tocilizumab a un protocolo de tratamiento estándar en el tratamiento de pacientes con COVID-19 con enfermedad crónica a través de biomarcadores hematológicos y de laboratorio.. Este estudio se realizó de forma retrospectiva en 68 pacientes COVID-19 con enfermedad crónica que fueron tratados por diferentes protocolos terapéuticos. Los pacientes se clasificaron en cuatro grupos: el grupo de control representaba los resultados de laboratorio de los pacientes en el momento de la admisión antes de que se aplicaran los protocolos de tratamiento; el grupo 1 incluyó a pacientes tratados con anticoagulantes, hidroxicloroquina y antibióticos; el grupo 2 estaba compuesto por pacientes tratados con dexametasona; y el grupo 3 incluyó a pacientes tratados con dexametasona y tocilizumab.. El estudio allana el camino hacia la eficacia de la combinación de dexametasona con tocilizumab en el tratamiento de pacientes con COVID-19 con enfermedades crónicas.. The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.. Six ceria supports synthesized by various synthesis methodologies were used to deposit cobalt oxide. The catalysts were thoroughly characterized, and their catalytic activity for complete methane oxidation was studied. The supports synthesized by direct calcination and precipitation with ammonia exhibited the best textural and structural properties as well as the highest degree of oxidation. The remaining supports presented poorer textural properties to be employed as catalytic supports. The cobalt deposited over the first two supports presented a good dispersion at the external surface, which induced a significant redox effect that increased the number of Co. Some studies show that children with obesity are more likely to receive a diagnosis of depression, anxiety, or attention-deficit hyperactivity disorder (ADHD). But this does not necessarily mean obesity causes these conditions. Depression, anxiety, or ADHD could cause obesity. A child's environment, including family income or their parents' mental health, could also affect a child's weight and mental health. Understanding the nature of these relationships could help scientists develop better interventions for both obesity and mental health conditions. Genetic studies may help scientists better understand the role of the environment in these conditions, but it's important to consider both the child's and their parents’ genetics in these analyses. This is because parents and children share not only genes, but also environmental conditions. For example, families that carry genetic variants associated with higher body weight might also have lower incomes, if parents have been affected by biases against heavier people in society and the workplace. Children in these families could have worse mental health because of effects of their parent’s weight, rather than their own weight. Looking at both child and adult genetics can help disentangle these processes. Hughes et al. show that a child's own body mass index, a ratio of weight and height, is not strongly associated with the child’s mental health symptoms. They analysed genetic, weight, and health survey data from about 41,000 8-year-old children and their parents. The results suggest that a child's own BMI does not have a large effect on their anxiety symptoms. There was also no clear evidence that a child's BMI affected their symptoms of depression or ADHD. These results contradict previous studies, which did not account for parental genetics. Hughes et al. suggest that, at least for eight-year-olds, factors linked with adult weight and which differ between families may be more critical to a child's mental health than a child’s own weight. For older children and adolescents, this may not be the case, and the individual’s own weight may be more important. As a result, policies designed to reduce obesity in mid-childhood are unlikely to greatly improve the mental health of children. On the other hand, policies targeting the environmental or societal factors contributing to higher body weights, bias against people with higher weights, and poor child mental health directly may be more beneficial.. The development of an efficient photocatalyst for C2 product formation from CO. Оценка антиастенического эффекта последовательной терапии левокарнитином (ЛК) и ацетилкарнитином (АЛК) пациентов с артериальной гипертензией и/или ишемической болезнью сердца (ИБС) с астеническим синдромом (АС).. В открытое сравнительное исследование были включены 120 пациентов в возрасте 54—67 лет с артериальной гипертензией и/или ИБС с АС. Пациенты 1-й группы (. У больных 1-й группы отмечено статистически значимое уменьшение различных проявлений АС. Отличия носили достоверный характер по сравнению как с исходным уровнем, так и со 2-й группой. Установлено эндотелийпротективное действие ЛК и АЛК.. Полученные результаты свидетельствуют, что у таких коморбидных пациентов использование ЛК и АЛК уменьшает выраженность проявлений АС, а установленные эндотелиотропные свойства препаратов позволяют рекомендовать их в составе комплексной персонифицированной терапии пациентов с сердечно-сосудистыми заболеваниями.. Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.. Сравнительный анализ эффективности и безопасности новой комбинации напроксена натрия и дифенгидрамина у пациентов с неспецифическим болевым синдромом в пояснично-крестцовом отделе спины (M54.5 «Боль внизу спины») и нарушением сна (G47.0 «Нарушения засыпания и поддержания сна [бессонница]»).. Проведено проспективное многоцентровое рандомизированное открытое сравнительное в параллельных группах клиническое исследование. Пациенты были рандомизированы в 3 группы. Больные 1-й группы получали напроксен натрия (440 мг) и дифенгидрамин (50 мг), 2-й — напроксен натрия (550 мг), 3-й — парацетамол (1000 мг) и дифенгидрамин (50 мг). Исследуемые препараты пациенты принимали однократно перед сном в течение 3 дней. Все пациенты также принимали 275 мг (1 таблетка) напроксена натрия в качестве препарата фоновой терапии. Первичным критерием эффективности было общее время бодрствования после наступления сна (WASO), измеряемое методом актиграфии. Также использовались критерии оценки продолжительности и качества сна и выраженности боли.. Анализ эффективности проведен для ITT популяции (. Применение комбинации напроксена натрия (440 мг) и дифенгидрамина (50 мг) характеризовалось более выраженным поддержанием сна по сравнению с напроксеном натрия 550 мг и более высокой эффективностью в отношении снижения интенсивности боли по сравнению со 2-й и 3-й группами. Отмечена хорошая переносимость препарата, серьезных нежелательных явлений зарегистрировано не было.

Topics: Acetaminophen; Acetylcarnitine; Acetylcholinesterase; Acids; Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Psychological; Adolescent; Adsorption; Adult; Aged; Alcohol Drinking; Alzheimer Disease; Amikacin; Ammonia; Anaerobiosis; Animals; Anorexia; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Anxiety; Aptamers, Nucleotide; Asthenia; Attention Deficit Disorder with Hyperactivity; Bacterial Proteins; Beryllium; beta-Lactamases; Biofuels; Biomass; Biosensing Techniques; Bismuth; Blister; Body Mass Index; Body Surface Area; Boronic Acids; Brain; Breast Neoplasms; Butyrylcholinesterase; Cannabis; Carbapenems; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carboxylic Acids; Carcinoma, Hepatocellular; Cardiovascular Diseases; Carnitine; Case-Control Studies; Catalysis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Child; China; Cholinesterase Inhibitors; Clarithromycin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cohort Studies; Colistin; Colitis; Colon; Coloring Agents; Coronary Artery Bypass; Creatinine; Crystalloid Solutions; Cytokines; Depression; Dextran Sulfate; Dextrans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diarrhea; Dietary Supplements; Diphenhydramine; Disease Models, Animal; Disease Outbreaks; Double-Blind Method; Doxorubicin; Drosophila; Drug Tapering; Dysbiosis; Electrons; Escherichia coli; Extracellular Vesicles; Fatigue; Female; Fermentation; gamma-Cyclodextrins; Gastrointestinal Microbiome; Glucose; Graft Survival; Graft vs Host Disease; Head and Neck Neoplasms; Heart Arrest, Induced; Hematopoietic Stem Cell Transplantation; High-Intensity Interval Training; Hippocampus; Humans; Hydrogen-Ion Concentration; Hypertension; Incidence; Interferon-gamma; Italy; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Lactoferrin; Larva; Length of Stay; Lignin; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Low Back Pain; Lung; Lung Volume Measurements; Macrophages; Male; Melphalan; Men; Mendelian Randomization Analysis; Meropenem; Methane; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitochondrial Proteins; Molecular Docking Simulation; Molecular Structure; Mothers; Motivation; Mycoplasma; Mycoplasma hominis; Mycoplasma Infections; NAD; Nanocomposites; Nanoparticles; Nanotubes, Carbon; Naproxen; Neovascularization, Pathologic; Neurons; Nitrates; Nucleolin; Opuntia; Paratyphoid Fever; Phenotype; Phosphatidylinositol 3-Kinases; Phytochemicals; Plant Extracts; Pregnancy; Prevalence; Prospective Studies; Proto-Oncogene Proteins c-akt; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Wistar; Resveratrol; Retrospective Studies; Rifampin; Risk Factors; RNA, Messenger; Selenium; Sleep; Social Behavior; Soil; Soil Pollutants; Squamous Cell Carcinoma of Head and Neck; Staphylococcus aureus; Structure-Activity Relationship; Suicidal Ideation; Suicide; Superoxide Dismutase-1; Surveys and Questionnaires; Swimming; Syndrome; Tannins; Temperature; Transforming Growth Factor beta; Transplantation Conditioning; Treatment Outcome; Triple Negative Breast Neoplasms; Troponin T; Tumor Microenvironment; United Kingdom; Ureaplasma; Ureaplasma urealyticum; Urinary Tract Infections; Viscum; Waste Disposal Facilities; Wastewater; Water; Water Pollutants, Chemical; Wolfiporia; Young Adult

We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy.. This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality.. Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118-.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021-9.202]).. Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy.. NCT01732250.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Data Interpretation, Statistical; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB).. This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching.. The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality.. Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Treatment Outcome

Efficacy of colistin and ampicillin-sulbactam have not been compared in treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of colistin and ampicillin-sulbactam in combination with meropenem were compared in treatment of ventilator-associated pneumonia due to carbapenem-resistant A. baumannii.. 47 patients with ventilator-associated pneumonia due to carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological responses and 28-day mortality were considered as outcomes.. Clinical response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p = 0.59) were comparable between meropenem/colistin and meropenem/ampicillin-sulbactam groups, respectively.. In this study, clinical and microbiological response were comparable between the meropenem/colistin and meropenem/ampicillin-sulbactam groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiratory Tract Infections; Treatment Outcome

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Endpoint Determination; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Rifampin; Risk Assessment

The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes.. Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Disease Outbreaks; Feces; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Meropenem; Prospective Studies; Thienamycins

Ninety-four patients infected with carbapenem-resistant Acinetobacter baumannii were randomized to receive colistin alone or colistin plus fosfomycin for 7 to 14 days. The patients who received combination therapy had a significantly more favorable microbiological response and a trend toward more favorable clinical outcomes and lower mortality than those who received colistin alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01297894.).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Pilot Projects; Treatment Outcome

Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone.. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length.. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization.. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit.. NCT01577862.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Rifampin; Survival Analysis; Tertiary Care Centers; Treatment Outcome

The aim of this study was to compare the responses of colistin treatment alone vs. a combination of colistin and rifampicin in the treatment of ventilator-associated pneumonia (VAP) caused by a carbapenem-resistant A. baumannii strain. Forty-three patients were randomly assigned to one of two treatment groups. Although clinical (P = 0·654), laboratory (P = 0·645), radiological (P = 0·290) and microbiological (P = 0·597) response rates were better in the combination group, these differences were not significant. However, time to microbiological clearance (3·1 ± 0·5 days, P = 0·029) was significantly shorter in the combination group. The VAP-related mortality rates were 63·6% (14/22) and 38·1% (8/21) for the colistin and the combination groups (P = 0·171), respectively. Our results suggest that the combination of colistin with rifampicin may improve clinical and microbiological outcomes of VAP patients infected with A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Rifampin; Treatment Outcome

The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients.. The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function.. This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day.. Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients.. CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Sepsis

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance.. A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).. Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

To determine the efficacy and safety of colistin (colistimethate sodium) produced by a local pharmaceutical company in Thailand for the treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii.. Patients hospitalized at Siriraj Hospital between January 2005 and April 2006, who had infections caused by MDR P. aeruginosa or A. baumannii, were enrolled in the study. Colistin (colistimethate sodium) at a dosage of 5 mg/kg/day was given intravenously in two divided doses. Primary outcomes were the clinical response and 30-day mortality; secondary outcomes were microbiological response and adverse events.. Ninety-three patients infected with MDR P. aeruginosa and A. baumannii were enrolled. Seventy-eight patients (71 with A. baumannii and seven with P. aeruginosa) received colistin, whereas 15 patients (12 with A. baumannii and three with P. aeruginosa) received other antibiotics. The mean age, gender, underlying conditions and severity of illness of the patients in both groups were not significantly different. In the colistin group, 63 patients (80.8%) had a favorable clinical response and 94.9% had a microbiological response. The overall mortality of the patients in the colistin group was 46.2% and that in the non-colistin group was 80%. Nephrotoxicity was found in 24 patients (30.8%) in the colistin group and 17 of them had predisposing factors contributing to their renal dysfunction. No neurotoxicity was observed among the 78 patients.. Locally produced colistin appears to be safe and effective for the treatment of infections caused by MDR P. aeruginosa and A. baumannii in Thai adult patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Thailand; Treatment Outcome

The increased incidence of nosocomial infections by multi-drug resistant Acinetobacter baumannii creates demand on the application of some combinations of older antimicrobials on that species. We conducted the present observational study to evaluate the efficacy of intravenous and aerosolized colistin combined with rifampicin in the treatment of critically patients with nosocomial infections caused by multiresistant A. baumannii.. Critically ill patients with nosocomial infections caused by A. baumannii resistant to all antibiotics except colistin in a medical intensive care unit. Diagnosis of infection was based on clinical data and isolation of bacteria. The bacterial susceptibilities to colistin were tested. Clinical response to colistin+rifampicin was evaluated.. Twenty-six patients (43.58+/-18.29 years, Acute Physiology and Chronic Health Evaluation II Score (APACHE II): 6.35+/-2.99), of whom 16 cases of nosocomial pneumonia treated by aerosolized colistin (1x10(6) IU three times/day) associated with intravenous rifampicin (10 mg/kg every 12h), nine cases of bacteraemia treated by intravenous colistin (2x10(6)IU three times/day) associated with intravenous rifampicin (10 mg/kg every 12h) in which three cases associated with ventilator associated pneumonia and one case of nosocomial meningitis treated by intrathecal use of colistin associated with intravenous rifampicin. The clinical evolution was favourable for all ill patients. Concerning side effects, we have noticed a moderate hepatic cytolysis in three patients.. This is the first clinical report of colistin combined with rifampicin for treatment of A. baumannii infection. Despite the lack of a control group and the limited number of patients, the results seem to be encouraging.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Rifampin; Treatment Outcome

To assess renal dysfunction and outcome in patients treated exclusively with colistin vs. other antibiotics.. Prospective cohort study in a mixed ICU in a university-affiliated hospital.. 185 patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin group, similar in age, APACHE II, medical status, and SOFA score.. We recorded data on epidemiology and severity of illness, site of infection, renal function before and after treatment, clinical cure, and mortality. Clinical cure was defined as simultaneous normalization of central temperature (< or = 38 degrees), leukocyte count (< or = 10,000/mm3), and PaO2/FIO2 ratio (>187). Before treatment creatinine was 0.9+/-0.2 in the colistin group and 0.9+/-0.1 in the noncolistin group; after treatment the value was 1.0+/-0.3 in both groups. The most frequent infection was ventilator-associated pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively, Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the noncolistin group 81% of patients were treated with carbapenems. Inadequate empirical antimicrobial treatment was more frequent in the colistin group (100% vs. 8%), but there were no differences in the frequency of clinical cure on day 6 of treatment (15% and 17%) or in mortality (29% and 24%).. Colistin appears to be as safe and as effective as other antimicrobials for treatment of sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; APACHE; Argentina; Blood Gas Analysis; Cohort Studies; Colistin; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas; Pseudomonas Infections; Treatment Outcome

Sixty nosocomial infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant to aminoglycosides, cephalosporins, quinolones, penicillins, monobactams, and imipenem were treated with colistin (one patient had two infections that are included as two different cases). The infections were pneumonia (33% of patients), urinary tract infection (20%), primary bloodstream infection (15%), central nervous system infection (8%), peritonitis (7%), catheter-related infection (7%), and otitis media (2%). A good outcome occurred for 35 patients (58%), and three patients died within the first 48 hours of treatment. The poorest results were observed in cases of pneumonia: only five (25%) of 20 had a good outcome. A good outcome occurred for four of five patients with central nervous system infections, although no intrathecal treatment was given. The main adverse effect of treatment was renal failure; 27% of patients with initially normal renal function had renal failure, and renal function worsened in 58% of patients with abnormal baseline creatinine levels. Colistin may be a good therapeutic option for the treatment of severe infections caused by multidrug-resistant P. aeruginosa and A. baumannii.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Creatinine; Cross Infection; Drug Resistance, Multiple; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pseudomonas Infections

Antimicrobial susceptibility testing (AST) in RPMI 1640, a more physiologically relevant culture medium, revealed that a substantial proportion of carbapenem-resistant Acinetobacter baumannii isolates were susceptible to azithromycin, a macrolide antibiotic not currently considered effective against A. baumannii. Experiments using Galleria mellonella validated these

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Azithromycin; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Moths

Multidrug-resistant (MDR)

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Peru

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Susceptibility; Humans; Intensive Care Units; Pneumonia, Ventilator-Associated; Prevalence; Renal Dialysis; Retrospective Studies

To characterise 11 colistin- and carbapenem-resistant Acinetobacter baumannii isolates recently emerging in hospital settings.. A. baumannii isolates were collected from hospitalised patients under colistin treatment in three countries of Southeast Europe: Turkey, Croatia, and Bosnia and Herzegovina. Isolates were identified using molecular methods.. Isolates from Turkey and Croatia belong to the sequence types ST195 or ST281 of the clone lineage 2, while the single isolate from Bosnia and Herzegovina belongs to the ST231 of clone lineage 1. All isolates turned out to be highly resistant to colistin (MIC ≥ 16 mg/L) and have point mutations in pmrCAB operon genes. The colistin-resistant isolate from Bosnia and Herzegovina had a unique P170L point mutation in the pmrB gene and the R125H point mutation in the pmrC gene. The L20S mutation in the pmrA gene was detected only in isolates from Croatia and has never been reported before in isolates from this country.. Colistin resistance in A. baumannii in hospitalised patients receiving colistin treatment is a result of chromosomal mutations. The pattern of point mutations in pmrCAB genes suggests a spread of specific colistin-resistant isolates within the hospital.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Drug Resistance, Bacterial; Europe; Humans

The treatment options are limited in Acinetobacter baumannii infections. In this study, the effectiveness of colistin monotherapy and combinations of colistin with different antibiotics were investigated in an experimental pneumonia model induced by carbapenem-resistant A. baumannii strain. Mice in the study were divided into five groups as control (no treatment), colistin monotherapy, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline combinations. The modified experimental surgical pneumonia model of Esposito and Pennington was applied to all groups. The presence of bacteria in blood and lung samples was investigated. Results were compared. In blood cultures, while there was no difference between the control and colistin groups, there was a statistical difference between the control and the combination groups (P = 0.029). When the groups were compared in terms of lung tissue culture positivity, there was a statistical difference between the control group and all treatment groups (colistin, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline) (P = 0.026, P < 0.001, P < 0.001, and P = 0.002, respectively). The number of microorganisms that grew in the lung tissue was found to be statistically significantly lower in all treatment groups in comparison with the control group (P = 0.001). Both monotherapy and combination therapies of colistin were found to be effective in the treatment of carbapenem-resistant A. baumannii pneumonia, but the superiority of combination therapies over colistin monotherapy has not been demonstrated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Imipenem; Mice; Microbial Sensitivity Tests; Sulbactam; Tigecycline

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to major antibiotics such as penicillin, cephalosporin, fluoroquinolone and aminoglycoside, and has become a significant nosocomial pathogen. The efficacy of rifampicin and colistin combination against CRAB could be dependent on the administration routes and drug concentrations at the site of infection.. The objective is to predict drug disposition in biological tissues. Treatment efficacy is extrapolated by assessing respective pharmacodynamic (PD) indices, as well as parameters associated with the emergence of resistance.. Physiologically-based pharmacokinetic models of rifampicin and colistin were utilized to predict tissue exposures. Dosing regimens and administration routes for combination therapy were evaluated in terms of in vitro antimicrobial susceptibility of A. baumannii associated with targeted PD indices and resistance parameters.. Simulated exposures in blood, heart, lung, skin and brain were consistent with reported penetration rates. The results demonstrated that a combination of colistin and rifampicin using conventional intravenous (i.v.) doses could achieve effective exposures in the blood and skin. However, for lung infections, colistin by inhalation would be required due to low lung penetration from intravenous route. Inhaled colistin alone provided good PD coverage but this practice could encourage the emergence of additional resistance which may be overcome by a combination regimen that includes inhaled rifampicin.. This in silico extrapolation provides valuable information on dosing regimens and routes of administration against CRAB infections in specific tissues. The PBPK modeling approach could be a non-invasive way to inform therapeutic benefits of combination antimicrobial therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Rifampin

Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Prevalence

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Multilocus Sequence Typing

We investigated the presence of heteroresistance against both tigecycline and colistin in Acinetobacter baumannii and then evaluated the effectiveness of combined antibiotic treatment given the existence of discrete tigecycline- and colistin-resistant subpopulations.. We performed population analysis profiling (PAP) to evaluate the degree of composite heteroresistance in A. baumannii isolates, with the extent of this resistance quantified using subsequent antibiotic susceptibility testing. We then evaluated the amino acid sequence of PmrBAC and the relative mRNA expression levels of pmrB. Finally, we investigated the combined antibiotic efficacy of tigecycline and colistin in multiple-heteroresistant isolates using dual PAP and in vitro time-killing assays.. All tigecycline-heteroresistant A. baumannii isolates, with the exception of one colistin-resistant isolate, were also heteroresistant to colistin. Evaluations of the colistin-resistant subpopulations revealed amino acid alterations in PmrA and PmrB and increased expression of pmrB. All tigecycline-resistant subpopulations were susceptible to colistin, and all colistin-resistant subpopulations were susceptible to tigecycline. Dual PAP analysis using tigecycline and colistin showed no heteroresistance, and in vitro time-killing assays revealed that a combination of these two antibiotics effectively eliminated the bacterial cells.. Our results suggest that multiple heteroresistance to tigecycline and colistin is highly prevalent among A. baumannii clinical isolates and that these resistant subpopulations exist independently in single multiple heteroresistant isolates. Therefore, our findings may explain the success of combined antibiotic therapies in these infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Tigecycline

Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly found nosocomial infections in critically ill patients. However, the appropriate treatment period for a specific group of critically ill patients with CRAB infection is currently being debated. Therefore, our study aimed to evaluate the optimal courses of therapy for critically ill patients with CRAB infection by comparing the outcomes of colistin therapy of short duration (<14 days) versus long duration (≥ 14 days).. A retrospective cohort study was conducted at Nakornping Hospital on critically ill patients with CRAB infection who received either a short or long course of colistin treatment between 2015 and 2022. The primary outcome was the 30-day mortality rate while secondary outcomes were clinical response, microbiological response, and nephrotoxicity. Propensity score matching with a 1: 1 ratio was performed to reduce potential biases. Furthermore, a logistic regression model was used to estimate the odds ratio (OR).. A total of 374 patients met the inclusion criteria. Two hundred and forty-eight patients were recruited after utilizing propensity scores to match patients at a 1: 1 ratio. The results from the propensity score matching analysis demonstrated that the long-course therapy group had a lower 30-day mortality rate compared to the short-course therapy group (adjusted OR (aOR) = 0.46, 95% CI: 0.26-0.83, p = 0.009). The clinical response and microbiological response rates were higher in patients who received the long course of colistin therapy compared to those receiving the short course (aOR = 3.24, 95% CI: 1.78-5.92, p = 0.001; aOR = 3.01, 95% CI: 1.63-5.57, p = 0.001). There was no significant different in the occurrence of nephrotoxicity (aOR = 1.28, 95% CI: 0.74-2.22, p = 0.368) between the two treatment groups.. A long course of colistin therapy resulted in a lower 30-day mortality rate in critically ill patients, and better clinical and microbiological outcomes, but similar nephrotoxicity as compared to a short course of colistin therapy. Therefore, a specific subset of critically ill patients who had CRAB infection needed to be considered for a long course of therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Humans; Propensity Score; Retrospective Studies

Bacteriophage (phage) therapy, exploiting phages which are the natural enemies of bacteria, has been re-introduced to treat multidrug-resistant (MDR) bacterial infections. However, some intrinsic drawbacks of phages are overshadowing their clinical use, particularly the narrow host spectrum and rapid emergence of resistance upon treatment. The use of phage-antibiotic combinations exhibiting synergistic bacterial killing [termed 'phage-antibiotic synergy' (PAS)] has therefore been proposed. It is well reported that the types and doses of phages and antibiotics are critical in achieving PAS. However, the impact of treatment order has received less research attention. As such, this study used an Acinetobacter baumannii phage vB_AbaM-IME-AB2 and colistin as a model PAS combination to elucidate the order effects in-vitro. While application of the phage 8 h before colistin treatment demonstrated the greatest antibacterial synergy, it failed to prevent the development of phage resistance. On the other hand, simultaneous application and antibiotic followed by phage application were able to suppress/delay the development of resistance effectively, and simultaneous application demonstrated superior antibacterial and antibiofilm activities. Further in-vivo investigation is required to confirm the impact of treatment order on PAS.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriophages; Colistin; Drug Resistance, Multiple, Bacterial; Humans

This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB).. BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay.. Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h.. In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Fosfomycin; Interleukin-6; Mesenchymal Stem Cells; Mice; Microbial Sensitivity Tests; Sepsis

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG prepa

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Immunoglobulins, Intravenous; Meropenem; Microbial Sensitivity Tests

Acinetobacter baumannii is an emerging multidrug-resistant bacterium and is considered as one of the important causes of nosocomial infections.. The main objectives are to determine the drug-resistant pattern of beta-lactamase-producing A. baumannii, colistin-induced structural and biochemical changes.. A. baumannii strains were isolated from the restrooms using the selective media, viz., restroom door, restroom floor, washing area, and restroom tap. A total of 120 samples were collected from all four sampling sites. These strains and their drug-resistance patterns were identified. Then carbapenem-resistance was analyzed and the occurrence of the drug-resistant gene (blaOXA-23) was determined. Colistin was applied at various concentrations (20 - 100 µg/mL) and the molecular mechanism of A. baumannii was analysed.. The bacterial population was high on doors (53 ± 2 CFU/mL), followed by restroom tap (19 ± 1 CFU/mL), restroom floor (14 ± 3 CFU/mL), and washing area (3 ± 0 CFU/mL), respectively. A total of 343 A. baumannii strains were isolated from the 120 samples obtained for one year from the restroom. The isolated bacteria showed resistance to selected carbapenems, with 100% isolates being resistant to imipenem, followed by cefotaxime (1.4 ± 0.2% susceptibility). More blaOXA-23 gene carrying strains were isolated from restroom tap(89 ± 2.1%) than other sources. Colistin exhibited bactericidal activity against drug-resistant A. baumannii. Treating A. baumannii strain with 100 µg/mL colistin induced cell membrane roughness in vitro. Scanning Electron Microscopy (SEM) analysis revealed moderate cell shrinkage after treatment with colistin. Bacterial cells treated with hydrogen peroxide or colistin for 30 min induced the production of hydroxyl radicals. The bacterial lysis increased fluorescence and hydroxyl radicals, and released cellular protein and sugars.. The isolated A. baumannii was resistant to imipenem and showed susceptibility to colistin. Colistin disrupted cell membrane in drug-resistant A. baumannii in vitro. The regular screening for drug-resistance among A. baumannii strains can help monitor the outbreak of A. baumannii and manage control measures.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Imipenem; Microbial Sensitivity Tests

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cerebral Ventriculitis; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis

Drug combinations may have a crucial role in treating infections due to multidrug resistant Acinetobacter spp. One suggested combination is colistin with teicoplanin. The effect of colistin on Acinetobacter spp. outer membrane can permit teicoplanin to its target in the cell wall. The aim of this study was to evaluate the synergistic activity of colistin and teicoplanin combination against 29 multidrug resistant isolates of Acinetobacter spp. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed using MIC and time-kill assays. The combination of 1 mg/l colistin and 10 mg/l teicoplanin showed in vitro synergism against all tested Acinetobacter isolates except one (Acinetobacter lowffii). The combination of 1 mg/l colistin and 10 mg/l teicoplanin was bactericidal at 6 h against 100% of Acinetobacter baumannii isolates with no bacterial regrowth at 24 h. The same combination was bactericidal against three out of seven non-baumannii Acinetobacter isolates. The increased concentration of teicoplanin (20 mg/l) was synergistic but still not bactericidal against the four remaining isolates. The combination of colistin and teicoplanin was synergistic against all tested Acinetobacter spp It is therefore recommended that clinical trials are conducted to clarify the therapeutic potential of the combination.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Teicoplanin

Guidelines for treatment of resistant Acinetobacter baumannii (AB) are limited, leaving a knowledge gap in best practices for treatment. This study described treatments and outcomes of extensively-drug resistant (XDR) AB.. Retrospective cohort study including patients with XDRAB (non-susceptible to at least 1 agent in all but 2 or fewer classes) and antibiotic treatment between 2012 and 2018 at Veterans Affairs Medical Centers. Descriptive statistics summarized antibiotics; propensity score adjusted regression models were fit to compare outcomes.. Two hundred and seventy-six patients with 439 XDRAB cultures and Gram-negative targeted antibiotic treatment were included. One hundred and eighteen (43%) patients received monotherapy while 158 (57%) received combination therapy, most commonly including a carbapenem (n = 106, 67%) and polymyxin (n = 66, 42%). One hundred and eighty-four (67%) patients received inadequate treatment. In adjusted models, combination therapy did not decrease the odds of in-hospital (aOR 1.24, 95%CI 0.60-2.59) or 30-day (aOR 1.43, 95%CI 0.86-2.38) mortality, or median postculture length of stay (aIRR 1.11, 95%CI 0.86-1.43). Likewise, receipt of inadequate treatment was not associated with poorer outcomes.. In this national cohort of patients with XDRAB, neither combination therapy nor receipt of adequate treatment improved outcomes. Further research is needed on optimal management of this difficult-to-treat pathogen with few effective antibiotic options.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Microbial Sensitivity Tests; Retrospective Studies; Veterans

The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) has been increasingly reported, leading to greater challenges in treating infections. With the development of phage therapy and phage-antibiotic combinations, it is promising to improve the treatment of bacterial infections. In the present study, a novel vB_AbaP_WU2001 (vWU2001) phage-specific CRAB with a genome of 40,792 bp was isolated. Genomic analysis disclosed that it belongs to the Autographiviridae family of the order Caudovirales. Phage vWU2001 had a broad host range with a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. Evaluation of its therapeutic potential showed that the combination of phage and colistin resulted in a significantly greater increase in G. mellonella survival and in bacterial clearance, as compared with that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacteriophages; Biofilms; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Synergism; Phage Therapy; Podoviridae

Colistin is currently considered an essential therapeutic option for the treatment of hospital-acquired infections caused by resistant isolates of. Susceptibility data for. This study quantifies the effect of colistin use on the development of resistant strains. These findings can assist antimicrobial stewardship teams to elaborate their plans and predict the effect of their interventions.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Hospitals; Humans; Microbial Sensitivity Tests; Time Factors

Multidrug-resistant Acinetobacter baumannii is an important causal pathogen of healthcare-associated infections, and colistin-resistant strains have recently emerged owing to the increased use of colistin. Using next-generation sequencing (NGS), a single whole-genome sequencing (WGS) protocol can identify and type pathogens, analyze genetic relationships among different pathogens, predict pathogenic transmissions, and detect antibiotic resistance genes. However, only a few studies have applied NGS in studying the resistance mechanism and epidemiology of colistin-resistant A. baumannii. This study aimed to elucidate the resistance mechanism of colistin-resistant A. baumannii and analyze its molecular epidemiology through WGS.. The subjects in this study were patients who visited a university hospital between 2014 and 2018. Thirty colistin-resistant strains with high minimum inhibitory concentrations were selected from various patient samples, and WGS was performed. Comparative genomic analysis was performed for the 27 colistin-resistant A. baumannii strains using a colistin-susceptible strain as the reference genome.. The WGS analysis found no mutation for lpxA, lpxC, lpx D, pmrA, pmrB, and mcr1, the genes known to be associated with colistin resistance. Fifty-seven coding sequences (CDS) showed differences; they included 13 CDS with known names and functions that contained 21 genes. From the whole-genome multi-locus sequence typing (wgMLST) and single nucleotide polymorphism (SNP) analyses, two major clusters were found for the colistin-resistant A. baumannii strains. However, no differences were observed by the time of detection for each cluster, the samples, the pattern of antibiotic resistance, or the patient characteristics. In the conventional MLST following the Oxford scheme, the typing result showed ST1809, ST451, ST191, ST1837, and ST369 in the global clone 2 (GC2), without any relation with the results of wgMLST and SNP analyses.. Based on the findings of the resistance gene analysis through WGS and comparative genomic analysis, the potential genes associated with colistin-resistance or CDS were examined. Furthermore, the analysis of molecular epidemiology through WGS regarding colistin-resistant A. baumannii may prove helpful in preventing infection by multidrug-resistant bacteria and controlling healthcare-associated infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing

Colistin is a last-line antibiotic which acts by causing membrane permeabilization in Gram-negative bacteria. However, its clinical value has been limited by its toxicity and the emergence of resistant organisms. In this study, we showed that econazole and colistin can act synergistically to produce a strong antimicrobial effect sufficient for eradication of starvation-induced tolerant and multidrug-resistant populations of Acinetobacter baumannii, a notorious pathogen causing recalcitrant infections, both

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Econazole; Mice; Microbial Sensitivity Tests

We investigated the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. The in vitro activity of six two-drug combinations against CRAB isolates collected from the blood samples of patients with bloodstream infection was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, and 2 × minimum inhibitory concentration (MIC)] to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates. The effects of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam combinations were investigated. All 10 CRAB isolates in our study produced the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinases. The colistin-ceftolozane/tazobactam combination showed synergistic effects in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method. It also showed bactericidal effects in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there was substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assays (with a concordance of 31.7%). Our study demonstrated that two-drug combinations of colistin and ceftolozane/tazobactam could be useful treatment alternatives for CRAB infections. The effects of these antibiotic combinations should be evaluated using in vivo experimental models.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cephalosporins; Colistin; Drug Combinations; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Rifampin; Tazobactam; Tigecycline

To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii.. Chequerboard and time-kill assays were employed to explore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16-256 μg ml. These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies.. Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Nanoparticles; Selenium

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Ethanolamines; Humans; Lipid A; Microbial Sensitivity Tests; Phosphatidylethanolamines; Sulbactam

Emerging resistance to colistin in Acinetobacter baumannii clinical strains is concerning because of the limited therapeutic choices for these important clinical pathogens. We studied the in vitro activities of different colistin-based antimicrobial agent combinations against colistin-resistant Acinetobacter baumannii. Fourteen clinical isolates of colistin-resistant Acinetobacter baumannii were obtained between 2015 and 2016. To identify colistin-based combinations with synergistic activities, multiple two antimicrobial combinations based on 8 commercially available drugs were evaluated by the checkerboard method. The most effective colistin-based combinations were vancomycin, aztreonam, ceftazidime and imipenem which showed synergistic activities against all examined strains. Colistin-rifampin showed synergy against four strains. Colistin-tigecycline and colistin-amikacin mostly showed indifferent results. By using the checkerboard tests, we were able to find the most promising colistin-based combinations that may provide more therapeutic options against colistin-resistant Acinetobacter baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Genetic Variation; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction

We aimed to provide an analysis of A. baumannii complex (ABC) isolated from blood cultures in South Africa.. ABC surveillance was conducted from 1 April 2017 to 30 September 2019 at 19 hospital sites from blood cultures of any age and sex. Organism identification was performed using the MALDI-TOF MS and antimicrobial susceptibility testing (AST), MicroScan Walkaway System. We confirmed colistin resistance with Sensititre, FRCOL panel, and selected for whole-genome sequencing.. During the study period, we identified 4822 cases of ABC, of which 2152 cases were from 19 enhanced surveillance sites were reported during the enhanced surveillance period (1 August 2018 to 30 September 2019). Males accounted for 54% (2611/4822). Of the cases with known age, 41% (1968/4822) were infants (< 1-year-old). Seventy-eight percent (1688/2152) of cases had a known hospital outcome, of which 36% (602/1688) died. HIV status was known for 69% (1168/1688) of cases, and 14% (238/1688) were positive. Eighty-two percent (1389/1688) received antimicrobial treatment in admission. Three percent (35/1389) of cases received single colistin. Four percent (75/2033) were resistant to colistin. At least 75% of the isolates (1530/2033) can be classified as extensively drug-resistant (XDR), with resistance to most antibiotics except for colistin. The majority, 83% (20/24), of the colistin-resistant isolates were of the sequence type (ST) 1. Resistance genes, both plasmid- and chromosomal- mediated were not observed. Although all isolates had, nine efflux pump genes related to antimicrobial resistance.. Our surveillance data contributed to a better understanding of the natural course of A. baumannii disease, the patient characteristics among infants, and the level of resistance. At least two-thirds of the isolates were extensively drug-resistant, and four percent of isolates were resistant to colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Infant; Male; Microbial Sensitivity Tests; South Africa

The combination of polymyxins, meropenem, and sulbactam demonstrated efficacy against multi-drug-resistant bacillus Acinetobacter baumannii. These three antibiotics are commonly used against major blood, skin, lung, and heart muscle infections.. The objective of this study was to predict drug disposition and extrapolate the efficacy in these tissues using a physiologically based pharmacokinetic modeling approach that linked drug exposures to their target pharmacodynamic indices associated with antimicrobial activities against A. baumannii.. An adult physiologically based pharmacokinetic model was developed for meropenem, colistin, and sulbactam and scaled to pediatrics accounting for both renal and non-renal clearances. The model reliability was evaluated by comparing simulated plasma and tissue drug exposures to observed data. Target pharmacodynamic indices were used to evaluate whether pediatric and adult dosing regimens provided sufficient coverage.. The modeled plasma drug exposures in adults and pediatric patients were consistent with reported literature data. The mean fold errors for meropenem, colistin, and sulbactam were in the range of 0.710-1.37, 0.981-1.47, and 0.647-1.39, respectively. Simulated exposures in the blood, skin, lung, and heart were consistent with reported penetration rates. In a virtual pediatric population aged from 2 to < 18 years, the interpretive breakpoints were achieved in 85-90% of subjects for their targeted pharmacodynamic indices after administration of pediatric dosing regimens consisting of 30 mg/kg of meropenem, and 40 mg/kg of sulbactam three times daily as a 3-h or continuous infusion and 5 mg/kg/day of colistin base activity.. The physiologically based pharmacokinetic modeling supports pediatric dosing regimens of meropenem/colistin/sulbactam in a co-administration setting against infections in the blood, lung, skin, and heart tissues due to A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Child; Colistin; Humans; Meropenem; Reproducibility of Results; Sulbactam

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phenotype

Colistin, which targets lipopolysaccharide (LPS), is used as a last-resort drug against severe infections caused by drug-resistant Acinetobacter baumannii. However, A. baumannii possesses two colistin-resistance mechanisms. LPS modification caused by mutations in

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Ciprofloxacin; Colistin; Disinfectants; Drug Resistance, Multiple, Bacterial; Humans; Lipopolysaccharides; Meropenem; Microbial Sensitivity Tests

We investigated activities of cefiderocol combination therapy against carbapenem-resistant Acinetobacter baumannii (CR-AB). A total of 123 clinical isolates of CR-AB, including 44 cefiderocol-resistant isolates were tested. Cefiderocol functioned synergistically with tigecycline in most cefiderocol-susceptible isolates (84.8%, 67/79), but not with colistin or meropenem by checkerboard method. Cefiderocol functioned synergistically with tigecycline, colistin, and meropenem in 90.9% (40/44), 47.7% (21/44), and 79.5% (35/44) cefiderocol-resistant isolates, respectively. The time-kill assay and the in vivo Galleria mellonella model confirmed these observations. In summary, cefiderocol combined with tigecycline showed synergistic effects against both cefiderocol-susceptible and -resistant CR-AB, suggesting a potentially valuable combination regimen.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Mice; Sulbactam

Acinetobacter baumannii is known as the most frequent species in clinical samples that is responsible for a large number of nosocomial infection outbreaks. The colistin-resistance of this bacterium has been found to be increasing. This study aimed to evaluate the immune response to colistin-susceptible and colistin-resistant A. baumannii isolates in a mouse model. Samples were prepared from the wounds of patients suspected of A. baumannii admitted to the intensive care unit of Namazi Hospital in Shiraz. Antibiotic susceptibility was studied by disk diffusion and broth microdilution according to CLSI and EUCAST criteria. Among the isolates, one colistin-sensitive isolate and one colistin-resistant isolate were injected intraperitoneally to BALB/C mice. Blood samples were collected after 4 h and cytokines (IL1-β, IL-12, IFN γ, and IL-10) and surface markers (CD4, CD8, CD3, and CD45) were determined by ELISA and flow cytometry. Then, hematologic and histopathological factors were analyzed, and colony count in lung, liver, kidney, and spleen tissues were also performed. The results showed that levels of cytokines (IL1-β, IL-12, IFN γ, and IL-10) and markers (CD4, CD8, CD3 and CD45) were higher in mice receiving colistin-resistant A. baumannii isolates than in mice receiving colistin-sensitive A. baumannii isolates, indicating that colistin-resistant isolates 4 h following the intraperitoneal injection stimulated host innate immune system better and produced a stronger immune response. On the other hand, histopathological findings showed inflammatory cell infiltration, hyperemia, and tissue damage. In addition, the bacterial load and tissue damage in the lung was higher than other tissues. The results of this study can have promising potential for the development of a prevention and treatment strategy based on cellular immune response for infection caused by colistin-sensitive and colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Immunity; Interleukin-10; Interleukin-12; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests

Antibiotics at suboptimal doses promote biofilm formation and the development of antibiotic resistance. The underlying molecular mechanisms, however, were not investigated. Here, we report the effects of sub-minimum inhibitory concentrations (sub-MICs) of imipenem and colistin on genes associated with biofilm formation and biofilm-specific antibiotic resistance in a multidrug-tolerant clinical strain of

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Microbial Sensitivity Tests; Virulence

The progressively increasing antimicrobial-resistant Acinetobacter baumannii infections have enforced the use of colistin as the last option for therapy, resulting in the colistin resistance evolution. This work aimed to study the pmrCAB expression in A. baumannii isolates as well as the presence of the mcr-1 gene. Colistin MICs of 100 A. baumannii isolates were measured using the broth microdilution assay. In four colistin-susceptible and four colistin-resistant isolates, the relative expression of the pmrA, pmrB, and pmrC genes was determined using reverse transcription PCR, and then selected isolates were sequenced using the Sanger technique. Finally, the mcr-1 gene was detected using conventional PCR. The colistin resistance rate among the studied isolates was 49%. The expression levels of pmrA and pmrB were statistically significantly higher in colistin-resistant isolates than in colistin-susceptible ones, while the pmrC expression had no statistically significant change. There was a weak positive correlation between colistin MICs and the expression levels of each of the pmrA and pmrB genes. By sequencing, two colistin-resistant strains with low pmrCAB expression showed insertion mutations 3277188_3277189T in pmrB and 1185149_1185150T in pmrC. Only one isolate (1%) was positive for the presence of mcr-1. We concluded that pmrCAB increased expression and/or mutations may cause colistin resistance in A. baumannii. However, increased pmrC expression may not necessarily result in colistin resistance. In Egypt, this is the first study to reveal the existence of mcr-1 in A. baumanni. This should attract attention in clinical settings due to the ultimate tendency of spreading colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests

Infections caused by extensively drug-resistant (XDR)

Topics: Acinetobacter; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Transcription Factors

Extensively drug-resistant Acinetobacter baumannii (XDRAB) pulmonary infection is a serious respiratory system infection. Patients are often very sick and even need to be admitted to the ICU for treatment. In this case report, we presented our treatment experience of one XDRAB pulmonary infection patient. A 71-year-old male patient was admitted to our hospital complaining of "fatigue accompanied by fever for 2 days and shortness of breath for 1 day". The patient's admission diagnosis was as follows: severe pneumonia, acute respiratory distress syndrome, I type respiratory failure, septic shock, cardiac insufficiency, liver insufficiency, and hypertension. Imipenem/cilastatin sodium combined with moxifloxacin were first applied. Then, tigecycline, imipenem/cilastatin and caspofungin were used. The drug sensitivity results suggested that the XDRAB strain of this patient's sputum culture was sensitive to polymyxin only. Thus, colistin sulfate and cefoperazone/sulbactam were applied. The medication process of the patient was monitored. We found that a colistin sulfate intravenous injection combined with aerosol route combined with cefoperazone/sulbactam was effective in the treatment of XDRAB pulmonary infection, and no adverse drug reactions were observed during the treatment. The anti-infection therapy of intravenous colistin sulfate combined with nebulization and cefoperazone/sulbactam could be a good choice for the treatment of XDRAB lung infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Pharmaceutical Preparations; Pneumonia

As carbapenem-resistant Acinetobacter baumannii is dominant in clinical settings, the old polymyxin antibiotic colistin has been revived as a therapeutic option. The development of colistin resistance during treatment is becoming a growing concern.. To access low- to mid-level colistin-resistant A. baumannii blood isolates recovered from an outbreak in a tertiary care hospital from a national antimicrobial surveillance study.. The entire bacterial genome was sequenced through long-read sequencing methodology. Quantitative RT-PCR was carried out to determine the level of gene expression. Relative growth rates were determined to estimate fitness costs of each isolate caused by the genetic alterations.. The A. baumannii isolates belonged to global clone 2 harbouring two intrinsic phosphoethanolamine transferases. Cumulative alterations continuing the colistin resistance were observed. PmrC overproduction caused by the PmrBA226T alteration was identified in A. baumannii isolates with low-level colistin resistance and an additional PmrCR109H substitution led to mid-level colistin resistance. Truncation of the PmrC enzyme by insertion of ISAba59 was compensated by ISAba10-mediated overproduction of EptA and, in the last isolate, the complete PmrAB two-component regulatory system was eliminated to restore the biological cost of the bacterial host.. During the in-hospital outbreak, a trajectory of genetic modification in colistin-resistant A. baumannii isolates was observed for survival in the harsh conditions imposed by life-threatening drugs with the clear purpose of maintaining drug resistance above a certain level with a reasonable fitness cost.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Microbial Sensitivity Tests

The upgrowth and rapid prevalence of pandrug-resistant Acinetobacter baumannii strains that have a pathogenic activity to cause several infections are of considerable influence on the health of communities worldwide. No infections by these bacterial strains were recorded before 1998, and currently, the numbers are on the rise.. The A. baumannii strains were isolated from male and female patients in Medical Microbiology Department, King Fahd Medical City (KFMC) in Riyadh, Saudi Arabia between 1/1/2020 to 29/12/2020. The statistical analysis was performed base on sex, age, source of samples, and response to commercially available antibiotics. The A. baumannii strains that resisted all the antibiotics including colistin and imipenem were selected for the synergic test.. The data showed that 62.28%, 77.07% of 342 A. baumannii strains were isolated from males and patients over 35 years of age. A. baumannii strains (pandrug-A. baumannii) that can resist all tested antibiotics were 8.19%. The major source of the A. baumannii isolates was the respiratory system (>50%). Among all isolates (N = 342), azidothymidine-resistant A. baumannii strains were more than 85%. There is a statistically significant difference (P < 0.05) in the number of colistin-resistant A. baumannii strains isolated from males comparing with the female. The combinations of colistin and silver nanoparticles or imipenem and silver nanoparticles resulted in synergistic action led to reduction of MICs of colistin, imipenem, and silver nanoparticles (more than four-fold reduction). Also, the combinations of colistin and imipenem had high synergistic action.. The pandrug-resistant A. baumannii strains may represent a current and future threat that must be fought, and the synergy action of antibiotics and nanoparticles may be one of the available, rapid, and easy strategies to confront this global problem.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Humans; Imipenem; Male; Metal Nanoparticles; Microbial Sensitivity Tests; Silver

Multidrug-resistant bacterial infections are becoming increasingly common, with only few last-resort antibiotics such as colistin available for clinical therapy. An alternative therapeutic strategy gaining momentum is phage therapy, which has the advantage of not being affected by bacterial resistance to antibiotics. However, a major challenge in phage therapy is the rapid emergence of phage-resistant bacteria. In this work, our main aim was to understand the mechanisms of phage-resistance used by the top priority pathogen

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriophages; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Whole Genome Sequencing

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cancer Care Facilities; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Egypt; Hospitals, Pediatric; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Whole Genome Sequencing

Acinetobacter baumannii is a successful nosocomial pathogen due to its genomic plasticity. Homologous recombination allows genetic exchange and allelic variation among different clonal lineages and is one of the mechanisms associated with horizontal gene transfer (HGT) of resistance determinants. The main mechanism of colistin resistance in A. baumannii is mediated through mutations in the

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Brazil; Clone Cells; Colistin; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Mutation

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Meropenem

Novel therapeutics are urgently required for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) causing critical infections with high mortality. Here we assessed the therapeutic potential of the clinical-stage drug candidate EBL-1003 (crystalline free base of apramycin) in the treatment of CRAB lung infections.. The genotypic and phenotypic susceptibility of CRAB clinical isolates to aminoglycosides and colistin was assessed by database mining and broth microdilution. The therapeutic potential was assessed by target attainment simulations on the basis of time-kill kinetics, a murine lung infection model, comparative pharmacokinetic analysis in plasma, epithelial lining fluid (ELF) and lung tissue, and pharmacokinetic/pharmacodynamic (PKPD) modelling.. Resistance gene annotations of 5451 CRAB genomes deposited in the National Database of Antibiotic Resistant Organisms (NDARO) suggested >99.9% of genotypic susceptibility to apramycin. Low susceptibility to standard-of-care aminoglycosides and high susceptibility to EBL-1003 were confirmed by antimicrobial susceptibility testing of 100 A. baumannii isolates. Time-kill experiments and a mouse lung infection model with the extremely drug-resistant CRAB strain AR Bank #0282 resulted in rapid 4-log CFU reduction both in vitro and in vivo. A single dose of 125 mg/kg EBL-1003 in CRAB-infected mice resulted in an AUC of 339 h × μg/mL in plasma and 299 h × μg/mL in ELF, suggesting a lung penetration of 88%. PKPD simulations suggested a previously predicted dose of 30 mg/kg in patients (creatinine clearance (CLCr) = 80 mL/min) to result in >99% probability of -2 log target attainment for MICs up to 16 μg/mL.. This study provides proof of concept for the efficacy of EBL-1003 in the treatment of CRAB lung infections. Broad in vitro coverage, rapid killing, potent in vivo efficacy, and a high probability of target attainment render EBL-1003 a strong therapeutic candidate for a priority pathogen for which treatment options are very limited.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Animals; Anti-Bacterial Agents; Colistin; Lung; Mice; Microbial Sensitivity Tests; Nebramycin

The nosocomial opportunistic Gram-negative bacterial pathogen

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Mutagenesis, Insertional

Recently, we reported rifabutin hyperactivity against

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Rifabutin

Acinetobacter baumannii complex are microorganisms of critical priority of resistance, being associated with higher costs and negative outcomes for hospitalized patients. Thus, the study aimed to analyse the factors associated with A. baumannii complex infection in various hospital sectors.. This is a case-control study that included patients hospitalized from January 2017 to June 2019. Demographic, microbiological and clinical variables were collected from each patient. All cases had positive culture results for A. baumannii complex resistant to more than three classes of antimicrobials. Carbapenem-resistance was examined by the disk diffusion test, while the broth microdilution method was used to determine the susceptibility to colistin.. A. baumannii complex infection was mostly present in ICU (74.2%) than in other hospital areas. The bacteria was also linked with the length of hospitalization until the results for the culture (OR = 1.13; 95% CI: 1.06 - 1.21; p < 0.001) and with pneumonia associated with mechanical ventilation (OR = 4.48; 95% CI: 1.55 - 13.00; p = 0.006). Moreover, patients exposed to infection with multidrug-resistant A. baumannii complex had higher risks of death (OR = 3.25; 95% CI: 1.06 - 9.91; p = 0.039).. This study provides evidence that A. baumannii complex infection is associated with the number of days of hospitalization up to culture positivity, pneumonia associated with the use of mechanical ventilation and death. Infections appear to be more critical in ICU when compared to other areas. Taken together, these findings could support hospital infection surveillance programs, as well as prevention measures to reduce mortality rates and other complications.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Brazil; Carbapenems; Case-Control Studies; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Hospitals; Humans; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Risk Factors; Young Adult

Colistin is an, antibiotic used to treat carbapenem-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Function Tests; Male; Middle Aged; Organ Dysfunction Scores; Risk Factors

The aim of this study was to report the clinical experience of intraventricular colistin for the treatment of multi-resistant Gram-negative post-surgical meningitis in a tertiary hospital. Post-neurosurgical meningitis (PNM) is one of the life-threatening complications of neurosurgical procedures, and is frequently sustained by Acinetobacter baumannii and Klebsiella pneumoniae. Here we describe our experience of five cases of PNM caused by gram-negative multi-drug resistant (MDR) bacteria, treated with intraventricular (IVT) colistin, admitted to the Neurosurgery Unit of A.R.N.A.S. Civico of Palermo, Italy, from January 2016 to June 2020. In four patients the cerebrospinal fluid (CSF) culture was positive for A. baumannii, while in one patient it was positive for K. pneumoniae. IVT colistin therapy was administered for a median time of 18 days (range 7-29). The median time to CSF negativization was seven days (range 5-29). IVT colistin administration was associated with intravenous administration of meropenem and colistin in all patients. As regards clinical outcome, four patients were successfully treated and were subsequently discharged, while one patient died following respiratory complications and subsequent brain death. IVT colistin administration is an effective therapy for MDR post-neurosurgical meningitis and its administration is also prescribed by guidelines. However, IVT therapy for Gram-negative ventriculitis is mostly understudied. Our paper adds evidence for such treatment that can actually be considered life-saving.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Meningitis, Bacterial; Neurosurgical Procedures

Acinetobacter baumannii has emerged as one of the common multidrug resistance pathogens causing hospital-acquired infections. This study was conducted to elucidate the distribution of antimicrobial resistance genes in the bacterial population in Thailand. Multidrug-resistant A. baumannii (MDR A. baumannii) isolates were characterized phenotypically, and the molecular epidemiology of clinical isolates in 11 tertiary hospitals was investigated at a country-wide level.. A total of 135 nonrepetitive MDR A. baumannii isolates collected from tertiary care hospitals across 5 regions of Thailand were examined for antibiotic susceptibility, resistance genes, and sequence types. Multilocus sequence typing (MLST) was performed to characterize the spread of regional lineages.. ST2 belonging to IC2 was the most dominant sequence type in Thailand (65.19%), and to a lesser extent, there was also evidence of the spread of ST164 (10.37%), ST129 (3.70%), ST16 (2.96%), ST98 (2.96%), ST25 (2.96%), ST215 (2.22%), ST338 (1.48%), and ST745 (1.48%). The novel sequence types ST1551, ST1552, ST1553, and ST1557 were also identified in this study. Among these, the blaoxa-23 gene was by far the most widespread in MDR A. baumannii, while the blaoxa-24/40 and blaoxa-58 genes appeared to be less dominant in this region. The results demonstrated that the predominant class D carbapenemase was blaOXA-23, followed by the class B carbapenemase blaNDM-like, while the mcr-1 gene was not observed in any isolate. Most of the MDR A. baumannii isolates were resistant to ceftazidime (99.23%), gentamicin (91.85%), amikacin (82.96%), and ciprofloxacin (97.78%), while all of them were resistant to carbapenems. The results suggested that colistin could still be effective against MDR A. baumannii in this region.. This is the first molecular epidemiological analysis of MDR A. baumannii clinical isolates at the national level in Thailand to date. Studies on the clonal relatedness of MDR A. baumannii isolates could generate useful data to understand the local epidemiology and international comparisons of nosocomial outbreaks.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Ciprofloxacin; Clone Cells; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Thailand

Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial.. The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset.. Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14.. The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice.. The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Greece; Humans; Israel; Italy; Logistic Models; Male; Meropenem; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Antimicrobial resistance is now globally recognised amongst the greatest threat to human health. Acinetobacter baumannii's' (A. baumannii) clinical significance has been driven by its ability to obtain and transmit antimicrobial resistance factors. In South Africa, A. baumannii is a leading cause of healthcare associated infections (HAI). In this study, we investigated the genetic determinants of multi-drug resistant A. baumannii (MDRAB) at a teaching hospital in Pretoria, South Africa.. One hundred non repetitive isolates of A. baumannii were collected for the study. Antimicrobial susceptibility testing was performed using the VITEK2 system. The prevalence of antibiotic resistance associated genes and AdeABC efflux pump system were investigated using conventional PCR. Genetic relatedness of isolates was determined using rep-PCR.. Seventy (70) of 100 isolates collected were confirmed multi-drug resistant and were bla. The major genotypic determinant for drug resistances is oxacillinases bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; South Africa; Tertiary Care Centers; Tigecycline

Nowadays, Acinetobacter baumannii is resistant to almost all available antibiotics. The evaluation of synergistic effects between the antibiotics against this pathogen is among the efforts to counteract its antimicrobial resistance. This study aimed to evaluate possible synergistic effect of colistin and ampicillin/sulbactam (separately) with several antibiotics against clinical isolates of multi-drug resistant (MDR) A. baumannii.. Acinetobacter baumannii strains were isolated from biological samples of hospitalized patients with any type of nosocomial infection related to this pathogen. Only MDR strains (resistance to at least three classes of antibiotics including cephalosporins, fluoroquinolones, and aminoglycosides) were included in the study. After determining the minimum inhibitory concentration (MIC) of antibiotics against the isolates by broth microdilution test, the checkerboard method was used for evaluation of any possible synergistic effect of both colistin and ampicillin/sulbactam with several other antibiotics.. Twenty isolates underwent synergy test for colistin and 20 isolates for ampicillin/sulbacatam. Doxycycline (55%), azithromycin (35%), and co-trimoxazole (35%) had the most frequency of synergistic effect with colistin. On the other hand, amikacin and gentamicin (55%), doxycycline (50%), co-trimoxazole (45%), azithromycin (40%), and cefepime (40%) had the most frequency of synergistic effect with ampicillin/sulbactam. No antagonistic effect was observed for both antibiotics.. Colistin and ampicillin/sulbactam have substantial synergistic effect with several antibiotics especially doxycycline, co-trimoxazole, azithromycin, and amikacin (with ampicillin/sulbactam) against MDR strains of Acinetobacter baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Ampicillin; Anti-Bacterial Agents; Azithromycin; Colistin; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination

Nosocomial meningitis caused by Gram-negative bacteria is associated with increasingly common neurosurgical procedures in children, with an increase in incidence recently reported. These infections are associated with an increased risk of mortality, prolonged hospitalisation, and increased costs. In this report, we describe two paediatric cases with central nervous system infections caused by extensively drug-resistant Gram-negative bacteria that were successfully treated with intraventricular colistin. To the best of our knowledge, this is the first comprehensive review and discussion of intraventricular antimicrobial therapy in a paediatric population. Based on our comprehensive review of the relevant literature, it appears that intraventricular administration of colistin may be a promising and effective option in the treatment of central nervous system infections in children who do not respond to other treatment options.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Child, Preschool; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Injections, Intraventricular; Male; Meningitis, Bacterial; Pseudomonas Infections

Extremely drug-resistant (XDR) Acinetobacter baumannii is a notorious and frequently encountered pathogen demanding novel therapeutic interventions. An initial monoclonal antibody (MAb), C8, raised against A. baumannii capsule, proved a highly effective treatment against a minority of clinical isolates. To overcome this limitation, we broadened coverage by developing a second antibody for use in a combination regimen. We sought to develop an additional anti-A. baumannii MAb through hybridoma technology by immunizing mice with sublethal inocula of virulent, XDR clinical isolates not bound by MAb C8. We identified a new antibacterial MAb, 65, which bound to strains in a pattern distinct from and complementary to that of MAb C8. MAb 65 enhanced macrophage opsonophagocytosis of targeted strains and markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia murine models of A. baumannii infection. MAb 65 was also synergistic with colistin, substantially enhancing protection compared to monotherapy. Treatment with MAb 65 significantly reduced blood bacterial density, ameliorated cytokine production (interleukin-1β [IL-1β], IL-6, IL-10, and tumor necrosis factor), and sepsis biomarkers. We describe a novel MAb targeting A. baumannii that broadens immunotherapeutic strain coverage, is highly potent and effective, and synergistically improves outcomes in combination with antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Biomarkers; Colistin; Cytokines; Drug Resistance, Multiple, Bacterial; Mice; Microbial Sensitivity Tests; Sepsis

To identify the molecular mechanism of colistin resistance in an MDR Acinetobacter baumannii clinical strain isolated in 2008 from a meningitis case in Brazil.. Long- and short-read WGS was used to identify colistin resistance genes in A. baumannii strain 597A with a colistin MIC of 64 mg/L. MS was used to analyse lipid A content. mcr was cloned into pET-26b (+) and transformed into Escherichia coli BL21(λDE3)pLysS for analysis.. A novel plasmid (pAb-MCR4.3) harbouring mcr-4.3 within a Tn3-like transposon was identified. The A. baumannii 597A lipid A MS spectra showed a main molecular ion peak at m/z=2034, which indicated the addition of phosphoethanolamine to the lipid A structure. E. coli BL21 transformed with pET-26b-mcr-4.3 gained colistin resistance with a colistin MIC of 8 mg/L.. Colistin resistance in A. baumannii 597A was correlated with the presence of a novel plasmid-encoded mcr-4.3 gene.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Brazil; Colistin; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Meningitis, Bacterial; Microbial Sensitivity Tests; Plasmids; Whole Genome Sequencing

LpxB is an enzyme involved in the biosynthesis pathway of lipid A, a component of LPS.. To evaluate the lpxB gene in Acinetobacter baumannii as a potential therapeutic target and to propose antisense agents such as peptide nucleic acids (PNAs) as a tool to combat bacterial infection, either alone or in combination with known antimicrobial therapies.. RNA-seq analysis of the A. baumannii ATCC 17978 strain in a murine pneumonia model was performed to study the in vivo expression of lpxB. Protein expression was studied in the presence or absence of anti-lpxB (KFF)3K-PNA (pPNA). Time-kill curve analyses and protection assays of infected A549 cells were performed. The chequerboard technique was used to test for synergy between pPNA and colistin. A Galleria mellonella infection model was used to test the in vivo efficacy of pPNA.. The lpxB gene was overexpressed during pneumonia. Treatment with a specific pPNA inhibited LpxB expression in vitro, decreased survival of the ATCC 17978 strain and increased the survival rate of infected A549 cells. Synergy was observed between pPNA and colistin in colistin-susceptible strains. In vivo assays confirmed that a combination treatment of anti-lpxB pPNA and colistin was more effective than colistin in monotherapy.. The lpxB gene is essential for A. baumannii survival. Anti-lpxB pPNA inhibits LpxB expression, causing bacterial death. This pPNA showed synergy with colistin and increased the survival rate in G. mellonella. The data suggest that antisense pPNA molecules blocking the lpxB gene could be used as antibacterial agents.

Topics: A549 Cells; Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Biosynthetic Pathways; Colistin; DNA, Antisense; Drug Synergism; Gene Expression; Humans; Lipid A; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Moths; Peptide Nucleic Acids; RNA-Seq

To investigate clinical and microbiological response, and 30-day mortality of pneumonia involving multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex treated with colistin, and identify associated factors of these outcomes.. A retrospective study of 183 adult patients with colistin treatment for at least 7 days between January 2014 and October 2017.. The mean age was 76.8 years, and mean Acute Physiology and Chronic Health Evaluation II score was 17.7. Eighteen (9.8%) and 128 (69.9%) patients had intravenous (IV) colistin alone and inhaled (IH) colistin alone, respectively. Thirty-seven patients had both IV and IH colistin, including 5 (2.7%) with concurrent, and 32 (17.5%) with non-concurrent use of IV and IH colistin. The 30-day mortality rate was 19.1% and 131 (71.6%) patients had clinical response. In the 175 patients with available data, 126 (72%) had microbiological eradication. The multivariate analyses revealed that IH colistin alone was an independent predictor for 30-day survival, clinical response, and microbiological eradication, and IV colistin alone was an independent predictor for clinical failure. Patients with IV colistin alone had a significantly higher nephrotoxicity rate than IH colistin alone (37.5% vs 6.1%, P = 0.001). Sub-group analysis of 52 patients with IV colistin for ≧ 4 days revealed that 14 (26.9%) patients had inappropriate dose, and inappropriate dose was an independent predictor for 30-day mortality.. IH colistin provided good outcomes with few side effects, and appropriate dosing of IV colistin was important to avoid excess mortality.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Pneumonia; Treatment Outcome

Colistin and carbapenem-resistant Acinetobacter calcoaceticus- Acinetobacter baumannii complex (CCR-Acb complex) was isolated from two consecutive patients in the neurological intensive care unit (NICU). An urgent reaction to this desperate situation was required.. Screening cultures were taken from the other patients sharing the NICU with index patients and repeated periodically. NICU was closed for new admissions. Infection control precautions (ICP) such as hand hygiene, cohorting patients colonized with CCR-Acb complex, cohorting the staff caring for these patients, daily bathing with chlorhexidine gluconate impregnated clothes, using gowns when contacting with patients and patient care area, and sodium hypochlorite tablets for environmental cleaning were enforced.. Screening cultures revealed carbapenem-resistant Acb complex in 12 out of 32 patients and 8 of them were colonized with CCR-Acb complex. NICU was opened for new admissions one month later. No further new cases with CCR-Acb complex were detected by screening cultures after 6 weeks with enforcement of ICP. Moreover, the rate of nosocomial infections caused by other multi-drug resistant Gram-negative bacilli (MDR-GNB) decreased significantly when rates before and after closing the NICU were compared.. ICP were effective not only to limit the spread of CCR-Acb complex but also decreased the incidence of other MDR-GNB infections when applied adequately.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aged; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Carbapenems; Colistin; Humans; Treatment Outcome

Background The Gastrointestinal Surgery Center (GISC)-Mansoura University, faced a series of extensive drug resistant (XDR) A. baumannii cases, that were microbiologically resistant to penicillins, cephalosporins, fluoroquinolones, aminoglycosides, carbapenems and tigecycline. Colistin would have been a last resort therapy in such situation, however, intravenous polymyxins E (colistin) is relatively unavailable in Egypt. Many practitioners tried to form antibiotic combinations from the available antibiotics to overcome the resistance mechanisms of the pathogen. Objective Evaluate the clinical outcomes of these combinations retrospectively. Setting The study took place at the GISC, which is an academic specialized center affiliated with Mansoura University-Egypt. Method Clinical data were collected from the patients' files, where the subjects were classified into two major groups according to the therapeutic intervention. Group 1 included 24 patients divided into 4 subgroups. The first was treated by a Cephalosporin with a Fluoroquinolone (1A), The second was treated by a Carbapenem with a Fluoroquinolone (1B), The third was treated by a B-lactam with an Aminoglycoside (1C) and the fourth was treated by Carbapenem with a Glycylcycline (1D). Group 2 included 6 patients, treated with Tigecycline and Ampicillin-Sulbactam. Main outcome measure Primary outcomes are the A. baumannii microbiological culture negativity after 14 days of therapy and the 30 days' survival after the antibiotic course, while the secondary outcomes are the expected therapies' side effects. Results Group 2 is associated with significant higher primary outcomes without a significant difference regarding the secondary outcomes. Conclusion The combination of Tigecycline and Ampicillin-Sulbactam, appears to be a clinically effective therapy against XDR A. baumannii, despite each agent being resistant alone, without alerting adverse effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Ampicillin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Retrospective Studies; Sulbactam; Tigecycline

To describe colistin-resistant Acinetobacter baumannii isolates in Cape Town, South Africa.. A. baumannii isolates identified on Vitek 2 Advanced Expert System were collected from Tygerberg Hospital referral laboratory between 2016 and 2017. Colistin resistance was confirmed using broth microdilution and SensiTest. mcr-1-5 were detected using PCR and strain typing was performed by rep-PCR. Whole genome sequencing (WGS) was performed on a subset of isolates to identify chromosomal colistin resistance mechanisms and strain diversity using multilocus sequence typing (MLST) and pairwise single nucleotide polymorphism analyses.. Twenty-six colistin-resistant and six colistin-susceptible A. baumannii were collected separately based on Vitek susceptibility; 20/26 (77%) were confirmed colistin-resistant by broth microdilution. Four colistin-resistant isolates were isolated in 2016 and 16 in 2017, from five healthcare facilities. Thirteen colistin-resistant isolates and eight colistin-susceptible isolates were identical by rep-PCR and MLST (ST1), all from patients admitted to a tertiary hospital during 2017. The remaining colistin-resistant isolates were unrelated.. An increase in colistin-resistant A. baumannii isolates from a tertiary hospital in 2017 appears to be clonal expansion of an emerging colistin-resistant strain. This strain was not detected in 2016 or from other hospitals. Identical colistin-susceptible isolates were also isolated, suggesting relatively recent acquisition of colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; South Africa

Colistin resistance rates are rising globally among multidrug-resistant Gram-negative bacilli, including Acinetobacter baumannii (A. baumannii). A new type of resistance - heteroresistance - has also been reported to colistin in clinical A. baumannii isolates. This study investigated the presence of colistin heteroresistance in carbapenem-resistant A. baumannii clinical isolates.. Different clinical specimens from hospitalised patients were investigated for A. baumannii. The MICs to imipenem, meropenem and colistin were determined by broth microdilution. PCR was performed to detect OXA-type carbapenemase genes (bla. A. baumannii with a colistin heteroresistance phenotype was common. This could be of great concern since colistin is often used as a last-resort drug for treating A. baumannii infections, highlighting that care is necessary with colistin monotherapy. In addition, more effective strategies and surveillance are required to confine and prevent the inter-hospital and/or intra-hospital dissemination of A. baumannii between therapeutic centres.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Humans; Iran

Colistin is one of the most effective alternatives for treating Acinetobacter baumannii infections. The aim of this study was to determine colistin resistance and heteroresistance rates in A. baumannii from clinical samples in Hacettepe University clinical microbiology laboratory between June 2016 and January 2017. A total of 200 isolates were included in the study. In vitro susceptibility to amikacin, gentamicin, ceftazidime, piperacillin/tazobactam, meropenem, ciprofloxacin, and tigecycline were determined by disk diffusion test. Most isolates were multiresistant as they exhibited resistance to aminoglycosides, β-lactams, and fluoroquinolones. Colistin susceptibility was determined by broth microdilution (BMD) test (EUCAST standards) and was compared with E-test (bioMérieux, France) in 120 isolates. In 14 blood isolates that were susceptible to colistin (MIC ≤ 2 mg/L), heteroresistance was investigated with the population analysis profile (PAP) method. Overall resistance (n = 200) to colistin was 28% by BMD. Among the 120 isolates where the two tests were compared, resistance to colistin was 25.8% versus 4.2% with BMD and E-test, respectively. Three blood isolates (21.4%) were heteroresistant to colistin. With E-test, a majority of the resistant isolates are overlooked and in vitro susceptibility to colistin should be determined with broth dilution method. This is the first study in Turkey reporting heteroresistance in A. baumannii isolates by the PAP method and emphasizes the need to test for heteroresistance in relation to clinical outcome in serious infections due to A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; beta-Lactams; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Tetracyclines; Turkey

This study aimed to investigate the mechanisms of colistin resistance in 64 Acinetobacter baumannii isolates obtained from patients with ventilator-associated pneumonia hospitalised in Greece, Italy and Spain. In total, 31 A. baumannii isolates were colistin-resistant. Several novel amino acid substitutions in PmrCAB were found in 27 colistin-resistant A. baumannii. Most substitutions were detected in PmrB, indicating the importance of the histidine kinase for colistin resistance. In two colistin-resistant isolates, 93 amino acid changes were observed in PmrCAB compared with A. baumannii ACICU, and homologous recombination across different clonal lineages was suggested. Analysis of gene expression revealed increased pmrC expression in isolates harbouring pmrCAB mutations. Complementation of A. baumannii ATCC 19606 and ATCC 17978 with a pmrAB variant revealed increased pmrC expression but unchanged colistin MICs, indicating additional unknown factors associated with colistin resistance. Moreover, a combination of PmrB and PmrC alterations was associated with very high colistin MICs, suggesting accumulation of mutations as the mechanism for high-level resistance. The pmrC homologue eptA was detected in 29 colistin-susceptible and 26 colistin-resistant isolates. ISAba1 was found upstream of eptA in eight colistin-susceptible and one colistin-resistant isolate and eptA was disrupted by ISAba125 in two colistin-resistant isolates. Whilst in most isolates an association of eptA with colistin resistance was excluded, in one isolate an amino acid substitution in EptA (R127L) combined with a point mutation in ISAba1 upstream of eptA contributed to elevated colistin MICs. This study helps to gain an insight into the diversity and complexity of colistin resistance in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Greece; Humans; Pneumonia, Ventilator-Associated

Colistimethate sodium (colistin) is used to treat multidrug-resistant gram negative infections. We describe the profile and outcomes of patients given colistin in a tertiary level government hospital in Manila, Philippines.. We performed a retrospective study of adult patients given intravenous colistin between January 2015 to June 2018 in the Philippine General Hospital. We defined clinical success as a composite of hemodynamic stability, quick Sequential Organ Failure Assessment (qSOFA) score, and microbiological cure.. 250 patients were included, half (49.2%) were admitted in the ICU. Median age was 55 years. There was an increase in qSOFA, APACHE II score, and septic shock from baseline to 24 h prior to colistin use. Most patients had pneumonia (90.8%) with extensively drug-resistant Acinetobacter baumannii as the most common isolate (78.8%). Colistin was given in combination with meropenem (96.4%) for a median of 12 days. Nephrotoxicity was seen in 30.8%, with renal replacement therapy needed in 6%. Clinical success was seen in 61.2% of patients and overall mortality was 41.6%.. Colistin was frequently used in combination with a carbapenem for treatment of XDR-related respiratory infections. Nephrotoxicity was a common adverse effect. Clinical success was modest and overall mortality was high.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Male; Meropenem; Middle Aged; Organ Dysfunction Scores; Philippines; Respiratory Tract Infections; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult

Colistin is a last-resort antibiotic for the treatment of infections caused by multidrug and carbapenem-resistant Gram-negative bacteria. Colistin resistance has been emerging and multiple outbreaks have been reported in Europe and elsewhere. It has been most frequently reported in carbapenem-resistant K. pneumoniae. In this study, 24 multidrug and colistin-resistant clinical isolates (14 K. pneumoniae, one E. aerogenes, one E. cloacae, and eight A. baumannii) were collected from four hospitals in Croatia from 2013 to 2018, in order to analyse the molecular epidemiology and mechanisms of antibiotic resistance. β-lactamase and carbapenemase genes were detected by PCR. Genotyping was done on selected isolates by rep-PCR. Whole genome sequencing (WGS) was performed to discover possible molecular mechanisms for the observed colistin resistance. All isolates, except two K. pneumoniae isolates, were extensively drug resistant. Ten out of 16 (63%) K. pneumoniae isolates possessed bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Croatia; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Phylogeny; Whole Genome Sequencing

This study aimed to investigate the characteristics and mechanisms responsible for heteroresistance to colistin in Acinetobactor baumannii clinical isolates from a Chinese teaching hospital. Five hundred and seventy-six nonduplicate A. baumannii clinical isolates isolated from 2014 to 2015 were tested. Colistin heteroresistance was determined using population analysis profiles (PAPs). Susceptibility testing was conducted using the broth microdilution method (BMD). The ability to form biofilm formation was determined using 96-well flat bottom microtiter plates. Time-kill assays were also conducted. PCR and sequencing were used to detect the presence of resistant genes. Expression levels of efflux pump genes were determined by qRT-PCR. LPS analysis was conducted by SDS-PAGE. Lipid A characteristic were determined via MALDI-TOF MS. Nine colistin heteroresistant A. baumannii clinical isolates which were selected by PAPs, exhibited multidrug-resistant phenotypes. The microplate biofilm assay revealed that colistin heteroresistant A. baumannii clinical isolates had weaker biofilm formation capacity than A. baumannii ATCC19606. Colistin-heteroresistant A. baumannii isolates exhibited regrowth after 12 h at 0.5 × MIC, 1 × MIC, and 2 × MIC. The results of PCR and sequencing revealed mutations of lpxACD in some colistin heteroresistant A. baumannii isolates. qRT-PCR also showed that the expressions of efflux pump genes were upregulated in some of the heteroresistant isolates. Our study was the first report of colistin heteroresistant A. baumannii clinical isolates in China. The transition of colistin heteroresistance to resistance should be of concern in future clinical surveillance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

This study was aimed to evaluate occurrence of antibiotic resistance and the presence of resistance determinants among clinical isolates of Acinetobacter baumannii. This cross-sectional study from January to September 2018 was performed on 59 A. baumannii strains isolated from clinical samples in the north of Iran. Isolates were identified by standard microbiologic tests and molecular method. Antimicrobial susceptibility testing was carried out by disk diffusion and broth microdilution methods. The presence of carbapenem resistance genes was detected by PCR method. All isolates were resistant to cefepime, meropenem, imipenem and ceftazidime. The lowest resistance rate was observed against doxycycline with 33.9%. Minimum inhibitory concentration (MIC) results showed that all carbapenem-resistant A. baumannii (CRAB) isolates were susceptible to colistin with MIC50 and MIC90 values of 1/2 µg/mL. Among 59 CRAB, blaOXA-23-like was the most prevalent gene (86.4%) followed by blaOXA-24-like (69.5%). Meanwhile, none of the clinical isolates harbored blaOXA-58-like gene. We found a high prevalence of CRAB strains harboring OXA-type carbapenemases in the north of Iran. Our results suggests that the presence of OXA-type genes was not directly correlated with the increase of imipenem MIC level, but can be clinically important as they contribute to the selection of CRAB strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Bacteriological Techniques; beta-Lactamases; Carbapenems; Colistin; Cross-Sectional Studies; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Humans; Iran; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Prevalence; Young Adult

Colistin was considered as the most effective antibiotic against Acinetobacter baumannii, a widely-known opportunistic pathogen. In recent years, a number of colistin resistant strains have also been reported.. This work is commenced to investigate the contribution of efflux pumps toward resistance to colistin-like cyclic polypeptide antibiotics, since the efflux pumps serve as the escape routes leading to drug-resistance.. RNA was extracted from A. baumannii isolates cultured from samples procured by tracheal aspiration of infected patients. The expressions of gene(s) that played major roles in the regulation of efflux pump families and involvement of integron systems were studied using real time PCR. Antimicrobial susceptibility tests were conducted to investigate antibiotic resistance of the isolates.. It was observed that genes coding for sugE, ydhE, ydgE, mdfA, ynfA and tolC significantly contributed to resistance against colistin antibiotics, however, no significant transcriptional change was observed in the efflux pump, MexAB-OprM. Results suggest that A. baumanii readily pumps out colistin via efflux pumps belonging to MATE and SMR family.. Integral role of efflux pumps and integron 1 genetic system was elucidated towards evolution of multi-drug resistant strain(s). Therefore, for accurate therapeutics, an early detection of efflux genes is crucial before prescribing against colistin resistant A. baumanii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Paracentesis; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Up-Regulation

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Comorbidity; Drug Resistance, Bacterial; Female; Genome, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Operon; Prognosis; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Meropenem

In blood samples taken for testing purposes during drug infusion in the intensive care unit, there is a risk of interference due to drug-reactive interaction during the analysis.. A 19-year-old female patient had undergone surgery for intracranial astrocytoma, 12 years ago. Acinetobacter baumannii was found in the blood culture and deep tracheal aspiration fluid of the patient who had a fever (39.2 °C) with a body temperature during the follow-up. The patient was started on colistin 2 * 4.5 million IU. After the colistin infusion, biochemical tests were requested to control the patient's clinical situation. CK-MB mass and ProBNP values were measured in high concentrations. Cardiology consultation was requested to evaluate the increase in the CK-MB mass and ProBNP values. The patient's ECG and echocardiography showed no abnormality. The increase in cardiac markers was neither clinically acceptable nor insignificant. There was no hemolysis in the sample or analytical error in the device. Variability in the tests was thought to be due to the interference. As the bloodletting time was questioned, it was determined that it was taken during colistin treatment. In order to determine the effect of colistin-related interference on the other tests, the laboratory was contacted and additional tests (TSH, FT4, Anti- TPO, B-HCG, Estradiol, Prolactin, CA 125, CA 15-3, CA 19-9, Vitamin B12, C-Peptide, DDimer, PTH, 25 hydroxy vitamin D, PT, INR, APTT) were conducted. During colistin treatment, in many tests, bias was detected between -75 and + 268.80%.. Clinicians should consider suspicious test results that are incompatible with the diagnosis for the possibility of erroneous measurements due to colistin interference and review the sampling processes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; C-Peptide; CA-125 Antigen; CA-19-9 Antigen; Colistin; Critical Care; Estradiol; False Positive Reactions; Female; Humans; Mucin-1; Prolactin; Vitamin B 12; Young Adult

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Meropenem

Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital.. This study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis.. The adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem.. There were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Kidney; Kidney Diseases; Male; Meropenem; Middle Aged; Retrospective Studies; Thailand

Industry screens of large chemical libraries have traditionally relied on rich media to ensure rapid bacterial growth in high-throughput testing. We used eukaryotic, nutrient-limited growth media in a compound screen that unmasked a previously unknown hyperactivity of the old antibiotic, rifabutin (RBT), against highly resistant Acinetobacter baumannii. In nutrient-limited, but not rich, media, RBT was 200-fold more potent than rifampin. RBT was also substantially more effective in vivo. The mechanism of enhanced efficacy was a Trojan horse-like import of RBT, but not rifampin, through fhuE, only in nutrient-limited conditions. These results are of fundamental importance to efforts to discover antibacterial agents.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gene Deletion; Gene Expression Regulation, Bacterial; High-Throughput Screening Assays; Male; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Nutrients; Receptors, Cell Surface; Rifabutin; Rifampin

To evaluate the activity of the novel broad-spectrum serine β-lactamase inhibitor durlobactam (ETX2514) combined with sulbactam against global isolates of carbapenem-resistant Acinetobacter baumannii with defined carbapenem resistance mechanisms compared with reference antimicrobials with known activity against Acinetobacter spp.. The susceptibility of 246 carbapenem-resistant non-duplicate A. baumannii isolates to sulbactam/durlobactam, amikacin, colistin, imipenem/sulbactam/durlobactam, imipenem, meropenem, minocycline and sulbactam was tested using broth microdilution. Isolates were obtained from various body sites from patients in 37 countries and from six world regions between 2012 and 2016. Identification of carbapenem resistance mechanisms and assignment to A. baumannii clonal lineages was based on WGS.. Sulbactam/durlobactam showed excellent activity comparable to colistin but superior to amikacin, minocycline and sulbactam. The sulbactam/durlobactam MIC50/90 values were 1/4 and 2/4 mg/L and the colistin MIC50/90 values were 0.5 and 1 mg/L, respectively. Comparatively, amikacin, minocycline and sulbactam MIC50/90 values were 256/≥512, 2/16 and 16/64 mg/L, respectively.. Sulbactam/durlobactam had excellent in vitro potency against A. baumannii isolates, including those that were resistant to imipenem/meropenem, amikacin, minocycline and colistin, compared with other compounds. Sulbactam/durlobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Microbial Sensitivity Tests; Sulbactam

Carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA), as well as polymyxin-resistant A. baumannii (PMR-AB) and P. aeruginosa (PMR-PA), were used to test different enrichment strategies from spiked stools. Three procedures were compared, namely, direct inoculation on selective plates and plating after a 24-h enrichment step in tryptic soy broth with or without antibiotics. Selective agar plates were used including CHROMagar-Pseudomonas supplemented with meropenem (2 mg/L), and CHROMagar-MDR-Acinetobacter agar and CHROMagar COL-APSE plates. Use of enrichment broths significantly enhanced the recovery of CRAB, CRPA, PMR-AB, and PMR-PA. However, supplementing or not the pre-enrichment broth with antibiotics had no impact. The proposed strategy for screening multidrug-resistant nonfermenters is of low cost, is easy to implement, and might be useful for outbreak containment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriological Techniques; Carbapenems; Colistin; Culture Media; Drug Resistance, Multiple, Bacterial; Feces; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sensitivity and Specificity

A. baumannii is one of the most important multidrug-resistant microorganisms in hospital units. It is resistant to many classes of antibiotics and the development of new therapeutic strategies is necessary. The aim of this study was to evaluate the antibacterial activity of a set of piperazine-derived thioureas against 13 clinical strains of colistin-resistant A. baumannii. Six derivatives were identified to inhibit bacterial growth of 46% of the A. baumannii strains at low micromolar concentrations (Minimum Inhibitory Concentration from 1.56 to 6.25 μM). A common structural feature in most active compounds was the presence of a 3,5-bis-trifluoromethyl phenyl ring at the thiourea function. In addition, the ability of the compounds to inhibit production of nitric oxide (NO) was examined in RAW 264.7 murine macrophages, highlighting the potential of piperazine-derived thioureas as promising scaffolds for the design of new combined anti-bacterial/anti-inflammatory agents.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Colistin; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Mice; Microbial Sensitivity Tests; Nitric Oxide; Piperazines; RAW 264.7 Cells; Structure-Activity Relationship; Thiourea

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Coinfection; Colistin; COVID-19; Drug Resistance, Bacterial; Humans; Models, Theoretical; Pneumonia, Ventilator-Associated

The blaOXA resistance genes and ISAba1 were examined in 70 samples from lower respiratory tract of hospitalized patients.. Of the 67 isolates obtained, almost half (46.3%) of them were from endotracheal aspirate, and most were collected from the intensive care units of the reanimation (37.3%) and internal medicine (32.8%) units.. Three samples from the internal medicine intensive care unit had positive cultures. Of the multidrug resistant (MDR) samples, 70 isolates (>50%) were moderately sensitive, while fewer (10%) were resistant to tigecycline. In contrast, 100% were sensitive to colistin. All strains were found to be positive for blaOXA-23-like and blaOXA-51-like genes, whereas no blaOXA-40-like and blaOXA-58-like genes were detected. The ISAba1 positivity rate was 90.0%. Pattern 5 was mainly identified among the 22 different patterns. Of note, 50% of Pattern 5 was found in the patients of the internal medicine intensive care unit, and a third was associated with ventilator-associated pneumonia. Importantly, the internal medicine unit's equipment was found to be culture positive.. Findings obtained from this study suggest that isolates can easily spread through the hospital via isolate cross-contamination caused by health personnel. These contaminating isolates may be able to maintain their presence within the hospital for a long time.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genes, Bacterial; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Multiplex Polymerase Chain Reaction; Tertiary Care Centers

Approximately 2-3% of hospitalized patients are known to experience an adverse drug reaction (ADR). Dermatologic ADRs account for 10-30% of ADRs, and are commonly reported to be associated with antibiotic use. The classes of antibiotics most commonly reported to cause cutaneous reactions are the penicillins, cephalosporins, and fluoroquinolones. Polymyxin E is known to cause such reactions, but rarely. Here, we report a case of a colistin- induced maculopapular rash in an 84-year-old male. To the best of our knowledge, this is the first case of colistin-induced maculopapular rash to be reported in India.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Exanthema; Humans; Male

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Genomics; Microbial Sensitivity Tests; Mutagenesis, Insertional; Transcription Factors

Acinetobacter baumannii is an opportunistic pathogen associated with increased morbidity and mortality in Healthcare-associated infections (HAI). Combination antimicrobial therapy, meropenem, amikacin and colistin, has been used as an alternative in multidrug-resistant (MDR) A. baumannii infections due to reduced treatment options. However, these combinations are not always effective and exhibit high toxicity. Empiric therapy of intravenous immunoglobulin (IVIG) associated with antimicrobials has shown promising results in bacterial infections, considering the immunomodulatory action of IVIG. Thus, the aim of this study was to determine the combined antimicrobial action and to describe the ultrastructural changes caused in ten MDR A. baumannii isolates submitted to IVIG alone and in combination with colistin, meropenem and amikacin. Minimum Inhibitory Concentration (MIC) of antimicrobials and checkerboard were determined. Isolates were submitted to 4 mg/mL of IVIG alone and in combination with different synergistic sub-MIC of antimicrobials tested, and processed for scanning electron microscopy. Nine bacterial isolates showed meropenem-resistant, two isolates had colistin-intermediate, and four isolates were considered intermediate to amikacin. Synergism in five isolates for meropenem/amikacin and meropenem/colistin were observed. Bacterial cells submitted to IVIG and meropenem, amikacin and colistin presented several ultrastructural changes, such as cell elongation and rupture, membrane roughness, incomplete cell division, cell surface "bubbles" and "depression". A. baumannii isolates presented high resistance to meropenem and synergism among evaluated antimicrobials. In addition, it was possible to verify in vitro that IVIG associated with meropenem, amikacin and colistin is a promising alternative for MDR A. baumannii infections. Thus, these data support the continued empirical use and stimulate in vivo analyzes with IVIG to search for new therapeutic options for HAI.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Immunoglobulins, Intravenous; Meropenem; Microbial Sensitivity Tests

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin-linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin-linezolid combination. The survival rates of colistin-linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin-linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin-linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin-linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Antitubercular Agents; Colistin; Disease Models, Animal; Drug Synergism; Extensively Drug-Resistant Tuberculosis; Female; Linezolid; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Time Factors; Tuberculosis, Multidrug-Resistant

Extensively drug resistant Acinetobacter baumannii (XDR-Ab), has emerged as an important pathogen in several outbreaks. The aim of our study was to investigate the eventual genetic relatedness of XDR-Ab strains recovered from burn patients and environment sites in the largest Tunisian Burn Intensive Care Unit (BICU) and to characterize β-lactamase encoding genes in these strains. Between March 04th, 2019 and April 22nd, 2019 an outbreak of XDR-Ab was suspected. Environmental screening was done. All isolates were screened by simplex PCR for β-lactamase genes. Genetic relatedness was determined by pulsed field gel electrophoresis (PFGE) of ApaI-digested total DNA. During the study period, 21 strains of A. baumannii were isolated in burn patients, mainly in blood culture (n = 7) and central vascular catheter (n = 6). All strains were susceptible to colistin but resistant to imipenem (n = 23), ciprofloxacin (n = 23), amikacin (n = 22), tigecyclin (n = 5) and rifampicin (n = 4). The blaOXA-51-like, blaOXA23, and blaADC genes were present in all strains. These resistance determinants were associated with blaPER-1 in 10 strains. The ISAba1 was inserted upstream of blaOXA-23 in all isolates. PFGE revealed two major clusters A (n = 11) and B (n = 5). This is the first description in Tunisia of clonally related PER-1 producing XDR-Ab in burn patients with probable environmental origin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Burn Units; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Tunisia

Acinetobacter baumannii is an opportunistic pathogen, which causes a wide range of infections in hospitals, especially in intensive care units. Nowadays, due to the high resistance of Acinetobacter bumanni to antibiotics, this study, in addition to the phenotypic and genotypic investigations of drug resistance, focused on determining the molecular types of Acinetobacter baumannii isolated from patients in Khorramabad city by the pulsed-field gel electrophoresis (PFGE) method.. In this cross-sectional study, 50 samples of Acinetobacter baumannii were collected from educational hospitals in Khorramabad city, Iran, from January to August 2015. They were identified in the laboratory using biochemical tests and culture methods. After determining the drug resistance pattern by the disc diffusion method and percentage of resistance genes to carbapenems, Acinetobacter baumannii isolates were analyzed using the PFGE method using the Apa1 enzyme.. The highest antibiotic resistance observed for Acinetobacter baumannii strains was against ampicillin-sulbactam (100%) and aztreonam (98%). The highest sensitivity was to polymixin B (100%) and colistin (94%), and also to the OXA-51-like gene present in all samples. The OXA-23-like gene was positive in 44 (88%) samples. PFGE results showed that Acinetobacterbaumannii strains had 33 different pulsotype patterns, of which 27 patterns had more than one strain and 23 had only one strain.. Due to the high resistance of Acinetobacter baumannii and its ease of spread and its ability to transfer resistance genes, resistance control methods should be used in the disinfection of hospital areas. Hospital staff should observe hygiene standards and there should also be a reduction in antibiotic use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Cross-Sectional Studies; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Iran; Microbial Sensitivity Tests; Sulbactam

The present study was conducted to investigate the mechanism of carbapenem resistance and the molecular epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates collected from two nearby hospitals in Tehran, Iran.. A total of 180 CRAB isolates were studied. Antimicrobial susceptibility testing was performed using disk diffusion and Epsilometer tests. The detection of OXA-23, -24 and -58 was implemented for all isolates using polymerase chain reaction. Subsequently, isolates harbouring OXA-24 and -58 were investigated for the presence of resistance determinants of Ambler class A, metallo-β-lactamases (MBLs), and carbapenem-hydrolysing class D β-lactamases, ISAba1, and the genetic relatedness between them was analysed using pulsed-field gel electrophoresis (PFGE). All isolates were found to be resistant to imipenem with a MIC of ≥8 µg ml. The findings showed that the refractory CRAB isolates were transmitted intra- and inter-hospital, particularly in the ICU due to shortcomings in infection control surveillance.. Carbapenem resistance is a substantial threat in the treatment of infections caused by A. baumannii due to limitations in the therapeutic options.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Imipenem; Iran; Microbial Sensitivity Tests

The increasing use of polymyxins as last-resort drugs for managing infections by Acinetobacter baumannii has led to the emergence of resistance. This study aimed to determine the resistance mechanisms in Acinetobacter baumannii isolates with colistin MIC ≥ 4 mg/L and to relate the mechanisms of resistance with the difficulties in detecting them. Absolute agreement among the different methodologies (Phoenix automatized system, broth and agar dilution, and a rapid colorimetric test) in the 140 colistin-susceptible isolates was observed; whereas in the 25 resistant isolates, the performance varied according to the colistin MIC value. Most of the discrepancies (irrespective of the methodology that was used) were observed in isolates with an MIC value close to the breakpoint. The number of errors in each method in the resistant isolates was as follows: rapid test, four of 25 (16%); agar dilution, eight of 25 (32%); Phoenix system, 13 of 25 (52%) and its manual reading at 24 h, eight of 25 (32%). Categorical errors were detected in 13 isolates: slow growth was the main reason in five isolates, whereas in the remaining eight isolates, slow growth was detected together with a low proportion of colistin-resistant subpopulations and the colistin MIC value was close to the breakpoint value. To understand the probable reason for the observed MIC values, sequencing of genes associated with colistin resistance was performed. Mutations at lpxA, lpxC, and pmrB genes were detected and it was observed that isolates carrying mutations in lpxC presented slow growth at killing curves.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acyltransferases; Amidohydrolases; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

Carbapenem resistance among Acinetobacter species has become a life-threatening problem. As a last resort in the treatment of gram-negative bacteria infection, resistance to colistin is also a serious problem. The aim of study was to analyze the mechanism of resistance and perform genotyping of carbapenem-resistant Acinetobacter from clinical infection and fecal survey samples in Southern China.. One hundred seventy and 74 carbapenem-resistant Acinetobacter were isolated from clinical infection samples and fecal survey samples, respectively. We detected the related genes, including carbapenemase genes (bla. Among the 244 carbapenem-resistant Acinetobacter, the common carbapenemase-positive genes included the following: bla. The bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Colistin; Communicable Diseases; Drug Resistance, Bacterial; Feces; Genetic Variation; Genotype; Humans; Integrons; Microbial Sensitivity Tests; Polymerase Chain Reaction; Sequence Analysis, DNA

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline

We investigated the intracellular survival of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates in macrophages, after phagocytosis, to determine their virulence characteristics. After ATCC 19606 and 5 clinical isolates of MDRAB were phagocytosed by mouse and human macrophages, the bacterial count of MDRAB strains, R4 and R5, increased in the mouse macrophages, 24 hours after phagocytosis. Bacterial count of the strains, R1 and R2, was almost equal 4 and 24 hours after phagocytosis. Intracellular reactive oxygen species was detected in the macrophages after phagocytosis of these bacteria. Further, the strains R1, R2, R4, and R5 showed higher catalase activity than ATCC 19606. Additionally, strains R1, R4, and R5 grew more efficiently than ATCC 19606 in the presence of H

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Catalase; Cell Line; Colistin; Cytokines; Drug Resistance, Multiple, Bacterial; Humans; Hydrogen Peroxide; Macrophages; Mice; Phagocytosis; Reactive Oxygen Species; Tigecycline; Virulence

The spread of carbapenem-resistant Acinetobacter baumannii (CRAB) is difficult to control especially in the hospitals due to the successful mobilization and evolution of the genetic elements harboring the resistant determinants. The study was conducted to examine the distribution of aminoglycosides, tetracycline, and sulfonamide-resistant determinants among CRAB isolates that carry the blaOXA-23 gene.. For a total of 160 CRAB strains isolated at tertiary care hospitals of Pakistan that mainly carried blaOXA-23 gene were included in the study to evaluate the assortment of antibiotic resistance genes.. The susceptibility rates of CRAB for other than beta-lactam drugs were 2.5% for both ciprofloxacin and aminoglycosides and 18% and 25% for sulfonamides and tetracyclines, respectively. Polymyxin B (MIC90, 1 g/mL) Colistin (MIC90, 1 g/mL) and Tigecycline (MIC90, 2 g/mL) were most active against these extensively drug-resistant CRAB isolates. The isolates were found to possess various genes mainly the tetB and sul2 for tetracycline and sulfonamide but the genes conferring resistance to aminoglycosides were varied with various combinations.. Despite the CRAB clones containing blaOXA-23 have been previously reported in Pakistani hospitals, the screening of genetic determinants responsible for other antimicrobial agents is crucial for developing an effective surveillance and mitigation system for infection management.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Microbial; Female; Humans; Male; Microbial Sensitivity Tests; Pakistan; Tertiary Care Centers; Tigecycline

Acinetobacter baumannii is naturally resistant to several classes of antibiotics and readily develops further resistance mechanisms under antibiotic pressure. For patients infected with extremely drug-resistant organisms, effective antibiotic treatments are intravenous and often require inpatient hospitalization for monitoring and dose adjustment. A 31-year-old active duty service member, stationed in Southeast Asia, sustained thermal burns from an electrical arc injury to over 40% of his total body surface area. His hospital course was complicated by multiple extensively drug resistant (XDR) A. baumanii infections including bacteremia and hepatic abscesses. To facilitate discharge to his family, his hepatic abscesses were treated successfully as an outpatient with several weeks of parenteral colistin monotherapy. With regular renal function testing, his dosages were held and/or adjusted to compensate for acute kidney injuries, and he was successfully cleared of his infection. Up to 50% of A. baumannii isolates in American hospitals, including major DOD facilities, are carbapenem resistant. As a result, historically last-line therapies, such as polymyxins, are increasingly used as treatment. New dosing guidance is emphasized to minimize renal toxicities. This case demonstrates the ability to administer parenteral colistin as an outpatient under close supervision.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Liver Abscess; Male; Microbial Sensitivity Tests

Acinetobacter baumannii meningitis and ventriculitis are difficult issues, because of the low diffusion of antibiotics in the cerebrospinal fluid and bacterial multidrug resistance. The presence of an infected intraventricular hematoma, constituting an equivalent of undrained abscess, may promote biofilm formation and failure of medical treatment.. In this case of ventriculostomy-related infection after ventricular hemorrhage, Acinetobacter baumannii was sensitive only to colistin and tigecycline. Despite a combination therapy involving intraventricular injections of colistin, we observed clinical and bacteriologic failure. Therefore, at day 4 of antibiotic therapy, we performed intraventricular fibrinolysis, which dissolved the clot, enabling sterilization of the cerebrospinal fluid after 48 hours.. This clinical case suggests the usefulness of intraventricular fibrinolysis to lyse the clot and optimize the action of antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Middle Aged; Postoperative Complications; Thrombolytic Therapy; Tigecycline; Ventriculostomy

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Catheter-Related Infections; Cerebrospinal Fluid; Colistin; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Meningitis, Bacterial; Microbial Sensitivity Tests; Salvage Therapy; Tigecycline; Ventriculoperitoneal Shunt

The emergence of Acinetobacter baumannii with resistance to colistin (ABRC) led to the investigation of daptomycin as an adjunctive to colistin for these isolates. In this study, one ABRC carbapenemase-producing bloodstream isolate was examined. Minimum inhibitory concentrations (MICs) were >512, >512 and 8 µg/mL for imipenem, daptomycin and colistin, respectively. First, a 'humanised' model of the pharmacokinetics of daptomycin and colistin was developed in 18 male C57BL/6 mice. Then, 112 mice were infected by intraperitoneal injection of the ABRC isolate and were randomly assigned into four groups of once-daily treatment for 7 days: group A, controls treated with saline; group B, treated with 20 mg/kg colistin; group C, treated with 50 mg/kg daptomycin; and group D, treated with both agents. Survival was recorded for 7 days in ten mice per group. The remaining mice were sacrificed at regular time intervals following bacterial challenge and the bacterial outgrowth in the liver, lung and right kidney was determined. Mean serum concentrations of daptomycin at 15, 30 and 60 min post-dose were 121.8, 110.3 and 100.4 µg/mL, respectively. The respective concentrations of colistin were 13.9, 9.1 and 7.5 µg/mL. The 7-day mortality in groups A, B, C and D was 100%, 50%, 100% and 0%, respectively. Tissue outgrowth of the right kidney was significantly decreased in group D compared with group B after 72 h. Daptomycin used in combination with colistin leads to prolonged survival in an experimental infection by ABRC. Failure of colistin alone is probably related to rebound of tissue outgrowth.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Daptomycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Male; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests

Acinetobacter baumannii is a critical nosocomial pathogen. A. baumannii infections have become a grave challenge due to their ability to develop resistance to different antimicrobial agents. The current study aimed to evaluate the potential synergism and bactericidal activity of a combination of colistin and cotrimoxazole against carbapenem-resistant A. baumannii (CRAB) in a Galleria mellonella model.. Four clinical A. baumannii isolates were biochemically and molecularly identified. Their antimicrobial susceptibility levels were established and the molecular characterization of the carbapenemase-encoding genes was performed. The synergism and bactericidal effect of the colistin/cotrimoxazole combination was assessed using the checkerboard assay and time-kill experiments. An in vivo evaluation of the activity of the combination was performed using the Galleria mellonella model.. A fractional inhibitory concentration index (FICI) of ≤0.5 was found for all strains, indicating that the colistin/cotrimoxazole combination exhibited powerful synergistic activity. The combination displayed both synergistic and bactericidal activity at sub-breakpoint concentrations for all strains. Cotrimoxazole monotherapy showed the least protective activity in the G. mellonella model. The survival rate ranged from 66.7-79.2 % at 24 h and was 29.2-60.4 % at 96 h for the tested isolates. Colistin monotherapy performed better than cotrimoxazole monotherapy; the G. mellonella survival rate ranged from 77.1-97.9 %, at 24 h and from 64.5-72. % at 96 h. The colistin/cotrimoxazole combination improved G. mellonella's survival rate at 96 h remarkably in comparison to colistin or cotrimoxazole monotherapy.. Finally, the combination of colistin and cotrimoxazole appears to be a promising therapeutic option for the management of CRAB-associated infections. It is essential to assess the clinical application and the dose-response relationships of combinations such as colistin plus cotrimoxazole.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Lepidoptera; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biological Transport; Catalase; Colistin; DNA-Binding Proteins; Gentamicins; Glutathione; Humans; Hydrogen Peroxide; Microbial Sensitivity Tests; Oxidative Stress; Rifampin; Superoxide Dismutase; Superoxides; Tigecycline; Zinc

This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections.. This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement.. Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching.. TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Retrospective Studies; Shock, Septic; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination

Multi-drug resistant Acinetobacter baumannii has emerged as important nosocomial pathogen associated with various infections including lower respiratory tract. Limited therapeutic options contribute to increased morbidity and mortality. Acinetobacter baumannii has the ability to persist in the environment for prolonged periods. Breach in infection control practices increases the chances of cross transmission between patients and inter/intraspecies transmission of resistance elements. The present prospective work was conducted among patients with lower respiratory tract infections (LRTI) in the intensive care unit (ICU) to study the etiology with special reference to Acinetobacter baumannii and the role of immediate patient environment in the ICU as possible source of infection. Acinetobacter baumannii were characterized for antimicrobial susceptibility, mechanism of carbapenem resistance and virulence determinants. Molecular typing of the clinical and environmental isolates was undertaken to study the probable modes of transmission.. Appropriate respiratory samples from 107 patients with LRTI admitted to ICU during September 2016 to March 2017 were studied for likely bacterial pathogens. Environmental samples (n = 71) were also screened. All the samples were processed using conventional microbiological methods. Consecutive Acinetobacter spp. isolated from clinical and environmental (health care workers and environment from ICU) samples were included in the study. Antimicrobial susceptibility was performed as per CLSI guidelines. Carbapenem resistance, mediated by carbapenemase genes (bla. Carbapenem resistant Acinetobacter baumannii (CRAB) is an important cause of LRTI in the ICU. PFGE suggests spread of carbapenem resistant isolates via cross transmission among patients and the environment. The detection of bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biofilms; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Genotype; Hospitals; Humans; India; Intensive Care Units; Microbial Sensitivity Tests; Microbiological Techniques; Molecular Typing; Phenotype; Prevalence; Prospective Studies; Respiratory Tract Infections; Species Specificity; Virulence

Colistin resistance in

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Humans; Lipid A; Microbial Sensitivity Tests; Moths; Transcription Factors

The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.. For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192 mg/L for colistin and 1-8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.. A PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain.. Fusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Synergism; Fusidic Acid; Humans; Microbial Viability; Models, Theoretical

This study reported a hospital outbreak due to an extensively drug-resistant (XDR) OXA-72-producing strain of Acinetobacter baumannii (A. baumannii).. The isolates were found to be genotypically indistinguishable by whole-genome multiple locus sequence typing, and to belong to the international clonal complex CC2. One of these isolates sequentially developed a high resistance to colistin and rifampicin under treatment, as a result of mutations in genes pmrB and rpoB, respectively. The bla. This report highlighted the need to carefully monitor the emergence of colistin and rifampicin resistance in patients treated for infections with multidrug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Conjugation, Genetic; Cross Infection; Disease Outbreaks; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Female; Gene Transfer, Horizontal; Genotype; Humans; Male; Molecular Typing; Mutation; Plasmids; Rifampin; Sequence Analysis, DNA; Transcription Factors

The increasing incidence and emergence of multi-drug resistant (MDR) Acinetobacter baumannii has become a major global health concern. Colistin is a historic antimicrobial that has become commonly used as a treatment for MDR A. baumannii infections. The increase in colistin usage has been mirrored by an increase in colistin resistance. We aimed to identify the mechanisms associated with colistin resistance in A. baumannii using multiple high-throughput-sequencing technologies, including transposon-directed insertion site sequencing (TraDIS), RNA sequencing (RNAseq) and whole-genome sequencing (WGS) to investigate the genotypic changes of colistin resistance in A. baumannii. Using TraDIS, we found that genes involved in drug efflux (adeIJK), and phospholipid (mlaC, mlaF and mlaD) and lipooligosaccharide synthesis (lpxC and lpsO) were required for survival in sub-inhibitory concentrations of colistin. Transcriptomic (RNAseq) analysis revealed that expression of genes encoding efflux proteins (adeI, adeC, emrB, mexB and macAB) was enhanced in in vitro generated colistin-resistant strains. WGS of these organisms identified disruptions in genes involved in lipid A (lpxC) and phospholipid synthesis (mlaA), and in the baeS/R two-component system (TCS). We additionally found that mutations in the pmrB TCS genes were the primary colistin-resistance-associated mechanisms in three Vietnamese clinical colistin-resistant A. baumannii strains. Our results outline the entire range of mechanisms employed in A. baumannii for resistance against colistin, including drug extrusion and the loss of lipid A moieties by gene disruption or modification.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; High-Throughput Nucleotide Sequencing; Lipid A; Mutation; Phospholipids; Vietnam

Persister cells following antibiotic exposure may cause failure of antibiotic treatment. The synergistic effects of antibiotic combinations with respect to eliminating persister cells were investigated based on their characteristics.. For Acinetobacter baumannii clinical isolates, persister assays were performed using colistin, amikacin, imipenem and ciprofloxacin in various ways, including exposure to antibiotics in combination and sequentially. Persister phenotypes were observed through analysis of ATP concentration, membrane potential and transmission electron microscopy.. Each A. baumannii isolate showed a specific survival rate of persister cells against each antibiotic. The persister cells were eradicated effectively by exposure to the combination of colistin and amikacin, especially in the sequential order of colistin then amikacin. While the persister cells were not identified after 6 h when exposed to the antibiotics in the order colistin then amikacin, they remained at 0.016% when antibiotic exposure was done in the order amikacin then colistin. Although membrane potential was low in both colistin and amikacin persisters, depletion of the intracellular ATP concentration was only observed in colistin persisters. In addition, transmission electron microscopy analysis showed that colistin persisters have a unique morphology with a rough and rippled membrane and many outer membrane vesicles. Empty pore-like structures surrounded by cracks were also observed.. In A. baumannii, the combination of colistin and amikacin was most effective for eradication of persister cells, probably due to different mechanisms of persister cell formation between antibiotics. It was also identified that the sequential order of colistin followed by amikacin was important to eradicate the persister cells.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adenosine Triphosphate; Amikacin; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Membrane Potentials; Microbial Sensitivity Tests; Microbial Viability

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Egypt; Hospitals, University; Humans; Microbial Sensitivity Tests; Rifampin

The phenomenon of colistin dependence in Acinetobacter baumannii has been described in a situation in which colistin is now considered as the last resort for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. In this study, we aimed to reveal a gene associated with colistin dependence in A. baumannii.. The colistin-dependent A. baumannii H08-391D strain was isolated from a patient, and target gene-inactivation mutants were constructed. We investigated the effects of target gene on colistin dependence with quantitative real-time PCR and endotoxin assay. Also, we observed the change of cell morphology by electron microscopy.. The expression of ACICU_02898, encoding a soluble lytic transglycosylase associated with cell-wall degradation and recycling, was increased by eight-to 42-fold in colistin-dependent mutants, and deletion of ACICU_02898 in a colistin-dependent strain led to colistin susceptibility (MIC = 8 mg/L). Endotoxin activity was significantly low in a colistin-dependent derivative ACICU_02898-inactivated mutant and a complemented mutant. In addition, the ACICU_02898-inactivated mutant showed a highly reduced growth rate. The colistin-dependent derivative and ACICU_02898-inactivated mutant showed clearly distinguished absorption profiles in the red/green fluorescence dot blot with regard to their membrane potential. Electron microscopy revealed that the deletion mutant cells were elongated compared to the colistin-susceptible wild-type strain and colistin-dependent strain.. A colistin-dependent A. baumannii strain exhibited a deficiency in its outer membrane integrity and high expression of lytic transglycosylase was required for survival. This study reveals why the colistin-dependent mutant can tolerate high antibiotic concentrations.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cell Membrane; Colistin; Drug Resistance, Multiple, Bacterial; Endotoxins; Gene Expression Regulation, Bacterial; Glycosyltransferases; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Microbial Viability; Mutation

Topics: Acinetobacter baumannii; Acinetobacter Infections; beta-Lactam Resistance; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Rifampin; Vancomycin

Here, we identified

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Bacterial; Feces; Gene Transfer, Horizontal; Microbial Sensitivity Tests; Plasmids; Swine; Swine Diseases

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Promoter Regions, Genetic; Transcription Factors

Post-surgical intra-abdominal infections (IAIs) due to carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult to treat due to suboptimal peritoneal penetrations of several antimicrobial agents. Tigecycline has favorable outcomes of treating IAIs due to multidrug-resistant organisms but occurrence of breakthrough bacteremia has been observed because this agent has low serum level. Colistin has in vitro activity against CRAB but data on treatment of IAIs is limited due to poor peritoneal penetration. The purpose of this retrospective study is to explore the outcomes of adjunctive intravenous (IV) colistin to IV tigecycline in the treatment of IAIs caused by CRAB. Of 28 patients with non-bacteremic post-surgical IAIs due to CRAB, 14 patients received IV tigecycline alone and 14 patients received IV tigecycline with IV colistin. The 14-day, 30-day, in-hospital mortality rates, the rate of breakthrough bacteremia and the rate of bacterial eradication were not significantly different. The adjunctive therapy of IV colistin was associated with significantly higher rates of renal complications (10/14) than those receiving IV tigecycline alone (3/14) (P value = 0.023). In addition, the patients receiving adjunctive IV colistin had significantly more unfavorable non-clinical outcomes including longer length of hospital stay (P value = 0.049) and higher antimicrobial cost (P value = 0.008) and non-antimicrobial costs (P value = 0.037). In this study, adjunctive IV colistin to conventional IV tigecycline in the treatment of non-bacteremic post-surgical IAIs caused by CRAB did not yield clinical benefit but caused higher renal complication and unfavorable non-clinical outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Carbapenems; Colistin; Drug Resistance, Microbial; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Postoperative Complications; Renal Insufficiency; Retrospective Studies; Tigecycline

The synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A. baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0.5 to 256 mg l

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Tetracyclines

Carbapenem-resistant Acinetobacter baumannii infections are a major public health problem worldwide, requiring the use of "old" antibiotics such as polymyxin B and E (colistin). However, there is concern regarding the emergence of isolates resistant to these antibiotics.. We report a case of a 64-year-old mestizo man hospitalized in an intensive care unit of a health institution in Colombia with identification and clinical and molecular typing of a colistin- and carbapenem-resistant A. baumannii isolate with mechanisms of resistance to colistin not previously reported, causing bacteremia.. We have identified a strain of A. baumannii with mechanisms of resistance to colistin not previously reported in a patient with bacteremia who required treatment with multiple antibiotic schemes and had an adequate response.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheters, Indwelling; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Glycopeptides; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Pneumonia; Survival Rate; Teicoplanin; Vancomycin

Treatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Moths; Mutation; Transcription Factors; Virulence

Colistin resistance in Acinetobacter baumannii often results from mutational activation of the two-component system PmrAB and subsequent addition of phospho-ethanolamine (pEtN) to lipooligosaccharide by up-regulated pEtN transferase PmrC.. To characterize mechanisms of colistin resistance independent of PmrCAB in A. baumannii.. Twenty-seven colistin-resistant A. baumannii were collected from 2012 to 2018. Analysis of operon pmrCAB was performed by PCR and sequencing. Seven strains were investigated further by WGS and whole-genome MLST (wgMLST).. Seven out of the 27 selected isolates were found to overexpress eptA, a gene homologous to pmrC, likely as a consequence of upstream insertion of an ISAba1 element. Insertion sites of ISAba1 were mapped 13, 18 and 156 bp ahead of the start codon of eptA in five strains, one strain and one strain, respectively. The finding that the isolates did not cluster together when compared by wgMLST analysis supports the notion that distinct insertion events occurred in close, but different, genetic backgrounds.. Activation of eptA and subsequent addition of pEtN to the cell surface represents a novel mechanism of resistance to colistin in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Operon; Transcription Factors; Whole Genome Sequencing

Multidrug-resistant (MDR) Acinetobacter baumannii infections are considered as emerging nosocomial infections particularly in patients hospitalized in intensive care units (ICUs). Therefore, reliable detection of MDR strains is crucial for management of treatment but also for epidemiological data collections. The purpose of this study was to compare antimicrobial resistance and the clonal distribution of MDR clinical and environmental A. baumannii isolates obtained from the ICUs of 10 different hospitals from five geographical regions of Turkey in the context of the demographic and clinical characteristics of the patients.. A multicenter-prospective study was conducted in 10 medical centers of Turkey over a 6 month period. A total of 164 clinical and 12 environmental MDR A. baumannii isolates were included in the study. Antimicrobial susceptibility testing was performed for amikacin (AN), ampicillin-sulbactam (SAM), ceftazidime (CAZ), ciprofloxacin (CIP), imipenem (IMP) and colistin (COL) by microdilution method and by antibiotic gradient test for tigecycline (TIG). Pulsed-field gel electrophoresis (PFGE) was performed to determine the clonal relationship between the isolates. The detection of the resistance genes, bla. The mortality rate of the 164 patients was 58.5%. The risk factors for mortality included diabetes mellitus, liv1er failure, the use of chemotherapy and previous use of quinolones. Antimicrobial resistance rates for AN, SAM, CAZ, CIP, IMP, COL and TIG were 91.8%, 99.4%, 99.4%, 100%, 99.4%, 1.2% and 1.7% respectively. Colistin showed the highest susceptibility rate. Four isolates did not grow on the culture and were excluded from the analyses. Of 172 isolates, 166 (96.5%) carried bla. Colistin is still the most effective antibiotic for A. baumannii infections. The gene bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Imipenem; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Phylogeny; Prospective Studies; Turkey

Acinetobacter baumannii has emerged as a major cause of nosocomial infections. Various resistance mechanisms of A. baumannii against antibiotics have transformed it into a successful nosocomial pathogen. Because of the limited number of available antibiotics, we used a medicinal plant with an antibacterial effect. Zataria multiflora Boiss (ZMB) extract and its components were used for the treatment of pneumonic mice infected with A. baumannii. The biological effects of this extract and the regulation of the outer membrane protein A (ompA) gene were used in a mouse model.. In the lung tissue culture of pneumonic mice infected with standard or clinical isolate, no colony was detected when treated with the ZMB extract after 2 and 3 days (P < 0.01), respectively. In the carvacrol-treated group, bacterial clearance was seen at day 4 and day 5 (P < 0.05). Bacterial clearance was seen 5 days after treatment with thymol and imipenem and 6 days after ampicillin/sulbactam treatment. The regulation of ompA gene was significantly decreased in this order: ZMB extract, carvacrol, thymol, imipenem, and ampicillin/sulbactam.. The ZMB extract had a potent bactericidal effect against A. baumannii that could downregulate the ompA gene. ZBM extract and carvacrol could be novel therapeutic agents for antibiotic-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Colistin; Cymenes; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Imipenem; Lamiaceae; Lung; Lung Diseases; Mice, Inbred BALB C; Microbial Sensitivity Tests; Plant Extracts; Thymol

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Lepidoptera; Microbial Sensitivity Tests; Minocycline; Tigecycline; Virulence

Acinetobacter baumannii primarily causes colonization, yet it can be an opportunistic pathogen associated with hospital-acquired infections. Many countries report rapid spread of carbapenem-resistant Acinetobacter baumannii (CRAb) which limits treatment options, with colistin frequently being the last line treatment option. The aim of our study was to evaluate a recently developed rapid method, namely the Rapid ResaPolymyxin test, for detection of colistin resistance (ColR) in Acinetobacter baumannii. This test was used for rapid screening of colistin resistance in a clinical setting where there is endemicity of CRAb isolates. A total of 82 A. baumannii clinical isolates were included in the evaluation. The majority of them were resistant to carbapenems (75/82, 91.5%). A total of 37 isolates (45.1%) were resistant to colistin, all being resistant to carbapenems. None of the ColR isolates carried the plasmid-mediated mcr-1 to -5 genes. The Rapid ResaPolymyxin NP test reached a 95.1% categorical agreement with results of reference broth microdilution method, with 93.3% sensitivity and specificity, and positive and negative predictive values being respectively at 92.3% and 97.7%. The Rapid ResaPolymyxin NP test performed well on our collection of clinical and surveillance CRAb isolates from the Central Slovenia region. The test is inexpensive and easy to integrate into laboratory workflow. The main value of the test is rapid categorization of susceptibility and resistance which has important implications with respect to the treatment strategy as well as the infection control measures.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Diagnostic Tests, Routine; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Indicators and Reagents; Microbial Sensitivity Tests; Oxazines; Reagent Kits, Diagnostic; Sensitivity and Specificity; Xanthenes

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Colistin; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Tetracyclines

Acinetobacter baumannii infections in neonates are not uncommon but rarely studied.. Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed.. Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-bla. To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Polymerase Chain Reaction; Risk Factors; Taiwan; Tigecycline

The authors report on the use of combination intravenous and inhaled colistin therapy in 2 patients with major burns admitted to an American Burn Association-verified burn center during a multidrug-resistant (MDR) Acinetobacter baumannii outbreak. Both patients had documented, culture-proven MDR Acinetobacter ventilator-associated pneumonia and bacteremia leading to sepsis. Both patients were successfully extubated and subsequently discharged from hospital. In this article, the authors provide the timeline of events and treatments that were used in these 2 cases. Combination intravenous and inhaled colistin therapy may be a valuable tool against MDR Acinetobacter infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Burn Units; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Infusions, Intravenous; Male; Middle Aged

To assess the association of survival and treatment with colistin and tigecycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.. An observational cohort study was carried out. Targeted therapy consisted of monotherapy with colistin (9 million UI/day) or combined therapy with colistin and tigecycline (100 g/day). The primary outcome was 30-day crude mortality. The association between combined targeted therapy and mortality was controlled for empirical therapy with colistin, propensity score of combined therapy and other potential confounding variables in a multivariate Cox regression analysis.. A total of 118 cases were analysed. Seventy-six patients (64%) received monotherapy and 42 patients (36%) received combined therapy. The source of bacteraemia was primary in 18% (21/118) of the patients, ventilator-associated pneumonia in 64% (76/118) and other sources in 14% (16/118). The 30-day crude mortality rate was 62% (42/76) for monotherapy and 57% (24/42) for combined therapy. The variables associated with 30-day crude mortality were: Charlson index (hazard ratio (HR) 1.16, 95% CI 1.02-1.32; p 0.028), empirical therapy with colistin (HR 2.25, 95% CI 1.33-3.80; p 0.003) and renal dysfunction before treatment (HR 1.91, 95% CI 1.01-3.61; p 0.045). Combined targeted therapy was not associated with lower adjusted 30-day crude mortality (adjusted HR 1.29, 95% CI 0.64-2.58; p 0.494).. Combined targeted therapy with high-dose colistin and standard dose tigecycline was not associated with lower crude mortality of bacteraemia due to carbapenem-resistant A. baumannii in critically ill patients.. Registered in ClinicalTrials.gov. Identifier: NCT02573064.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Carbapenems; Cohort Studies; Colistin; Critical Illness; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Propensity Score; Survival Analysis; Tigecycline; Treatment Outcome

The aim of this study was to determine the prevalence of β-lactamases in Acinetobacter spp. recovered from Lebanese patients over a 1-year period using phenotypic and molecular methods.. A total of 100 non-duplicate consecutive Acinetobacter spp. isolates were collected from various clinical specimens. Antimicrobial susceptibility testing was performed by the disk diffusion method. Susceptibility to colistin, imipenem and meropenem was determined by broth microdilution. The β-lactamase inhibitors phenylboronic acid, cloxacillin and ethylene diamine tetra-acetic acid (EDTA) were used for presumptive detection of KPC-type β-lactamase, AmpC β-lactamase and metallo-β-lactamase (MBL), respectively. Simplex PCR was conducted for molecular detection of β-lactamases. Trilocus PCR typing was performed to determine the clonality of the isolates.. A high rate of carbapenem resistance, with a predominance of OXA-23-like and IC II, was shown in this study. Moreover, the inhibitor-based method was shown not to be accurate for the prediction of carbapenemases in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Genotype; Humans; Imipenem; Lebanon; Meropenem; Microbial Sensitivity Tests; Phenotype

Bacterial meningitis is a medical emergency needing quick and timely diagnosis. Even though meningitis caused by Acinetobacter baumannii is relatively rare, it is associated with high mortality rates especially in neurosurgery patients and represents a serious therapeutic problem due to the limited penetration of effective antibiotics into the cerebrospinal fluid. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been effectively used as a rapid method for microbial identification. In this case report we identified A. baumanni by MALDI-TOF technique directly from the CSF drawn from the external ventricular drainage of a patient with severe confusional state and signs of meningism. Simultaneously the antibiotic susceptibility test was performed by automated method from the pellet of the broth-enriched sample. The MALDI-TOF technique allowed microbial identification in less than 30 minutes, and the susceptibility test result was available in eight hours, thus allowing a fast diagnosis ready for prompt and targeted antimicrobial therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Meningitis, Bacterial; Middle Aged; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Klebsiella pneumoniae; Lung; Mice; Microbial Sensitivity Tests; Respiratory Tract Infections

The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. The 14-day, 30-day and in-hospital mortality rates were nominally lower for patients who received ITH/IVT colistin adjunctive therapy versus patients who received only IV colistin (24% vs. 38%, 29% vs. 56% and 29% vs. 56%, respectively). The costs of treatment were significantly lower, the lengths of hospital and intensive care unit (ICU) stay were significantly shorter, and the number of ventilator days was significantly less among patients who received ITH/IVT colistin compared with patients who did not receive ITH/IVT colistin. The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08-1.46) and 0.77 (0.44-0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Anti-Bacterial Agents; Blood-Brain Barrier; Carbapenems; Cerebral Ventriculitis; Colistin; Female; Humans; Injections, Intraventricular; Injections, Spinal; Male; Meningitis, Bacterial; Middle Aged; Retrospective Studies; Surgical Wound Infection

The rapid increase of drug resistance and failure of available antibiotics to treat biofilm-associated infections is of great health concern. Accordingly, our study aimed to evaluate the synergistic antibacterial, biofilm inhibitory, and biofilm removal activities of melittin in combination with colistin, imipenem, and ciprofloxacin against multidrug-resistant (MDR) strong biofilm producer Acinetobacter baumannii isolates. The kinetics of biofilm formation were evaluated for the isolates for 144 h. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and biofilm removal activities for melittin and combinations with antibiotics were determined. Inhibition of biofilm-associated protein (bap) expression by melittin was evaluated with real-time polymerase chain reaction (PCR). Field emission scanning electron microscopy (FE-SEM) was used to visualize the effect of synergism on the inhibition of biofilm production. The geometric means of the fractional inhibitory concentration index (FICi) for melittin-colistin, melittin-imipenem, and melittin-ciprofloxacin combinations were calculated as 0.31, 0.24, and 0.94, respectively. Comparing the geometric means of the removal activity for melittin, colistin, imipenem, and combinations of them in both 6 and 24 h showed a significant difference between the groups (p-value < 0.05). Exposure to melittin induced a statistically significant downregulation of bap mRNA levels in all isolates at sub-MIC doses. Analysis of the FE-SEM results demonstrated that the synergism of melittin-colistin at 0.125-0.25 μg inhibited biofilm formation completely. In conclusion, our findings indicate that melittin possesses considerable potential for use in combination with colistin and imipenem to treat infections caused by MDR strong biofilm producer A. baumannii isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Kinetics; Melitten; Microbial Sensitivity Tests

With the increasing threat of multidrug-resistant organisms, such as Acinetobacter baumannii, the polymyxin class of drugs (colistin and polymyxin B) has become popular in clinical practice. A better understanding of antimicrobial susceptibility testing methods for colistin and polymyxin B is needed for optimal patient management.. Forty-two carbapenem-resistant A. baumannii isolates were subjected to susceptibility testing for colistin and polymyxin B using the following methods: broth microdilution (BMD) (glass-coated plates [BMD-Gs] and polystyrene plates [BMD-Ps]), agar dilution (AD), E-test. With BMD-Gs as reference, reliability was high for BMD-Ps and moderate for AD and Vitek for both the drugs. Similar results were obtained when the BMD-P was used as reference, but drug-polystyrene interaction was observed.. Different susceptibility testing methods for polymyxins show great variation in their results and BMD using glass-coated plates can be considered the best candidate for gold standard.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Agar; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Polymyxin B; Polystyrenes; Reproducibility of Results

Acinetobacter baumannii is a nosocomial pathogen responsible for various infections, including bloodstream infections, meningitis and ventilator-associated pneumonia. It is resistant to most antimicrobial agents, including colistin, and the development of colistin-resistant A. baumannii is of serious concern in the hospital setting. In this study, the whole-genome shotgun sequences of seven colistin-resistant A. baumannii isolates from bloodstream infections were characterised.. Colistin susceptibility testing was performed by broth microdilution. Whole genomes of all seven isolates were sequenced using an Ion Torrent™ PGM platform with 400-bp chemistry.. All seven isolates were confirmed to be resistant to colistin, with minimum inhibitory concentrations (MICs) ranging from 8μg/mL to 64μg/mL. Various antimicrobial resistance genes were present. The mcr1-5 genes were absent in all seven isolates. Chromosomal mutations that could be responsible for colistin resistance were observed. Six isolates belonged to ST848 and one isolate belonged to ST451.. Increased colistin resistance among clinical isolates of A. baumannii is alarming. Several mutations that could be responsible for colistin resistance were observed in all seven isolates. However, the significant contribution of these mutations requires further confirmation. However, genome information for these colistin-resistant A. baumannii isolates will be helpful for further comparative analysis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests

Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Fosfomycin; Humans; Microbial Sensitivity Tests; Thailand

This study aimed to determine potential host-, pathogen-, infection- and treatment-related risk factors that might predict a fulminant fatal course of bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR-Aba).. Eighty-seven patients with monomicrobial growth of XDR-Aba in blood cultures within a 6-year period (2011-2016) were studied. Patients were divided into three groups according to ICU outcome: Group A (n=40) consisted of patients who survived; Group B (n=10) included patients with fulminant sepsis who died early (≤48h); and Group C (n=37) included patients who died later (>48h) after the onset of bacteraemia.. Regarding patient co-morbidities, patients who died from fulminant XDR-Aba bacteraemia had a significantly higher prevalence of chronic renal failure compared with patients who survived (40.0% vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ dysfunction based on SOFA score compared with survivors (10.83±2.93 vs. 6.65±3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate treatment were similar among the three outcome groups. Patients with fulminant bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug-resistant strains, although not statistically significant.. Patients suffering from a fulminant course of XDR-Aba bacteraemia showed significantly higher rates of chronic renal failure and multiple organ dysfunction. Resistance patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect outcomes. Further studies including larger samples of patients along with investigation of specific virulence determinants of individual Aba strains are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis

Polymyxins are one of the last-line antibiotics for multidrug-resistant Acinetobacter baumannii. Reports have demonstrated the emergence of colistin heteroresistance in A. baumannii, which can complicate assessment of minimum inhibitory concentrations and promote resistance to colistin. We aimed to determine the presence of colistin heteroresistance in A. baumannii isolates and correlate the results with clinical and microbiological outcomes via a retrospective study of 24 adult patients: 12 blood and 12 invasive respiratory cultures positive for colistin-susceptible A. baumannii between 1 January 2013 and 31 July 2015. Heteroresistance testing was performed by plating a 100-μL bacterial cell suspension on Mueller-Hinton agar plates containing 0, 1, 2, and 4 μg/mL colistin, and assessing for growth at 24 and 48 h. Colistin heteroresistance was exhibited in 83% of isolates. Median age was 56 [43-65] years, 10 (42%) patients resided at a facility prior to admission, 5 (21%) had a chronic tracheostomy, 18 (75%) were in the intensive care unit at the time of culture collection, and median infection-related length of stay was 12 [7-15] days. Clinical and microbiological cures were achieved in 75% of patients. Overall infection-related mortality was 21%. Our study demonstrated a high rate of colistin heteroresistance in clinical isolates of colistin-susceptible A. baumannii, although this was not associated with suboptimal clinical outcomes due to the use of aggressive colistin dosing and combination therapy. Further studies are needed to establish the association between in vitro colistin heteroresistance and clinical and microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies

The impact of multidrug-resistant organisms (MDROs), including non-fermentative bacilli (NFBs), is rising and underestimated, especially in intensive care units (ICUs). The growing prevalence of multidrug resistance (MDR) and extensive drug resistance (XDR) is challenging for clinicians, as the treatment options are limited.. The purpose of this study was to analyze the extent of the epidemiological problem of multidrugresistant, extensively drug-resistant and pandrug-resistant (PDR) non-fermentative bacilli isolated from pneumonia and bloodstream infections (BSIs) in patients hospitalized in southern Poland.. This study included 253 NFBs belonging to Acinetobacter sp. (ACI), Pseudomonas sp. (PAR), and Stenotrophomonas sp. (STM). The microorganisms were identified, and susceptibility testing was performed using a semi-automatic system. The different patterns of resistance were defined as MDR, XDR, or PDR strains. Epidemiological typing of A. baumannii from ICUs was performed by repetitive polymerase chain reaction (rep-PCR).. More than half of the strains (57.7%) were isolated within ICUs. ACI-strains came significantly more often from ICU wards. The highest prevalence of ACI and PAR was found in pneumonia, whereas STM dominated in BSIs. ACIs were more frequently resistant than other pathogens to all studied antibiotics except colistin (n = 76; 58.9%), and they belonged to the XDR category. DiversiLab demonstrated the presence of 2 dominant clones in the ACI group, both classified as European Clone 2 (EUII).. Our results indicate serious potential therapeutic problems related to high antibiotic resistance of ACI isolates. The stratification of drug resistance (MDR/XDR/PDR) may become an important tool for the assessment of public health epidemiology and microbiological hazards at the local, national, and international level. It allows clear presentation of the issues concerning the epidemiology of highly resistant bacilli, and the exchange of information between medical staff and local representatives of public health for the implementation of effective measures to reduce drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Poland; Prevalence; Pseudomonas; Pseudomonas Infections; Stenotrophomonas

β-lactam-β-lactamase inhibitors (BLIs) have previously demonstrated antimicrobial activity against Acinetobacter baumannii (AB). Colistin retains the highest susceptibility rate against A. baumannii, and has demonstrated synergy with other antimicrobials, including β-lactam-BLIs. Therefore, we assessed the potential individual activity and synergistic combinations in vivo against carbapenem-susceptible (CS) and multidrug-resistant (MDR) A. baumannii isolates in neutropenic thigh and lung infection models. In vitro, colistin and tazobactam MICs were 1 and 16 µg/mL against AB 25-49 (CS) and 1 and 128 µg/mL against AB 5075 (MDR) respectively. In the lung model, tazobactam alone and in combination with colistin achieved a 1-log reduction in CFU, while colistin alone was not active against AB 25-49. No activity was observed against AB 5075. In the thigh model, tazobactam with and without colistin was bacteriostatic against AB 25-49 but did not demonstrate any activity against AB 5075. Avibactam and colistin alone and in combination were not active against either isolate. No synergy was observed; however, we found tazobactam activity against A. baumannii. This activity was not observed for the non-β-lactam-BLI, avibactam. This suggests that binding to penicillin-binding proteins of the β-lactam molecule is required for tazobactam activity against A. baumannii. These data point to an added role of β-lactam-BLIs beyond their primary purpose of β-lactamase inhibition in the treatment of MDR A. baumannii infections by enhancing the activity of peptide antibiotics, a property that is not shared by the novel non-β-lactam-BLIs. Future studies are needed to define tazobactam and colistin activity in an A. baumannii infection model.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Humans; Lung; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Penicillanic Acid; Tazobactam; Thigh

Acinetobacter baumannii is one of the most challenging nosocomial pathogens due to the emergence and widespread of antibiotic resistance. We aimed to provide the first analysis of global prevalence of antibiotic resistance in A. baumannii infections, by synthesizing data and knowledge through a systematic review. We searched studies reporting antibiotic resistance in A. baumannii infections using the Medline, Embase, Web of Science, and Cochrane databases from January 2000 to December 2016. Studies were eligible if they investigated and reported antibiotic resistance in A. baumannii infections with inpatients or outpatients in hospital. Our investigation showed a high prevalence of resistance to the common prescribed antibiotics in A. baumannii infections in both OECD (Organization for Economic Co-operation and Development) and non-OECD countries. Strikingly, though OECD countries have substantially lower pooled prevalence of resistance compared to non-OECD countries based on the data during 2006-2016, a further investigation in a time scale disclosed a faster increase in OECD countries during the past 11 years, and currently both of them have a comparable prevalence of resistance (2011-2016). Tigecycline and colistin are still active but their resistances are expected to become common if the preventative measures are not taken. Antibiotic resistance in A. baumannii infection developed fast and is a crisis for both OECD and non-OECD countries. A "post-antibiotic era" for A. baumannii infection is expected in the next 10-20 years without immediate actions from pharmaceutical companies and governments.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Organisation for Economic Co-Operation and Development; Prevalence; Tigecycline

We investigated the numbers of planktonic and biofilm cells and the expression levels of genes encoding efflux pumps and biofilm-related proteins in 10 clinical isolates of multi-drug resistant Acinetobacter baumannii (MDRA) as well as in its standard strain ATCC 19606 in the presence of colistin (CST), polymyxin B (PMB), minomycin (MIN), and tigecycline (TGC) at their respective sub-MICs. The number of planktonic and biofilm cells of ATCC 19606 decreased in the presence of all aforementioned antibiotics in a dose-dependent manner. Cell number also decreased in two representative MDRA strains, R2 and R3, in the presence of MIN and TGC in a dose-dependent manner. In contrast, the number of biofilm cells in these two strains increased in the presence of CST, while they increased significantly in the presence of PMB in R2 only. Pearson correlation analysis revealed that the number of biofilm cells was positively and significantly correlated with the mRNA levels of genes encoding efflux pumps (adeB and adeG) and autoinducer synthase (abaI) in strain R2 and adeB, adeG, adeJ, poly-acetyl-glucosamine-porin (pgaA), and abaI in strain R3 in the presence of CST. It was positively and significantly correlated with the mRNA levels of genes encoding adeB in strain R2 and an outer membrane protein A (ompA) and biofilm-associated protein (bap) in strain R3 in the presence of PMB. These results provide valuable insights into the biofilm formation potency of clinical isolates of MDRA that depends on efflux pumps and biofilm-related genes and its regulation by antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Biofilms; Colistin; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Polymyxin B; RNA, Messenger

No animal model studies have been conducted in which the efficacy of herbal compounds has been tested against multidrug-resistant Acinetobacter baumannii infections. Very few antibiotics are available for the treatment of pulmonary infections caused by extensively drug-resistant Acinetobacter baumannii (XDRAB). To find alternative treatments, traditional Chinese herbs were screened for their antimicrobial potential.. The present study screened 30 herbs that are traditionally used in Taiwan and that are commonly prescribed for heat clearing and detoxification. The herbs with antibacterial activities were analysed by disc diffusion assays, time-kill assays and a murine lung infection model.. Of the 30 herbs tested, only Scutellaria barbata demonstrated 100% in vitro activity against XDRAB. Furthermore, we compared the antibacterial effect of the S. barbata extract with that of colistin, and the S. barbata extract showed better antibacterial effect. In the XDRAB pneumonia murine model, we compared the antimicrobial effects of the orally administered S. barbata extract (200 mg/kg, every 24 h), the intratracheally administered colistin (75,000 U/kg, every 12 h), and the control group. The bacterial load in the lungs of the treatment group that received the oral S. barbata extract showed a significant decrease in comparison to that in the lungs of the control group. In addition, histopathological examinations also revealed better resolution of perivascular, peribronchial, and alveolar inflammation in the oral S. barbata extract-treated group.. Our in vitro and in vivo data from the animal model support the use of S. barbata as an alternate drug to treat XDRAB pulmonary infections. However, detailed animal studies and clinical trials are necessary to establish the clinical utility of S. barbata in treating XDRAB pulmonary infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Drug Resistance, Bacterial; Female; Humans; Lung Diseases; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Plant Extracts; Scutellaria; Taiwan

Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings.. The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains.. Clinical and environmental isolates of A. baumannii were obtained from patients, staff, and environment of an educational hospital in Tehran. Antimicrobial susceptibility testing was carried out using the disk diffusion and E-test methods. Multiplex PCR was performed for detection of OXA-type genes (bla. All the isolates were found to be susceptible to colistin and most of them (77%) were non-susceptible to tigecycline. A majority of the clinical and environmental isolates (97%) were considered as MDR strains and 41% as XDR. In multiplex detection, bla. The present study highlights the circulation of drug-resistant A. baumannii strains in different wards of hospitals principally in intensive care unit (ICU) as a nosocomial pathogen due to unwise managements.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Communicable Diseases, Emerging; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Genotype; Hospitals, Teaching; Humans; Intensive Care Units; Iran; Minocycline; Molecular Typing; Tigecycline

Colistin is considered a last-hope antibiotic against extensively drug-resistant isolates of Acinetobacter baumannii. Resistance to colistin has been rarely reported for A. baumannii. Genetic alterations in the PmrA-PmrB two-component system and lipid A biosynthesis genes may be associated with colistin resistance. We investigated molecular mechanisms of colistin resistance in three clinical colistin-resistant (ColR) and two colistin-susceptible (ColS) A. baumannii isolates. A ColR mutant was generated in vitro by repetitive drug exposure. The pmrA, pmrB, lpxA, lpxC, and lpxD genes were amplified and sequenced. To evaluate association between colistin resistance and upregulation of pmrCAB operon, transcriptional level of the pmrC gene encoding for lipid A phosphoethanolamine (PEtN) transferase was quantified by reverse transcription quantitative PCR (RT-qPCR) analysis. All clinical and in vitro-selected ColR isolates harbored at least one point mutation in the pmrB gene, including A142V, P233S, T235I, and A227V substitutions as well as duplication of H325. No alteration was found in the pmrA and other amino acid substitutions identified in the pmrB as well as lpx genes did not seem to be involved in colistin resistance as they were found in both ColS and ColR isolates. RT-qPCR analysis revealed a correlation between colistin resistance and pmrC overexpression. Specific alterations in the PmrB, linked to overproduction of PEtN transferase, triggered colistin resistance in the studied A. baumannii isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Mutation; Operon; Transcription Factors

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adenosine Diphosphate; Adenosine Triphosphate; Anti-Bacterial Agents; Bacterial Proteins; Catalase; Colistin; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Gentamicins; Hydrogen Peroxide; Iron; Microbial Sensitivity Tests; Minocycline; Mutation; NAD; Oxidative Stress; Reactive Oxygen Species; Repressor Proteins; Rifampin; Superoxide Dismutase; Tigecycline

Acinetobacter baumannii can acquire resistance to colistin via complete loss of lipopolysaccharide (LPS) biosynthesis due to mutations in the lpxA, lpxC and lpxD genes. However, although colistin is increasingly being used for the treatment of multidrug resistant infections, very few A. baumannii clinical isolates develop colistin resistance through loss of LPS biosynthesis. This may suggest that LPS loss affects virulence traits that play a role in the transmission and pathogenesis of A. baumannii. In this study we characterize multiple virulence phenotypes of colistin resistant, LPS-deficient derivatives of the ATCC 19606 strain and five multidrug resistant clinical isolates and their colistin resistant, LPS-deficient derivatives. Our results indicate that LPS loss results in growth defects compared to the parental strain in vitro both in laboratory media and human serum (competition indices of 0.58 and 7.0 × 10

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Female; Humans; Interleukin-6; Lipopolysaccharides; Mice, Inbred C57BL; Microbial Sensitivity Tests; Phenotype; Tumor Necrosis Factor-alpha; Virulence

The mechanisms underlying colistin heteroresistance in Acinetobacter baumannii are not fully understood. Here, we investigated the role of efflux in colistin-heteroresistant populations of a multidrug-resistant (MDR) A. baumannii clinical isolate.. Three colistin-resistant A. baumannii strain variants isolated from the same clinical sample were studied for the presence of heteroresistance to colistin by drug susceptibility testing, genotyping and drug resistance target mutation analysis. The existence of active efflux was studied by synergism assays with efflux inhibitors, real-time efflux activity measurements and analysis of the mRNA transcriptional levels of selected efflux pump genes in response to colistin.. All of the strain variants belong to the ST218, clonal complex 92, international clonal lineage II. Different colistin susceptibility levels were observed among the three strain variants, indicating that colistin-heteroresistant subpopulations were being selected upon exposure to colistin. No mutations were found in the genes lpxACD and pmrAB, which are associated with colistin resistance. The results showed the existence of synergistic interactions between efflux inhibitors and colistin and ethidium bromide. Real-time efflux assays demonstrated that the three strain variants had increased efflux activity that could be inhibited in the presence of the inhibitors. The efflux pump genes adeB, adeJ, adeG, craA, amvA, abeS and abeM were found to be overexpressed in the strain variants in response to colistin exposure.. This study shows that efflux activity contributes to colistin heteroresistance in an MDR A. baumannii clinical isolate. The use of efflux inhibitors as adjuvants of the therapy can resensitize A. baumannii to colistin and prevent the emergence of drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Dogs; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Serbia; Urinary Tract Infections

Acinetobacter baumannii causes difficult-to-treat nosocomial infections, which often lead to morbidity due to the development of antimicrobial drug resistance and expression of virulence genes. Data regarding the association of resistance to colistin, a last treatment option, and the virulence gene expression of A. baumannii is scarce.. We evaluated the MLVA genotype, antimicrobial resistance, and biofilm formation of 100 A. baumannii isolates from burn patients, and further compared the in vitro and in vivo expression of four virulence genes among five colistin-resistant A. baumannii (Cst-R-AB) isolates. Five Cst-R-AB isolates were tested; one from the present study, and four isolated previously.. Our results showed that reduced expression of recA, along with increased in vivo expression of lpsB, dnaK, and blsA; are associated with colistin resistance among Cst-R-AB isolates. Differences in virulence gene expressions among Cst-R-AB isolates, may in part explain common discrepant in vitro vs. in vivo susceptibility data during treatment of infections caused by Cst-R-AB.. Our findings highlight the intricate relationship between colistin-resistance and virulence among A. baumannii isolates, and underscore the importance of examining the interactions between virulence and antimicrobial resistance toward efforts to control the spread of multidrug-resistant A. baumannii (MDR-AB) isolates, and also to reduce disease severity in burn patients with MDR-AB infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Biofilms; Burns; Colistin; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Humans; Mannosyltransferases; Microbial Sensitivity Tests; Rec A Recombinases; Virulence

Antibiotic resistance has become increasingly prevalent over the past few decades, and this combined with a dearth in the development of new classes of antibiotics to treat multidrug resistant Gram-negative infections has led to a significant global health problem and the increased usage of colistin as the last resort antibiotic. Colistin, however, presents dose dependent toxicity in the clinic. One potential approach to combatting this problem is the use of an antibiotic adjuvant, a compound that is nontoxic to the bacteria that enhances the potency of colistin and ultimately allows for reducing dosing. Herein, we present a new urea-containing class of 2-aminoimidazole-based adjuvants that potentiates colistin activity against colistin-sensitive Acinetobacter baumannii. Lead compounds enabled 1000-fold reduction in the minimum inhibitory concentration of colistin in vitro and showed efficacy in a Galleria mellonella infection model, representing the first step toward validating the potential of employing these adjuvants to lower colistin dosage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adjuvants, Pharmaceutic; Animals; Anti-Bacterial Agents; Colistin; Drug Synergism; Humans; Imidazoles; Moths

Multidrug-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Transcription Factors

In this study we retrospectively reviewed A. baumannii meningitis cases treated with tigecycline including regimens and evaluated the efficacy of tigecycline in the therapy.. Study was performed in seven tertiary-care educational hospitals from five cities of Turkey and one center from France. We extracted data and outcomes of all adult (aged >18) patients with culture proven A. baumannii meningitis treated with tigecycline including antibiotic therapy until April 2016.. A total of 23 patients (15 male and eight female) fulfilled our inclusion criteria. All Acinetobacter strains were carbapenem-resistant and susceptible to tigecycline. Six cases received tigecycline monotherapy while 17 received tigecycline including combination therapy (10 with colistin, 4 with netilmicin, 3 with amikacin, 4 with meropenem). Seven of 23 cases (30%) died during the tigecycline including therapy (1 in monotherapy, 4 in colistin, 2 in netilmicin, 1 amikacin, one case received tigecycline + netilmicin followed by tigecycline + colistin). Hence, overall end of treatment (EOT) success was 70%. However, since further 27% died due to additional nosocomial infections, overall clinical success (relieved symptoms at the EOT and one-month post-therapy survival without any relapse or reinfection) decreased to 43%.. We conclude that tigecycline may be an alternative in the salvage treatment of nosocomial multidrug-resistant Acinetobacter spp. meningitis. Acinetobacter spp. Meningitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Tigecycline

The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined.. We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls.. Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups.. Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Lipid A; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Young Adult

Extensively drug-resistant (XDR) Acinetobacter baumannii strains have emerged rapidly worldwide. The antibiotic resistance characteristics of XDR A. baumannii strains show regional differences; therefore, it is necessary to analyze both genomic and proteomic characteristics of emerging XDR A. baumannii clinical strains isolated in Korea to elucidate their multidrug resistance. Here, we isolated new sequence type of XDR A. baumannii clinical strain (KAB03) from Korean hospitals and performed comprehensive genome analyses. The strain belongs to new sequence type, ST451. Single nucleotide polymorphism (SNP) analysis with other types of A. baumannii strains revealed that KAB03 has unique SNP pattern in the regions of gyrB and gpi of MLST profiles. A. baumannii KAB03 harbours three antibiotic resistance islands (AbGRI1, 2, and 3). AbGRI1 harbours two copies of Tn2006 containing bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactamases; Carbapenems; Colistin; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Polymorphism, Single Nucleotide; Republic of Korea

"Healthcare-associated ventriculitis and meningitis" is a potentially devastating illness following neurosurgical procedures. Multidrug resistant (MDR) and extensively drug resistant (XDR) organisms such as Acinetobacter baumannii and Klebsiella pneumoniae have increasingly been isolated in ventriculitis and meningitis episodes. The treatment of these infections can be challenging, as the antimicrobial options are restricted. Regarding Central Nervous System (CNS) infections the transfer of the antibiotics to the Cerebrospinal Fluid (CSF) is often low which results in decreased drug levels at the infection site. The intraventricular (IVT) administration of antibiotics can be used as an adjunct to the intravenous (IV) treatment of Gram-negative MDR ventriculitis and meningitis, yet pertinent data is scarce. We present the successful management of three cases of healthcare-associated ventriculitis and meningitis due to XDR species with the combined intraventricular administration of colistin and off-label tigecycline, after the initial regimen of colistin given alone through both IVT and IV routes had failed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Central Nervous System; Cerebral Ventriculitis; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Encephalitis; Female; Humans; Infusions, Intraventricular; Injections, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Research Design; Tigecycline; Young Adult

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Carbon; Colistin; Drug Resistance, Bacterial; Hospitals; Humans; Korea; Microbial Sensitivity Tests

Acinetobacter baumannii is a healthcare-associated pathogen with high rates of carbapenem resistance. Colistin is now routinely used for treatment of infections by this pathogen. However, colistin use has been associated with development of resistance to this agent.. To elucidate the phylogenomics of colistin-susceptible and -resistant A. baumannii strain pairs from a cohort of hospitalized patients at a tertiary medical centre in the USA.. WGS data from 21 pairs of colistin-susceptible and -resistant, XDR clinical strains were obtained and compared using phylogeny of aligned genome sequences, assessment of pairwise SNP differences and gene content.. Fourteen patients had colistin-resistant strains that were highly genetically related to their own original susceptible strain with a median pairwise SNP distance of 5.5 (range 1-40 SNPs), while seven other strain pairs were divergent with ≥84 SNP differences. In addition, several strains from different patients formed distinct clusters on the phylogeny in keeping with closely linked transmission chains. The majority of colistin-resistant strains contained non-synonymous mutations within the pmrAB locus suggesting a central role for pmrAB mutations in colistin resistance. Excellent genotype-phenotype correlation was also observed for carbapenems, aminoglycosides and tetracyclines.. The findings suggest that colistin resistance in the clinical setting arises through both in vivo evolution from colistin-susceptible strains and reinfection by unrelated colistin-resistant strains, the latter of which may involve patient-to-patient transmission.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Genomics; Hospitalization; Humans; Microbial Sensitivity Tests; Mutation; Phylogeny; Polymorphism, Single Nucleotide; Tertiary Care Centers; United States; Whole Genome Sequencing

Preventing bacterial contact with host cells can provide an additional approach to tackling MDR Acinetobacter baumannii. Recently, we identified AOA-2 as a potential blocker of A. baumannii outer membrane protein A without presenting bactericidal activity. Here, we aimed to study whether AOA-2 can increase the activity of colistin against colistin-resistant A. baumannii in vitro and in vivo.. Reference and clinical A. baumannii strains susceptible and resistant to colistin (CST-S and CST-R) were used. Microdilution and time-kill curve assays were performed to determine the synergy between AOA-2 and colistin. SDS-PAGE assays with CST-S and CST-R outer membrane proteins and MALDI-TOF-TOF (MS-MS/MS) analysis were performed to determine the AOA-2 and colistin synergy mechanism. In a murine peritoneal sepsis model, the therapeutic efficacy of AOA-2 (10 mg/kg/24 h) in combination with a sub-optimal dose of colistin (10 mg/kg/24 h) against CST-R was evaluated by determining the bacterial load in tissues and blood, and mouse survival.. We showed that AOA-2 increased the in vitro colistin susceptibility of reference and clinical CST-S and CST-R strains. This combination also enhanced their killing activity after 24 h of drug exposure. This synergy is mediated by the overexpression of Omp25. In vivo, the combination of AOA-2 with colistin significantly reduced the bacterial load in tissues and blood, and increased mouse survival, compared with colistin monotherapy.. We identified a novel class of antimicrobial agents that has proven to be effective in combination with colistin in an experimental model of severe infection by CST-R A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Colistin; Disease Models, Animal; Drug Synergism; Enzyme Inhibitors; Female; Mice, Inbred C57BL; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Treatment Outcome

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients' 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients.A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96-142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27-1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Survival Rate; Taiwan; Tigecycline; Treatment Outcome

Amidst the ever-rising threat of antibiotics resistance, colistin, a decade-old antibiotic with lingering toxicity concern, is increasingly prescribed to treat many drug-resistant, gram-negative bacteria. With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. Subsequent stabilization by DSPE-PEG and homogenization through micro-fluidization of the liquid coacervates yielded nanoparticles 8 nm in diameter. In vitro assessment showed that the colistin antimicrobial activity against multiple drug-resistant bacterial strains was retained and, in some cases, enhanced following the nanoparticle assembly. In vivo administration in mice demonstrated improved safety of the colistin nanoparticle, which has a maximal tolerated dose of 12.5 mg/kg compared to 10 mg/kg of free colistin. Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin. In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin. These results demonstrate coacervation-induced nanoparticle assembly as a promising approach towards improving colistin treatments against bacterial infections. STATEMENT OF SIGNIFICANCE: Improving the safety of colistin while retaining its antimicrobial activity has been a highly sought-after objective toward enhancing antibacterial treatments. Herein, we demonstrate formation of stabilized colistin nanocomplexes in the presence of anionic polypeptides and DSPE-PEG stabilizer. The nanocomplexes retain colistin's antimicrobial activity while demonstrating improved safety upon in vivo administration. The supramolecular nanoparticle assembly of colistin presents a unique approach towards designing antimicrobial nanoparticles.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Bacteremia; Colistin; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred BALB C; Nanoparticles; Pneumonia, Bacterial

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Reproducibility of Results; Sulbactam

The emergence of polymyxin resistance threatens to leave clinicians with few options for combatting drug-resistant Acinetobacter baumannii . The objectives of the current investigation were to define the in vitro emergence of polymyxin resistance and identify a combination regimen capable of eradicating A. baumannii with no apparent drug susceptibilities.. Two clonally related, paired, A. baumannii isolates collected from a critically ill patient who developed colistin resistance while receiving colistin methanesulfonate in a clinical population pharmacokinetic study were evaluated: an A. baumannii isolate collected before (03-149.1, polymyxin-susceptible, MIC 0.5 mg/L) and an isolate collected after (03-149.2, polymyxin-resistant, MIC 32 mg/L, carbapenem-resistant, ampicillin/sulbactam-resistant). Using the patient's unique pharmacokinetics, the patient's actual regimen received in the clinic was recreated in a hollow-fibre infection model (HFIM) to track the emergence of polymyxin resistance against 03-149.1. A subsequent HFIM challenged the pan-resistant 03-149.2 isolate against polymyxin B, meropenem and ampicillin/sulbactam alone and in two-drug and three-drug combinations.. Despite achieving colistin steady-state targets of an AUC 0-24 >60 mg·h/L and C avg of >2.5 mg/L, colistin population analysis profiles confirmed the clinical development of polymyxin resistance. During the simulation of the patient's colistin regimen in the HFIM, no killing was achieved in the HFIM and amplification of polymyxin resistance was observed by 96 h. Against the polymyxin-resistant isolate, the triple combination of polymyxin B, meropenem and ampicillin/sulbactam eradicated the A. baumannii by 96 h in the HFIM, whereas monotherapies and double combinations resulted in regrowth.. To combat polymyxin-resistant A. baumannii , the triple combination of polymyxin B, meropenem and ampicillin/sulbactam holds great promise.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Meropenem; Microbial Sensitivity Tests; Polymyxin B; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Viability; Republic of Korea; Treatment Failure

Intravenous colistimethate sodium (CMS) use in burn center patients is increasing due to the emergence of multidrug-resistant gram-negative bacteria. However, optimal dosing strategies and factors that may contribute to treatment failure are limited. The purpose of this study was to determine factors that may contribute to treatment failure in colistin-treated burn center patients.. This retrospective, observational study included burn center patients that received ≥48h of intravenous CMS between June 1, 2009 and June 30, 2014. Data was collected utilizing the institution's electronic medical record system. Statistical analysis included demographic, univariable, and multivariable analysis to determine factors that may predict clinical failure of burn center patients requiring intravenous CMS.. Eighty-one patients were included in this study, with 55 patients (68%) achieving clinical success. A total daily dose (TDD) of >5mg/kg ideal body weight (IBW) was associated with significantly less clinical failure (odds ratio=0.21; 95% CI, 0.05, 0.91). Additionally, clinical failure was significantly higher in patients with wounds as the primary source of infection, creatinine clearances of 91-120mL/min, and those receiving renal replacement therapy. No difference was observed in nephrotoxicity when comparing TDD >5mg/kg IBW and TDD ≤5mg/kg IBW.. Clinical success was significantly higher with larger intravenous CMS doses in burn center patients. Higher CMS doses were not found to be associated with increased nephrotoxicity within this patient group.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Replacement Therapy; Retrospective Studies; Treatment Failure

Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug resistance among A. baumannii isolates led to the use of colistin, subsequently giving rise to colistin-resistant strains. In this study, the genetic and phenotypic profiles of two colistin-resistant A. baumannii isolates were investigated. Two A. baumannii isolates were obtained from Patient 1 (C071 and C440) and three isolates were obtained from Patient 2 (C080, C314 and C428). Susceptibility profiles were determined by VITEK

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Typing; Multiplex Polymerase Chain Reaction; Mutation; Random Amplified Polymorphic DNA Technique; Transcription Factors; Virulence

Few studies have compared nebulized and intravenous (IV) colistin for multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia. This study compared the nephrotoxicity and clinical outcomes for these two delivery routes.. This study retrospectively compared 95 critically ill surgical patients who were diagnosed with Acinetobacter baumannii ventilator associated pneumonia and received colistin between March 2013 and January 2016.. The most common diagnoses were brain hemorrhage (27.4%), traumatic brain injury (20%), traumatic thoracic injury (15.8%), and secondary peritonitis (11.6%). Compared to the IV group, the nebulizer group was significantly older (60.0 vs. 67.5years, p=0.010), had higher APACHE II scores (16.3 vs. 19.9, p=0.001), and more frequently had diabetes mellitus (6.8% vs. 21.6%, p=0.043). Nephrotoxicity was more common in the IV group (60.5% vs. 15.7%, p<0.0001). Both groups had similar microbiological and clinical outcomes (p=0.921 and p=0.719, respectively). Patients with nephrotoxicity exhibited prolonged IV or nebulized colistin treatment and more frequent combination with vancomycin. Nephrotoxicity was independently associated with IV delivery (odds ratio: 8.48, 95% confidence interval: 2.95-24.39, p<0.0001).. Nebulized colistin may have less nephrotoxicity and provide similar clinical results, compared to IV colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Colistin; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Intensive Care Units; Lebanon; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prevalence; Respiration, Artificial; Retrospective Studies; Risk Factors; Shock, Septic; Steroids; Tigecycline; Treatment Outcome; Young Adult

Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii).. This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed.. Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin.. Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Chemotherapy, Adjuvant; Colistin; Cross Infection; Drug Therapy, Combination; Edetic Acid; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Thienamycins

Acinetobacter baumannii has emerged worldwide as a dominant pathogen in nosocomial infections. In this study, we report the draft genome sequence of a clinical multidrug-resistant (MDR) A. baumannii ST191 (CC92) strain. Whole-genome sequencing of the isolate was performed using an Illumina HiSeq™ 2500 system, and bioinformatics analysis was also performed. The draft genome length was 4,259,210bp, harbouring 14 gene sequences relevant to antibiotic resistance. Antimicrobial susceptibility testing revealed that the isolate was resistant to all of the tested antibiotics except for tigecycline and colistin. These data will facilitate further understanding of the genomic and resistance features of MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; China; Colistin; Computational Biology; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genes, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Tigecycline; Whole Genome Sequencing

The worldwide increase in the emergence of carbapenem resistant

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Disk Diffusion Antimicrobial Tests; DNA, Bacterial; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Female; Genes, Bacterial; Humans; Lebanon; Male; Microbial Sensitivity Tests

Colistin is commonly needed for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) and the determination of its in vitro activity is obviously important. However, the accurate routine antimicrobial susceptibility testing (AST) of colistin is still challenging. The only acceptable method for colistin AST is broth microdilution (BMD); disc and gradient diffusion assays are inappropriate and the performance of semi-automated systems has not been validated.. In the present study, two commonly used semi-automated systems were evaluated for colistin AST of contemporary CRAB clinical isolates.. A total of 117 single-patient CRAB isolates collected randomly during 2015 from distinct tertiary hospitals located throughout Greece were tested. Colistin MICs were determined using the semi-automated systems Phoenix100 and Vitek2 and also agar dilution (AD), compared with the reference BMD.. Colistin resistance rates for Phoenix100/Vitek2/AD/BMD were 15.4%/16.2%/35.9%/24.8%. The essential/categorical agreement rates were as follows: Phoenix100, 91.5%/88.9%; Vitek2, 88.9%/89.7%; and AD, 93.2%/87.2%. Alarmingly high rates of very major errors (VMEs) were observed for Phoenix100 (41.4%) and Vitek2 (37.9%), while major errors (MEs) were limited (1.1% by both systems); VMEs were much more common for isolates with MICs of 2 mg/L than for isolates with MICs of ≤ 1 mg/L, as determined by automated methods. AD produced considerably higher colistin MICs, yielding MEs of 15.9%.. Colistin resistance of A. baumannii is greatly underestimated by Phoenix100/Vitek2, potentially leading to inappropriate colistin administration. Colistin AST results by automated systems within the susceptible range, particularly those at the susceptibility breakpoint (2 mg/L), need to be validated by BMD.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Automation; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Greece; Humans; Microbial Sensitivity Tests; Tertiary Care Centers

Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Phenotype

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Host defense peptides are preferably administered as topical therapeutic agents. We have investigated whether peptide A3-APO can enter the circulation when applied to the ear skin. Efficacy of peptide monotherapy as transdermal administration option was assessed in a systemic mouse Acinetobacter baumannii model. A3-APO reduced mortality and demonstrated a statistically significant reduction of blood bacterial counts, regardless whether it was administered prior or after bacterial challenge. The peptidic metabolite of A3-APO was efficacious when applied to the ear or tail.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Cutaneous; Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Arginine; Bacteremia; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Ear; Humans; Mice; Proline; Skin; Survival Analysis

We present the case of a patient with ventilator-associated pneumonia (VAP) caused by a pan-resistant Acinetobacter baumannii successfully treated with the combination colistin plus vancomycin plus rifampin, whose in vitro activity was investigated by checkerboard method and killing testing. Furthermore, the serum bactericidal activity (SBA) was assessed. Our case shows that an innovative regimen consisting of colistin plus antimicrobials active only against Gram-positive microorganisms might represent a valid therapeutic option for severe infections caused by colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Microbial Sensitivity Tests; Neurosurgical Procedures; Pneumonia, Ventilator-Associated; Rifampin; Subarachnoid Hemorrhage; Vancomycin

During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia.. The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia.. Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170-7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970-9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p=0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility after adjustment for other variables (adjusted OR 1.884, 95% CI 0.298-11.920; p=0.501).. These data suggest that tigecycline non-susceptible Acinetobacter spp have emerged and disseminated in the hospital in association with a recent exposure to carbapenems and an immunosuppressed state. This indicates that the rational use of antibiotics through a comprehensive antimicrobial stewardship program, especially in immunosuppressed patients, may be essential in limiting the emergence and spread of multidrug-resistant organisms such as tigecycline-resistant Acinetobacter spp, which are difficult to treat.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Disease Susceptibility; Drug Resistance, Bacterial; Female; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline; Risk Factors; Tigecycline

Acinetobacter species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P = 0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; P = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03-5.28; P = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13-2.85; P = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenems; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Leukopenia; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Severity of Illness Index; Survival Analysis; Thrombocytopenia

Acinetobacter baumannii is a Gram-negative bacterium of increasing concern due to its virulence and persistence in combat and healthcare environments. The incidence of both community-acquired and nosocomial A. baumannii infections is on the rise in foreign and domestic healthcare facilities. Treatment options are limited due to the acquisition of multidrug resistance to the few effective antibiotics. Currently, the most effective pharmaceutically based treatment for multidrug-resistant A. baumannii infections is the antibiotic colistin (polymyxin E). To minimize side effects associated with administration of colistin or other toxic antimicrobial agents, we propose the development of a nanotechnology-mediated treatment strategy. In this design-based effort, colistin-functionalized multilayered, inorganic, magnetoplasmonic nanoconstructs were fabricated to bind to the surface of A. baumannii. This result, for the first time, demonstrates a robust, pharmaceutical-based motif for high affinity, composite nanoparticulates targeting the A. baumannii surface. The antibiotic-activated nanomaterials demonstrated cytocompatibility with human cells and no acute bacterial toxicity at nanoparticle to bacterial concentrations <10 000:1. The magnetomotive characteristics of the nanomaterial enabled magnetic extraction of the bacteria. In a macroscale environment, maximal separation efficiencies exceeding 38% were achieved. This result demonstrates the potential for implementation of this technology into micro- or mesofluidic-based separation environments to enhance extraction efficiencies. The future development of such a mesofluidic-based, nanotechnology-mediated platform is potentially suitable for adjuvant therapies to assist in the treatment of sepsis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Ferric Compounds; Humans; Microbial Sensitivity Tests

The purpose of this study is to investigate the predominant clones of carbapenem-resistant Acinetobacter baumannii (CRAB) in our hospital in Taiwan by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) technique.. We collected 108 non-duplicate A. baumannii clinical blood isolates from January 2012 to December 2013 in MacKay Memorial Hospital. PFGE and MLST were used for typing the A. baumannii isolates and for investigation of the predominant clones. Bacteria isolates were screened by polymerase chain reaction for the presence of the carbapenemase-encoding genes.. All 108 isolates were classified as 33 pulsotypes by PFGE. The predominant clones were pulsotype 10 (12.04%) in 2012 and pulsotype 8 (16.67%) in 2013, respectively. The 31 predominant pulsotype isolates were typed by MLST, and ST787 (54.84%) and ST455 (45.16%) were identified. All isolates carried bla. To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymerase Chain Reaction; Taiwan; Tertiary Care Centers

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

To determine the impact of using colistin for multidrug-resistant organisms in neonates.. This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis.. Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone.. Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.

Topics: Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Asphyxia Neonatorum; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Male; Neonatal Sepsis; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Tracheitis

Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions.. We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate.. C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0.5 μg/mouse (0.0167 mg/kg) markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia models of XDR A. baumannii infection. C8 was also synergistic with colistin, substantially improving survival compared to monotherapy. Treatment with C8 significantly reduced blood bacterial density, cytokine production (tumor necrosis factor α, interleukin [IL] 6, IL-1β, and IL-10), and sepsis biomarkers. Serial in vitro passaging of A. baumannii in the presence of C8 did not cause loss of mAb binding to the bacteria, but did result in emergence of less-virulent mutants that were more susceptible to macrophage uptake. Finally, we developed a highly humanized variant of C8 that retains opsonophagocytic activity in murine and human macrophages and rescued mice from lethal infection.. We describe a promising and novel mAb as therapy for lethal, XDR A. baumannii infections, and demonstrate that it synergistically improves outcomes in combination with antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Biomarkers; Colistin; Cytokines; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; HL-60 Cells; Humans; Macrophages; Male; Mice; Mice, Inbred C3H; Sepsis; Treatment Outcome

Acinetobacter baumannii outer membrane protein A (AbOmpA) is involved in bacterial pathogenesis. However, the role of AbOmpA in the antimicrobial resistance of A. baumannii has not been fully elucidated. This study aimed to investigate the role of the OmpA-like domain of AbOmpA in the antimicrobial resistance of A. baumannii.. The MICs of antimicrobial agents for the WT A. baumannii ATCC 17978, ΔompA mutant, OmpA-like domain-deleted (amino acids 223-356) AbOmpA mutant and single-copy ompA-complemented strain were determined by the Etest method. The MICs of antimicrobial agents for MDR strain 1656-2 and its ΔompA mutant strains were also determined.. The ΔompA mutant strain of ATCC 17978 was more susceptible to trimethoprim (>5.3-fold) and other antimicrobial agents tested (<2.0-fold), except tigecycline, than the WT strain. The ΔompA mutant strain of 1656-2 was more susceptible to trimethoprim (>4.0-fold), tetracycline (2.3-fold) and other antimicrobial agents (<2.0-fold), including tigecycline, colistin and imipenem, than the WT strain. The MICs of gentamicin, imipenem and nalidixic acid for the WT ATCC 17978 and ΔompA mutant strains were decreased in the presence of an efflux pump inhibitor. A mutant strain of ATCC 17978 with the OmpA-like domain of AbOmpA deleted was more susceptible (≥2.0-fold) to substrates of the resistance-nodulation-division efflux pumps, including aztreonam, gentamicin, imipenem and trimethoprim, than the WT strain.. This study demonstrates that AbOmpA contributes to the antimicrobial resistance of A. baumannii through the OmpA-like domain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Gene Deletion; Gene Expression Regulation, Bacterial; Humans; Imipenem; Microbial Sensitivity Tests; Mutation; Protein Domains; Trimethoprim

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam

Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable.. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates.. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem.. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain.. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Automation; Aztreonam; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Rifampin; Technology, Pharmaceutical

Pseudomonas aeruginosa and Acinetobacter spp. are found to be associated with biofilm and metallo-β-lactamase production and are the common causes of serious infections mainly in hospitalized patients. So, the main aims of this study were to determine the rates of biofilm production and metallo beta-lactamase production (MBL) among the strains of Pseudomonas aeruginosa and Acinetobacter spp. isolated from hospitalized patients.. A total of 85 P. aeruginosa isolates and 50 Acinetobacter spp. isolates isolated from different clinical specimens from patients admitted to Shree Birendra Hospital, Kathmandu, Nepal from July 2013 to May 2014 were included in this study. The bacterial isolates were identified with the help of biochemical tests. Modified Kirby-Bauer disc diffusion technique was used for antimicrobial susceptibility testing. Combined disc diffusion technique was used for the detection of MBL production, while Congo red agar method and tube adherence method were used for detection of biofilm production.. Around 16.4% of P. aeruginosa isolates and 22% of the strains of Acinetobacter spp. were metallo β-lactamase producers. Out of 85 P. aeruginosa isolates, 23 (27.05%) were biofilm producers according to tube adherence test while, only 13 (15.29%) were biofilm producers as per Congo red agar method. Similarly, out of 50 Acinetobacter spp. 7 (14%) isolates were biofilm producers on the basis of tube adherence test, while only 5 (10%) were positive for biofilm production by Congo red agar method. Highest rates of susceptibility of P. aeruginosa as well as Acinetobacter spp. were seen toward colistin.. In our study, biofilm production and metallo beta-lactamase production were observed among Pseudomonas aeruginosa and Acinetobacter spp. However, no statistically significant association could be established between biofilm production and metallo beta-lactamase production.

Topics: Acinetobacter; Acinetobacter Infections; Adhesins, Bacterial; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Biofilms; Colistin; Disk Diffusion Antimicrobial Tests; Humans; Nepal; Pseudomonas aeruginosa; Pseudomonas Infections; Tertiary Care Centers

Colistin loading dose (LD) has been postulated as an advance in therapy. The clinical, microbiological effectiveness and nephrotoxicity of adding an LD to systemic colistin in ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remain unknown. In this quasi experimental study, the efficacy, outcomes and nephrotoxicity in 30 adults who received intravenous colistin with LD for MDR A. baumannii ventilator associated pneumonia were compared with 22 in absence of LD. Adding LD, the clinical cure rate at 14 days of therapy increased from 47.6% to 56.7% (p>0.397). No significant differences in bacteriological clearance (80 vs 81%), ICU mortality (50% vs 54.2%) or ICU length of stay (median: 32 vs 36 days) were identified. Mortality increased (76.2% vs 35.5%, p=0.004) in patients with nephrotoxicity, with age (median 67.0 vs. 50.0 years, p=0.002) being the only risk factor for nephrotoxicity. The nephrotoxicity rate increased from 27.3% in absence of LD to 35.3% with LD and SOFA <8, and 69.2% (p= 0.065) with LD and SOFA >7. Overall, nephrotoxicity was more severe in the LD group according to RIFLE criteria (p=0.015). Adding LD to systemic colistin for MDR A. baumannii VAP had no significant effect on clinical cure rates, bacteriologic clearance or pre-defined outcomes. However, the nephrotoxicity rate increased with LD, with special risk in adults with high organ failure development or advanced age. Further evidence regarding the risks and benefits of LD is required. The development of newer agents and strategies is urgently needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Area Under Curve; Burns; Colistin; Female; Humans; Male; Middle Aged

A rapid increase was observed in the incidence of extensively drug-resistant Acinetobacter baumannii (XDR Aba) isolates in a Greek hospital during 2014. To investigate the causes of this rise, the antimicrobial resistance profiles of all carbapenem-resistant (CARB-R) Aba isolates recovered during 2014-2015 were determined. Selected XDR Aba isolates (n = 13) were characterized by molecular methods. XDR Aba (48 isolates) represented 21.4% of the 224 CARB-R Aba recovered during the study period. The 13 selected XDR Aba isolates were positive for the blaOXA-23, the intrinsic blaOXA-51, and the adeB gene of the AdeABC efflux pump, and all belonged to the 3LST ST101, corresponding to the international clone II. Three bloodstream isolates possessed two amino acid substitutions (A138T+A226V) in the deduced amino acid sequences of the pmrB gene, which may be implicated in colistin resistance. This study demonstrates that this clone still evolves by obtaining an ever-increasing arsenal of antibiotic resistance mechanisms. The clinical characteristics of the intensive care unit (ICU) patients with XDR Aba were reviewed retrospectively. Infected ICU patients with XDR Aba displayed higher death rates compared with infected ICU patients susceptible to colistin and tigecycline CARB-R Aba, although there were no statistically significant differences. Conclusively, continuous surveillance and molecular characterization of XDR Aba, combined with strict infection control measures are mandatory for combating nosocomial infections caused by this organism.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gene Expression; Greece; Hospitals; Humans; Intensive Care Units; Male; Membrane Transport Proteins; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mutation; Retrospective Studies; Survival Analysis; Tigecycline; Transcription Factors

In this study, 38 Acinetobacter baumannii isolates successively isolated from blood, skin swabs and tracheal aspirates from a single patient who died from haemophagocytic lymphohistiocytosis were investigated. The isolates were collected between March 2012 and August 2012. A. baumannii genotypes were determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In vitro antimicrobial susceptibility testing was performed and colistin heteroresistance and persistence were evaluated. The structure of AbaR resistance islands was explored, and serum sensitivity was determined. Based on MLST analysis, all 38 A. baumannii isolates showed the same sequence type (ST138). However, PFGE analysis showed that isolates from blood samples belonged to different genotypes depending on the isolation time: whilst blood isolates obtained at the early stages showed restriction patterns similar to those of isolates from other sources, isolates obtained at later stages exhibited a distinct pattern. All isolates were resistant to imipenem, cefepime, ciprofloxacin and piperacillin/tazobactam. Five isolates from tracheal aspirates and one from a skin swab were resistant to polymyxins, and two isolates from skin swabs and one from another source were non-susceptible to tigecycline. All colistin-susceptible isolates showed heteroresistance to colistin, and four were persisters. Isolates from blood showed higher survival rates against human serum than those from other sources. This study shows that the patient was infected with more than one A. baumannii strain. Heteroresistance, persistence or evasion of the innate immune response may explain the failure of antimicrobial treatments in this patient.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Blood Bactericidal Activity; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gene Order; Genes, Bacterial; Genetic Variation; Genomic Islands; Genotype; Humans; Longitudinal Studies; Lymphohistiocytosis, Hemophagocytic; Multilocus Sequence Typing

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cephalosporins; Ciprofloxacin; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Hospitals; Humans; Isoenzymes; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Saudi Arabia; Serogroup; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; beta-Lactamase Inhibitors; Cathelicidins; Cell Membrane; Colistin; Daptomycin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillanic Acid; Pneumonia, Bacterial; Tazobactam

The loss of fitness in colistin-resistant (CR)

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adaptation, Physiological; Adult; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Genetic Fitness; Humans; Hydrogen Peroxide; Male; Mice; Oxidative Stress; Time Factors; Virulence; Wounds, Gunshot

The emergence and spread of multidrug-resistant (MDR) Acinetobacter baumannii isolates is now frequently associated with nosocomial infections. The aim of this study was to evaluate the genetic relatedness and patterns of antimicrobial resistance amongst A. baumannii isolated from a burn centre at a teaching hospital in Iran.. A total of 54 A. baumannii isolates were collected from burn wound infections of hospitalised patients. Antimicrobial susceptibility of the isolates was determined, and genotyping analysis was performed by repetitive extragenic palindromic PCR (rep-PCR). PCR assay was performed to investigate the distribution of β-lactamase, aminoglycoside-modifying enzyme and efflux pump genes.. Etest results revealed that the most active antimicrobial agent was colistin (100% susceptibility), followed by tigecycline (96.3%). The bla. The elevated prevalence of MDR A. baumannii strains in this burn centre suggests that local antibiotic prescription policies should be precisely revised. Moreover, strict infection control procedures to prevent further dissemination need to be prioritised immediately.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Burn Units; Burns; Child; Child, Preschool; Colistin; Cross-Sectional Studies; Disk Diffusion Antimicrobial Tests; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genes, Bacterial; Genetic Variation; Hospitals, Teaching; Humans; Infant; Iran; Male; Middle Aged; Molecular Epidemiology; Polymerase Chain Reaction; Prevalence; Tigecycline; Wound Infection; Young Adult

To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin.. This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis.. Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (CI), 1.004-1.067; p=0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p=0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality.. The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Cerebral Ventriculitis; Colistin; Female; Humans; Injections, Spinal; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Thienamycins; Young Adult

Nosocomially-acquired multi-, extensively-, and pandrug resistant (MDR, XDR, and PDR) strains of microorganisms such as Acinetobacter baumannii remain a serious cause of infection and septic mortality in burn patients. Treatment of patients with nosocomial burn wound infections is often complicated by drug-resistant strains of A. baumannii. Today, many researchers are focusing on the investigation of novel non-antibiotic strategies such as photodynamic therapy (PDT). We report a new PDT strategy that suppresses colistin resistance in PDR A. baumannii by interfering with the expression of a pmrA/pmrB two-component system. In the current study, A. baumannii with a PDR feature isolated from a burn patient was used as a test strain. PDT was carried out using toluidine blue O (TBO) and light-emitting diode (LED) as a photosensitizer and radiation source, respectively. The antimicrobial susceptibility profiles were assessed for cells surviving PDT. The effects of sub-lethal PDT (sPDT) on the expression of the pmrA/pmrB two-component signal transduction system were evaluated by real-time quantitative reverse transcription PCR. Results of drug susceptibly testing (DST) in LED and TBO groups separately showed that the bacteria were resistant to all tested antibiotics, while the DST result of the LED+TBO group showed highly declining bacterial growth when compared with the control group. Reduction in the expression of pmrA and pmrB was observed in the treated strains after sPDT. This represents the first conclusive example of a direct role for the PDT in breaking antibiotic resistance by directly modulating two-component system activity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Burns; Colistin; Combined Modality Therapy; Decontamination; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Resistance, Multiple, Bacterial; Humans; Photochemotherapy; Photosensitizing Agents; Tolonium Chloride; Treatment Outcome

Combination antimicrobial therapy is an important option in the fight against Gram-negative 'superbugs'. This study systematically investigated the synergistic effect of colistin (CST) and chloramphenicol (CHL) in combination against extensively drug-resistant Acinetobacter baumannii (XDR-AB). The microtitre plate chequerboard assay was used to test synergy against 50 XDR-AB clinical strains. Then, three XDR-AB clinical isolates and the type strain A. baumannii ATCC 19606 were chosen for further synergy studies using time-kill assay, mutant prevention concentration (MPC) assay and real-time population analysis profile (PAP) assay. In the chequerboard assays, synergistic or additive effects [defined as a fractional inhibitory concentration index (FICI) of ≤0.5 and 0.5 < FICI < 1, respectively] were observed in all 50 isolates. In further synergy testing, the results of time-kill assays indicated that CST monotherapy produced rapid bacterial killing followed by rapid re-growth, with the emergence of CST resistance; CHL monotherapy was largely ineffective. The combination CST/CHL, however, showed a synergistic effect and enhanced bacterial killing in the four tested strains. It also significantly delayed re-growth and suppressed the emergence of CST resistance. In the MPC assay, a decrease in MPCs for CST was observed in the two CST-susceptible strains. PAP assay showed that both CST-resistant strains were heteroresistant.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Chloramphenicol; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Microbial Viability

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Brain Injuries, Traumatic; Cerebrospinal Fluid Shunts; Colistin; Coma; Craniotomy; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis, Bacterial; Postoperative Complications; Tigecycline

Colistin is the last hope to treat extensively drug resistance (XDR) Acinetobacter baumannii (A. baumannii) infections, but resistance to colistin is currently reported in clinical centers all over the world. Here, we studied two colistin-resistant A. baumannii isolates with a difference in minimum inhibitory concentrations (MICs) that were isolated from a single burn patient during treatment in the hospitalization period. The international clonal (IC) lineage, multilocus sequence typing (MLST), and multiple loci variable number tandem repeat (VNTR) analysis (MLVA) typing were used to characterize the relatedness of A. baumannii isolates. Lipopolysaccharides (LPS) and PmrAB system analysis by PCR sequencing, polyacrylamide gel electrophoresis (PAGE), and real-time PCR were performed to determine the intactness and probable modifications of the LPS as the main resistance mechanisms to colistin. A combination of PCR, sequencing, and restriction fragment length polymorphism (RFLP) was used for A. baumannii resistance islands (AbaR) mapping as resistance-determinant reservoirs. Two isolates were identical at all MLST and VNTR marker loci that indicated the isolates were the same strain. In comparison to colistin-heteroresistant A. baumannii strain TEH267 (MIC = 1.5 mg/L), colistin-resistant A. baumannii strain TEH273 (MIC ≥256 mg/L) acquired two genomic regions including Tn6018-topA sequence and topA sequence-3' CS in its AbaR structure containing ispA and cadA genes which, it would appear, could be associated with eightfold increase in colistin MIC. Both isolates had new variants of AbaR-like structures which could be derivatives of the typical AbaR3. According to the results of this study, AbaRs could be associated with an increase in MIC to colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Burns; Colistin; DNA Transposable Elements; Electrophoresis, Polyacrylamide Gel; Genes, Bacterial; Genotype; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Minisatellite Repeats; Multilocus Sequence Typing; Polymerase Chain Reaction; Transcription Factors

Infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB) has become a major problem in intensive care units (ICUs), with high incidence and mortality. This prospective study investigated the diagnostic value and influence of active surveillance, followed by isolation and enhanced contact precaution (IECP), on the subsequent CRAB infection and colistin use.. The study prospectively enrolled 1,115 patients who were admitted to the medical ICU of Chonnam National University Hwasun Hospital between April 2011 and November 2014. Active surveillance cultures were obtained from the throat or trachea, skin, and urine. IECP was performed beginning April 2013.. Active surveillance detected CRAB in 168 (15%) patients and CRAB infection developed in 70 (6%) patients. Endotracheal tube was independently associated with both CRAB colonization and infection, whereas IECP was inversely associated with both CRAB colonization and infection in multivariate analysis (all P values <.001). The sensitivity, specificity, and positive and negative predictive values of active surveillance for subsequent CRAB infection were 84%, 90%, 47%, and 98%, respectively. The rate of CRAB acquisition, CRAB infection, and the use of colistin were significantly lower during the IECP period compared with the control period (6.5 vs 34.1, 2.6 vs 14.7, and 19.9 vs 65.5 per 1,000 patient-days, respectively; all P <.001).. Active surveillance has good specificity and negative predictive value for subsequent CRAB infection. Active surveillance followed by IECP was inversely associated with the acquisition of CRAB and subsequent CRAB infection, and was associated with a reduction in colistin use in ICU patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Patient Isolation; Population Surveillance; Predictive Value of Tests; Prospective Studies

The increasing use of polymyxins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drug Synergism; Gram-Negative Bacteria; Pentamidine

Aerosolized colistin methanesulfonate (CMS) has been used for the treatment of extensively drug-resistant Acinetobacter baumannii (XDRAB) pneumonia and eradication of XDRAB colonization in the respiratory tract. The aims of this study were to compare the efficacy, adverse effects, clinical outcomes, and microbiological eradication of the cases of XDRAB pneumonia or colonization.. We retrospectively reviewed the medical records of patients who received aerosolized CMS for the treatment of pneumonia and airway colonization due to XDRAB.. Clinical data from 118 patients were studied. The mean age of 57 patients in the pneumonia group was 79.4 years, and that of 61 patients in the colonization group was 80.0 years. Patients with XDRAB pneumonia were more likely to be ventilator-dependent than colonized patients (46.5% vs. 21.3%; p = 0.005), receive steroid therapy (49.1% vs. 31.1%; p = 0.046), and be admitted to an intensive care unit (ICU) at the time of aerosolized CMS treatment (56.1% vs. 32.8%; p = 0.011). The in-hospital mortality rate was higher in the pneumonia group than the colonization group (50.9% vs. 33.3%; p = 0.05). Microbiological eradication of XDRAB in airway samples was achieved in 75% (89 of 118) patients. In pneumonia patients, XDRAB eradication was associated with resolution or improvement of presenting symptoms and signs of infection by the end of treatment relative to the noneradicated group (57.8% vs. 25%; p = 0.044), but had no influence on 30-day mortality. In colonized patients, no difference in clinical outcomes was noted between the eradicated and noneradicated groups.. Aerosolized CMS therapy has acceptable efficacy for XDRAB pneumonia, but no proven efficacy for XDRAB airway colonization.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

Identification of risks of mortality for carbapenem-resistant Acinetobacter baumannii (CRAB), with early implementation of an appropriate therapy, is crucial for the patients' outcome. The aim of this study was to survey mortality risk factors in 182 patients with CRAB bacteremia in a medical center in Taiwan.. A total of 182 isolates of CRAB bacteremia were collected from 2009 to 2012 in Mackay Memorial Hospital, Taipei, Taiwan These isolates were identified by using the genotypic method. Risk of attributable mortality analysis was carried out with a Cox proportional hazards model.. The 182 CRAB isolates belonged to 38 different pulsotypes. The attributable mortality rate of the 182 patients was 58.24%. The risk factors for attributable mortality included intensive care unit stay [hazard ratio (HR): 2.27; p = 0.011], an Acute Physiology and Chronic Health Evaluation II score of >20 (HR: 2.19; p < 0.001), respiratory tract as the origin of bacteremia (HR: 3.40; p < 0.001), and previous use of ceftriaxone (HR: 2.51; p = 0.011). The appropriateness of antimicrobial therapy was 18.87% (20/106) in the mortality group versus 88.16% (67/76) in the survivor group (p < 0.001). The sensitivity of CRAB to colistin was 100% and to tigecycline was 40.11%.. The risk factors for mortality for CRAB included intensive care unit stay, a high Acute Physiology and Chronic Health Evaluation II score, respiratory tract as the origin of bacteremia, and previous use of ceftriaxone. Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Tigecycline

Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin.. In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin).. Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8-48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered.. Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intraventricular; Male; Meningitis, Bacterial; Middle Aged; Outcome Assessment, Health Care

Previous studies found short postantibiotic effect of colistin on Acinetobacter baumannii. Many studies have evaluated the potential for synergy between colistin and other antibiotics against A. baumannii. The aim of this study was to determine in vitro synergy and postantibiotic effect (PAE) of colistin alone and combined with other antibiotics (vancomycin or meropenem) against eight carbapenem-non-susceptible Acinetobacter spp. strains with defined resistance mechanisms. It was hypothesised that vancomycin or meropenem would prologue the PAE of colistin since it was previously found that they exert synergism with colistin in time-kill kinetics and chequerboard analysis. After exposure of 1 hour colistin alone exhibited the negative ( - 0.07 hour) (OXA-143), short (0.2-1.82 hours) (OXA-24, OXA-58, OXA-72, VIM-1+OXA-23, OXA-58+NDM-1, ISAba1/OXA-69) or moderate PAE (3.2 hours) for OXA-23 positive strain. When combined with vancomycin, the PAE was moderate (1.7-4 hours) with OXA-23, OXA-23+VIM-1, OXA-72 and OXA-24 positive strains while with OXA-58, OXA-143, OXA-58/NDM-1 and ISAba1/OXA-69 positive strains, it was not possible to calculate mean duration of PAE because there was no regrowth after exposure to antibiotics or it was longer than 5 hours. The combination with meropenem resulted in short (0.2 hours) (OXA-143), moderate (2.4-3.73 hours) (OXA-24, OXA-58, OXA-23, OXA-23+VIM-1), long PAE of 5 hours (OXA-23) or longer than 5 hours (OXA-58+VIM-1, ISAba1/OXA-69). From the clinical point of view, the prolongation of colistin PAE when combined with other antibiotics could provide a rationale for the modification of the dosing interval and could be important for the optimization of the treatment regimen and the minimization of drug-induced side effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Meropenem; Microbial Sensitivity Tests; Thienamycins; Vancomycin

With increasing antibiotic resistance, the selection of effective treatment of A. baumannii infections is particularly challenging.. This study assessed the activities of the combination of vancomycin and colistin combination in vitro and in vivo using a Galleria mellonella model against four colistin-susceptible or colistin-resistant A. baumannii strains.. In checkerboard assays, synergy was observed between vancomycin and colistin for all four strains tested (0.156 ≤ Fractional inhibitory concentration indices [FICI] ≤ 0.281). In time-kill assays, the combination showed continued bactericidal activity and synergy after 24 h for colistin-susceptible strains. For colistin-resistant strains, the combination resulted in bactericidal activity within 8 h, but sustained bacterial re-growth was then observed. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii (except 19606R) resulted in significantly increased survival rates when vancomycin was given with colistin compared to colistin treatment alone (p < 0.05).. These findings suggest that regimens containing vancomycin may be useful for infections due to multidrug-resistant Acinetobacter baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Larva; Moths; Vancomycin

Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.. Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 μg/mL, doripenem 8 μg/mL) and achievable tissue levels (tigecycline 2 μg/mL) for each antibiotic were used in this study.. The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, the-doripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bactericidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.. The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropriate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Tigecycline

The aim of this work is to evaluate the outcome of patients treated with intrathecal colistin for meningitis/ventriculitis.. This retrospective case series study included patients presenting with nosocomial meningitis/ventriculitis following neurosurgical interventions and having intravenous (IVC group) or intravenous and intrathecal/intraventricular colistin (ITC group) treatment between 2006 and 2014.. Thirty-four patients presented nosocomial meningitis/ventriculitis; 11 (32.5 %) were included in the IVC group and 23 (67.6 %) in the ITC group. The most frequent isolated bacteria were Acinetobacter baumannii. The mean dose was 170,000 (±400) IU and the duration of intraventricular treatment was 16.0 (±8.3) days. The duration of intravenous treatment was 16.0 (±8.3) days in the ITC group and 15.3 ± 7.6 days in IVC group. Hospital mortality was significantly lower in the ITC group compared with the IVC group (13 vs. 72.7 %, p = 0.001).. The combination of intravenous plus intraventricular (IV-IVT) colistin therapy may improve outcomes in patients attending with meningitis/ventriculitis due to multi-drug resistance infections.

Topics: Acinetobacter Infections; Administration, Intravenous; Adult; Anti-Bacterial Agents; Cerebral Ventriculitis; Colistin; Female; Humans; Injections, Intraventricular; Male; Meningitis, Bacterial; Middle Aged

Neonatal sepsis caused by multidrug-resistant gram-negative bacteria has been reported in different parts of the world. It is a major threat to neonatal care, carrying a high rate of morbidity and mortality. While Colistin is the treatment of choice, few studies have reported its use in neonatal patients.. A retrospective descriptive study of all neonatal patients who had multidrug-resistant Acinetobacter sepsis and were treated with Colistin over a 2-year period. Patients' charts and hospital laboratory data were reviewed.. During the study period, 21 newborns were treated with Colistin. All had sepsis evident by positive blood culture and clinical signs of sepsis. The median gestational age and birth weight were 33 weeks (26-39) and 1700 g (700-3600), respectively. Nine (43 %) were very low birth weight infants. Eighteen (86 %) were preterm infants. Nineteen (91 %) newborns survived. No renal impairment is documented in any of our patients. Fourteen (67 %) of our patients had elevated eosinophil counts following Colistin treatment, for those patients, the average eosinophilic counts ± standard deviation before and after Colistin therapy were 149.08 ± 190.38 to 1193 ± 523.29, respectively, with a p value of less than 0.0001.. Our study showed that Colistin was both effective and safe for treating multidrug-resistant Acinetobacter neonatal sepsis. This is a retrospective study. No universal protocol was used for the patients. The factors that might affect the response or cause side effects are difficult to evaluate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Sepsis

In the present study, our objective was to evaluate and compare the clinical and microbiological results in patients receiving systemic and systemic plus inhaled colistin therapy due to nosocomial pneumonia (NP) or ventilator associated pneumonia (VAP) caused by Acinetobacter baumannii.. A retrospective matched case-control study was performed at the ICUs at Izmir Katip Celebi University Ataturk Training and Research Hospital from January 2013 to December 2014. Eighty patients who received only systemic colistin were matched 43 patients who received systemic colistin combined with inhaled therapy.. In 97.6 % of the patients colistin was co-administered with at least one additional antibiotic. The most frequently co-administered antibiotics were carbapenems (79.7 %). The patient groups did not differ significantly in terms of the non-colistin antibiotics used for treatment (p > 0.05). Acute renal injury was observed in 53.8 % and 48.8 % of the patients who received parenteral colistin or parenteral plus inhaler colistin, respectively (p = 0.603). There were no significant differences between the groups in terms of clinical success (p = 0.974), clinical failure (p = 0.291), or recurrence (p = 0.094). Only, a significantly higher partial clinical improvement rate was observed in the systemic colistin group (p = 0.009). No significant differences between the two groups in terms of eradication (p = 0.712), persistence (p = 0.470), or recurrence (p = 0.356) rates was observed. One-month mortality rate was similar in systemic (47.5 %) and systemic plus inhaled (53.5 %) treatment groups (p = 0.526).. Our results suggest that combination of inhaled colistin with intravenous colistin had no additional therapeutic benefit in terms of clinical or microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Cross Infection; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Treatment Outcome

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

We characterized an outbreak of imipenem-resistant Acinetobacter baumannii with clinical and environmental isolates from a tertiary care hospital in San Luis Potosi, Mexico. During a 4-month period, a total of 32 nonrepetitive imipenem-resistant clinical isolates of A. baumannii were collected. All isolates were susceptible to colistin and tigecycline and resistant to cefepime, ceftazidime, ceftriaxone, imipenem, and meropenem. Genotyping by pulsed-field gel electrophoresis showed a major clone (A). Multilocus sequence type (MLST) analysis was performed, revealing sequence type (ST) 417 (ST417) and 208 (ST208). The blaIMP-, blaVIM-, blaGIM-, blaSIM-, blaNDM-type, and blaOXA-type (blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, and blaOXA-58-like) genes were screened and showed that the blaOXA-51-like and blaOXA-24-like genes were present in all isolates. Sequencing and southern hybridization were performed, confirming the presence of the blaOXA-72 gene and its plasmid-borne nature. In addition, the blaOXA-72-XerC/XerD-like association was identified. These findings indicate that a clonal spread of blaOXA-72-producing A. baumannii ST417 had occurred throughout the hospital. The ST417 corresponded with a previous ST described in the United States.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Colistin; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Humans; Isoenzymes; Mexico; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Plasmids; Sequence Analysis, DNA; Tertiary Care Centers; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Republic of Korea

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

Multidrug resistant Acinetobacter baumannii and its closely related species A. pittii and A. nosocomialis, all members of the Acinetobacter calcoaceticus-baumannii (Acb) complex, are a major cause of hospital acquired infection. In the burn wound center of the Queen Astrid military hospital in Brussels, 48 patients were colonized or infected with Acb complex over a 52-month period. We report the molecular epidemiology of these organisms, their clinical impact and infection control measures taken. A representative set of 157 Acb complex isolates was analyzed using repetitive sequence-based PCR (rep-PCR) (DiversiLab) and a multiplex PCR targeting OXA-51-like and OXA-23-like genes. We identified 31 rep-PCR genotypes (strains). Representatives of each rep-type were identified to species by rpoB sequence analysis: 13 types to A. baumannii, 10 to A. pittii, and 3 to A. nosocomialis. It was assumed that isolates that belonged to the same rep-type also belonged to the same species. Thus, 83.4% of all isolates were identified to A. baumannii, 9.6% to A. pittii and 4.5% to A. nosocomialis. We observed 12 extensively drug resistant Acb strains (10 A. baumannii and 2 A. nosocomialis), all carbapenem-non-susceptible/colistin-susceptible and imported into the burn wound center through patients injured in North Africa. The two most prevalent rep-types 12 and 13 harbored an OXA-23-like gene. Multilocus sequence typing allocated them to clonal complex 1 corresponding to EU (international) clone I. Both strains caused consecutive outbreaks, interspersed with periods of apparent eradication. Patients infected with carbapenem resistant A. baumannii were successfully treated with colistin/rifampicin. Extensive infection control measures were required to eradicate the organisms. Acinetobacter infection and colonization was not associated with increased attributable mortality.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Adolescent; Adult; Africa, Northern; Aged; Aged, 80 and over; Bacterial Typing Techniques; Belgium; Burns; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Multilocus Sequence Typing; Multiplex Polymerase Chain Reaction; RNA, Bacterial; RNA, Ribosomal, 16S; Treatment Outcome; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Risk Factors; Survival Analysis; Tertiary Care Centers

Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC) for meropenem (MIC ≤ 32 mg/L), combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Fosfomycin; Fusidic Acid; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Rifampin; Sulbactam; Thienamycins; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Humans; Reproducibility of Results

The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Decision Support Techniques; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Prognosis; Retrospective Studies; Survival Analysis; Young Adult

Tigecycline is a broad-spectrum antibiotic with activity against multidrug-resistant (MDR) bacteria. It has limited indications. Studies are necessary to elaborate new guidelines. Here we report a case of postoperative MDR Acinetobacter baumannii meningitis treated by tigecycline combined with colimycin for 21 days. The treatment was well tolerated with a favourable outcome. In conclusion, tigecycline was shown to be effective in a case of MDR A. baumannii meningitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis; Microbial Sensitivity Tests; Minocycline; Tigecycline

Increased use of colistin in a clinical setting had resulted in the emergence of colistin-resistant (CoR) Acinetobacter baumannii. Combination therapy has been studied as a new approach to treat infections caused by A. baumannii. Here, we investigated the in vitro antimicrobial synergistic activities of several antimicrobial agent combinations against CoR A. baumannii. A total of 41 non-duplicate clinical isolates of CoR A. baumannii from a tertiary care hospital in Korea were prospectively collected from April 2012 to December 2014. As a control group, 41 carbapenem-resistant but colistin-susceptible (CoS) A. baumannii strains were also evaluated. Minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by Etest in triplicate, and in vitro synergy tests were performed by the Etest MIC:MIC ratio method. Synergistic activity was determined as the sum of each antimicrobial agent's fractional inhibitory concentration evaluated (ΣFIC): synergy, ≤0.5; indifference, >0.5-4; and antagonism, >4. Synergistic activities were more frequently observed in the CoR group than the CoS group for combinations of colistin-rifampicin (80.5% vs. 14.6%, P< 0.0001), colistin-meropenem (85.4% vs. 4.9%, P< 0.0001), and colistin-imipenem (46.3% vs. 2.4%, P< 0.0001). Combination with rifampicin or meropenem lowered colistin MICs against CoR A. baumannii clinical isolates to the susceptible range (≤ 2 μg/mL) more frequently (61.0%, 25/41, both) than combination with imipenem (29.3%, 12/41). Clinical trials are needed to prove the in vivo efficacy of those antimicrobial combinations that exhibited significant in vitro antimicrobial synergistic effects against CoR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Prospective Studies; Republic of Korea; Rifampin; Tertiary Care Centers

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans

We herein report the first domestic case of bacteremia caused by an intrinsic strain of colistin-resistant Acinetobacter. The Acinetobacter species was detected in the hemocultures in a febrile patient. The patient was a 65-year-old-man who was admitted to our hospital for laparotomic gastrostomy. The patient's antimicrobial susceptibility patterns were atypical; they were colistin resistant but not multiple drug resistant. A sequence analysis of rpoB identified the bacterium as an Acinetobacter genomic species 13BJ/14TU, which had only been previously reported in South Korea. He had never traveled to South Korea but frequently had contact with the South Korean community. We therefore demonstrated that infection with this species could occur in domestic cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Japan; Male; Microbial Sensitivity Tests; Middle Aged

Acinetobacter baumannii strains, are opportunistic pathogens that cause severe nosocomial infections that are difficult to treat due to development of resistance to multiple antibiotics. As the antibiotic choices to be used in treatment are limited, combinations of a variety of antibiotics are used. The aims of this study were to identify the minimal inhibitory concentration (MIC) values of colistin and sulbactam against A.baumannii isolates and to determine the in vitro activity of colistin-sulbactam combination. A total of 50 A.baumannii strains isolated from different clinical specimens (32 tracheal aspirates, 10 blood, 6 urine and 2 wound samples) were included in the study. The identification of bacteria was performed by traditional methods and Vitek-2 (BioMerieux, France) automated system. Antibiotic susceptibilities were detected by Mueller-Hinton agar disk diffusion method and Vitek-2 automated system and the results were interpreted according to the CLSI standards. MIC values of colistin and sulbactam against A.baumannii strains and in vitro interactions of colistin-sulbactam combinations were determined with the E-test (BioMerieux, France). Fractional inhibitory concentration (FIC) index was used for the detection of efficacy of drug combinations. The presence of oxacillinase and metallo-beta-lactamase (MBL) genes that lead carbapenem resistance was investigated by polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE) was performed for the determination of clonal relationship. In our study, all strains (100%) were detected as susceptible to colistin, 48 (96%) to trimethoprim/sulphamethoxazole and 18 to (36%) tigecyclin; however all of them were resistant to the other studied antibiotics, including sulbactam and carbapenem. When the colistin-sulbactam combination was assessed according to FIC index, all strains were found to have antagonistic effect. All of the carbapenem-resistant strains were positive for OXA-51 and OXA-23, and 3 (6%) were positive for OXA-24. Among MBLs, OXA-58, OXA-48, IPM, SPM, SIM, GIM, VIM and NDM-1 genes were not detected. In the evaluation of PFGE results it was found that the clonal distribution of the strains, except one, were all pulsotype A. In the assessment of in vitro efficacy of the colistin-sulbactam combination against A.baumannii strains with multidrug resistance, antagonistic effect was observed in all strains. In the resistance and clonal analysis it was determined that the strains bel

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Bacteriuria; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Sulbactam; Trachea; Wound Infection

Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aorta; Colistin; Drug Therapy, Combination; Gentian Violet; Humans; Male; Mediastinitis; Middle Aged; Minocycline; Sulbactam; Tigecycline

Acinetobacter baumanni is known as a worldwide emerging nosocomial infections and it is classified as one of the six dangerous microorganisms by Diseases Society of America. Multi drug-resistant strains of A. baumannii have been reported in recent decades, which may be a result of the high use of antimicrobial agents. Colistin is the last form of treatment against this organism. The presence of pmrA and pmrB genes in A. baumannii causes the resistance of this organism against Colistin. This cross-sectional study was performed on 100 samples of A. baumannii isolated from ulcer, urinary, respiratory, blood of patients admitted to the intensive care unit of Shahid Rajai Shiraz hospital within a 12-month period. The diagnosis was performed by microscopic and biochemical testing using microgen kits. Determining Colistin resistance was carried out by Diffusion Disc, Colistin antibiotic disc of MAST- England and E-test. The analysis of genes pmrA and pmrB genes was done by PCR. 100 A. baumannii samples were diagnosed out of which using diffusion disk 94 cases were sensitive to Colistin and 6 cases were resistant to it. The E-test results in resistant samples presented an MIC equal to 64 micrograms per milliliter. The PCR results in sensitive and resistant to Colistin samples presented the existence of pmrA and pmrB genes. The results indicated the presence of pmrA and pmrB genes that are the main reason of A. baumannii resistance against the last line of treatment of this organism to Colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Cross Infection; Cross-Sectional Studies; Drug Resistance, Bacterial; Iran; Microbial Sensitivity Tests; Polymerase Chain Reaction; Transcription Factors

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aztreonam; Bacteremia; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Rifampin; Teicoplanin; Thienamycins; Vancomycin

Comprehensive data on drug-resistant patterns of Acinetobacter baumannii isolates in developing countries is limited. We conducted a multihospital study to assess the rate and trend of drug-resistant phenotypes in Ac. baumannii using standardized definitions and to determine the remaining therapeutic options against resistant phenotypes. The 401 nonduplicate isolates were collected from six hospitals which are geographically distributed across Tehran, Iran over a 3-year period. Following PCR of bla. The high frequency of drug-resistant phenotypes including carbapenem-resistant Acinetobacter baumannii, multidrug-resistant, and extensively resistant has been demonstrated in Ac. baumannii isolates tested here. As the antibiotic resistance pattern of isolates varies in different geographical regions, this study can provide comprehensive information about the antibiotic resistance profile of Ac. baumannii isolates in Tehran. In addition, the resistance profiles could be effectively considered by clinicians to manage antibiotic therapy. This work also emphasizes on the prudent use of antibiotics and the monitoring of antibiotic susceptibility trend and rate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Iran; Microbial Sensitivity Tests; Minocycline; Sulbactam; Tigecycline; Tobramycin

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important clinical threat. Combination therapy that exerts a synergistic effect has become a potential solution to combat CRAB. However, choosing an optimal combination regimen is challenging. A dynamic in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that can simulate the pharmacokinetic profiles of antibiotics provides a powerful tool to compare antibacterial responses to different clinical dosage regimens. In this study, the synergistic effect of the combination of meropenem and colistin was tested in 12 clinical CRAB isolates from Chinese patients using the chequerboard technique. The antibacterial effect was investigated in an in vitro PK/PD diffusion model by simulating different dosage regimens: meropenem monotherapy (0.5 g with 0.5-h infusion or 1 g with 3-h infusion); colistin monotherapy (fixed unbound concentration maintained at 0.25, 0.5 or 1 mg/L); and combination of meropenem and colistin. The chequerboard method showed that the combination of meropenem and colistin had synergistic effects against all 12 isolates, with fractional inhibitory concentration indices (FICIs) of ≤0.5. Moreover, the dynamic in vitro PK/PD model demonstrated that for clinical CRAB isolates with a meropenem MIC of 128 mg/L, the combination (meropenem 1 g with 3-h infusion combined with colistin maintained at 1 mg/L) could achieve 3.8 log

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Asian People; beta-Lactam Resistance; Carbapenems; Colistin; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Models, Biological; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Daptomycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Male; Mice, Inbred BALB C; Microbial Sensitivity Tests; Sepsis; Survival Analysis; Teicoplanin; Treatment Outcome

There has been increased incidence and high mortality in cases with ventilator-associated pneumonia (VAP) caused by colistin-only-susceptible Acinetobacter baumannii (COS-AB). Colistin has emerged as a therapeutic option for VAP caused by multidrug-resistant Gram-negative organisms including COS-AB. A retrospective study was conducted to examine the impact of early versus late initiation of colistin on 30-day mortality of critically ill patients with VAP caused by COS-AB.. Critically ill patients with VAP caused by COS-AB who received colistin were enrolled. The receiver operating characteristic (ROC) curve was used to identify the temporal breakpoint that maximized the difference in 30-day mortality.. A total of 56 patients (34 men and 22 women) were included in the study. About 86% of all cases were late-onset VAP. The 30-day mortality was 46.4%. The rate was higher among patients with admission Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 18 and patients with a delay of more than four days in initiating colistin treatment. The mortality rate was 26.9% among patients with treatment delay of four or fewer days and 63.3% for patients with a treatment delay of more than four days.. A delay of four days or more in initiating colistin in patients with VAP caused by COS-AB significantly increases mortality. Colistin should be considered in the empirical protocols in late-onset VAP cases when COS-AB is highly suspected.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Survival Analysis; Time Factors; Young Adult

Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antirheumatic Agents; Auranofin; Bacterial Infections; Colistin; Drug Combinations; Drug Discovery; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa

Acinetobacter baumannii has emerged as an important and problematic pathogen causing bloodstream infections (BSI) in hospitalized patients. Results of an 8-year period from a university hospital are presented. Identification of A. baumannii was performed by Gram-negative BD BBL Crystal ID and VITEK(®)2 system, whereas, susceptibility testing by VITEK2, Kirby-Bauer disc system, and Etest strips. Interpretation of results was based on CLSI criteria and, regarding tigecycline, Food and Drug Administration (FDA) criteria. Between 2006 and 2013, 441 among 7088 BSI cases were attributed to A. baumannii. Of all isolates, 92·1% were resistant to more than three classes of antibiotics and 79·4% were resistant to all but one or two categories of antimicrobials. Resistance to ampicillin-sulbactam, meropenem, gentamicin, ciprofloxacin, minocycline, and tigecycline increased during the study period (P<0·05). Although tigecycline resistance was low during the first 4 years of the study (25·5%), it increased up to 66·5% during 2010-2013. No isolate was colistin resistant.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tigecycline; Time Factors

In the present study, we challenged the concept that levofloxacin should not be used for the management of ventilator-associated pneumonia (VAP) when minimum inhibitory concentrations (MICs) exceed 2 μg/ml. Multidrug-resistant (MDR) and genetically distinct isolates of Pseudomonas aeruginosa (n = 49) and Acinetobacter baumannii (n = 29) from patients with VAP were exposed over time to levofloxacin, imipenem, colistin and their combinations. Synergy between levofloxacin and imipenem was found in 55.3 % and between levofloxacin and colistin in 90.9 % of isolates of P. aeruginosa within the first 4 h of growth. Synergy with imipenem but not with colistin was dependent of the MIC. Synergy between levofloxacin and imipenem was found in 58.6 % of isolates of A. baumannii after 24 h of growth. Considerable synergy was found between levofloxacin and colistin, reaching 84.8 % of isolates of A.baumannii after 6 h of growth. Synergy was independent from the MIC. These results create hopes that levofloxacin can be used as combination therapy for infections by MDR bacteria.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonal Acinetobacter baumannii and receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC24/MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of ≥ 60 at an MIC of ≥ 1 μg/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 μg/ml, with free colistin levels ranging from 0.4 to 2.2 μg/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Colistin; Drug Resistance, Multiple, Bacterial; Hemofiltration; Humans; Male

Acinetobacter baumannii, a substantial nosocomial pathogen, has developed resistance to almost all available antimicrobial drugs. Bacteriophage therapy is a possible alternative treatment for multidrug-resistant (MDR) bacterial infections. In this study, we have successfully isolated bacteriophage active against clinical strains of A. baumannii by enrichment from hospital sewage sludge using representatives of those strains. The bacteriophage isolated against A. baumannii formed plaques against beta-lactamases producing strains of A. baumannii. The utility of bacteriophage specific for A. baumannii to resolve wound infection in uncontrolled diabetic rats was evaluated. Five groups of uncontrolled diabetic rats were used. Group I was noninfected (Control), Group II was infected with MDR A. baumannii and challenged with bacteriophage, Group III was infected with MDR A. baumannii, Group IV was infected with MDR A. baumannii and challenged with antibiotic colistin, and Group V consisted of noninfected rats and sprayed with phage (Phage control). A significant decrease in infection, period of epithelization, and wound contraction was observed in the phage-challenged group when compared with antibiotic-treated uncontrolled diabetic rats and the control group. To conclude the study, new insights are provided into the biology of the broad host range of A. baumannii phage, demonstrating that A. baumannii phage has prospects for the treatment of infections caused by the MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteriophages; beta-Lactamases; Colistin; Cross Infection; Diabetes Mellitus, Experimental; Drug Resistance, Multiple, Bacterial; Male; Microbial Sensitivity Tests; Rats; Rats, Wistar; Wound Infection

Antimicrobial treatment of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections continues to pose significant challenges. With limited options, clinicians have been pushed towards using unorthodox combinations of licensed antibiotics. Although daptomycin/colistin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the A. baumannii-Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of MDR-AB infections. The antimicrobial activity of colistin alone and in combination with daptomycin was assessed versus an A. baumannii type strain (ATCC 19606) and a MDR-AB clinical strain (GN2231) isolated in Anhui, China. Synergy studies were performed using the microtitre plate chequerboard assay and time-kill methodology. The in vivo activity of daptomycin/colistin combination was assessed using a G. mellonella larvae model. The combination of daptomycin and colistin was bactericidal against both strains tested. In chequerboard assays, daptomycin was highly active against A. baumannii when combined with colistin [fractional inhibitory concentration index (FICI) of <0.5]. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when daptomycin was given with colistin compared with colistin treatment alone (P<0.05). This work suggests that daptomycin/colistin combination is highly active against A. baumannii both in vitro and in a simple invertebrate model of infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Lepidoptera

Few studies have focused on multidrug-resistant Acinetobacter baumannii (MDRAB) infection in neonates. The aim of this study was to investigate risk factors for mortality in neonates with MDRAB infection.. This retrospective case-series study was conducted at the Children's Hospital of China Medical University, Taichung, Taiwan. All patients hospitalized between January 2010 and December 2013 in the neonatal intensive care unit (NICU) with MDRAB infections were reviewed.. A total of 67 isolates from 59 neonatal patients were positive for MDRAB. Of the 67 isolates, 38 were from blood (56.72%), 16 from sputum (23.88%), seven from pus (10.45%), three from ascites (4.48%), two from cerebrospinal fluid (2.99%), and one from pleural fluid (1.49%). There were five episodes of MDRAB clusters consisting of 28 cases during the study period. The mortality rate due to MDRAB sepsis was 20.34% (12/59). The statistically significant risk factors for mortality due to MDRAB infection were being infected with MDRAB within 7 days of admission to the NICU, use of umbilical vein catheters, absolute neutrophil count < 1500/mm(3), platelet count < 100,000/mm(3), and a delay in initiating adequate antibiotic treatment.. MDRAB infection is responsible for a high mortality rate among neonates in the NICU, especially in those who have neutropenia or thrombocytopenia. Infection control and appropriateness of the initial antimicrobial agent with colistin play an important role in reducing mortality.

Topics: Academic Medical Centers; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Male; Retrospective Studies; Survival Analysis; Taiwan

Acinetobacter baumannii can cause serious infection in susceptible patients, but little has been published regarding risk factors for infection and outcomes in solid organ transplant (SOT) recipients.. We identified A. baumannii infection among adult SOT recipients that occurred between January 2001 and March 31, 2008 at a Chicago transplant center and evaluated characteristics of these infections and outcomes.. Thirty-three individuals developed A. baumannii infection during the study period. Seventy-nine percent had healthcare-associated infection with respiratory tract as the most common site of infection (64%). Eighty-two percent of patients had received antibiotics within two wk prior to A. baumannii infection and multidrug resistance (MDR) or extensive resistance (XDR) occurred in 85%. The median time to onset of infection was five months after transplant. The 30-d mortality was 24% and was associated with XDR. Administration of an appropriate antibiotic within three d was associated with lower 30-d mortality (OR 0.16, p = 0.047). All isolates tested against colistin were susceptible.. SOT recipients with A. baumannii infection had high mortality associated with delay in appropriate antibiotic therapy and XDR organisms. The use of colistin-containing treatment regimens should be considered in these patients when A. baumannii infection is suspected or identified in patients who have received prior antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Humans; Immunocompromised Host; Logistic Models; Male; Middle Aged; Organ Transplantation; Postoperative Complications; Retrospective Studies; Risk Factors

The aim of this study was to investigate the prevalence and the mechanisms of carbapenem and colistin resistance in Acinetobacter baumannii clinical isolates in an Algerian hospital.. Twelve isolates were collected between October 2013 and March 2014. All isolates were resistant to almost all antibiotics tested with a high-level resistance to imipenem (minimum inhibitory concentrations [MICs] >32 mg/L) with one strain showing resistance to colistin (MIC=16 mg/L). The results of the modified Hodge test and the modified Carba NP test were positive for all isolates. Besides, the activity of β-lactamases was inhibited by EDTA in only two isolates. All the 12 isolates contained the naturally occurring blaOXA-51-like gene. Ten of them harbored the OXA β-lactamases: blaOXA-23 (six isolates) and blaOXA-24 (four isolates) genes, while two isolates were positive for blaNDM-1 gene. The colistin-resistant isolate producing OXA-24 enzyme harbored a single mutation in the pmrB gene. Multilocus sequence typing demonstrated that the 12 isolates belonged to 2 clones: 10 to ST2 and 2 to ST85.. Here, we describe the mechanisms of carbapenem resistance and we report the first colistin and carbapenemase-producing A. baumannii clinical isolate from a patient in Algeria.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Algeria; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; beta-Lactamases; Clone Cells; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Edetic Acid; Female; Gene Expression Regulation, Bacterial; Humans; Imipenem; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Multilocus Sequence Typing; Mutation; Phylogeny; Plasmids; Sequence Alignment; Sequence Analysis, DNA; Transcription Factors

The aim of this study was to investigate the prevalence and characteristics of imipenem-resistant Acinetobacter baumanni isolated from surgical wards in a university hospital, China. A total of 143 non-duplicate A. baumannii were isolated from 517 inpatients in surgery intensive care units (ICUs), burn wards, and general surgery wards. Of these, 102 isolates of A. baumannii (71.3%) were resistant to imipenem. Among imipenem-resistant isolates, all isolates were resistant to almost all antimicrobial agents except polymyxin E, all isolates were positive for blaOXA-23 and blaOXA-51 in addition to ISAba1, 52 (51%) were positive for blaOXA-58, 8 (7.8%) contained blaVIM-2, which co-harbored with blaOXA-58. Molecular typing revealed the presence of three clones among imipenem-resistant isolates. This study confirmed that A. baumannii strains harboring OXA or VIM type β-lactamases are widely distributed throughout the surgery wards. The data demonstrate that there was a high prevalence of imipenem-resistant A. baumannii infection in the region.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; beta-Lactamases; China; Colistin; Cross Infection; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Hospital Units; Hospitals, University; Humans; Imipenem; Intensive Care Units; Microbial Sensitivity Tests; Molecular Typing

With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.. Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.. Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.. Colistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Ampicillin; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electronic Health Records; Electrophoresis, Gel, Pulsed-Field; Ethanolamines; Female; Humans; Lipid A; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Pneumonia, Ventilator-Associated; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulbactam

Topics: Acinetobacter baumannii; Acinetobacter Infections; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male

Biofilm formation, a virulence factor of Acinetobacter baumannii, is associated with long-term survival in hospital environments and provides resistance to antibiotics. Standard tests for antibiotic susceptibility involve analyzing bacteria in the planktonic state. However, the biofilm formation ability can influence antibiotic susceptibility. Therefore, here, the biofilm formation ability of A. baumannii clinical isolates from Korea was investigated and the susceptibility of biofilm and planktonic bacteria to colistin was compared. Of the 100 clinical isolates examined, 77% exhibited enhanced biofilm formation capacity relative to a standard A. baumannii strain (ATCC 19606). Differences between the minimal inhibitory concentrations and minimal biofilm-inhibitory concentrations of colistin were significantly greater in the group of A. baumannii that exhibited enhanced biofilm formation than the group that exhibited less ability for biofilm formation. Thus, the ability to form a biofilm may affect antibiotic susceptibility and clinical failure, even when the dose administered is in the susceptible range.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Republic of Korea

Acinetobacter baumannii is the most common species to have developed resistance to antibiotics. Due to increasing levels of drug resistance, the available therapeutic options are insufficient in A. baumannii infections. This study investigated the efficacy of doripenem monotherapy versus doripenem combination therapy with sulbactam, amikacin, colistin and tigecycline in experimental sepsis. A carbapenem-resistant A. baumannii was used to develop a sepsis model in 8-10-week-old Balb/c mice by intraperitoneal injection. Antibiotic therapies were initiated two hours after injection of bacterial suspension. Necropsy was performed at 24, 48 and 72 hours and cultures were made from heart, lung, liver and spleen samples. Bacterial loads of lung and liver were calculated as CFU/g. Combination therapies with doripenem were more effective than monotherapy at 24 and 48 hours of infection but no differences between groups were detected at 72 hours. The combination of doripenem with tigecycline and amikacin began to eradicate the bacterial load of lung and liver after 48 hours of infection, whereas doripenem+sulbactam and doripenem+colistin were started to eradication at 72 hours. The results of the study showed that combination therapies with doripenem are more effective than monotherapy and the combination of doripenem with tigeycline or amikacin has more rapid bactericidal effect than that with sulbactam or colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Male; Mice; Mice, Inbred BALB C; Minocycline; Sepsis; Sulbactam; Tigecycline

Colistimethate sodium (CMS) is increasingly used to treat multidrug-resistant Gram-negative bacilli infections. However, the incidence of CMS-associated nephrotoxicity has not been evaluated in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. This retrospective study included 120 patients with CRAB pneumonia treated with intravenous CMS for ≥72 h. The objective of the study was to determine risk factors for CMS-induced nephrotoxicity and 30-day mortality in patients with CRAB pneumonia. Of the 120 patients with CRAB pneumonia, 61 (51%) developed nephrotoxicity. Multivariate analysis showed that dose per ideal body weight (IBW) [odds ratio (OR)=1.28, 95% confidence interval (CI) 1.01-1.62; P=0.04], Charlson co-morbidity index (OR=1.31, 95% CI 1.06-1.60; P=0.01) and septic shock (OR=3.16, 95% CI 1.32-7.60; P=0.01) were associated with CMS-associated nephrotoxicity. Thirty-day mortality was 33% (39/120). Multivariate analysis showed that higher daily doses of CMS per IBW [hazard ratio (HR)=0.81, 95% CI 0.67-0.98; P=0.03] and longer duration of CMS therapy (HR=0.86, 95% CI 0.79-0.95; P=0.002) were associated with increased survival. Septic shock (HR=3.91, 95% CI 1.95-7.83; P<0.001) and corticosteroid use (HR=3.49, 95% CI 1.67-7.28; P=0.001) were associated with decreased survival in patients with CRAB pneumonia. Higher daily doses of CMS per IBW, Charlson comorbidity index and septic shock were significant risk factors for CMS-associated nephrotoxicity. However, CMS-associated nephrotoxicity does not appear to have an impact on mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Female; Humans; Incidence; Male; Middle Aged; Pneumonia, Bacterial; Renal Insufficiency; Retrospective Studies; Treatment Outcome

Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations.. Prospective, observational, multicenter study.. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia.. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009).. Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

Topics: Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Organ Dysfunction Scores; Prospective Studies; Taiwan; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Thienamycins

The spread of extensively drug-resistant (XDR) gram-negative bacteria has boosted colistin use, with a resultant selection of colistin-resistant, often pandrug-resistant strains. Whether acquisition of further resistance mechanisms translates into a reduced virulence is the subject of active research. In this report, we describe clinical features of an immunocompromised patient who developed infection due to colistin-resistant Acinetobacter baumannii while on long-term colistin therapy. We analyzed phenotypic and genotypic characteristics, molecular mechanisms of colistin resistance, and in vitro and in vivo fitness of sequential colistin-sensitive and colistin-resistant strains isolated from the patient. Both colistin-sensitive and colistin-resistant strains were XDR and showed identical ST78 genotype. At variance with prior reports on colistin-resistant strains of A. baumannii, resistance to colistin due to P233S mutation in PmrB sensor kinase did not associate with any measurable reduction in strain fitness, growth characteristics, and virulence.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Female; Genotype; Humans; Immunocompromised Host; Male; Middle Aged; Mutation; Transcription Factors; Virulence; Young Adult

Multidrug-resistant Acinetobacter baumannii (MAB) is an important nosocomial pathogen.. To analyze the risk factors for acquiring MAB, and the clinical and microbiological characteristics of MAB bacteremia (MABB) in children.. Control-case study 2005-2008. Demographic and clinical data from all MABB and from non-multiresistant gram-negative bacteremias were recorded. Identification at species level, antimicrobial susceptibility tests, time-kill studies and clonally relationships were performed. Stata 8.0 was used for data analysis.. A total of 50 MABB and 100 controls were included. Ninety four percent of patients acquired MAB in ICU and the 88% had underlying diseases. All patients had invasive procedures previous to MABB. The median of hospitalization stay previous to MABB was different in cases than in controls (16 vs 7 days, p < 0.001). Five clones were detected among the MABB. Time-killing curves showed bactericidal activity of ampicillin/sulbactam plus gentamicin and polymixin B. Three patients with MAB died. In a multivariate analysis final predictors of MABB were: previous use of broad-spectrum antibiotics [OR: 7,0; IC 95% 1,93-25,0; p: 0,003] and mechanical ventilation [OR: 4,19; IC 95% 1,66-10,0; p: 0,002].. MABB were detected in patients with underlying conditions, invasive procedures and prolonged hospitalization. Predictors of MABB were mechanical previous use of broad-spectrum antibiotics and mechanical ventilation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacteremia; Case-Control Studies; Catheterization, Central Venous; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Intensive Care Units, Pediatric; Length of Stay; Male; Microbial Sensitivity Tests; Respiration, Artificial; Retrospective Studies; Risk Factors

The effect of antimicrobials on SOS-mediated mutagenesis induction depends on the bacterial species and the antimicrobial group. In this work, we studied the effect of different families of antimicrobial agents used in clinical therapy against Acinetobacter baumannii in the induction of mutagenesis in this multiresistant Gram-negative pathogen. The data showed that ciprofloxacin and tetracycline induce SOS-mediated mutagenesis, whereas colistin and meropenem, which are extensively used in clinical therapy, do not.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Mutagenesis; Rifampin; SOS Response, Genetics; Tetracyclines; Thienamycins

The emergence of colistin-resistant Acinetobacter baumannii is concerning, as colistin is often regarded as the last option for treating multidrug-resistant (MDR) A. baumannii infections. Using mRNA sequencing, we compared whole transcriptomes of colistin-susceptible and colistin-resistant A. baumannii strains, with the aim of identifying genes involved in colistin resistance. A clinical colistin-susceptible strain (06AC-179) and a colistin-resistant strain (07AC-052) were analysed in this study. In addition, a colistin-resistant mutant (06AC-179-R1) derived from 06AC-179 was also included in this study. High throughput mRNA sequencing was performed with an Illumina HiSeq TM 2000. In total, six genes were identified as associated with colistin resistance in A. baumannii. These six genes encode PmrAB two-component regulatory enzymes, PmrC (a lipid A phosphoethanolamine transferase), a glycosyltransferase, a poly-β-1,6-N-acetylglucosamine deacetylase, and a putative membrane protein. Matrix-assisted laser desorption/ionization time of flight mass spectrometry revealed that all three colistin-resistant strains used in this study had modified lipid A structure by addition of phosphoethanolamine. As genes found in our results are all associated with either lipopolysaccharide biosynthesis or electrostatic changes in the bacterial cell membrane, lipopolysaccharide modification might be one of the principal modes of acquisition of colistin resistance in some A. baumannii strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Gene Expression Profiling; Genes, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Lipid A; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Minocycline; Partial Thromboplastin Time; Renal Dialysis; Tigecycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

The clinical characteristics of patients with colistin-resistant Acinetobacter baumannii bacteraemia have been documented, but those of patients with bacteraemia caused by other Acinetobacter species remain unknown. Previous exposure to colistin has been shown to be associated with the emergence of colistin resistance, but may be not the only predisposing factor. In the current study, we highlight the risk and outcome of patients without previous exposure to colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN) bacteraemia. This 11-year single-centre retrospective study analysed 58 patients with ColRAN bacteraemia and 213 patients with colistin-susceptible A. nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined with an agar dilution method. The clonal relationship of ColRAN isolates was determined with pulsed-field gel electrophoresis. A conjugation mating-out assay was conducted to delineate the potential transfer of colistin resistance genes. Multivariable analysis was performed to evaluate the risk factors for ColRAN bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16 different ColRAN pulsotypes, and two major clones were found. Colistin resistance did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These results show that COPD is an independent risk factor for acquisition of ColRAN bacteraemia. The mortality rates were similar between patients with ColRAN and ColSAN bacteraemia.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Conjugation, Genetic; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gene Transfer, Horizontal; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Young Adult

The spread of multidrug-resistant Acinetobacter baumannii (MDRAB) has led to the renaissance of colistin (COL), often the only agent to which MDRAB remains susceptible. Effective therapy with COL is beset with problems due to unpredictable pharmacokinetics, toxicity, and the rapid selection of resistance. Here, we describe a potent synergistic interaction when COL was combined with fusidic acid (FD) against A. baumannii. Synergy in vitro was assessed against 11 MDRAB isolates using disc diffusion, checkerboard methodology (fractional inhibitory concentration index [FICI] of ≤ 0.5, susceptibility breakpoint index [SBPI] of >2), and time-kill methodology (≥2 log10 CFU/ml reduction). The ability of FD to limit the emergence of COL resistance was assessed in the presence and absence of each drug alone and in combination. Synergy was demonstrated against all strains, with an average FICI and SBPI of 0.064 and 78.85, respectively. In time-kill assays, COL-FD was synergistic and rapidly bactericidal, including against COL-resistant strains. Fusidic acid prevented the emergence of COL resistance, which was readily selected with COL alone. This is the first description of a novel COL-FD regimen for the treatment of MDRAB. The combination was effective at low concentrations, which should be therapeutically achievable while limiting toxicity. Further studies are warranted to determine the mechanism underlying the interaction and the suitability of COL-FD as an unorthodox therapy for the treatment of multidrug-resistant Gram-negative infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Fusidic Acid; Humans; Microbial Sensitivity Tests

Colistin use has increased over the last ten years because of multidrug-resistant microorganisms. The aim of this study was to compare the clinical and microbiological efficacy of colistin alone or in combination with sulbactam or carbapenem in the treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii.. Cases treated for VAP because of MDR and XDR A. baumannii between January 2011 and January 2013 were included in the study. The primary and secondary outcome for colistin alone, colistin with sulbactam, and colistin with carbapenems were evaluated. The primary outcomes were clinical efficacy and microbiological efficacy; the secondary outcomes were nephrotoxicity, length of hospitalization, and mortality.. A total of 70 VAP patients were evaluated. A total of 17 patients (24.3%) were administered colistin alone, 20 patients (28.6%) were administered colistin and sulbactam, and 33 patients (47.1%) were administered colistin and carbapenem. Clinical and microbiological response rates were higher in the carbapenem combination group (63.6% and 63.6% in both) than in the sulbactam combination group, which registered 55.0% and 60.0%, respectively. However, this did not represent a significant difference statistically (p > 0.05). There was also no significant difference between colistin alone and the combination groups regarding clinical and microbiological efficacy and mortality.. Neither the administration of colistin alone nor colistin combined with either sulbactam or carbapenem had any noticeable advantage in the treatment of VAP in terms of clinical response, microbiological response, nephrotoxicity, length of hospitalization, and mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Renal Insufficiency; Retrospective Studies; Sulbactam; Treatment Outcome

This study determined the mechanisms and patterns of antimicrobial resistance among the isolates obtained from different wards of a teaching hospital in the city of Mashhad in north-east Iran. Between January 2012 and the end of June 2012, 36 isolates of Acinetobacter baumannii were collected from different wards of Ghaem Hospital. Antimicrobial susceptibility testing and epsilometer testing (E-test) were performed. The genetic resistance determinants of A, B and D classes of β-lactamases, aminoglycoside modifying enzymes (AMEs), efflux pumps and ISAba1 elements were assessed by PCR. Repetitive extragenic palindromic element (REP)-PCR was performed to find the genetic relatedness of the isolates. Colistin was the most effective antibiotic of those tested, where all isolates were susceptible. E-test results revealed high rates of resistance to imipenem, ceftazidime and ciprofloxacin. The majority of isolates (97  %) were multidrug-resistant. OXA-51, OXA-23 and tetB genes were detected in all isolates, but OXA-58, IMP and tetA were not detected. The prevalence of OXA-24, bla(TEM), bla(ADC), bla(VIM) and adeB were 64, 95, 61, 64 and 86  %, respectively. ISAba1 was found to be inserted into the 5' end of OXA-23 in 35 isolates (97  %). Of the AMEs, aadA1 (89  %) was the most prevalent, followed by aphA1 (75  %). The band patterns reproduced by REP-PCR showed that 34 out of 36 isolates belonged to one clone and two singletons were identified. The results confirmed that refractory A. baumannii isolates were widely distributed and warned the hospital infection control team to exert strict measures to control the infection. An urgent surveillance system should be implemented.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Colistin; Cross Infection; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Female; Genetic Variation; Hospitals, Teaching; Humans; Iran; Male; Microbial Sensitivity Tests; Molecular Typing; Tetracycline Resistance

We compared six colistin susceptibility testing (ST) methods on 61 carbapenem-nonsusceptible Klebsiella pneumoniae (n = 41) and Acinetobacter baumannii (n = 20) clinical isolates with provisionally elevated colistin MICs by routine ST. Colistin MICs were determined by broth microdilution (BMD), BMD with 0.002% polysorbate 80 (P80) (BMD-P80), agar dilution (AD), Etest, Vitek2, and MIC test strip (MTS). BMD was used as the reference method for comparison. The EUCAST-recommended susceptible and resistant breakpoints of ≤2 and >2 μg/ml, respectively, were applied for both K. pneumoniae and A. baumannii. The proportions of colistin-resistant strains were 95.1, 77, 96.7, 57.4, 65.6, and 98.4% by BMD, BMD-P80, AD, Etest, MTS, and Vitek2, respectively. The Etest and MTS methods produced excessive rates of very major errors (VMEs) (39.3 and 31.1%, respectively), while BMD-P80 produced 18% VMEs, AD produced 3.3% VMEs, and Vitek2 produced no VMEs. Major errors (MEs) were rather limited by all tested methods. These data show that gradient diffusion methods may lead to inappropriate colistin therapy. Clinical laboratories should consider the use of automated systems, such as Vitek2, or dilution methods for colistin ST.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii remains a significant cause of morbidity and mortality. Increasing antimicrobial resistance influences the selection of antibiotic treatment especially pandrug-resistant A. baumannii. A retrospective cohort study was conducted in the Medical Intensive Care Unit to identify the risk factors of VAP caused by multidrug-resistant A. baumannii (MDR-AB), extensively drug-resistant A. baumannii (XDR-AB) and pandrug-resistant A. baumannii (PDR-AB). All 337 adult patients with confirmed A. baumannii VAP were included. The incidence of MDR-AB, XDR-AB and PDR-AB were 72 (21.4%), 220 (65.3%) and 12 (3.6%), respectively. The risk factor for MDR-AB was prior use of carbapenems (OR 5.20; 95% CI 1.41-19.17). Risk factors for XDR-AB were the prior use of carbapenems (OR, 6.30; 95% CI, 1.80-21.97) and a high Sequential Organ Failure Assessment (SOFA) score (OR 1.35; 95% CI 1.07-1.71). In PDR-AB, the risk factors were the prior use of colistin (OR, 155.95; 95% CI, 8.00-3041.98), carbapenems (OR, 12.84; 95% CI, 1.60-103.20) and a high Simplified Acute Physiology Score (SAPS II) (OR 1.10; 95% CI 1.01-1.22). In conclusion, previous exposure to antibiotics and severity of VAP were risk factors of drug-resistant A. baumannii. Judicious use of carbapenems and colistin is recommended to prevent the antimicrobial-resistant strains of this organism.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Pneumonia, Ventilator-Associated; Retrospective Studies; Risk Factors; Thailand

Recent studies suggested that high doses of colistin are necessary in the treatment of serious infections. However, few studies have evaluated such treatment. The objective of this study was to evaluate the effectiveness and nephrotoxicity of high-dose colistin in critically ill patients with respiratory infections associated with carbapenem-resistant Acinetobacter baumannii (CRAB).. This was a retrospective cohort study of critically ill cancer patients who received high-dose intravenous colistin for treatment of CRAB-related respiratory infections. Patients received colistimethate sodium 9 million IU/day or an equivalent dose, adjusted for renal function. Treatment effectiveness was evaluated by determining the microbiological clearance, recurrent and new CRAB-related infections, and mortality in the intensive care unit (ICU). Nephrotoxicity was defined according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.. A total of 89 patients met the inclusion criteria. Microbiological clearance was observed in 51 (66.2%) subjects who had at least 2 follow-up cultures (n = 77). In patients who achieved microbiological clearance, recurrent and new CRAB-related infections occurred in 3 (5.9%) and 9 (17.6%) subjects, respectively. Fifty-seven patients (64%) died in the ICU. Thirty-five (39.3%) subjects developed nephrotoxicity according to the RIFLE criteria, which was classified as risk in 4 (11.4%) subjects, injury in 8 (22.8%) subjects, and failure in 21 (60%) subjects.. In critically ill cancer patients, high-dose colistin was associated with microbiological clearance in about two-thirds of the subjects with CRAB-related respiratory infections but mortality was high. A significant portion of patients developed nephrotoxicity while receiving colistin therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Neoplasms; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome

Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediated by a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC, and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumannii is not well understood.. We investigated the genotypic and phenotypic changes that underlie pan-drug resistance mechanisms by determining differences between the alterations in extensively drug-resistant (XDR) A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart (AB003) recovered from one patient before and after antibiotic treatment, respectively.. All three clinical isolates shared an identical sequence type (ST138), belonging to the global epidemic clone, clonal complex 92, and all produced OXA-23 carbapenemase. The PDR AB003 showed two genetic differences, acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene, relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC, or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-time of flight analysis, the three isolates commonly showed two major peaks at 1728 m/z and 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detected only in the PDR A. baumannii AB003 isolate.. Our results show that changes in lipid A structure via a mutation in the pmrB gene and acquisition of armA gene might confer resistance to colistin and aminoglycosides to XDR A. baumannii strains, resulting in appearance of a PDR A. baumannii strain of ST138.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Male; Microbial Sensitivity Tests; Molecular Typing; Mutation; Polymerase Chain Reaction; Transcription Factors

In 2010 the Hellenic center for disease control and prevention launched the "Prokroustes" nationwide action plan to tackle the increasing rates of carbapenem resistance among gram-negative nosocomial pathogens. In the present report, data from a Greek tertiary-care hospital are presented three years after the adoption of the infection control measures. Carbapenem resistance rates have been contained for Klebsiella pneumoniae and Acinetobacter baumannii but not for Pseudomonas aeruginosa. More worryingly, in accordance with their overuse against carbapenem-resistant bacteria, resistance rates to colistin and tigecycline have risen significantly.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Containment of Biohazards; Cross Infection; Drug Resistance, Multiple, Bacterial; Gentamicins; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tigecycline

We report the emergence and analysis of a cluster of concurrent infections/colonisations with colistin-resistant Klebsiella pneumoniae and OXA-23 carbapenemase-producing Acinetobacter baumannii in patients who had undergone cardiac surgery. We describe the emergence of colistin-resistant K. pneumoniae harbouring blaCTX-M-15, blaSHV-11, blaOXA-1, blaTEM-1 beta-lactamases and aac(6')-Ib-cr fluoroquinolone resistance. Colistin-resistant K. pneumoniae infections (pneumonia, wound infection, urinary tract infections and bacteraemia) occurred in critically ill patients previously treated with colistin for post-surgery infections with carbapenem-resistant Pseudomonas aeruginosa and/or A. baumannii. Although the cause of death could not be directly attributed to a single pathogen, three patients co-infected/colonised with K. pneumoniae, P. aeruginosa and/or A. baumannii died, whilst a fourth patient who had a mono-microbial infection with colistin-resistant K. pneumoniae only survived. The use of mobile intubation equipment in patients that shared the same ward, the clustering of cases over a short period of time, as well as the pulsed-field gel electrophoresis (PFGE) data all suggest cross-contamination between patients, either through equipment or by staff contact transmission. This report presents the 'worst-case scenario' where concurrent infection/colonisation with pathogens exhibiting resistance to different types of last-resort antimicrobials occurred in some of the most debilitated intensive care unit (ICU) patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cardiology Service, Hospital; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Romania

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Minocycline; Pneumonia, Ventilator-Associated; Prognosis; Retrospective Studies; Salvage Therapy; Survival Analysis; Tigecycline; Tunisia

An alarming increase in the resistance rates of tigecycline and colistin among carbapenemase-producing Acinetobacter baumannii recovered from a Greek hospital over a 3-year period (2011-2013) was investigated. The antimicrobial resistance profiles and carbapenemase gene content were determined for a collection of colistin- and/or tigecycline-resistant carbapenemase-producing A. baumannii isolates (n = 42), which were recovered consecutively during the study period. A gradual increase in the incidence of blaOXA-23 producers was observed from 2011 to 2013. A cluster of 21 isolates comprised tigecycline-resistant blaOXA-23 producers displayed a single antimicrobial resistance pattern. The emergence of two blaOXA-23 producers resistant to both tigecycline and colistin was documented. Furthermore, determination of the mechanisms of colistin and tigecycline resistance and molecular typing by the tri-locus sequence typing (3LST) scheme for nine isolates recovered from bloodstream infections were performed. Out of nine isolates, five tigecycline- and two colistin-resistant isolates were blaOXA-23 producers of 3LST ST101 corresponding to the international clone II recovered during 2012-2013. All nine isolates were positive for the presence of the adeB gene of the AdeABC efflux pump. Three colistin-resistant isolates possessed novel substitutions in PmrB, which may be implicated in colistin resistance. To the best of our knowledge, this is the first report of the acquisition of tigecycline and colistin resistance among blaOXA-23-producing A. baumannii of 3LST ST101 in Greece; thus, continuous surveillance and molecular characterization, prudent use of antibiotics and implementation of infection control measures for A. baumannii are urgent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Greece; Humans; Minocycline; Tigecycline; Time Factors

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as one of the most troublesome pathogens in healthcare settings worldwide. The present study was conducted to analyze the genes encoding resistance to carbapenems and to determine in vitro activity of colistin and tigecycline against CRAB isolates from blood culture of hospitalized patients at Istanbul University Cerrahpasa Medical School hospital.. Between January 2012 and June 2014, a total of 72 CRAB isolates were isolated by conventional methods from blood cultures of patients with bacteremia who were hospitalized in intensive care units and in various departments of the hospital. The isolates were confirmed using a Phoenix automated system. Antibiotic susceptibilities were determined by disk diffusion method and Etest. Molecular detection of resistance genes were screened by multiplex real time polymerase chain reaction (qPCR) and PCR parameters.. CRAB isolates were highly resistant to tetracycline (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1 µg/mL) and colistin (MIC ranges 0.125-1.5 µg/mL) were found to be 0.5 µg/mL and 1 µg/mL, respectively. All isolates were positive for OXA-51 that shows molecular identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates were positive for OXA-23 and OXA-58 genes, re- spectively.. This study indicated the most of the CRAB isolates in our hospital carry the OXA-23 gene. Colistin and tigecycline resistance were not detected. However, significant effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and continuous monitoring of drug resistance is necessary in clinical settings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genotype; Hospitals, University; Humans; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multiplex Polymerase Chain Reaction; Tigecycline; Turkey

Acinetobacter nosocomialis has increasingly been reported as an opportunistic pathogen causing nosocomial infections. Although it is more susceptible to all antimicrobial agents than Acinetobacter baumannii, MDR clinical isolates have also been described. In addition, several studies have shown a high percentage of resistance to colistin. Therefore, in the present study we investigated the mechanism of resistance to colistin in this microorganism.. Colistin-resistant strains were selected from the original colistin-susceptible A. nosocomialis strain following multi-step mutant selection. Comparative genomic and proteomic analyses of both colistin-susceptible and colistin-resistant A. nosocomialis strains were performed. In addition, virulence was investigated using the Caenorhabditis elegans assay.. The colistin-resistant mutants selected showed a lower resistance profile for other types of antibacterial agents together with a significant decrease in virulence. The LT50 (i.e. time required to kill 50% of the nematodes) for the colistin-susceptible strain (WT) was 7 days compared with 9 days for the colistin-resistant strain (256) (P < 0.0001). In the genomic studies, several mutations were observed in the lpxD genes, leading to the loss of LPS in the colistin-resistant strains. The proteomic studies showed several up- and down-regulated proteins that may be involved in colistin resistance or in a decrease in the resistance profile for several antibiotics.. This study shows that the mechanism of resistance to colistin by A. nosocomialis is mainly associated with the loss of LPS due to mutations in the lpxD gene, although changes in the expression of some proteins cannot be ruled out. In addition, the acquisition of colistin resistance is related to a decrease in virulence.

Topics: Acinetobacter; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Caenorhabditis elegans; Colistin; Disease Models, Animal; DNA Mutational Analysis; Drug Resistance, Bacterial; Genome, Bacterial; Lipopolysaccharides; Mutation; Proteome; Serial Passage; Virulence; Virulence Factors

This study investigated the exposure-response relationships between unbound colistin in plasma and antibacterial activity in mouse thigh and lung infections.. Dose fractionation studies (subcutaneous colistin sulphate at 1.25-160 mg/kg/day) were conducted in neutropenic mice in which infection (three strains of Pseudomonas aeruginosa and three strains of Acinetobacter baumannii) had been produced by intramuscular thigh injection or aerosol lung delivery. Bacterial burden was measured at 24 h after initiation of colistin treatment. Plasma protein binding was measured by rapid equilibrium dialysis and ultracentrifugation. The inhibitory sigmoid dose-effect model and non-linear least squares regression were employed to determine the relationship between exposure to unbound colistin and efficacy.. Plasma binding of colistin was constant over the concentration range ∼2-50 mg/L. The average ± SD percentage bound for all concentrations was 92.9 ± 3.3% by ultracentrifugation and 90.4 ± 1.1% by equilibrium dialysis. In the thigh model, across all six strains the antibacterial effect of colistin was well correlated with fAUC/MIC (R(2) = 0.82-0.94 for P. aeruginosa and R(2) = 0.84-0.95 for A. baumannii). Target values of fAUC/MIC for 2 log10 kill were 7.4-13.7 for P. aeruginosa and 7.4-17.6 for A. baumannii. In the lung model, for only two strains of P. aeruginosa and one strain of A. baumannii was it possible to achieve 2 log10 kill (fAUC/MIC target values 36.8-105), even at the highest colistin dose tolerated by mice. This dose was not able to achieve bacteriostasis for the other two strains of A. baumannii.. Colistin was substantially less effective in lung infection. The pharmacokinetic/pharmacodynamic target values will assist in the design of optimized dosage regimens.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Female; Lung; Mice; Microbial Sensitivity Tests; Plasma; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Soft Tissue Infections; Thigh; Treatment Outcome

Extensively drug-resistant (XDR) Acinetobacter spp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR Acinetobacter baumannii in an in vitro pharmacokinetics-pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDR A. baumannii were investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log10 CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log10 CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log10 CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin-plus-imipenem combinations reduced the levels of log10 CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistant A. baumannii. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Area Under Curve; beta-Lactams; Colistin; Colony Count, Microbial; Daptomycin; Drug Administration Schedule; Drug Combinations; Drug Resistance, Multiple, Bacterial; Ertapenem; Humans; Imipenem; Limit of Detection; Microbial Sensitivity Tests; Models, Biological; Models, Statistical

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A. baumannii clinical isolates that acquired colistin resistance due to mutations in lpxA, lpxC and lpxD as well as their colistin-susceptible counterparts. A dramatic increase in antibiotic susceptibility (≥16-fold increase) was observed upon LPS loss for azithromycin, rifampicin and vancomycin, whereas a moderate increase in susceptibility was seen for amikacin, ceftazidime, imipenem, cefepime and meropenem. Importantly, concentrations ranging from 8 mg/L to 32 mg/L of the six AMPs were able to reduce bacterial viability by ≥3 log10 in growth curve assays. We also demonstrate that colistin resistance results in partial colistin dependence for growth in LPS-deficient strains containing mutations in lpxA, lpxC and lpxD, but not when colistin resistance occurs via LPS modification due to mutations in the PmrA/B two-component system. The results of this study indicate that loss of LPS expression results in collateral sensitivity to azithromycin, rifampicin and vancomycin, and that the six AMPs tested retain activity against LPS-deficient strains, indicating that these antibiotics may be viable treatment options for infections caused by these strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Azithromycin; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Lipid A; Lipopolysaccharides; Microbial Sensitivity Tests; Microbial Viability; Rifampin; Vancomycin

Acinetobacter baumannii has been associated with high morbidity and mortality rates, even in pediatric patients. Therapeutic options are limited, especially when the strain is multidrug resistant.. Clinical and microbiological analyses of 4 cases of systemic infections caused by multi drug resistant A. baumannii treated with colistin/vancomycin combination at a Pediatric Intensive Care Unit were performed in order to explore the potential synergistic activity of colistin plus vancomycin. All the patients were treated with colistin, meropenem and vancomycin.. Four severe infections due to MDR A. baumannii were observed. All patients treated with colistin/vancomycin combination had a positive outcome with no infection relapses. Most importantly, no significant adverse events related to the simultaneous administration of COL plus VAN were observed. In our in-vitro experiments, the synergistic effect of the combination COL plus VAN showed an early bactericidal activity even at VAN concentration of 16 mg/L, which reflects the serum trough concentrations obtained in patients.. An antimicrobial strategy based on the activity of colistin plus vancomycin was in-vitro and in-vivo effective in life-threatening infections caused by multidrug-resistant A. baumannii in a Pediatric Intensive Care Unit, in the absence of adverse effects. Colistin plus vancomycin were highly synergic and bactericidal against carbapenem-resistant, colistin sensitive A. baumannii whereas the addition of meropenem did not enhance the in-vitro activity of colistin plus vancomycin.. Our results confirm existing data on the potential synergistic activity of a therapeutic strategy including colistin plus vancomycin and provide important new clinical information for its potential use as a therapeutic option against MDR A. baumannii infections, especially in the pediatric population.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins; Vancomycin; Young Adult

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Acinetobacter baumannii is an important hospital-acquired pathogen in healthcare facilities that frequently causes bacteraemia and ventilator-associated pneumonia in intensive care units. Acinetobacter baumannii can be isolated from various sites in the hospital environment like medical equipment, bed linen, medical personnel and indwelling catheters. It is difficult to treat A. baumannii infections because of their highly resistant antimicrobial profiles. The purpose of this study was to determine the prevalence of β-lactamase genes in multidrug-resistant (MDR) clinical A. baumannii isolates using Multiplex-PCR (M-PCR) assays.. One hundred MDR A. baumannii isolates were collected from the diagnostic division of the Department of Medical Microbiology after routine analysis of the submitted specimens. All collected isolates were identified and tested for susceptibility using the VITEK 2® system (bioMérieux, France). Six isolates were excluded from this study because the isolates were incorrectly identified as A. baumannii with the VITEK 2® system (bioMérieux, France). Molecular tests, namely M-PCR assays, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed. MLST analyses were performed on representative isolates from the four major pulsotypes (≥5 isolates with 80 % similarity) and selective isolates from each minor pulsotype.. All the A. baumannii isolates showed 100 % resistance to ampicillin, amoxicillin, cefuroxime, cefuroximine axetil, cefoxitin, cefotaxime and nitrofurantoin. Seven percent of the isolates were resistant to amikacin. Two percent of the isolates were classified as having intermediate susceptibility to tigecycline. A. baumannii isolates showed an antibiotic resistance profile of 67 % and higher to antibiotics, such as ceftazidime, cefepime, imipenem, meropenem, gentamicin, ciprofloxacin and trimethoprim/sulfamethoxazole. None of the isolates were resistant to colistin. The M-PCR assays showed that 99 % of the isolates contained the OXA-51 gene and 77 % contained the OXA-23 gene. None of the isolates contained the GES, GIM, IMP, KPC, NDM, OXA-24, OXA-58, PER, SIM, SPM, VEB and VIM genes. Representative A. baumannii isolates were grouped into five existing sequence types (ST): ST106, ST258, ST339, ST502, ST758 and ST848. Isolates belonging to the pan-European clonal lineages I and II (EUI and EUII) were identified.. The high prevalence of MDR A. baumannii isolates has a severe impact on available treatment choices and this in return impacts on treatment outcomes in the studied healthcare facilities. The most dominant ST among the collected isolates was ST758, member of the EUI group. The presence of the OXA-23 gene was not restricted to a specific ST. Continuous research and surveillance is necessary to monitor the circulating β-lactamase genes in clinical settings to guide infection control policies in order to try and curb the spread of this bacterium.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Infant; Infant, Newborn; Intensive Care Units; Middle Aged; Multilocus Sequence Typing; Multiplex Polymerase Chain Reaction; South Africa; Young Adult

The present study evaluates the synergistic effect of sulbactam/tazobactam in combination with meropenem or colistin against multidrug resistant (MDR) Acinetobacter baumannii isolated from hospitalized patients from a tertiary care hospital in Saudi Arabia. During the study period, 54 multidrug and carbapenem-resistant isolates of A. baumannii isolates were collected from blood and respiratory samples of patients with ventilator-associated pneumonia or bacteremia. Microbroth checkerboard assay (CBA) and E-test were performed to look for synergistic interface of sulbactam and tazobactam with meropenem or colistin. All 54 MDR isolates of A. baumannii were resistant to carbapenem. Minimum inhibitory concentration [50/90] value against sulbactam, tazobactam, meropenem, colistin was found to be 64/128, 64/128, 64/256, and 0.5/1.0 respectively. Synergy was detected in more isolates with CBA compared to E-test. All four combinations showed significant synergistic bactericidal activity. However, the combination with colistin showed greater synergistic effect than combination with meropenem. Antagonism was not detected with any of the combinations and any method, but indifference was seen in tazobactam and colistin combination alone. A significant bactericidal effect was seen with sulbactam combination with meropenem or colistin in both methods. A combination therapy can be a choice of treatment. As colistin is known to exhibit nephrotoxicity, the combination of sulbactam and meropenem might be considered as an alternative antibiotic treatment for such multi- and extremely resistant bacteria. Yet, sample size is small in our study, so further well-designed in vitro and clinical studies on large scale should confirm our findings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Prospective Studies; Sulbactam; Tazobactam; Thienamycins

Colistin-resistant/carbapenem-resistant Acinetobacter baumannii is a significant challenge for antibiotic treatment and infection control policies. Since 2012, in Central Greece an increase of colistin/pan- resistant A. baumannii has occurred, indicating the need for further analysis.. A total of 86 colistin-resistant/carbapenem-resistant out of 1228 A. baumannii clinical isolates, consecutively collected between 2012 and 2014 in a tertiary Greek hospital of Central Greece, as well as one environmental isolate from surveillance cultures were studied. Molecular typing and mechanisms of resistance to colistin and to carbapenems were assessed, whereas, epidemiological and clinical data of the patients were reviewed.. During the study period, the rate of colistin resistance gradually increased and reached 21.1 % in 2014. All colistin-resistant/carbapenem-resistant A. baumannii belonged to 3LST ST101 clone that corresponds to the international clonal lineage II. Carbapenem resistance was associated with the presence of bla oxa-23-like, while resistance to colistin probably correlated with G54E and R109H amino acid substitutions in PmrA and PmrC, respectively.. Epidemiological data of the patients indicated that the first detection of colistin-resistant/carbapenem-resistant ST101 clone in the University Hospital of Larissa (UHL) was associated with a patient who previously had received colistin, while, the movement of the infected patients into the hospital probably resulted to its spread.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Greece; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing

In two pairs of clinical colistin-susceptible/colistin-resistant (Cst(s)/Cst(r)) Acinetobacter baumannii strains, the Cst(r) strains showed significantly decreased biofilm formation in static and dynamic assays (P < 0.001) and lower relative fitness (P < 0.05) compared with those of the Cst(s) counterparts. The whole-genome sequencing comparison of strain pairs identified a mutation converting a stop codon to lysine (*241K) in LpsB (involved in lipopolysaccharide [LPS] synthesis) in one Cst(r) strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Outer Membrane Proteins; Bacterial Proteins; Biofilms; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Lipopolysaccharides; Mannosyltransferases; Microbial Sensitivity Tests; Porins

To compare clinical and microbiological efficacy of colistin and colistin/sulbactam for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii VAP in intensive care units (ICUs).. In this retrospective analysis, patients (>16 years-old) who received IV colistin or colistin/sulbactam for the treatment of MDR A. baumannii VAP were evaluated. The clinical and microbiological responses to therapies were assessed on the fifth day and at the end of the therapy.. During the study period, 89 patients were enrolled into the study. Fifty-two (58.4 %) patients received colistin and 37 (41.6 %) patients received colistin/sulbactam therapy. The median APACHE II score was higher and diabetes mellitus was more common in the colistin/sulbactam group (p < 0.05). However, other demographic characteristics were not statistically significant between groups. On the fifth day of colistin and colistin/sulbactam therapies, clinical response rates were 40.4 and 43.2 %, respectively. At the end of the therapies, clinical response rates were 29.8 and 40 %, respectively. The bacteriological response rates were 72.3 and 85.7 % in colistin and colistin/sulbactam groups, respectively. There were no statistically significant differences in clinical cure rates or bacteriological clearance rates between the two groups.. The colistin/sulbactam combination therapy is promising in severe MDR A. baumannii VAP. Although, the difference was not statistically significant, clinical cure rates or bacteriological clearance rates were better in the combination group than colistin monotherapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Treatment Outcome; Young Adult

The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates.. Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction.. A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively.. The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice.

Topics: Academic Medical Centers; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Imipenem; Microbial Sensitivity Tests; Molecular Typing; Polymorphism, Restriction Fragment Length

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Colistin; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation, Missense; Pseudomonas aeruginosa; Pseudomonas Infections; Selection, Genetic

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Rifampin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Rifampin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cerebral Ventriculitis; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Meningitis, Bacterial

We compared in vitro killing of colistin, doripenem, and sulbactam by time-kill methods against Acinetobacter baumannii isolates collected from patients before and after colistin-doripenem treatment (initial and recurrent isolates, respectively). Colistin-doripenem bactericidal activity against recurrent isolates was attenuated (mean log10 kill, -5.74 versus -2.88; P = 0.01) but was restored by adding sulbactam. Doripenem MICs rather than colistin MICs correlated with the activity of colistin-doripenem. Among colistin-resistant isolates, colistin-doripenem-sulbactam combinations achieved greater killing than colistin-doripenem alone (-5.65 versus -2.43; P = 0.04).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Administration Schedule; Drug Combinations; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Sulbactam

Two colistin-susceptible/colistin-resistant (Col(s)/Col(r)) pairs of Acinetobacter baumannii strains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Col(s) isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Col(r) isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressed pmrCAB genes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Col(r) isolate Ab347, tested by proteomic analysis in comparison with its Col(s) counterpart Ab299, underexpressed the proteins CsuA/B and C from the csu operon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Col(s) isolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Col(r) isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Col(s) isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Col(r) isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aconitate Hydratase; Aged; Anti-Bacterial Agents; Bacterial Proteins; Catalase; Clone Cells; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Operon; Peroxiredoxins; Superoxide Dismutase

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 50 patients between July 2011 and July 2012 at the University Hospital A Coruña (NW Spain). These multidrug-resistant isolates, which belonged to a single clone, remained only susceptible to tigecycline, minocycline, and colistin and produced the carbapenem-hydrolyzing oxacillinase, OXA-23. This is the first reported outbreak of OXA-23-producing A. baumannii isolates in Spain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Gene Expression; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Spain; Survival Analysis; Tigecycline

Colistin resistance remains rare among clinical isolates of Acinetobacter species. We noted the emergence of colistin-resistant bloodstream isolates of the Acinetobacter genomic species (GS) 13BJ/14TU from patients at a university hospital between 2003 and 2011. We report here, for the first time, the microbiological and molecular characteristics of these isolates, with clinical features of Acinetobacter GS 13BJ/14TU bacteremia. All 11 available patient isolates were correctly identified as Acinetobacter GS 13BJ/14TU using partial rpoB gene sequencing but were misidentified using the phenotypic methods Vitek 2 (mostly as Acinetobacter baumannii), MicroScan (mostly as A. baumannii/Acinetobacter haemolyticus), and the API 20 NE system (all as A. haemolyticus). Most isolates were susceptible to commonly used antibiotics, including carbapenems, but all were resistant to colistin, for which it is unknown whether the resistance is acquired or intrinsic. However, the fact that none of the patients had a history of colistin therapy strongly suggests that Acinetobacter GS 13BJ/14TU is innately resistant to colistin. The phylogenetic tree of multilocus sequence typing (MLST) showed that all 11 isolates formed a separate cluster from other Acinetobacter species and yielded five sequence types. However, pulsed-field gel electrophoresis (PFGE) revealed 11 distinct patterns, suggesting that the bacteremia had occurred sporadically. Four patients showed persistent bacteremia (6 to 17 days), and all 11 patients had excellent outcomes with cleared bacteremia, suggesting that patients with Acinetobacter GS 13BJ/14TU-associated bacteremia show a favorable outcome. These results emphasize the importance of precise species identification, especially regarding colistin resistance in Acinetobacter species. In addition, MLST offers another approach to the identification of Acinetobacter GS 13BJ/14TU, whereas PFGE is useful for genotyping for this species.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Child; Colistin; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Sequence Data; Multilocus Sequence Typing

Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P=0.06]. In the Cox regression model, doses ≥2million International Units (MIU) of PMB or >9MIU of CMS were the only variable independently associated with AKI [adjusted hazard ratio (aHR)=2.11, 95% confidence interval (CI) 1.01-4.41; P=0.04]. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR=2.22, 95% CI 0.98-5.04; P=0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR=1.74, 95% CI 0.82-3.69; P=0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Hospital Mortality; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Vancomycin

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Sulbactam; Treatment Outcome

The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller-Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time-kill methodology using tubes containing an inoculum of 5×10(5)CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24h for colony counting. Synergy was defined as ≥2log10CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate-concentration combinations in time-kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5h and 24h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time-kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Colistin; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Microbial Sensitivity Tests

Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.. The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009-2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.. A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).. Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Taiwan; Tigecycline

Colistin and tigecycline are the only therapeutic options for extensively drug resistant Acinetobacter baumannii (XDR-AB), but there is little comparative study. This retrospective observation study evaluated two-colistin and tigecycline-antibiotics profiles like treatment success rate, negative conversion rate, the length of hospital stay, intensive care unit (ICU) stay and antibiotics use, mortality rate during hospital stay and adverse event rate, based on the medical record of XDR-AB positive patients who were treated at least 5 d with those intravenous antibiotics. Treatment success rate of colistin (n=39) and tigecycline (n=16) were not different: 48.7% and 43.8%, respectively (p=0.737), though negative conversion rate was significantly higher in the colistin group: 46.2% against 12.5% (p=0.049). There was no statistically significant difference in mortality rate between two groups during hospital stay (43.6% vs. 56.3%, p=0.393). There were no significant differences in the following parameters: the median length of hospital stay (46.0 d vs. 72.5 d), the median length of intensive care units stay (26.0 d vs. 27.0 d), the median length of antibiotics use (15.0 d vs. 13.0 d). The colistin group showed serum creatinine elevation (defined as elevation more than 2.0 mg/dL and 50% increase from the baseline) as 43.6% when compared with 12.5% of the tigecycline group (p=0.028). As a therapeutic option of XDR-AB, colistin showed significantly better negative conversion rate than tigecycline with more frequent nephrotoxic prevalence, and treatment success rate and mortality rate were not different from both antibiotics groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney; Length of Stay; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment.. The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects.. A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients.. We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Cross Infection; Electrolytes; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Magnesium; Male; Microbial Sensitivity Tests; Retrospective Studies; Sepsis; Water-Electrolyte Imbalance

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Tigecycline; Treatment Outcome; Young Adult

Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become an important healthcare-associated problem, particularly in intensive care units (ICUs).. To investigate the emergence of carbapenem- and colistin-resistant A. baumannii infections in two Sicilian hospitals.. From October 2008 to May 2011, a period which included two Italian Nosocomial Infections Surveillance in ICUs network (SPIN-UTI) project surveys, all carbapenem-resistant A. baumannii isolates from the ICUs of two hospitals in Catania, Italy, were prospectively collected. Minimum inhibitory concentrations (MICs) were measured by agar dilution, and phenotypic testing for metallo-β-lactamase (MBL) production was performed. Carbapenem resistance genes and their genetic elements were identified by polymerase chain reaction and sequencing. Genotypic relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. Patient-based surveillance was conducted using the SPIN-UTI protocol and previous antibiotic consumption was recorded.. Twenty-six carbapenem-resistant A. baumannii were identified. Imipenem and meropenem MICs ranged from 4 to >32 mg/L, and 15 isolates exhibited high-level colistin resistance (MICs >32 mg/L). PFGE demonstrated that all isolates belonged to a unique clonal type and were assigned to ST2 of the international clone II. They harboured an intrinsic blaOxA-51-like carbapenemase gene, blaOxA-82, which was flanked upstream by ISAba1.. The dissemination of clonally related isolates of carbapenem-resistant A. baumannii in two hospitals is described. Simultaneous resistance to colistin in more than half of the isolates is a problem for effective antibiotic treatment. Prior carbapenem and colistin consumption may have acted as triggering factors.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Polymerase Chain Reaction; Sicily

This study was performed to investigate the mechanisms of in vivo acquisition of colistin resistance in A. baumannii during colistin treatment. Three colistin-susceptible/resistant pairs of A. baumannii were recovered from patients who underwent colistin treatment. All of the 6 isolates included in this study shared an identical sequence type (ST), ST375, and they showed identical SmaI-macrorestriction patterns by pulsed-field gel electrophoresis. The individual colistin-resistant isolates harbored distinct mutations in the pmrB gene. Mutations detected in the pmrB gene were Ala227Val, Pro233Ser, and frame shift from Phe26. In matrix-assisted laser desorption ionization-time of flight analysis, colistin-resistant isolates were different from their colistin-susceptible counterparts, and they showed additional distinct peaks at 1852 m/z, 1937 m/z, 1954 m/z, 1975 m/z, 2034 m/z, and 2157 m/z. In vivo selection of colistin-resistant A. baumannii occurred independently in strains of ST357 during colistin treatment, and the strains acquired colistin resistance via mutations in the pmrB gene resulting in modification of lipid A components.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Male; Middle Aged; Molecular Typing; Mutation; Polymorphism, Restriction Fragment Length; Selection, Genetic; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcription Factors

Prosthetic joint infections are severe complications of joint implants. Further complications arise when polymicrobial and/or multidrug-resistant microorganisms are involved. Currently, there are limited data on the management of these infections and on the tolerability of long-term treatment with daptomycin, ceftazidime and colistin.. A 55-year-old Caucasian woman who had a right hip prosthesis removed 1 year prior because of infection was admitted for prosthesis reimplantation. On admission at our hospital, anamnesis regarding etiology and management of prosthesis infection was not available. On clinical, laboratory findings and imaging studies infection was not suspected. A hip prosthesis was reimplanted. At surgery, histopathological and microbiological investigations were not taken. Three weeks after reimplantation, surgical site infection due to Enterobacter cloacae was diagnosed and oral ciprofloxacin was prescribed. Four days later, a periprosthesis fluid collection was evidenced and a percutaneous needle aspirate grew Staphylococcus epidermidis and S. haemolyticus. Enterobacter genome was also detected from the same sample. Teicoplanin and meropenem were added to ciprofloxacin without clinical improvement. Moreover, acetabular cup dislocation was documented. She underwent prosthesis explantation, debridement, and positioning of an antimicrobial mixed spacer. From the intraoperatory cultures S. epidermidis and Acinetobacter baumannii were grown. Daptomycin, ceftazidime, colistin and rifampin were administered. Four days later, rifampin was stopped due to a suspected liver toxicity. While undergoing therapy she presented recurrent episodes of wound dehiscence and on the 22nd week of treatment a further surgical debridement was performed, upon which the spacer was removed. At this time, intraoperative cultures resulted negative. Three months later, after a total of 8 months, antimicrobials were interrupted. Subsequently, a femoral transcondylar traction was positioned, and 3 weeks later a new prosthesis was reimplanted. At over 1 year after reimplantation she is well.. Our findings suggest that microbiologic investigations are mandatory even when prosthetic joint infection is not suspected. Molecular methods for identification of microorganisms can be used in addition to conventional cultures especially when patients are under antibiotic treatment. Daptomycin, ceftazidime and colistin can be administered for several months without side effects. Guidelines specifically addressing the diagnosis and the management of polymicrobial, multidrug-resistant prosthetic joint infections need to be developed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Ceftazidime; Coinfection; Colistin; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Hip Prosthesis; Humans; Middle Aged; Prosthesis-Related Infections; Recurrence; Reoperation; Staphylococcal Infections; Staphylococcus epidermidis; Staphylococcus haemolyticus; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Female; Humans; Male; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Female; Humans; Male; Pneumonia, Ventilator-Associated

The aim of this study was to investigate the in vitro activities of rifampin, colistin, sulbactam and tigecycline alone and in combination against extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Twenty-five XDR-Ab strains were isolated from patients. Broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) for rifampin, colistin, sulbactam and tigecycline against XDR-Ab strains. The checkerboard microdilution method was used to determine the in vitro activities of potential therapeutic combinations of these four antimicrobial agents. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated for each of the combinations. According to our results, when tested as single drugs, rifampin, colistin or tigecycline had good bacteriostatic activity against XDR-Ab, whereas sulbactam was not as active against XDR-Ab isolates. On the other hand, when tested in combination, the combinations of colistin/rifampin, rifampin/sulbactam, rifampin/tigecycline and sulbactam/tigecycline showed good in vitro activities against XDR-Ab isolates. More importantly, these combination regimens could exert addictive or partially synergistic effects at the sub-MIC levels against XDR-Ab strains. Compared with single drugs, most of the combinations of these antimicrobial agents could exert partially synergistic and/or addictive effects, which might provide a better alternative when treating XDR-Ab infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Sulbactam; Tigecycline

Acinetobacter baumannii is one of the most important antibiotic-resistant nosocomial bacteria. We investigated changes in the clinical and molecular epidemiology of A. baumannii over a 10-year period. We compared the data from 2 prospective multicenter cohort studies in Spain, one performed in 2000 (183 patients) and one in 2010 (246 patients), which included consecutive patients infected or colonized by A. baumannii. Molecular typing was performed by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). The incidence density of A. baumannii colonization or infection increased significantly from 0.14 in 2000 to 0.52 in 2010 in medical services (p < 0.001). The number of non-nosocomial health care-associated cases increased from 1.2% to 14.2%, respectively (p < 0.001). Previous exposure to carbapenems increased in 2010 (16.9% in 2000 vs 27.3% in 2010, p = 0.03). The drugs most frequently used for definitive treatment of patients with infections were carbapenems in 2000 (45%) and colistin in 2010 (50.3%). There was molecular-typing evidence of an increase in the frequency of A. baumannii acquisition in non-intensive care unit wards in 2010 (7.6% in 2000 vs 19.2% in 2010, p = 0.01). By MSLT, the ST2 clonal group predominated and increased in 2010. This epidemic clonal group was more frequently resistant to imipenem and was associated with an increased risk of sepsis, although not with severe sepsis or mortality. Some significant changes were noted in the epidemiology of A. baumannii, which is increasingly affecting patients admitted to conventional wards and is also the cause of non-nosocomial health care-associated infections. Epidemic clones seem to combine antimicrobial resistance and the ability to spread, while maintaining their clinical virulence.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacterial Typing Techniques; Carbapenems; Cohort Studies; Colistin; Colony Count, Microbial; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Incidence; Male; Middle Aged; Spain

Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii.. The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin.. The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis.. Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii.

Topics: Acetamides; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Linezolid; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Oxazolidinones; Time Factors; Vancomycin

Acinetobacter baumannii has become a serious concern in clinical practice owing to its multiple resistance to antimicrobial agents. Tigecycline and colistin may be used as alternative therapies, although they lack practical susceptibility testing guidelines. This study assessed the reliability of commonly used methods (disc diffusion, Etest and VITEK(®) 2) for testing sensitivity to both agents compared with the reference broth microdilution (BMD) method against 290 A. baumannii clinical isolates, including multidrug-resistant isolates. For tigecycline, essential agreement and categorical agreement (CA) of minimum inhibitory concentration (MIC) testing were most correlated with BMD when using a breakpoint of susceptible (S)≤1/resistant (R)>2 mg/L; 94.8% and 84.5% (Etest) and 99.3% and 75.5% (VITEK 2), respectively. A disc diffusion zone diameter breakpoint of S≥17/R≤12 mm showed good agreement. All three methods did not show major errors or very major errors. For colistin, a BMD MIC breakpoint of S≤2/R>4 mg/L was proposed. The disc diffusion method was highly reproducible with a zone diameter breakpoint of S≥12/R≤9 mm. However, Etest results showed a different MIC range, and the MIC breakpoint should be modified to S≤0.5/R>2 mg/L, whilst a similar MIC breakpoint to BMD could be applied for VITEK 2. Both Etest and VITEK 2 showed a high CA for isolates with colistin-susceptible and -resistant results. We recommend that disc diffusion, Etest and VITEK 2 may be used with caution for testing tigecycline and colistin based on our proposed breakpoints. The reliability of individual methods will be discussed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reproducibility of Results; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Interactions; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

The purpose of our study was to share experience on demographic characteristics and clinical outcome of the patients infected with extensively drug-resistant Acinetobacter baumannii (XDRAB) in haematology clinics, focusing on the period with a sudden increase in the number of XDRAB cases. A regular patient-based infection control programme was set up in haematology clinics and haematopoietic stem cell transplant centre starting from 2008. An infection control nurse visited all patients daily. A form including demographic data and laboratory results were recorded for all patients. The source of infections was identified according to the criteria proposed by the Centers for Disease Control and Prevention. While haematology ward-acquired XRDAB was rare before 2012, between January 2012 and July 2013, 29 A. baumannii infection episodes were detected in 28 patients. All but one isolate were MDR and 72.4% (21 out of 29) were XDR. Blood cultures revealed A. baumannii in 26 out of 29 episodes. While the haematological malignancy was relapsing or not under remission in 15 patients, four patients were under remission, and 10 patients were newly diagnosed. The mortality rate was 81.2%. All patients with a poor outcome died in the first week after the index blood culture was performed. In 16 out of 29 episodes, the patients died before the culture results became available. Colistin was initiated for the treatment in 11 out of 29 episodes. Three patients received colistin combined with sulbactam or sulbactam containing beta-lactams; the remaining eight patients who received colistin monotherapy were already under carbapenems. In conclusion, XDRAB infections can easily become nightmares for haematology clinics without any reliable treatment option.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Hematology; Hospitals, Teaching; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Retrospective Studies; Sulbactam; Survival Rate; Treatment Outcome; Turkey

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii is increasing. It has a high mortality rate but experience in using inhaled colistin as monotherapy for VAP in children, especially pre-term infants, is limited. This study presents experiences using aerosolized colistin as monotherapy for VAP due to A. baumannii infection in pre-term infants.. Eight pre-term infants (gestational age 25-36 weeks) admitted to the neonatal intensive care unit (NICU) of Kaohsiung Chang Gung Memorial Hospital in Taiwan from January 2006 to December 2010 who received inhaled colistin as monotherapy for VAP due to A. baumannii infection were retrospectively evaluated. Of the isolated microorganisms, five were multi-drug resistant strains of A. baumannii (MDR-AB) but all were sensitive to colistin. All patients received inhaled colistin at a dose of 1,000,000 IU (33.4 mg) twice daily for an average of 9.1 days (range, 4-22 days).. All pre-term infants were cured, with A. baumannii eradicated from airway secretions. There were no clinical or laboratory adverse events related to colistin use.. Aerosolized colistin may be used as monotherapy for VAP due to A. baumannii infection in pre-term infants. A larger controlled study is warranted to corroborate the findings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pneumonia, Ventilator-Associated; Retrospective Studies

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Infection Control; Intensive Care Units; Male; Microbial Sensitivity Tests

We evaluated three commercial colistin susceptibility testing methods using 213 bloodstream Acinetobacter isolates identified by gene sequencing. Compared to the agar dilution reference method, excellent categorical agreements (both 99.1%) were observed using Vitek 2 and Etest, compared to 87.3% (95.7% for Acinetobacter baumannii and 80.7% for non-baumannii Acinetobacter isolates) using MicroScan.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Hospitals, University; Humans; Microbial Sensitivity Tests; Republic of Korea

Bacterial whole-genome sequencing (WGS) of human pathogens has provided unprecedented insights into the evolution of antibiotic resistance. Most studies have focused on identification of resistance mutations, leaving one to speculate on the fate of these mutants once the antibiotic selective pressure is removed. We performed WGS on longitudinal isolates of Acinetobacter baumannii from patients undergoing colistin treatment, and upon subsequent drug withdrawal. In each of the four patients, colistin resistance evolved via mutations at the pmr locus. Upon colistin withdrawal, an ancestral susceptible strain outcompeted resistant isolates in three of the four cases. In the final case, resistance was also lost, but by a compensatory inactivating mutation in the transcriptional regulator of the pmr locus. Notably, this inactivating mutation reduced the probability of reacquiring colistin resistance when subsequently challenged in vitro. On face value, these results supported an in vivo fitness cost preventing the evolution of stable colistin resistance. However, more careful analysis of WGS data identified genomic evidence for stable colistin resistance undetected by clinical microbiological assays. Transcriptional studies validated this genomic hypothesis, showing increased pmr expression of the initial isolate. Moreover, altering the environmental growth conditions of the clinical assay recapitulated the classification as colistin resistant. Additional targeted sequencing revealed that this isolate evolved undetected in a patient undergoing colistin treatment, and was then transmitted to other hospitalized patients, further demonstrating its stability in the absence of colistin. This study provides a unique window into mutational pathways taken in response to antibiotic pressure in vivo, and demonstrates the potential for genome sequence data to predict resistance phenotypes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genetic Fitness; Genome, Bacterial; Genomics; High-Throughput Nucleotide Sequencing; Humans; Microbial Sensitivity Tests; Mutation; Polymorphism, Single Nucleotide

Treatment results of six post-neurosurgical ventriculitis and meningitis cases caused by extensively drug-resistant Acinetobacter baumannii after application of an intraventricular loading dose of 500000 IU (40 mg) of colistin followed by a dose of 125000-250000 IU (10-20 mg) every 24-48 h plus parenteral colistin are reported. Simultaneous bacteraemia with an identical Acinetobacter strain was observed in three patients. The mean duration of treatment was 17.2 days (range 15-21 days) and the median time of sterilisation of cerebrospinal fluid was 2.5 days (range 1-5 days). All patients were cured, however one patient presented with chemical meningitis and one with chemical ventriculitis, conditions that clinically and biochemically resemble bacterial meningitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intraventricular; Male; Meningitis; Middle Aged; Surgical Wound Infection; Time Factors; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Rifampin

The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay.. Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods.. This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tertiary Healthcare; Tigecycline

The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. IMPORTANCE Increased use of the cationic antibiotic colistin to treat multidrug-resistant Acinetobacter baumannii has led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cathelicidins; Colistin; Drug Resistance, Bacterial; Humans; Muramidase

Serratia marcescens causes health care-associated infections with important morbidity and mortality. Particularly, outbreaks produced by multidrug-resistant isolates of this species, which is already naturally resistant to several antibiotics, including colistin, are usually described with high rates of fatal outcomes throughout the world. Thus, it is important to survey factors associated with increasing frequency and/or emergence of multidrug-resistant S. marcescens nosocomial infections. We report the investigation and control of an outbreak with 40% mortality due to multidrug-resistant S. marcescens infections that happened from November 2007 to April 2008 after treatment with colistin for Acinetobacter baumannii meningitis was started at hospital H1 in 2005. Since that year, the epidemiological pattern of frequently recovered species has changed, with an increase of S. marcescens and Proteus mirabilis infections in 2006 in concordance with a significant decrease of the numbers of P. aeruginosa and A. baumannii isolates. A single pulsed-field gel electrophoresis (PFGE) cluster of S. marcescens isolates was identified during the outbreak. When this cluster was compared with S. marcescens strains (n = 21) from 10 other hospitals (1997 to 2010), it was also identified in both sporadic and outbreak isolates circulating in 4 hospitals in Argentina. In132::ISCR1::blaCTX-M-2 was associated with the multidrug-resistant cluster with epidemic behavior when isolated from outbreaks. Standard infection control interventions interrupted transmission of this cluster even when treatment with colistin continued in several wards of hospital H1 until now. Optimizing use of colistin should be achieved simultaneously with improved infection control to prevent the emergence of species naturally resistant to colistin, such as S. marcescens and P. mirabilis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Argentina; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Hospitals; Humans; Male; Meningitis, Bacterial; Middle Aged; Molecular Epidemiology; Molecular Typing; Retrospective Studies; Serratia Infections; Serratia marcescens; Young Adult

Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Typing Techniques; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Iran; Microbial Sensitivity Tests; Minocycline; Multiplex Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prevalence; Rifampin; Sulbactam; Tertiary Healthcare; Tigecycline; Tobramycin

Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Critical Illness; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Plasma; Pneumonia, Bacterial

Colistin resistance is of concern since it is increasingly needed to treat infections caused by bacteria resistant to all other antibiotics and has been associated with poorer outcomes. Longitudinal data from in vivo series are sparse.. Under a quality-improvement directive to intensify infection-control measures, extremely drug-resistant (XDR) bacteria undergo phenotypic and molecular analysis.. Twenty-eight XDR Acinetobacter baumannii isolates were longitudinally recovered during colistin therapy. Fourteen were susceptible to colistin, and 14 were resistant to colistin. Acquisition of colistin resistance did not alter resistance to other antibiotics. Isolates had low minimum inhibitory concentrations of an investigational aminoglycoside, belonged to multi-locus sequence type 94, were indistinguishable by pulsed-field gel electrophoresis and optical mapping, and harbored a novel pmrC1A1B allele. Colistin resistance was associated with point mutations in the pmrA1 and/or pmrB genes. Additional pmrC homologs, designated eptA-1 and eptA-2, were at distant locations from the operon. Compared with colistin-susceptible isolates, colistin-resistant isolates displayed significantly enhanced expression of pmrC1A1B, eptA-1, and eptA-2; lower growth rates; and lowered fitness. Phylogenetic analysis suggested that colistin resistance emerged from a single progenitor colistin-susceptible isolate.. We provide insights into the in vivo evolution of colistin resistance in a series of XDR A. baumannii isolates recovered during therapy of infections and emphasize the importance of antibiotic stewardship and surveillance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Genotype; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Molecular Typing; Operon; Point Mutation; Transcription Factors; Wound Infection

A carbapenem-resistant Acinetobacter baumannii strain was isolated from the peritoneal fluid of a patient with complicated intra-abdominal infection and evaluated at the Multidrug-resistant Organism Repository and Surveillance Network by whole-genome sequencing and real-time PCR. The isolate was sequence type 25 and susceptible to colistin and minocycline, with low MICs of tigecycline. blaNDM-1 was located on a plasmid with >99% homology to pNDM-BJ02. The isolate carried numerous other antibiotic resistance genes, including the 16S methylase gene, armA.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; High-Throughput Nucleotide Sequencing; Honduras; Humans; Male; Methyltransferases; Minocycline; Peritonitis; Plasmids; Tigecycline

The fitness and virulence costs associated with the clinical acquisition of colistin resistance by Acinetobacter baumannii were evaluated. The growth of strain CR17 (colistin resistant) was less than that of strain CS01 (colistin susceptible) when the strains were grown in competition (72-h competition index, 0.008). In a murine sepsis model, CS01 and CR17 reached spleen concentrations when coinfecting of 9.31 and 6.97 log10 CFU/g, respectively, with an in vivo competition index of 0.016. Moreover, CS01 was more virulent than CR17 with respect to mortality and time to death.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Female; Genetic Fitness; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Sepsis; Survival Analysis; Virulence

The lack of active antimicrobial agents against multidrug-resistant (MDR) Acinetobacter baumannii has posed great threat to the public health. Combination therapies with antibiotics owning different antimicrobial mechanisms have been proposed as good options for treating MDR A. baumannii infections. This study was aimed to investigate the in vitro effects of tigecycline in combination with colistin and sulbactam against MDR A. baumannii. A total of 70 strains from two hospitals in China were examined in the study. The checkerboard method was used for determining synergistic activity of different antibiotic combinations. Tigecycline/colistin combination displayed synergistic and partial synergistic activity in 24.3% of the isolates, whereas the tigecycline/sulbactam combination showed synergistic and partial synergistic activity in 64.3% of the isolates. Neither of the combinations showed antagonism in this study. In addition, for evaluating the ability of combinations on resistance prevention, mutant prevention concentrations (MPCs) of tigecycline, colistin, sulbactam alone and tigecycline in combination with colistin and sulbactam were studied against MDR A. baumannii. Compared with tigecycline used alone, combination therapies could achieve lower MPCs of tigecycline. However, when the MPCs of dual-drug therapy were in conjunction with clinical pharmacokinetic profiles, combinations may not strictly curb the occurrence of resistance at current dosage regimen. In summary, this study suggested that combination therapy was a good option for treating MDR A. baumannii infections. But the finding that combination with these drugs at current dosage regimen may not prevent emergence of resistance warranted further studies on dosage of combined antibiotics required for achieving resistance prevention.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Sulbactam; Tigecycline

Colistin is an old antibiotic which has been used as a therapeutic option for carbapenem- and multidrug-resistant Gram-negative bacteria, like Acinetobacter baumannii. This pathogen produces life-threatening infections, mainly in patients admitted to intensive care units. Rapid detection of resistance to colistin may improve patient outcomes and prevent the spread of resistance. For this purpose, Micromax technology was evaluated in four isogenic A. baumannii strains with known mechanisms of resistance to colistin and in 66 isolates (50 susceptible and 16 resistant). Two parameters were determined, DNA fragmentation and cell wall damage. To assess DNA fragmentation, cells trapped in a microgel were incubated with a lysing solution to remove the cell wall, and the released nucleoids were visualized under fluorescence microscopy. Fragmented DNA was observed as spots that diffuse from the nucleoid. To assess cell wall integrity, cells were incubated with a lysis solution which removes only weakened cell walls, resulting in nucleoid release exclusively in affected cells. A dose-response relationship was demonstrated between colistin concentrations and the percentages of bacteria with DNA fragmentation and cell wall damage, antibiotic effects that were delayed and less frequent in resistant strains. Receiver operating characteristic (ROC) curves demonstrated that both DNA fragmentation and cell wall damage were excellent parameters for identifying resistant strains. Obtaining ≤11% of bacteria with cell wall damage after incubation with 0.5 μg/ml colistin identified resistant strains of A. baumannii with 100% sensitivity and 96% specificity. Results were obtained in 3 h 30 min. This is a simple, rapid, and accurate assay for detecting colistin resistance in A. baumannii, with strong potential value in critical clinical situations.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriolysis; Cell Wall; Chromosomes, Bacterial; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests

Despite many theoretical and in vitro advantages, clinical data comparing combination therapy with colistin + rifampicin to colistin alone for infection due to extremely-drug resistant (XDR) Acinetobacter baumanni are scarce and limited by small numbers and/or low quality evidence. This article represents the first large, randomized, controlled, prospective study comparing colistin monotherapy and combination therapy. The reviewed article found no difference in all cause or infection related mortality, though there was an improved rate of microbiological clearance in the combination therapy arm. This study adds important new data to the literature and sets the stage for future studies that can be designed to overcome the limitations of this study, which are discussed in detail below. Based on this study, we cannot say definitively that combination therapy is not warranted for treatment of invasive infection due to A. baumannii, but the results do suggest that rifampicin is not an ideal agent to be combined with colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Rifampin

Acinetobacter baumannii is the most important agent of nosocomial infections within the Acinetobacter genus. This gram-negative coccobacillus is intrinsically resistant to many antibiotics used in antimicrobial therapy, and capable of developing resistance including carbapenems. The objective of this study was to develop a multiplex real time polymerase chain reaction (qPCR) kit for OXA subgroups in A.baumannii, and to investigate the distribution of OXA subgroups in A.baumannii strains isolated from geographically different regions of Turkey. A total of 834 A.baumannii clinical isolates collected from different state and university medical centers in 13 provinces (Afyonkarahisar, Ankara, Bolu, Elazig, Erzurum, Isparta, Istanbul, Kahramanmaras, Konya, Sakarya, Van) between 2008-2011, were included in the study. The isolates were identified by conventional methods and automated systems [Vitek2 (bioMerieux, ABD) and Phoenix (BD Diagnostic, MD)]. The susceptibility profiles of the isolates were studied with automated systems and standard disc diffusion method. All samples were subjected to qPCR to detect blaOXA-51-like, blaOXA-23-like and blaOXA-58-like genes. A conventional PCR method was also used to detect blaOXA-24-like gene. The resistance rates observed during the study period were as follows: 96.8% for amoxicillin-clavulanate, 86.8% for ciprofloxacin, 74.7% for gentamicin, 71.7% for amikacin, 73.5% for cefaperozone-sulbactam, 72.1% for imipenem and 73% for meropenem. Six hundred and two (72.2 %) isolates were resistant to both imipenem and meropenem. Colistin was found to be the most effective antibiotic against A.baumannii isolates with 100% susceptibility rate. All isolates were positive for blaOXA-51-like, however blaOXA-24-like gene could not be demonstrated in any isolate. Total positivity rates of blaOXA-23-like and blaOXA-58-like genes were found as 53.7% and 12.5%, respectively, while these rates were 74.4% and 17.3% in carbapenem-resistant isolates, respectively. Twenty-five isolates were positive for both blaOXA-23-like and blaOXA-58-like genes. All of the carbapenem-resistant isolates have OXA type genes with the exception of blaOXA-24-like gene. The positivity rates for blaOXA-23-like and blaOXA-58-like genes varied for each center. In addition, there was a decrease in the frequency of blaOXA-58-like gene, however both blaOXA-23-like gene and carbapenem resistance rates increased during the study period. In conclusion, high rates of resist

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Reagent Kits, Diagnostic; Real-Time Polymerase Chain Reaction; Turkey

Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin.. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest.. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p <0.05) more frequently resistant to the other antibiotics than carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin.. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Nosocomial infection caused by carbapenem-resistant Acinetobacter baumannii is a worldwide problem and treatment options remain controversial. This study investigated the in vitro effect of various antibiotic combinations against carbapenem-resistant A. baumannii strains.. Antibiotic susceptibility of A. baumannii strains was analysed. In vitro synergistic efficacy of colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam was tested against carbapenem-resistant A. baumannii strains. Synergy studies were performed using an eplisometer test-strip method.. Of the 50 carbapenem-resistant A. baumannii strains tested, 96% were susceptible to colistin and 64% were susceptible to tigecycline. Colistin-tigecycline, colistin-cefoperazone/sulbactam and colistin-piperacillin/tazobactam combinations were found to have synergistic effects against six (12%), two (4%), and one (2%), respectively, of the strains tested.. Colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam revealed synergistic effects in some carbapenem-resistant A. baumannii strains. These results, together with the shortage of treatment options and the risk of developing resistance to colistin, suggest that clinicians should use colistin combined with other antibiotics or β-lactamase inhibitors when treating carbapenem-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Tigecycline

A potent synergy of a glycopeptide-colistin combination against Acinetobacter baumannii has recently been described. We set out to assess the efficacy and safety of this combination in a retrospective study including episodes of ventilator-associated pneumonia or bacteremia caused by carbapenem-resistant A. baumannii. We compared 29 patients (group I) treated with colistin plus vancomycin with 28 patients treated with colistin alone (group II). Group I received vancomycin (for empirical or targeted therapy) at the onset of colistin administration and both antimicrobials coincided for at least 5 days. Baseline characteristics, clinical cure, microbiological eradication, and mortality were similar in both groups but the rate of acute kidney injury was higher in group I (55.2 vs. 28%; p = 0.04). In critically ill patients with carbapenem-resistant A. baumannii infections, clinical outcomes do not differ in patients treated with colistin plus vancomycin from those receiving colistin without vancomycin. This combination significantly increases the risk of renal failure.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Middle Aged; Renal Insufficiency; Retrospective Studies; Treatment Outcome; Vancomycin

In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice.. Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points.. Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone.. These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Sulbactam; Tigecycline; Time Factors

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Child; Colistin; Drug Resistance, Multiple, Bacterial; Germany; Humans; Infusions, Intravenous; Intensive Care Units, Pediatric; Male; Pneumonia, Bacterial; Religion and Medicine; Russia; Seizures, Febrile; Water Microbiology

We compare the whole-genome sequences of two multidrug-resistant clinical Acinetobacter baumannii isolates recovered in the same patient before (ABIsac_ColiS susceptible to colistin and rifampin only) and after (ABIsac_ColiR resistant to colistin and rifampin) treatment with colistin and rifampin. We decipher all the molecular mechanisms of antibiotic resistance, and we found mutations in the rpoB gene and in the PmrAB two-component system explaining resistance to rifampin and colistin in ABIsac_ColiR, respectively.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Chromosomes, Bacterial; Colistin; Drug Resistance, Multiple, Bacterial; France; High-Throughput Nucleotide Sequencing; Humans; Rifampin; Sequence Analysis, DNA; Transcription Factors

Acinetobacter baumannii is a leading cause of multidrug-resistant infections worldwide. This organism poses a particular challenge due to its ability to acquire resistance to new antibiotics through adaptation or mutation. This study was undertaken to determine the mechanisms governing the adaptability of A. baumannii to the antibiotic colistin. Screening of a transposon mutant library identified over 30 genes involved in inducible colistin resistance in A. baumannii. One of the genes identified was lpsB, which encodes a glycosyltransferase involved in lipopolysaccharide (LPS) synthesis. We demonstrate that loss of LpsB function results in increased sensitivity to both colistin and cationic antimicrobial peptides of the innate immune system. Moreover, LpsB is critical for pathogenesis in a pulmonary model of infection. Taken together, these data define bacterial processes required for intrinsic colistin tolerance in A. baumannii and underscore the importance of outer membrane structure in both antibiotic resistance and the pathogenesis of A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Glycosyltransferases; Immune Tolerance; Immunity, Innate; Lipopolysaccharides; Lung; Mannosyltransferases; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Mutation; Pneumonia

Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug resistance and the lack of novel agents. There is now considerable interest in the potential of unorthodox combination therapies such as colistin and glycopeptides (e.g. vancomycin and teicoplanin), since potent synergy can be demonstrated in vitro. A simple invertebrate model (Galleria mellonella) has been developed to assess the in vivo activity of antimicrobial therapies and was used to investigate the efficacy of colistin combined with the lipoglycopeptide telavancin in the treatment of A. baumannii infection. Galleria mellonella larvae were inoculated with 10⁵ CFU/larvae of A. baumannii type strain ATCC 19606 or the multidrug-resistant clinical isolate AB210. Infected caterpillars were treated with either telavancin (10 mg/kg), colistin (2.5 mg/kg) or a telavancin/colistin combination. Larvae were incubated at 37 °C for up to 96 h and were scored daily. Survival curves were plotted and analysed using the log-rank test. The telavancin/colistin combination was effective in the treatment of larvae infected with both strains but was superior to colistin monotherapy in the treatment of A. baumannii AB210 (P<0.001). The combination of telavancin and colistin was effective in a simple invertebrate model of A. baumannii infection. This is in agreement with a previous in vitro study and provides preliminary in vivo evidence that such a combination might be useful therapeutically.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Therapy, Combination; Larva; Lepidoptera; Lipoglycopeptides; Survival Analysis; Treatment Outcome

The increasing emergence of multi-drug resistant Acinetobacter baumannii strains as nosocomial pathogens lead to the use of antimicrobial combinations in the treatment of infections due to these bacteria. The aim of this study was to determine the MIC values of colistin and ampicillin/sulbactam and their in vitro synergistic activities by E-test in order to evaluate the effect of this combination against imipenem-resistant A.baumannii isolates. A total of 33 A.baumannii strains isolated from clinical specimens as etiologic agents of nosocomial infections and identified as imipenem-resistant were included in the study. Identification of the isolates was performed by conventional methods and their imipenem resistance was detected with BD Phoenix automated system (Becton Dickinson, USA). MIC values and in vitro synergistic activity of colistin and ampicillin/sulbactam combination were analyzed by E-test (AB Biodisk, Sweden) on Mueller-Hinton agar medium. Synergistic, additive, indifferent and antagonist effects of A.baumannii strains were evaluated by fractional inhibitory concentration (FIC) index. The combination was considered to be synergistic when the FIC index was ≤ 0.5, additive when it was 1- > 0.5 and antagonistic when ≥ 2. Of the 33 strains included in the study, 21 were resistant to colistin; 30 were resistant and 3 were moderately susceptible to ampicillin/sulbactam. MIC50 and MIC90 values and MIC range of A.baumannii strains for colistin were 8, 32 and 0.13-128 µg/ml; for ampicillin/sulbactam those values were 48, 256 and 12-256 µg/ml, respectively. According to the FIC indices, 15 strains showed synergistic, four additive, five indifferent and nine antagonistic activity to colistin and ampicillin/sulbactam combination. Among the 12 colistin-susceptible strains, nine showed antagonistic, two indifferent and one synergistic activity to the tested combination while among the 21 colistin-resistant strains 14 showed synergistic, four additive and three indifferent activity. As a result, the combination of colistin with ampicillin/sulbactam, demonstrated high synergistic activity in vitro. While the synergistic effect of this combination was more significant in colistin-resistant strains, antagonistic effect of colistin-susceptible strains was found to be notable. Therefore, colistin resistance should be primarily determined before using colistin and ampicillin/sulbactam combination in A.baumannii infections since this combination seemed to be more e

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Sulbactam

This study aimed to address the relationship between the timing of colistin therapy and the outcome, defined as all-cause mortality in the intensive care unit (ICU). A retrospective study was undertaken in a 16-bed ICU of a 750-bed tertiary care hospital. A total of 46 patients who had been administered intravenous colistin treatment for colistin-susceptible-only Acinetobacter infections were included in the study. Colistin treatment was initiated in 26 (56.5 %) patients within 24 h of the diagnosis (early administration of colistin), whereas the rest of the patients had obtained delayed treatment (delayed administration of colistin). Of the 46 patients, 21 (45.6 %) died. With univariate analysis, age, age greater than 65 years, APACHE II score more than 20 at baseline, and delayed administration of colistin were found to be significant (p < 0.05). Logistic regression analysis revealed a significant association between delayed administration of colistin [adjusted odds ratio (OR), 5.06; confidence interval (CI), 1.18-21.67], and adverse outcome. Other variables included in the final model were underlying disease (OR, 2.81; CI, 1.15-6.84) and APACHE II score at baseline >20 (OR, 3.81; CI, 0.77-18.75). This study found that delayed administration of colistin and underlying disease were independently associated with adverse outcome.

Topics: Acinetobacter Infections; Adult; Aged; Analysis of Variance; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

The study aim was to describe the emergence of carbapenem resistance and clonal complexes (CC), defined by multilocus sequence typing (MLST), in Acinetobacter baumannii in a surveillance system for meningitis. Starting in 1996 in an urban setting of Brazil, surveillance detected meningitis by Acinetobacter sp for the first time in 2002. Up to 2008, 35 isolates were saved. Carbapenem resistance emerged in 2006, reaching 70% of A. baumannii isolates in 2008, including one that was colistin resistant. A. baumannii belonged to CC113/79 (University of Oxford/Institute Pasteur schemes), CC235/162 and CC103/15. Dissemination of infections resistant to all antimicrobial agents may occur in the future.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Brazil; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Female; Humans; Male; Meningitis, Bacterial; Middle Aged; Molecular Epidemiology; Multilocus Sequence Typing; Urban Population; Young Adult

At present, colistin is among the few antibiotics effective against Acinetobacter baumannii clinical isolates. However, in the last few years, colistin-resistant A. baumannii strains have been isolated. Therefore, antibiotics effective against these usually pan-resistant colistin-resistant A. baumannii strains are required. The main objective of this study was to analyse the activity of 15 peptides against colistin-susceptible and colistin-resistant A. baumannii. The MICs were determined by microdilution. Among these 15 antimicrobial peptides (AMPs), melittin, indolicidin and mastoparan showed good activity against both colistin-susceptible and colistin-resistant A. baumannii. Further studies of mastoparan with time-killing curves showed bactericidal activity at MIC ×8 for both colistin-susceptible and colistin-resistant A. baumannii. In conclusion, mastoparan may be a potential alternative for the treatment of colistin-resistant A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Sequence; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Drug Resistance, Bacterial; Inhibitory Concentration 50; Intercellular Signaling Peptides and Proteins; Melitten; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides; Time Factors; Wasp Venoms

Multidrug-resistant (MDR) gram-negative bacteria-related nosocomial infections and ventilator-associated pneumonia (VAP) presents an emerging challenge to clinicians. Older antimicrobial agents such as colistin have become life-saving drugs because of the susceptibility of these pathogens. We report our experience with aerosolized colistin in two preterm and one term neonate with Acinetobacter baumannii and Pseudomonas aeruginosa-related VAP who were unresponsiveness to previous antimicrobial treatment. All pathogens were isolated from tracheal aspirate. We used 5 mg/kg (base activity) aerosolized colistin methanesulfonate sodium in every 12 h as an adjunctive therapy for VAP. VAP was treated by 14, 14, and 16-day courses of aerosolized colistin in these patients, respectively. No adverse effect such as nephrotoxicity or neurotoxicity was observed. We found that aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. Further studies are needed to determine appropriate doses for aerosolized colistin and its eligibility as an alternative treatment choice in newborns.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Acinetobacter species are well-known causes of health care-associated infections. The longitudinal epidemiology of this species in the hospital setting is poorly understood. A sudden, persistent increase in multidrug-resistant (MDR) A baumannii infections occurred beginning in June 2006 at Temple University Hospital in Philadelphia. An analysis was done to describe the longitudinal molecular epidemiology of MDR A baumannii in a tertiary care hospital.. This was an epidemiologic investigation using repetitive extragenic palindromic-PCR (rep-PCR) of patients with a positive culture for MDR A baumannii admitted to the hospital between February 2006 and January 2010. MDR A baumannii were defined as susceptible only to colistin and/or tigecycline.. The incidence rate of MDR A baumannii rose from 0.36 cases per 1,000 patient-days (pre-epidemic) to 0.86 cases per 1,000 patient-days, due mainly to an increase in the surgical intensive care unit. Enhanced infection control measures were implemented, but waves of MDR A baumannii continued to be documented through routine surveillance. Of 32 strains collected in 2006-2007, a single predominant clone and 2 minor clones accounted for almost all of the cases of MDR A baumannii studied. Of 24 strains collected in 2008-2009, another clone, different from those studied in the earlier period, predominated, and was accompanied by 3 minor variants.. Following an outbreak in the surgical intensive care unit, MDR A baumannii persisted in our institution for a 3-year period despite rigorous infection control measures. An unexpected strain replacement occurred during this period, with the original predominant strain disappearing completely and new minor clones displacing the original minor clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Incidence; Intensive Care Units; Longitudinal Studies; Minocycline; Philadelphia; Polymerase Chain Reaction; Tigecycline

To assess the therapeutic effect and toxicity of intravenous colistin in the treatment of multidrug-resistant (MDR) Gram-negative bacteria in patients with severe burns.. The medical records of 930 patients admitted to the Burn Intensive Care Unit (ICU) at Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea between April 2007 and December 2009 were retrospectively reviewed. Of these, the 104 patients who had received intravenous colistin treatments (104 courses) during this period were enrolled in the study. Changes in creatinine level were analyzed in three groups: all patients receiving colistin (n = 104), patients with undergoing continuous renal replacement therapy (CRRT group; n = 38), and patients not undergoing CRRT (non-CRRT group; n = 66).. Among these patients, the burnt body surface area ranged from 5 to 96% (mean 49.7%). Thirty-five patients (33.7%) suffered inhalation injury, and CRRT was administered to 38 patients. The mean duration of colistin treatment was 14.7 (range 4-71) days. The total dose of colistin was 3,045.7 mg (range 100-13,800). The length of ICU stay was 48.9 (range 7-154) days. Forty patients (38.5%) died. The mean pre-colistin creatinine level of all patients was 1.04 mg/dL, and the mean post-colistin level was 1.34 mg/dL. The mean pre-colistin creatinine level of the CRRT group and non-CRRT group was 1.68 and 0.66 mg/dL, and the mean post-colistin level was 1.68 and 1.14 mg/dL, respectively.. Colistin appears to be a relatively safe and effective treatment for major burn patients with infections caused by MDR Gram-negative bacteria when no other drug is available. Additionally, we found no statistically significant impairment of creatinine levels.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged, 80 and over; Anti-Bacterial Agents; Burn Units; Burns; Child; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Female; Humans; Length of Stay; Male; Middle Aged; Pseudomonas; Pseudomonas Infections; Renal Replacement Therapy; Republic of Korea; Retrospective Studies; Young Adult

Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥ 3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26-6302.18, p <0.001), and shortened the duration of MDRAB recovery from the respiratory tract by 13.3 ± 1.45 days. The adverse effects were similar for both groups. The increase of colistin minimal inhibitory concentrations in the last isolate compared with the index isolate from the same patient did not differ between the two groups. In conclusion, our study demonstrated that inhaled CMS enhanced the eradication of MDRAB from the respiratory tract without significant clinical adverse effect or impact on colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Statistics, Nonparametric; Taiwan

The emergence of colistin or tigecycline resistance as well as imipenem resistance in Acinetobacter baumannii poses a great therapeutic challenge. The bactericidal and synergistic effects of several combinations of antimicrobial agents against imipenem-, colistin- or tigecycline-resistant A. baumannii isolates were investigated by in vitro time-kill experiments. Six imipenem-resistant A. baumannii blood isolates were examined in this study, including colistin- and tigecycline-susceptible, colistin-resistant but tigecycline-susceptible, and colistin-susceptible but tigecycline-resistant isolates. Time-kill studies were performed using five antimicrobial agents singly or in combinations (imipenem plus colistin, imipenem plus ampicillin-sulbactam, colistin plus rifampicin, colistin plus tigecycline, and tigecycline plus rifampicin) at concentrations of 0.5× and 1× their MICs. Only imipenem was consistently effective as a single agent against all six A. baumannii isolates. Although the effectiveness of combinations of 0.5× MIC antimicrobial agents was inconsistent, combination regimens using 1× MIC of the antimicrobial agents displayed excellent bactericidal activities against all six A. baumannii isolates. Among the combinations of 0.5× MIC antimicrobial agents, the combination of colistin and tigecycline showed synergistic or bactericidal effects against four of the isolates. This in vitro time-kill analysis suggests that antimicrobial combinations are effective for killing imipenem-resistant A. baumannii isolates, even if they are simultaneously resistant to either colistin or tigecycline. However, the finding that the combinations of 0.5× MIC antimicrobial agents were effective on only some isolates may warrant further investigation of the doses of combination agents needed to kill resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Blood; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline; Time Factors

We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971-4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface.

Topics: Acetylglucosamine; Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Secretion Systems; Biological Transport; Colistin; Drug Resistance, Bacterial; Fimbriae Proteins; Gene Expression Profiling; Gene Expression Regulation, Bacterial; High-Throughput Nucleotide Sequencing; Lipopolysaccharides; Lipoproteins; Mutation; Phospholipids

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans

The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).. A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 10⁷ colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined.. A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs.. Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Disease; Animals; Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Cytokines; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Female; Imipenem; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia, Bacterial; Stem Cells; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; France; Humans; Microbial Sensitivity Tests; Sulbactam

This study was conducted to investigate the molecular epidemiology and antimicrobial susceptibility of multidrug-resistant (MDR) Acinetobacter baumannii to three types of antibiotics.. One hundred and thirty-four specimens of MDR A baumannii were collected from three branches (Taipei, Dalin, and Hualien branches) of Buddhist Tzu Chi Hospital, which are located in northern, southern, and eastern Taiwan, during 2007. Genotyping was performed by pulsed-field gel electrophoresis. Antibiotic susceptibilities to colistin, rifampicin, and tigecycline were determined. The synergistic effects of rifampin and colistin were also evaluated.. Antibiotic susceptibility testing showed that 10.4%, 47.8% and 45.5% of the MDR A baumannii isolates are resistant to colistin, rifampicin, and tigecycline, respectively. A majority of the rifampicin-resistant isolates (62.7%) were found in the Haulien branch, whereas 62.2% of tigecycline-resistant isolates were found in the Taipei branch. The combination of colistin and rifampicin had a synergistic effect on all of the isolates. Genotyping by pulsed-field gel electrophoresis identified 17, 23, and 11 pulsotypes in the Taipei, Dalin, and Haulien branches, respectively. Furthermore, 74.5% of isolates in the Haulien branch were identified as one of three pulsotypes. Among 37 rifampicin-resistant and 22 tigecycline-resistant MDR A baumannii isolates found in the Haulien branch, 51.3% (19/37) and 50% (11/22) of the isolates belonged to the same clone, respectively.. This study confirms the high prevalence of resistance to rifampicin and tigecycline in MDR A baumannii in the three hospitals that were studied, and the high proportion of identical strains that exist in eastern Taiwan.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cluster Analysis; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Molecular Typing; Prevalence; Rifampin; Taiwan; Tigecycline

We report a case of post-neurosurgical meningitis, subdural empyema, and cerebral abscess caused by multidrug-resistant Acinetobacter baumannii (MRAB) poorly susceptible to colistin. A 49-year-old man was transferred to our hospital after surgical treatment for putaminal hemorrhage in a foreign country hospital. Several examinations revealed surgical site infection (SSI). From cerebro-spinal fluid examination via ventricular drainage, MRAB was recovered. The minimum inhibitory concentration (MIC) of colistin was 2 µg/mL. Intravenous administration of colistin with ceftazidime and rifampicin was started, with intrathecal colistin administration, based on the results of a Break-point Checkerboard examination, and resulted in effective infection control. Nosocomial infection by MRAB has become an emergent problem in many countries. In Japan, several outbreak accidents caused by MRAB have been reported so far. In this case, genetic analysis revealed that the pathogen had originated from a foreign country, and the prevalence of colistin-resistant pathogens has also increased in these countries. Besides adequate isolation precautions, strategies for post-neurosurgical SSI management and establishment of effective treatments are necessary against neurosurgical SSIs caused by colistin-resistant MRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Brain Abscess; China; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged; Surgical Wound Infection; Travel

Macrophage activation syndrome (MAS) is a systemic disorder with a high mortality, commonly associated with rheumatological conditions, but which can also occur as a complication of several infections. Here we present a case of MAS following Acinetobacter baumannii sepsis. Early institution of therapy with prednisolone, cyclosporine, colistin, and polymyxin resulted in a prompt clinical recovery. There are very few reported cases of Acinetobacter-related MAS that have been successfully treated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Cyclosporine; Drug Resistance, Multiple, Bacterial; Humans; Macrophage Activation Syndrome; Male; Polymyxins; Prednisolone; Sepsis

This study describes and analyzes Acinetobacter baumannii antibiotic susceptibly profile in Aleppo, Syria, thus providing vital information for guiding treatment of A baumannii infections. Two hundred sixty nonrepetitive A baumannii isolates were studied over 3.5 years. Resistance rates are at the higher end of globally reported levels. Newer cephalosporins and β-lactamase-resistant agents are becoming practically ineffective. Better activity is limited to carbapenems and colistin, which elicited the highest susceptibility levels.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Prevalence; Respiratory Tract Infections; Retrospective Studies; Syria; Urinary Tract Infections; Young Adult

Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes.. To assess outcomes associated with AAA for the treatment of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) VAP.. A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009 were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA).. Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n = 9, inhaled tobramycin n = 10). Patients receiving AAA were significantly more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P < .001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P < .001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P = .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test).. Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage; Colistin; Comorbidity; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Statistics, Nonparametric; Survival Rate; Tobramycin; Treatment Outcome

Extremely drug-resistant (XDR; i.e. resistant to all antibiotics except colistin or tigecycline) Acinetobacter baumannii has emerged as one of the most common and highly antibiotic-resistant causes of infection. Diabetes is a risk factor for acquisition of and worse outcomes from A. baumannii infection. We sought to develop diabetic mouse models of A. baumannii bacteraemia and pneumonia and validate these models by comparing the efficacy of antibiotic treatment in these models with the established neutropenic mouse models.. Diabetic or neutropenic mice were infected via intravenous inoculation or inhalation in an aerosol chamber with an XDR A. baumannii. Treatment with colistin started 24 h after infection and continued daily for 7 days. Survival served as the primary endpoint while tissue bacterial burden and histopathological examination served as secondary endpoints.. Lethal infection was achieved for the neutropenic and diabetic mice when infected intravenously or via inhalation. Neutropenic mice were more susceptible to infection than diabetic mice in the pneumonia model and equally susceptible in the bacteraemia model. Both models of bacteraemia were sensitive enough to detect virulence differences among different clinical strains of A. baumannii. In the pneumonia model, colistin treatment was effective in improving survival, reducing lung bacterial burden and histologically resolving the infection compared with placebo only in diabetic mice.. We developed novel models of A. baumannii bacteraemia and pneumonia in diabetic mice. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies and evaluate drug efficacies against highly lethal A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Colistin; Diabetes Complications; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Histocytochemistry; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Pneumonia, Bacterial; Survival Analysis; Treatment Outcome

Therapeutic options are limited for infections because of Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae (CRE). Study aim was to compare the efficacy of colistin to tigecycline for the treatment of these types of infections.. A retrospective study was conducted at the Detroit Medical Center. Adult patients with infections because of A baumannii or CRE in 2009 who received ≥2 doses of colistin or tigecycline were studied. Risk factors, outcomes, and costs were analyzed.. There were 82 patients with infections because of A baumannii, 12 with CRE, and 12 with A baumannii and CRE coinfection. Seventy-one patients received colistin, 16 received tigecycline, and 19 received both colistin and tigecycline. Seven isolates were nonsusceptible to colistin and 79 to tigecycline. Patients receiving colistin alone or in combination were more likely to die during their hospitalization than patients receiving only tigecycline (P = .002). However, patients receiving colistin had higher severity of acute illness and had notable delays in initiation of effective antimicrobial therapy (P < .001).. Compared with patients who received tigecycline alone, patients who received colistin alone or in combination had a higher severity of acute illness indices and delays in initiation of effective therapy. This increased severity of illness contributed to the increased rate of mortality among patients treated with colistin for A baumannii or CRE infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Cohort Studies; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Michigan; Middle Aged; Minocycline; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tigecycline; Treatment Outcome

In this study we aimed to assess the safety and efficacy of high-dose IV colistin (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator-associated pneumonia (VAP). Critically ill adult patients who received IV COL for multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of 45 patients were evaluated [15 patients with high-dose COL (2.5 mg/kg every 6 h), 20 patients with normal dose (2.5 mg/kg every 12 h), and 10 patients with low dose, determined according to creatine clearance]. Aerosolized COL was used in 29 patients treated with parenteral COL and 16 patients received only parenteral COL. The clinical response rates on the fifth day were 50, 30, and 27 % with the normal, low, and high doses, respectively. However, the clinical response rates at the end of the therapy had declined to 30, 30, and 7 % with the normal, low, and high doses, respectively. The bacteriological clearance rates at the end of the therapy were 65, 75, and 64 %, with the normal, low, and high doses, respectively. With the aerosolized COL, the clinical response rates on the fifth day and at the end of the therapy were 35 and 14 %, whereas these rates were 44 and 38 % without the aerosolized COL. Bacteriological clearance rates with and without the aerosolized COL were 76 and 69 %, respectively. The nephrotoxicity rate was 40 % for the high-dose COL, whereas it was 35 % for the normal dose, and 20 % for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL had no advantages over lower doses in alleviating multidrug-resistant A. baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the nephrotoxicity risk and seemed not to be safe.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Adult; Aerosols; Aged; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Statistics, Nonparametric; Turkey

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t(1/2λ)) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (C(trough)) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Central Nervous System Bacterial Infections; Colistin; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Injections, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

Multiple transposons, integrons and carbapenemases were found in Klebsiella pneumoniae colistin-resistant isolates as well as a genomic resistance island of the AbaR type in Acinetobacter baumannii colistin-resistant isolates from different hospitals from Buenos Aires City. PFGE analysis showed a polyclonal dissemination of antimicrobial resistance mechanisms among K. pneumoniae isolates, while in A. baumannii isolates the epidemic clone 1 from South America was found. Resistance determinants associated with horizontal gene transfer are contributing to the evolution to pandrug resistance in both epidemic and sporadic clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; Colistin; Cross Infection; DNA Transposable Elements; Drug Resistance, Bacterial; Epidemics; Gene Expression Regulation, Bacterial; Hospitals; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; South America

Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a common problem around the world, especially in Intensive Care Units. The aim of this study was to investigate the efficacy and safety of colistin therapy in paediatric patients with severe nosocomial infections caused by MDR Gram-negative bacteria. There were 87 episodes in 79 paediatric Intensive Care Unit patients in five different hospitals; each patient was treated intravenously with colistin and evaluated. Of the 79 patients, 54.4% were male and the median age was 30 months. The most commonly isolated microorganism was Acinetobacter baumannii, the most common isolation site was tracheal aspirate fluid and the most common type of infection was ventilator-associated pneumonia. The mean colistin dose in patients without renal failure was 5.4 ± 0.6 mg/kg/day, the mean therapy duration was 17.2 ± 8.4 days and the favourable outcome rate was 83.9%. Serious side effects were seen in four patient episodes (4.6%) during therapy; two patients suffered renal failure and the others had convulsive seizures. Other patients tolerated the drug well. The infection-related mortality rate was 11.5% and the probability of death within the first 9 days of treatment was 10 times higher than after the first 9 days. In conclusion, this study suggests that colistin is effective in the treatment of severe nosocomial infections caused by MDR Gram-negative bacteria and is generally well tolerated by patients, even after relatively long-term use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Child; Child, Preschool; Colistin; Cross Infection; Drug Administration Schedule; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Insufficiency; Retrospective Studies; Seizures; Time Factors; Treatment Outcome

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Lung; Minocycline; Pneumonia, Bacterial; Rats; Rats, Wistar; Tigecycline; Time Factors; Treatment Outcome

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Tobramycin

Acinetobacter baumannii is an opportunistic pathogen that is a cause of clinically significant nosocomial infections. Increasingly, clinical isolates of A. baumannii are extensively resistant to numerous antibiotics, and the use of polymyxin antibiotics against these infections is often the final treatment option. Historically, the polymyxins have been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism based on data demonstrating that polymyxins induce rapid cell death through hydroxyl radical production. Supporting this notion, we found that inhibition of radical production delays the ability of polymyxins to kill A. baumannii. Notably, we demonstrate that this mechanism of killing occurs in multidrug-resistant clinical isolates of A. baumannii and that this response is not induced in a polymyxin-resistant isolate. This study is the first to demonstrate that polymyxins induce rapid killing of A. baumannii and other Gram-negatives through hydroxyl radical production. This significantly augments our understanding of the mechanism of polymyxin action, which is critical knowledge toward the development of adjunctive therapies, particularly given the increasing necessity for treatment with these antibiotics in the clinical setting.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Free Radical Scavengers; Humans; Hydroxyl Radical; Microbial Sensitivity Tests; Microbial Viability; Polymyxin B

Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO(3))(3), the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO(3))(3) delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO(3))(3) activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO(3))(3) also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO(3))(3) inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO(3))(3) also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gallium; Humans; Inhibitory Concentration 50; Iron; Larva; Moths; Repressor Proteins

Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.. One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to β-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer.. After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference -1%, lower limit of 95% CI for difference -12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients.. Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous β-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Acinetobacter baumannii is an emerging gram-negative nosocomial pathogen that rarely causes infections in orthopaedic patients. We report a case of imipenem-resistant Acinetobacter baumannii paraarticular infection of the knee occurring in a healthy patient following one ambulatory steroid injection for the treatment of quadriceps tendinopathy. The infection was reduced by early surgical debridement of infected tissues, abscess drainage, and prolonged antibiotic therapy with colistin. To our knowledge, this is the first case in the literature reporting such an infection following single steroid injection in orthopaedic patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Cross Infection; Debridement; Drainage; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Injections, Intra-Articular; Knee Joint; Magnetic Resonance Imaging; Microbial Sensitivity Tests; Steroids; Tendinopathy; Treatment Outcome

Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients.. A retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence.. XDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p=0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p=0.01; odds ratio=7.88 [95% CI: 1.60-38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p=0.03).. XDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Retrospective Studies; Transplants; Young Adult

Infections caused by extensive drug-resistant Acinetobacter baumannii (XDR-AB) have been increasingly observed and are associated with a high mortality rate. We present our experience using aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) due to XDR-AB in neonates.. The clinical data of neonates who received aerosolized 4 mg per kg of colistin base twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008 and September 2009 were retrospectively reviewed. The outcomes were compared with the neonates with VAP from XDR-AB in October 2006-September 2007 who did not receive aerosolized colistin.. During the study period, eight neonates (three preterm and five term neonates) with VAP caused by XDR-AB received aerosolized colistin. All isolated pathogens from the tracheobronchial specimens of the eight patients were XDR-AB susceptible to colistin only. Six patients received aerosolized colistin without concomitant intravenous colistin. All children were cured with eradication of XDR-AB from respiratory secretions. Seven patients survived and were discharged from the hospital, and one died from bacterial sepsis unrelated to the VAP episode. There were no clinical or laboratory adverse events related to aerosolized colistin. Compared to the seven neonates in the earlier period, the neonates who received aerosolized colistin had higher birth weight and gestational age, and lower mortality rate (13% vs. 71%, P=0.04).. Aerosolized colistin may be a useful adjunctive therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should be investigated in a larger controlled study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Bacteremia; Birth Weight; Colistin; Drug Resistance, Bacterial; Female; Gestational Age; Humans; Infant, Newborn; Male; Pneumonia, Ventilator-Associated; Retrospective Studies; Thailand; Treatment Outcome

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Europe; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Piperacillin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Quinolones; Respiration, Artificial; Severity of Illness Index; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Encephalitis; Female; Humans; Lateral Ventricles; Male

electrostatic forces mediate the initial interaction between cationic colistin and Gram-negative bacterial cells. Lipopolysaccharide (LPS) loss mediates colistin resistance in some A. baumannii strains. Our aim was to determine the surface charge of colistin-susceptible and -resistant A. baumannii as a function of growth phase and in response to polymyxin treatment.. the zeta potential of A. baumannii ATCC 19606 and 10 clinical multidrug-resistant strains (MICs 0.5-2 mg/L) was assessed. Colistin-resistant derivatives (MIC >128 mg/L) of wild-type strains were selected in the presence of 10 mg/L colistin, including the LPS-deficient lpxA mutant, ATCC 19606R. To determine the contribution of LPS to surface charge, two complemented ATCC 19606R derivatives were examined, namely ATCC 19606R + lpxA (containing an intact lpxA gene) and ATCC 19606R + V (containing empty vector). Investigations were conducted as a function of growth phase and polymyxin treatment (1, 4 and 8 mg/L).. wild-type cells exhibited a greater negative charge (-60.5  ±  2.36 to -26.2  ±  2.56 mV) thancolistin-resistant cells (-49.2  ±  3.09 to -19.1  ±  2.80 mV) at mid-log phase (ANOVA, P  <  0.05). Opposing growth-phase trends were observed for both phenotypes: wild-type cells displayed reduced negative charge and colistin-resistant cells displayed increased negative charge at stationary compared with mid-logarithmic phase. Polymyxin exposure resulted in a concentration-dependent increase in zeta potential. Examination of ATCC 19606R and complemented strains supported the importance of LPS in determining surface charge, suggesting a potential mechanism of colistin resistance.. zeta potential differences between A. baumannii phenotypes probably reflect compositional outer-membrane variations that impact the electrostatic component of colistin activity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Electricity; Genes, Bacterial; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Mutation; Static Electricity

Acinetobacter baumannii (American Type Culture Collection strain 19606) acquires mutations in the pmrB gene during the in vitro development of resistance to colistin. The colistin-resistant strain has lower affinity for colistin, reduced in vivo fitness (competition index, .016), and decreased virulence, both in terms of mortality (0% lethal dose, 6.9 vs 4.9 log colony-forming units) and survival in a mouse model of peritoneal sepsis. These results may explain the low incidence and dissemination of colistin resistance in A. baumannii in clinical settings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Mice; Mice, Inbred C57BL; Mutation; Peritonitis; Sepsis; Survival Analysis; Transcription Factors; Virulence

Extensively drug-resistant (XDR) Acinetobacter baumannii infections caused 91% (10/11) mortality in transplant recipients. Isolates were colistin-susceptible initially, but susceptibility decreased during therapy in 40% (4/10). We tested antibiotic combinations against XDR Acinetobacter in vitro and demonstrated positive interactions for carbapenem-colistin. Subsequently, 80% (4/5) of transplant patients were treated successfully with carbepenem-colistin regimens.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Organ Transplantation; Transplantation; Treatment Outcome

Antimicrobial treatment of multidrug-resistant Acinetobacter baumannii (MDRAB) remains an important therapeutic challenge. With isolates resistant to all conventional agents now reported, clinicians are increasingly forced to turn to unorthodox combination treatments in the hope that these may be efficacious. Although a potent interaction between vancomycin and colistin has been demonstrated, there are concerns regarding the inherent toxicity of combining these agents in clinical practice. As teicoplanin has less nephrotoxic potential than vancomycin, we assessed whether a colistin/teicoplanin combination would have similar antimicrobial activities in vitro.. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed versus a collection of MDRAB belonging to a number of epidemic lineages present in the UK. Synergy studies were undertaken using microtitre plate chequerboard assays, an Etest agar dilution method and standard time-kill methodology.. The combination of teicoplanin and colistin was bactericidal versus all of the strains tested. In chequerboard assays, fractional inhibitory concentration indices of <0.5 were obtained, consistent with significant in vitro synergy. Using the Etest method the MIC of teicoplanin fell from >256 mg/L to ≤2 mg/L in the presence of subinhibitory concentrations of colistin.. Significant synergy was observed when colistin was combined with teicoplanin versus MDRAB in vitro. This may represent a useful therapeutic combination for the treatment of A. baumannii infections, especially when renal toxicity is a significant concern.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Microbial Viability; Teicoplanin; United Kingdom

Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with multidrug resistant (MDR) Acinetobacter species bloodstream infection and who were treated with or without colistin as part of their regimen. The colistin group was given colistin as part of therapy once colistin became available in 2006. The non-colistin group was derived from the patients who were treated with other antimicrobial regimens before 2006. Mortality within 30 days of the onset of bacteremia occurred for 11 of 31 patients in the colistin group and for 15 of 39 patients in the non-colistin group (35.5% vs 38.5%, respectively, P = 0.80). Renal dysfunction developed in 50.0% of the 20 evaluable patients in the colistin group, but in 28.6% of the 35 evaluable patients in the non-colistin group (P = 0.11). On multivariate analysis, only an Acute Physiological and Chronic Health Evaluation II score ≥ 21 was associated with mortality at 30 days. This result suggests that administering colistin, although it is the sole microbiologically appropriate agent, does not influence the 30 day mortality of patients with a MDR Acinetobacter spp. bloodstream infection.

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacteremia; Child; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Republic of Korea; Retrospective Studies; Risk; Treatment Outcome

To analyze the efficacy of nebulized colistin in the microbiological eradication and clinical improvement of patients with pulmonary infection by multi-resistant Acinetobacter baumannii (MAB).. A retrospective study.. Intensive Care Unit of a Tertiary hospital.. Hospitalized patients on invasive mechanical ventilation with positive MAB cultures of the airway.. All received treatment with colistin (CL). Nosocomial pneumonia (NP) or Tracheobronchitis (TB) was determined according to routine criteria and colonization (CO) was determined in the case of a positive culture in the absence of infection criteria. Three groups of patients were defined: those treated with nebulized CL, those treated with IV CL and those treated with IV CL plus nebulized CL.. Baseline characteristics. Microbiological eradication and clinical recovery were evaluated according to routine criteria.. 83 patients were studied, 54 of whom were treated, with the following diagnoses: 15 (27.8%) with NP, 16 (29.6%) with TB and 23 patients (42.6%) with CO. Nebulized CL was used in 36 patients (66.7%): 66.7% of which for CO, 33.3% in treatment for TB and in no case of NP. In 61.1% of the patients, IV CL was used: 22.2% of which for CO, 38.9% for TB and 38.9% in NP. The combination of IV CL and nebulized CL was used in 15 patients (27.8%): 5 patients (33.3%) CO, 2 patients (13.3%) TB and 8 patients (53.3%) NP. Microbiological eradication was achieved in 32 patients (59.3%), with the following distribution: 8 (47.1%) with IV CL, 15 (83.3%) with nebulized CL and 9 patients (69.2%) with a combination of IV CL and nebulized CL. Clinical recovery was achieved in 42 patients (77.8%): 12 (80%) with IV CL, 18 (94.7%) with nebulized CL and 12 (85.7%) with a combination of nebulized and IV CL. These differences were not significant. In the group of patients with infection due to TB and NP (31 patients, 57.4%), microbiological eradication was achieved in 5 patients (100%) treated with nebulized CL and in 6 of the 9 patients (42.9%) treated with IV CL, the difference being significant (P<.05). Clinical recovery in this group was 100% (6 patients) treated with nebulized CL and 75% (9 of the 12 patients) in the IV CL group. This difference was not significant.. Our study suggests that treatment with colistin in patients with pulmonary infection with multi-resistant Acinetobacter baumannii could be more efficient if it were to be administrated solely nebulized or in combination with IV colistin rather than administered solely intravenously.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Bronchitis; Colistin; Critical Illness; Cross Infection; Dose-Response Relationship, Drug; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Tracheitis; Tracheotomy

Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009.. The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out.. Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy.. Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Infective Agents; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Humans; Infection Control; Intensive Care Units; Italy; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

The development of resistance is a compelling reason for reviewing administration of antibiotics. Recently, most Acinetobacter infections are caused by multidrug-resistant (MDR) strains which have necessitated the use of tigecycline or colistin. This study was undertaken to determine the susceptibility of Acinetobacter spp. to these and other drugs. A total of 250 Acinetobacter isolates were collected from the 8 government hospitals over a period of 6 months. Susceptibility to 18 antibiotics, including tigecycline and colistin, was investigated by determining their minimum inhibitory concentrations using E test. Of the 250 isolates, 13.6% and 12% were resistant to tigecycline and colistin. A total of 25.2% and 37.2% were resistant to imipenem and meropenem, respectively. Of the 250 isolates 88.4% were MDR. This relatively high prevalence of tigecycline and colistin-resistant isolates indicates an emerging therapeutic problem which may severely compromise the treatment of MDR Acinetobacter spp. infections in Kuwait.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Imipenem; Kuwait; Meropenem; Microbial Sensitivity Tests; Minocycline; Thienamycins; Tigecycline

The treatment of Acinetobacter baumannii infections poses a significant clinical challenge, with isolates resistant to all commonly used agents increasingly being reported. With few new agents in the pipeline, clinicians are increasingly turning to combinations of antimicrobials in the hope that they may act synergistically together. In this study we assessed the activities of two glycopeptide-colistin combinations both in vitro and using a Galleria mellonella caterpillar model of A. baumannii infection. In checkerboard assays both vancomycin and teicoplanin were highly active against susceptible and multidrug-resistant strains of A. baumannii when combined with colistin (fractional inhibitory concentration [FIC] of <0.25). Treatment of G. mellonella caterpillars infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when either vancomycin or teicoplanin was given with colistin compared to colistin treatment alone (P < 0.05). This effect was most marked when vancomycin was the glycopeptide administered, although this agent was also highly effective as monotherapy, possibly through an immunomodulatory action on the G. mellonella response to A. baumannii infection. This work suggests that glycopeptide-colistin combinations are highly active against A. baumannii both in vitro and in a simple animal model of infection. They should be considered further as potential treatments for difficult-to-treat A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Lepidoptera; Microbial Sensitivity Tests

Topics: Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Topics: Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB) strains.. Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST12 h) in a time-kill study.. The time-kill studies indicated that the minimum inhibitory concentration (MIC) of colistin (0.5 or 0.25 μg/mL) completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL), minocycline (1 μg/mL) or rifampicin (0.06 μg/mL) did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL) with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL) with minocycline (0.5×MIC, 4 or 2 μg/mL) was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations) were significantly shorter than those of the single drugs (p<0.01).. This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; DNA Fingerprinting; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Molecular Typing; Polymerase Chain Reaction; Rifampin; Thienamycins; Time Factors

To determine whether the susceptibilities and the trends of nonsusceptibility of imipenem, meropenem, sulbactam, and colistin differed among Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and Acinetobacter genomic species 13TU (AGS 13TU) over 11 years.. A total of 1,039 nonduplicate blood isolates of A baumannii complex from bacteremic patients between 1997 and 2007 were collected at Taipei Veterans General Hospital and were identified to the species level using a multiplex polymerase chain reaction method and sequence analysis of 16S-23S intergenic spacer. The minimal inhibitory concentrations of antibiotics were determined by the agar dilution method.. The nonsusceptibility rates of carbepenems and sulbactam were highest in A baumannii, which also showed a trend toward increasing rate of carbapenems nonsusceptibility over the 11-year period of the study. AGS 13TU had the highest nonsusceptible rate to colistin, comparably increasing trend of carbapenem nonsusceptiblity as that of A baumannii, and is the only species with increasing sulbactam nonsusceptibility. AGS 3 had the lowest rate of nonsusceptibility to all four antimicrobial agents.. Although A baumannii had the highest nonsusceptibility rate to imipenem, meropenem, and sulbactam over the years, the higher rate of colistin nonsusceptibility and the emergence of nonsusceptibility of carbapenems and sulbactam in AGS 13TU suggested that this species might cause a great problem in the near future.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Cluster Analysis; Colistin; Drug Resistance, Bacterial; Enzyme Inhibitors; Genotype; Hospitals, Veterans; Humans; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Sequence Analysis, DNA; Sulbactam; Taiwan

Fifty Acinetobacter isolates were obtained from urinary tract infections and urinary catheter samples. Analytical profile index assays identified 47 isolates as Acinetobacter baumannii and three as Acinetobacter lwoffii. Six A. baumannii isolates (A1-A6) displayed hydrophobicity indices >70%. Twenty isolates exhibited lectin activity. Biofilm formation by these isolates was compared with those with low hydrophobicity index values (A45-A50). Biofilms on different surfaces were confirmed by light microscopy, epifluorescence microscopy and by obtaining scanning electron microscope images. Biofilm production was maximal at 30 °C, pH 7.0 in a medium with 5.0 g L(-1) NaCl, and its efficiency was reduced on urinary catheter surfaces at sub-minimum inhibitory concentration concentrations of colistin. Plasmid-mediated antibiotic resistance was observed in selected isolates of A. baumannii and experiments of conjugation and transformation showed the occurrence of gene transfer. Plasmid curing was used to examine the function of plasmids. Five plasmids of A. baumannii A3 were cured but no differences were observed between wild-type and plasmid-cured strains with respect to the biofilm formation capabilities. The prevalence of A. baumannii strains with biofilm mode of growth could explain their ability to persist in clinical environments and their role in device-related infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Catheters, Indwelling; Colistin; Conjugation, Genetic; Drug Resistance, Bacterial; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Lectins; Microbial Sensitivity Tests; Microscopy; Molecular Weight; Plasmids; Temperature; Urinary Catheterization; Urinary Tract Infections

A case of persistent multidrug-resistant (MDR) Acinetobacter baumannii ventriculitis successfully treated with a prolonged and novel combination of antimicrobials is reported.. A 38-year-old, 84-kg Caucasian woman with a recent history of craniotomy was admitted with nausea, fever, headache, photophobia, and drainage from her craniotomy incision. She underwent a repeat craniotomy on hospital day 4 with abscess debridement and repair of a cerebrospinal fluid leak. Cultures grew MDR A. baumannii, coagulase-negative Staphylococcus species, and methicillin-resistant Staphylococcus aureus. Based on the limited published pharmacokinetic and pharmacodynamic data for colistin, we determined a favorable outcome with i.v. colistin monotherapy was unlikely and decided to treat the patient with simultaneous i.v. and intraventricular colistin, as well as intraventricular tobramycin and i.v. rifampin. She was treated with a total of 36 days of intraventricular colistin, 40 days of intraventricular tobramycin, 51 days of i.v. colistin and rifampin, and 56 days i.v. vancomycin for infection that persisted despite multiple debridements. The patient had subsequent improvement in clinical manifestations and eradication of infection. She was subsequently discharged to an acute rehabilitation facility on hospital day 77 with posttreatment sequelae including mental impairment and renal failure requiring hemodialysis. Follow-up visits revealed significant improvement in her mental status, speech, and strength on the side not affected by the stroke.. Prolonged combination therapy with intraventricular colistin and tobramycin plus i.v. colistin, rifampin, and vancomycin led to the resolution of a persistent central nervous system infection caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cerebral Ventriculitis; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Rifampin; Tobramycin; Treatment Outcome; Vancomycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Female

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Female

The diminishing antimicrobial development pipeline has forced the revival of colistin as a last line of defence against infections caused by multidrug-resistant Gram-negative 'superbugs' such as Acinetobacter baumannii. The complete loss of lipopolysaccharide (LPS) mediates colistin resistance in some A. baumannii strains. Atomic force microscopy was used to examine the surface properties of colistin-susceptible and -resistant A. baumannii strains at mid-logarithmic and stationary growth phases in liquid and in response to colistin treatment. The contribution of LPS to surface properties was investigated using A. baumannii strains constructed with and without the lpxA gene. Bacterial spring constant measurements revealed that colistin-susceptible cells were significantly stiffer than colistin-resistant cells at both growth phases (P<0.01), whilst colistin treatment at high concentrations (32 mg/L) resulted in more rigid surfaces for both phenotypes. Multiple, large adhesive peaks frequently noted in force curves captured on colistin-susceptible cells were not evident for colistin-resistant cells. Adhesion events were markedly reduced following colistin exposure. The cell membranes of strains of both phenotypes remained intact following colistin treatment, although fine topographical details were illustrated. These studies, conducted for the first time on live A. baumannii cells in liquid, have contributed to our understanding of the action of colistin in this problematic pathogen.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Microscopy, Atomic Force; Microscopy, Confocal; Surface Properties

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans; Hydrocephalus; Infant, Newborn; Injections, Intraventricular; Magnetic Resonance Imaging; Male; Meningitis, Bacterial

The aim of the present study was to examine the in vitro antimicrobial activity of colistin, and ampicillin/sulbactam against A. baumannii isolated from pediatric patients and to compare the susceptibility testing using disc diffusion with minimal inhibitory concentration (MIC) E-test method.. One hundred strains of A. baumannii from various clinical isolates were included in the present study. Antimicrobial susceptibilities of A. baumannii to colistin, ampicillin/sulbactam were determined by disc diffusion and minimal inhibitory concentration (MIC) using E-test method. The analysis was stratified by carbapenem resistance status. Sensitivity and specificity of the disc diffusion test compared to the MIC E-test were estimated.. Ninety-seven strains of all isolates (97%) were sensitive to colistin using both disc diffusion and E-test methods. In contrast, 41% and 34% of the isolates were sensitive to ampicillin/sulbactam by disc diffusion and MICE-test, respectively. The colistin MIC50 and MIC90 for A. baumannii were 0.38 and 1 microg/mL, respectively. The ampicillin/sulbactam MIC50 and MIC90 were 16 and 89.6 microg/mL, respectively. Based on the results of MIC E-test, ninety-eight (n = 49) and six (n = 3) percent of carbapenem-resistant A. baumannii (n = 50) were susceptible to colistin and ampicillin/sulbactam, respectively. Sensitivity and specificity of disc diffusion test compared to MIC E-test were 99% and 66.7% for colistin and 80.5% and 98.3% for ampicillin/sulbactam, respectively.. The antimicrobial activities of colistin against A. baumannii isolates remained high for both cabapenem-susceptible and -resistant strains. However, the in vitro activity of ampicillin/sulbactam against A. baumannii was low. Thus, a combination, rather than monotherapy, of ampicillin/sulbactam with other antibiotics is strongly recommended when dealing with A. baumannii infection. In addition, disc diffusion test appeared to be a useful screening method for susceptibility testing for colistin and ampicillin/sulbactam against A. baumanii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Child; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospitals, Pediatric; Humans; Male; Microbial Sensitivity Tests; Sensitivity and Specificity; Sulbactam; Thailand

Acinetobacter baumannii is a Gram-negative coccobacillus causing serious nosocomial infections. The recent emergence of strains of bacteria, which are resistant to common antibiotics, has made the treatment of these infections increasingly complex. We report the case of a young patient affected by AIDS, who suffered brain toxoplasmosis and sepsis due to multidrug-resistant A baumannii. This bacterial infection was successfully treated with colistin and tigecycline. In addition, we review recent literature on this topic, from the year 2000 to date.

Topics: Acinetobacter baumannii; Acinetobacter Infections; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Child; Colistin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Humans; Magnetic Resonance Imaging; Male; Minocycline; Tigecycline; Tomography, X-Ray Computed

The aim of the present study was to assess the efficacy and safety of colistimethate sodium therapy in multidrug-resistant nosocomial infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii in neonates and children.. Pediatric patients hospitalized at the Uludag University Hospital who had nosocomial infections caused by multidrug-resistant P. aeruginosa or A. baumannii, were enrolled in the study. Colistimethate sodium at a dosage of 50-75 x 10(3) U/kg per day was given i.v. divided into three doses.. Fifteen patients received 17 courses of colistimethate sodium for the following infections: ventilator-associated pneumonia (n= 14), catheter-related sepsis (n= 1) and skin and soft-tissue infection (n= 2). The mean age of patients was 53.2 + 74.7 months (range, 8 days-15 years) and 60% were male. Mortality was 26.6%.. Colistimethate sodium appears to be safe and effective for the treatment of severe infections caused by multidrug-resistant P. aeruginosa or A. baumannii in pediatric patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Child; Child, Preschool; Colistin; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Hospitals, University; Humans; Infant; Infant, Newborn; Injections, Intravenous; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Male; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Statistics, Nonparametric; Treatment Outcome; Turkey

There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 +/- 0.27 [controls] versus 3.05 +/- 1.91, 2.07 +/- 1.82, 2.41 +/- 1.37, 3.4 +/- 3.07, 6.82 +/- 3.4, and 4.22 +/- 2.72 log(10) CFU/g, respectively [means +/- standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (-2.6 and -4.4 log(10) CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Meningitis, Bacterial; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rabbits; Rifampin; Sulbactam; Treatment Outcome

The emergence of highly resistant gram-negative pathogens in hospitals around the world has placed emphasis on colistin, a seemingly ancient drug. Respiratory failure from colistin was reported in the years following its release; however, there are no recent reports of colistin-induced respiratory failure. We report a case of intravenous colistin- and, later, inhalational colistin-induced respiratory failure.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Pneumonia, Bacterial; Respiratory Insufficiency

Multidrug-resistant (MDR) Acinetobacter baumannii are increasingly encountered and frequently susceptible only to colistin with their MIC values close to resistance breakpoint. Antibacterial activity of two carbapenem-based combinations were explored in order to overcome the bacterial resistance.. Thirty clinical isolates of MDRA. baumannii were employed to assess in vitro antibacterial activity of two carbapenem-based regimens. Imipenem combined with colistin and meropenem combined with colistin and sulbactam were the first and second regimens, respectively. All isolates were resistant to imipenem (MIC range: 8-128 microg/ml) and meropenem (MIC range: 64-256 microg/ml) but still susceptible to colistin (MIC range: 0.5-2 microg/ml). The MIC range of sulbactam was 4-64 microg/ml. None of the isolates produced metallo-beta-lactamase.. Synergistic antibacterial effect of imipenem combined with colistin was observed against 100 percent of A. baumannii isolates by the checkerboard microdilution panel method. In a subsequent time kill study, the most active concentration of this regimen was the combination of imipenem at the fixed concentration of 32 microg/ml and colistin at the 1/4 of the MIC values of each isolate that exerted significantly higher bactericidal activity than imipenem at 32 microg/ml alone and colistin alone at the 1/4 of the MIC values. The scanning electron micrographs demonstrated major cell morphological change and cell wall destruction after 2-hour exposure to this combination. The triple combinations of meropenem, sulbactam and colistin showed synergy against 96.7 percent of MDR A. baumannii while double combinations of either meropenem and sulbactam, meropenem and colistin, and sulbactam and colistin showed synergy effects of 70%, 73.3% and 53.3%, respectively The time kill study using ten isolates also showed better killing effect by the triple combination than any of the double combinations.. Antibacterial activity against MDR A. baumannii of imipenem plus colistin was superior over any single of the two agents. The addition of sulbactam to meropenem and colistin may further improve their antibacterial activity. The double or triple carbapenem-based combinations offer promising alternatives in the treatment of infections due to MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Analysis of Variance; Anti-Bacterial Agents; Area Under Curve; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Imipenem; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Sulbactam; Thienamycins

Multidrug-resistant strains of Acinetobacter baumannii have been reported increasingly around the world. The administration of an association of antibiotics has been proposed to create an active combination and to prevent the emergence of resistance.. The activity of colistin, rifampicin, gentamicin, imipenem and their associations was evaluated by means of killing curves in fourteen isolates belonging to three endemic PFGE types, in a university hospital of Buenos Aires city. The 14 isolates were selected on the basis of different mechanisms responsible for resistance to carbapenems and different susceptibility to colistin.. The mechanism responsible for the resistance to imipenem was the production of OXA-23 and OXA-58 carbapenemases. Heteroresistance to colistin was observed in six isolates. The associations colistin-rifampicin and colistin-imipenem were synergistic in heteroresistant isolates and prevented the development of colistin-resistant mutants. The association imipenem-gentamicin was bactericidal in gentamicin susceptible isolates, whereas the association imipenem-rifampicin was always indifferent.. The antimicrobial activity and the presence of synergy are related to the antimicrobials' susceptibilities irrespective of the PFGE type or the OXA-carbapenemase produced.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Endemic Diseases; Gentamicins; Humans; Imipenem; Microbial Sensitivity Tests; Rifampin

Acinetobacter baumannii (AB) nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. We report a case of a 42-year-old male patient affected by low-grade ependymoma who developed AB-MDR post-neurosurgical ventriculitis. Initially, because of in vitro susceptibility, we used a combination of intravenous colistin and tigecycline. This treatment resulted in the improvement of the patient's initial condition. However, soon after, the infection relapsed; tigecycline was stopped and treatment with intrathecal colistin was initiated. Cure was achieved by continuing this treatment for approximately three weeks, without adverse effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Brain Neoplasms; Cerebral Ventriculitis; Colistin; Drug Resistance, Multiple, Bacterial; Ependymoma; Humans; Injections, Intravenous; Injections, Spinal; Male; Postoperative Complications

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

Acinetobacter baumannii are emerging as the causal agents of healthcare-associated infections. We describe arenal transplant recipient who developed bacteremia caused by multiresistant A. baumannii, which received a combination of tigecycline, colistin, and meropenem in continuous infusion. The clinical outcome was favorable. In this article we made a molecular study of this multiresistant strain. Our analysis reveals the presence of abla-OXA-72 gene,a class D of oxacillinase belonging to bla-OXA-40-like group,which constitutes the most disseminated familiy of carbapenemases in Spain. Thus, we found different susceptibility patterns of A. baumannii when we used different Mueller-Hinton agars with different manganese concentrations. Lastly, we explain the combination of these three antibiotics administered to increase microbiologic and pharmacodynamic yield.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Meropenem; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Tigecycline

To elucidate the pharmacokinetic/pharmacodynamic (PK/PD) index that predicts colistin efficacy against Acinetobacter baumannii in neutropenic murine thigh and lung infection models, and to determine the extent of the emergence of resistance in vivo to colistin.. PK/PD of colistin was studied in thigh and lung infection models against A. baumannii ATCC 19606 and two multidrug-resistant clinical isolates (two of the three strains were colistin heteroresistant). Dose fractionation studies were conducted over a daily dose range of 1-160 mg/kg colistin sulphate. Bacterial burden in tissues was measured at 24 h. Non-linear least squares regression analyses were employed to determine the PK/PD index (fAUC/MIC, fC(max)/MIC or fT(>MIC)) best correlating with the efficacy of colistin in each model. Real-time population analysis profiles were conducted for tissue samples to monitor the emergence of resistance.. The fAUC/MIC was the PK/PD index that correlated best with efficacy in both thigh (R(2) = 0.90) and lung (R(2) = 0.80) infection models. The fAUC/MIC targets required to achieve stasis and 1 log kill against the three strains were 1.89-7.41 and 6.98-13.6 in the thigh infection model, respectively, while the corresponding values were 1.57-6.52 and 8.18-42.1 in the lung infection model. Amplification of colistin-resistant subpopulations was revealed for all strains in both models after 24 h colistin treatment.. This study indicates the importance of achieving adequate time-averaged exposure to colistin and defined target fAUC/MIC values for various magnitudes of kill. Amplification of resistant subpopulations indicates the importance of investigating rational combinations with colistin. The results will facilitate efforts to optimize colistin use in humans.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Area Under Curve; Colistin; Colony Count, Microbial; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Lung; Mice; Microbial Sensitivity Tests; Thigh

Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans; Imipenem; Immunosuppressive Agents; Lung Transplantation; Minocycline; Pneumonia, Bacterial; Radiography; Retrospective Studies; Tigecycline

Data regarding the role of inhaled colistin in critically ill pediatric patients without cystic fibrosis are scarce. Three children (one female), admitted to the intensive care unit (ICU) of a tertiary-care pediatric hospital in Athens, Greece, during 2004-2009 received inhaled colistin as monotherapy for tracheobronchitis (two children), and as adjunctive therapy for necrotizing pneumonia (one child). Colistin susceptible Acinetobacter baumannii and Pseudomonas aeruginosa were isolated from the cases' bronchial secretions specimens. All three children received inhaled colistin at a dosage of 75 mg diluted in 3 ml of normal saline twice daily (1,875,000 IU of colistin daily), for a duration of 25, 32, and 15 days, respectively. All three children recovered from the infections. Also, a gradual reduction, and finally total elimination of the microbial load in bronchial secretions was observed during inhaled colistin treatment in the reported cases. All three cases were discharged from the ICU. No bronchoconstriction or any other type of toxicity of colistin was observed. In conclusion, inhaled colistin was effective and safe for the treatment of two children with tracheobronchitis, and one child with necrotizing pneumonia. Further studies are needed to clarify further the role of inhaled colistin in pediatric critically ill patients without cystic fibrosis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Albuterol; Anti-Bacterial Agents; Bronchitis; Bronchodilator Agents; Case-Control Studies; Child; Child, Preschool; Colistin; Critical Care; Critical Illness; Cystic Fibrosis; Female; Hospitals, Pediatric; Humans; Infant; Ipratropium; Male; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Tracheitis; Treatment Outcome

Ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) Acinetobacter baumannii in critically ill patients presents an emerging challenge to clinicians. Administration of aerosolized colistin as an adjunctive therapy is one therapeutic option mentioned in limited evidence-based studies. This study aimed to evaluate the effectiveness of adjunctive aerosolized colistin treatment for VAP due to MDR pathogens.. We retrospectively reviewed the medical records of patients who had received aerosolized colistin for treatment of VAP due to MDR A. baumannii in our hospital from August to December 2008.. Forty-five patients were enrolled in our study. The mean age was 71 +/- 15 years. The mean Acute Physiological and Chronic Health Evaluation II (APACHE II) scores on the day of intensive care unit admission and on the first day of aerosolized colistin administration were 22.5 +/- 6.7 and 18.9 +/- 5.7, respectively. The mean duration of intensive care unit stay was 34 +/- 16 days. The mean daily dosage of aerosolized colistin was 4.29 +/- 0.82 million IU, and the mean duration of administration was 10.29 days. Seventeen patients (37.8%) had a favorable microbiological outcome and 26 (57.8%) showed a clinical response. Mortality due to all causes was 42.2%. No adverse effects related to inhaled colistin were recorded.. Aerosolized colistin may be considered as an adjunct to intravenous treatments in patients with VAP due to colistin-susceptible MDR A. baumannii in critically ill patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Hospitals; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Taiwan; Treatment Outcome

The designer antibacterial peptide A3-APO is efficacious in mouse models of Escherichia coli and Acinetobacter baumannii systemic infections. Here we compare the efficacy of the peptide with that of imipenem and colistin in A. baumannii wound infections after burn injury.. CD-1 mice were inflicted with burn wounds and different inocula of A. baumannii, isolated from an injured soldier, were placed into the wound sites. The antibiotics were given intramuscularly (im) one to five times. Available free peptide in the blood and the systemic toxicity of colistin and A3-APO were studied in healthy mice.. While toxicity of colistin was observed at 25 mg/kg bolus drug administration, the lowest toxic dose of A3-APO was 75 mg/kg. In the A. baumannii blast injury models, 5 mg/kg A3-APO improved survival and reduced bacterial counts in the blood as well as in the wounds and improved wound appearance significantly better than any other antibiotic treatment. The free peptide concentration in the blood did not reach 1 µg/mL.. Peptide A3-APO, with an intramuscular therapeutic index of 15, is more efficacious and less toxic than any existing burn injury infection therapy modality against multidrug-resistant Gram-negative pathogens. A3-APO administered by the im route probably binds to a biopolymer that promotes the peptide's biodistribution.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Burns; Colistin; Disease Models, Animal; Female; Humans; Imipenem; Injections, Intramuscular; Mice; Peptides; Plasma; Treatment Outcome; Wound Infection

Colistin sulfate and levofloxacin, alone and in combination with tigecycline, were investigated for their in vitro activities and postantibiotic effects (PAEs) on6 meropenem-resistant Acinetobacter baumannii.. The in vitro activities of colistin sulfate and levofloxacin in combination with tigecycline were determined using a microbroth checkerboard technique. The results were interpreted based on the fractional inhibitory concentration index. To determine the PAEs, A. baumannii strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation.. One synergistic interaction was observed for each of the tigecycline-colistin sulfate and tigecycline-levofloxacin combinations. Colistin sulfate produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent manner. PAEs were induced by levofloxacin (ranging from 0.35 to 2.45 h) and tigecycline (ranging from 0.05 to 1.40 h). In combination, tigecycline slightly changed the PAE of colistin sulfate and levofloxacin against the studied strains.. This study's findings could have important implications for the timing of doses during antimicrobial therapy with tigecycline, colistin sulfate, and levofloxacin alone and in combination.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Ofloxacin; Thienamycins; Tigecycline

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppression Therapy; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Pneumonia, Bacterial; Rifampin; Treatment Outcome

Multidrug-resistant Acinetobacter baumannii has presented a global medical problem. Emergence of colistin resistance, including hetero-resistance, has been increasingly reported. This study examined the susceptibility to colistin of multidrug-resistant A. baumannii from the Western Pacific region.. A total of 30 isolates were studied from 10 clinical centres in various countries. MICs were measured against 21 antibiotics by broth microdilution. Colistin population analysis profiles (PAPs) (0, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10mg/L) were determined. Time-kill kinetics of colistin against 3 isolates (2 colistin-susceptible (one of which was colistin hetero-resistant) and 1 colistin-resistant) were studied over a wide range of concentrations and development of resistance was monitored by measurement of colistin PAPs after 24-h exposure.. All the isolates were highly multiresistant. Colistin MICs were 0.5-2mg/L except one isolate which had an MIC of 128mg/L. Seven isolates were colistin hetero-resistant with subpopulations growing at >2mg/L. For the 2 colistin-susceptible isolates examined, >3log killing was observed within 3h even at 0.5x MIC. Interestingly, >3log killing was also observed with the colistin-resistant isolate within 1h even at 0.5mg/L. Regrowth occurred at 24h for both colistin-susceptible and -resistant isolates. Emergence of resistance to colistin after 24-h exposure was confirmed by PAP.. Colistin was very active against A. baumannii based upon MICs and initial killing in time-kill studies. Hetero-resistance in this group of A. baumannii isolates was less common than in previous studies. Nevertheless, care is required with colistin monotherapy for A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Microbial Viability; United States

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare.. Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series.. Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed.. The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dose delivery. To address this, we developed a mouse model with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic lesions that do not contain apparent biofilm. We also found that mice mount a specific IgG response against three proteins (40, 47, and 56 kDa) regardless of the strain used, suggesting that these may be immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a 100% infection rate with 75% of the MDR strains, and in vitro testing confirmed that all strains were sensitive to colistin. We also developed a real-time quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7 days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an unloaded PMMA bead control. While the parenteral colistin failed to demonstrate any significant effects versus the placebo, the colistin PMMA bead significantly reduced the infection rate such that only 29.2% of the mice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Fractures, Bone; Mice; Mice, Inbred C57BL; Osteomyelitis

In recent years there has been an increase in life-threatening infections caused by Acinetobacter baumannii with multiple antibiotic resistance, which has lead to the use of polymyxins, especially colistin, being reconsidered. The aim of this study was to investigate the colistin sensitivity of A. baumannii isolates with multiple antibiotic resistance via different methods, and to evaluate the disk diffusion method for colistin against multi-resistant Acinetobacter isolates, in comparison to the E-test and Phoenix system.. The study was carried out on 100 strains of A. baumannii (colonization or infection) isolated from the microbiological samples of different patients followed in the clinics and intensive care units of Uludağ University Medical School between the years 2004 and 2005. Strains were identified and characterized for their antibiotic sensitivity by Phoenix system (Becton Dickinson, Sparks, MD, USA).. In all studied A. baumannii strains, susceptibility to colistin was determined to be 100% with the disk diffusion, E-test, and broth microdilution methods. Results of the E-test and broth microdilution method, which are accepted as reference methods, were found to be 100% consistent with the results of the disk diffusion tests; no very major or major error was identified upon comparison of the tests. The sensitivity and the positive predictive value of the disk diffusion method were found to be 100%.. Colistin resistance in A. baumannii was not detected in our region, and disk diffusion method results are in accordance with those of E-test and broth microdilution methods.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Culture Media; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Predictive Value of Tests; Sensitivity and Specificity; Turkey

Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials.. A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture.. 32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p=0.54), nephrotoxicity (p=0.67), change in creatinine from baseline to highest subsequent value (p=0.11) and time to microbiological clearance (p=0.75). The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99).. Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumannii infections when the organism is resistant to other available antimicrobials.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cohort Studies; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Kaplan-Meier Estimate; Middle Aged; Retrospective Studies; Tobramycin; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Endometrial Neoplasms; Female; Humans; Middle Aged; Surgical Wound Infection; Uterine Cervical Neoplasms

Nosocomial infections by resistant gram-negative microorganisms are important causes of mortality in intensive care unit (ICU)'s. The treatment choices are limited in infections due to Acinetobacter baumannii and Pseudomonas aeruginosa, especially if they are panresistant. In these type of resistant infections, colistin--an old antibiotic--has become a current issue. The aim of this study was to evaluate the efficacy of colistin in 9 cases (6 males, mean age 75.8 +/- 9.4 years), with ventilator associated pneumonia (VAP) caused by panresistant A. baumannii and P. aeruginosa in respiratory ICU. All cases were referred to ICU from other hospitals or clinics. It was detected that 7 of 9 cases were treated with anti-pseudomonal antibiotics before the development of VAP. Panresistant A. baumannii was isolated in 5 cases and P. aeruginosa in 4 cases. VAP by these microorganisms was detected on the 26.6 +/- 12.4th days of invasive mechanical ventilation and the cases were followed up for 54.2 +/- 25.7 days in ICU. During colistin treatment, dermatitis (one case) and nephrotoxicity (one case) were observed as side effects. Microbiological response to colistin was obtained in 6 cases. Three cases died due to non-eradication of panresistant microorganisms and three cases died due to other infections during ICU follow-up. The data presented in this study demonstrates that colistin can be considered as a safe and effective antibiotic in the treatment of panresistant A. baumannii and P. aeruginosa infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections

High colistin resistance rates in Acinetobacter spp. were recently reported in Korean hospitals (J. Antimicrob. Chemother 2007;60:1163). In this study, we investigated if colistin-resistant Acinetobacter spp. isolates from Korean hospitals disseminated clonally or emerged independently. Multilocus sequence typing (MLST) analysis was performed for 58 colistin-resistant Acinetobacter spp. isolates: 8 isolates of the Acinetobacter baumannii subgroup A, 16 isolates of the A. baumannii subgroup B, and 34 isolates of the genomic species 13TU. A phylogenetic tree inferred from concatenated sequences of 7 MLST loci showed a clear distinction among the 3 Acinetobacter groups. In the MLST analysis, most colistin-resistant Acinetobacter spp. isolates showed different allele profiles at the 7 loci; that is, they belonged to different clones. Despite the clear distinction between the 3 Acinetobacter groups, interrelationships among the 3 groups were not consistent within the gene trees. In addition, some isolates showed clustering incongruent with their species or group identities in some gene trees. MLST analysis indicated that most colistin-resistant Acinetobacter spp. isolates from Korean hospitals arose independently. Considering the increasing use of colistin and the high recombination rate of Acinetobacter spp., independent but frequent emergence of colistin resistance in Acinetobacter spp. isolates is of great concern.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; Cluster Analysis; Colistin; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Humans; Korea; Molecular Epidemiology; Phylogeny; Sequence Analysis, DNA

Acinetobacter baumannii has emerged as an important nosocomial pathogen that can cause a multitude of severe infections. In neurosurgical patients the usual presentation is ventriculitis associated with external ventricular drainage. Carbapenems have been considered the gold standard for the treatment of Acinetobacter baumannii ventriculitis, but resistant isolates are increasing worldwide, reducing the therapeutic options. In many cases polymyxins are the only possible alternative, but their poor blood-brain barrier penetration could require them to be directly administered intraventricularly and clinical experience with this route is limited. We review the literature concerning intraventricular use of colistin (polymyxin E) for A. baumannii ventriculitis and add three cases successfully treated with this method. Our experience suggests that intraventricular colistin is a potentially effective and safe therapy for the treatment of multidrug-resistant A. baumannii central nervous system infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Brain; Cerebrospinal Fluid Shunts; Colistin; Cross Infection; Drug Resistance, Multiple; Encephalitis; Fatal Outcome; Female; Humans; Hydrocephalus; Injections, Intraventricular; Lateral Ventricles; Male; Meningitis, Bacterial; Middle Aged; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Treatment Outcome; Ventriculostomy

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; Humans; Microbial Sensitivity Tests; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections

Management of multidrug-resistant Acinetobacter baumannii (MDRAB) meningitis/ventriculitis is a difficult therapeutic problem owing to the limited penetration of antibiotics into cerebrospinal fluid (CSF). A 2-month-old girl with ventriculitis caused by MDRAB is reported. Despite therapy with intravenous (IV) colistin ventricular fluid, cultures remained positive for MDRAB. Institution of combination therapy with IV and intraventricular colistin resulted in a successful clinical and microbiological outcome. Intraventricular/intrathecal and IV colistin might be the best therapeutic option in the treatment of central nervous system infection caused by MDRAB. Further studies are required to evaluate pharmacokinetic and pharmacodynamic parameters of combined IV and intraventricular/intrathecal colistin administration, especially in children.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cerebral Ventricles; Colistin; Drug Resistance, Multiple, Bacterial; Encephalitis; Female; Humans; Infant; Injections, Intraventricular; Meningitis, Bacterial; Treatment Outcome

: To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia.. : A controlled, in vivo experimental study.. : Research laboratory of a medical center.. : Female BALB/c mice.. : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 10 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396.. : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia.. : The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Mice; Mice, Inbred BALB C; Pneumonia, Bacterial; Time Factors; Trachea

We retrospectively assessed the renal toxicity associated with the use of intravenous colistin. Fifty-four patients with multidrug-resistant Acinetobacter infections were included. At the end of therapy 6/54 patients (11%) suffered renal impairment. Renal impairment associated with the use of colistin is less frequent than initially reported.

Topics: Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Creatinine; Humans; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Microbial Sensitivity Tests; Retrospective Studies; Statistics, Nonparametric

We compared 41 patients who received colistimethate with 41 who received polymyxin B for the treatment of serious infections caused by carbapenem-resistant Acinetobacter spp. and found both polymyxins have similar efficacy and toxicity.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Colistin; Female; Humans; Kidney; Male; Middle Aged; Polymyxin B; Treatment Outcome; Young Adult

Colistin heteroresistance in Acinetobacter baumannii (Ab) has been reported, but the clinical impact and the antimicrobial treatment have not been established yet. We observed the selection intratreatment with colistin of Ab colistin-resistant strains from a colistin-heteroresistant isolate in one patient with postneurosurgical meningitis. The presence and the genetic relationship of heteroresistant Ab isolates from intensive care units (ICUs) obtained in the same period of the case report were analyzed. Twenty-eight isolates from patients admitted to the ICUs of an Argentinian university hospital during June to December 2004 were evaluated. Genomoespecie was determined by amplified ribosomal DNA restriction analysis, and genetic similarity among the strains was determined by pulsed-field electrophoresis. Colistin heteroresistance was observed in 46, 4% of these isolates. The majority belonged to clones previously identified as I and III.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; Bacterial Typing Techniques; Cluster Analysis; Colistin; Cross Infection; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Hospitals, University; Humans; Intensive Care Units; Male; Meningitis, Bacterial; Ribotyping; Selection, Genetic; Young Adult

Acinetobacter spp. are the frequent causes of nosocomial infections which are difficult to treat due to multidrug resistance. The aim of this study was to determine the antibiotic susceptibilities and the presence of metallo-beta-lactamases in Acinetobacter spp. isolated from patients admitted to Hacettepe University Adult Hospital. A total of 124 Acinetobacter spp. isolates were included in the study. Antibiotic susceptibilities against imipenem (IMP), meropenem (MER), ceftazidime (CAZ), ciprofloxacin (CIP) and aztreonam (AZT) were studied by microdilution susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Multidrug-resistant isolates (MDR) were further tested for susceptibility against colistin by microdilution, and against amikacin (AN), piperacillin-tazobactam (PIP-TAZ), cefepime (FEP), ceftriaxone (CRO), tetracycline (TET), trimetoprim-sulfomethoxazole (SXT) and mezlocillin (MEZ) by disk diffusion method according to CLSI guidelines. Each isolate was also tested for metallo-beta-lactamase (MBL) production by using IMP and EDTA combined disk diffusion test and molecular analysis for bla(IMP-1) and bla(VIM-2) genes was done by polymerase chain reaction (PCR). Among 124 non-duplicate isolates, 72 were identified as Acinetobacter baumannii and 52 as Acinetobacter lwoffii. Minimum inhibitor concentration 50 (MIC50) and minimum inhibitor concentration 90 (MIC90) values of the isolates were 32 and 128 microg/ml for IMP, 16 and 32 microg/ml for MER, 128 and 256 microg/ml for CIP, 64 and 256 microg/ml for CAZ, 128 and 256 microg/ml for AZT, respectively. Forty-three (34.7%) isolates were susceptible to IMP. Overall, 51 (41%) Acinetobacter spp. were found to be resistant to > or = 3 antibiotics belonging to different antimicrobial classes and defined as MDR. Colistin MIC50 and MIC90 values were 2 and 8 microg/ml, respectively and the rate of colistin resistance was 27.5% in MDR isolates. The resistance rates for AN, PIP-TAZ, FEP, CRO, TET, SXT and MEZ were 80.4%, 98%, 92.2%, 100%, 100%, 86.3% and 86.3%, respectively. Among 124 isolates, 64 (51.6%) yielded positive result by IMP-EDTA combined disk test, and all the isolates were negative in terms of the tested MBL genes by PCR. These data revealed high level resistance among the Acinetobacter population in our hospital. The high rate of carbapenem resistance and increasing colistin resistance among Acinetobacter isolates should be surveyed cautiously. The incr

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Hospitals, University; Humans; Microbial Sensitivity Tests; Turkey

Forty-two multidrug-resistant (MDR) Acinetobacter baumannii isolates were obtained during outbreaks in a Korean hospital. The co-carriage of bla(OXA-23), bla(OXA-51), bla(PER-1) and armA was observed in 23 isolates, and they were susceptible only to colistin and minocycline. The MDR A. baumannii isolates were found to belong to sequence group 1 using sequence-based typing.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Typing Techniques; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Korea; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Sequence Analysis, DNA

We present 6 cases of multidrug-resistant (MDR) Acinetobacter baumannii pneumonia in lung transplant recipients. All cases were treated with imipenem and/or non-traditional antibiotics, such as tigecycline and colistimethate, and had different microbiologic and clinical outcomes. Prior treatment with broad-spectrum anti-microbial therapy was the single most likely risk factor for the development of infection due to MDR Acinetobacter baumannii. Ideal preventive and therapeutic strategies for this pathogen in lung transplant recipients require further study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Lung Transplantation; Male; Minocycline; Pneumonia; Risk Factors; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Rifampin; Treatment Outcome

Meropenem (MEM; 2 g/8 hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus sulbactam (SUL; 1 g/8 hr; MIC = 128 mg/L) (two-drug-therapy period), and subsequent additional intravenous colistin (COL; 2.5 mg/kg/12 hr) and intraventricular (COL, 5 mg/day; MIC = 1 mg/L) (three-drug-therapy period) were sequentially used in a patient with postneurosurgery bacteremic meningitis due to a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We detected 4- to 32-fold increases in peak or trough cerebrospinal fluid bactericidal titer and serum bactericidal titer in three-drug-therapy period when comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL, and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16 mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)), by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL, and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good therapeutic options, even though MEM and SUL are in vitro resistance to the MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Neurosurgical Procedures; Postoperative Complications; Sulbactam; Thienamycins; Time Factors

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis, Bacterial

Emergence of multi and pan-drug resistant Gram-negative bacteria causing nosocomial infections in intensive care settings has become a challenge for clinicians. The mortality rate of ventilator-associated pneumonia (VAP) is known to increase when the initial microbiological diagnosis and antimicrobial therapy are inappropriate. We present a case of a 18-year-old man, who after being admitted following an accident, had developed VAP due to multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. and had a downhill clinical course despite broad-spectrum antibiotic treatment. The strains were found to be Col-S, as the susceptibility was tested. Colistin was instituted, with remarkable recovery. It is imperative to diagnose VAP with multi-drug resistant strains as early as possible; colistin, the 'last resort' antibiotic, if instituted with proper monitoring at the right time, can be life saving.

Topics: Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Treatment Outcome

Colistin heteroresistance has been reported among Acinetobacter isolates; however, its association with prior colistin therapy has not been not described. A population analysis profile identified resistant Acinetobacter subpopulations from colistin-susceptible clinical isolates. The proportion of cells exhibiting heteroresistance was significantly higher among isolates recovered from patients treated with colistin.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Amikacin; Brain Ischemia; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Humans; Hydrocephalus; Injections, Spinal; Male; Meningitis, Bacterial; Pseudomonas Infections; Shock, Septic; Surgical Wound Infection; Ventriculostomy

The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin.. Critically ill patients with pneumonia and bacteraemia caused by A. baumannii resistant to all antibiotics except colistin in medical and surgical intensive care units were enrolled. Clinical and microbiological responses and safety were evaluated.. Twenty-nine patients (47 +/- 14 years and APACHE II score 17.03 +/- 3.68), of whom 19 were cases of nosocomial pneumonia and 10 were cases of bacteraemia, were treated with intravenous colistin sulphomethate sodium (2 million IU three times a day) in addition to intravenous rifampicin (10 mg/kg every 12 h). All A. baumannii isolates were susceptible to colistin. The mean duration of treatment with intravenous colistin and rifampicin was 17.7 (+/-10.4) days (range 7-36). Clinical and microbiological responses were observed in 22 of 29 cases (76%) and the overall infection-related mortality was 21% (6/29). Three of the 29 evaluated patients (10%) developed nephrotoxicity when treated with colistin, all of whom had previous renal failure. No cases of renal failure were observed among patients with normal baseline renal function. No neurotoxicity was noted.. Colistin and rifampicin appears to be an effective and safe combination therapy for severe infections due to multidrug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Middle Aged; Prospective Studies; Rifampin; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Burns; Colistin; Drug Resistance, Bacterial; Female; Humans; Microbial Sensitivity Tests; Mutation

The study aimed to determine the incidence and mortality of multidrug-resistant Acinetobacter baumannii in cardiac surgery, to elucidate the effectiveness of colistin treatment and to identify if the additional measures to the recommended procedures were able to control the dissemination of the pathogen.. A prospective observational cohort was conducted among cardiac surgical patients from 1 September 2005 to 31 December 2006. We reviewed the prophylactic measures of the surgical intensive care unit and implemented a two scale multiple program. Scale I included classical infection control measures, while Scale II referred to the geographic isolation of multidrug-resistant Acinetobacter baumannii patients and environmental intense surveillance.. Among 151 out of 1935 infected patients 20 were colonized and infected by strains of multidrug-resistant A. baumannii susceptible only to colistin. Seventeen patients presented respiratory tract infection, one patient suffered deep surgical site infection and two patients catheter related infection. Transmission of the pathogen occurred via two patients transferred from two other institutions. They were all treated with colistin. Cure or clinical improvement was observed only in four patients (20%). Scale I measures were implemented for the whole 16-month period while scale II for two separate periods of 3 weeks. Environmental specimens (n>350) proved negative.. The increasing prevalence of multidrug-resistant A. baumannii in surgical intensive care unit patients creates demand on strict screening and contact precautions. Following this infection control strategy we were able to achieve intermittent eradication of the pathogen during a 16-month period with continuous function of the intensive care unit. Despite the significant in vitro activity of colistin against multidrug-resistant Acinetobacter baumannii the results were discouraging.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cardiac Surgical Procedures; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Postoperative Care; Prospective Studies; Risk Factors; Treatment Outcome

This study was designed to evaluate Acinetobacter baumannii infections incidence in our Surgical Intensive Care Unit, clinical features and outcome of these patients, and multi-resistance incidence to identify predictors of such a resistance.. Prospective study of all patients with ICU-acquired Acinetobacter baumannii infection from June 1, 2003 to May 31, 2005. Patients with multi-resistant infection, susceptible exclusively to colistin, were compared with those sustaining non-multi-drug resistant infection.. Among 411 patients, 52 (12.6%) developed Acinetobacter infection. Their mean age was 66.3 +/- 8.4 years and APACHE II 20.4 +/- 7.3 (men: 51.9%). Infection sites were: bloodstream (46.2%), respiratory tract (32.7%), central venous catheter (11.5%), surgical site (7.7%), and urinary tract (1.9%). High multi-resistance (44.2%), morbidity (63.4%), and mortality (44.2%) were identified. Colistin was the most effective antibiotic (100% susceptibility), whereas resistance against all other antibiotics was >60%. Previous septic shock (p = 0.04), previous adult respiratory distress syndrome (ARDS) (p = 0.01), number of previous antibiotics (p = 0.01), previous aminoglycoside use (p = 0.04), and reoperation (p = 0.01) were risk factors for multi-resistance in univariate analysis. Morbidity in the multi-resistant group was significantly higher than the non-multi-resistant group (82.6% vs. 48.2%, p = 0.02). Mortality in the multi-resistant group also was higher; however, this difference did not marginally reach statistical significance (60.8% vs. 31.1%, p = 0.06). Multivariate analysis identified previous septic shock (p = 0.04; odds ratio (OR), 9.83; 95% confidence interval (CI), 1.003-96.29) and reoperation (p = 0.01; OR, 8.45; 95% CI, 1.52-46.85) as independent predictors of multi-resistance.. Acinetobacter baumannii infections are frequent and associated with high morbidity, mortality, and multi-resistance. Avoidance of unnecessary antibiotics is a high priority, and specific attention should be paid to patients with previous ARDS and, particularly, previous septic shock and reoperation. When such risk factors are identified, colistin may be the only appropriate treatment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Care; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Risk Factors

The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial agents were determined by broth microdilution. The most active antimicrobial agents (> or =95% of isolates susceptible) were colistin, polymyxin B, and minocycline.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Military Personnel; Minocycline; Polymyxin B; United States; Warfare

A 16 year-old girl underwent a multifocal (lungs, skin, soft tissues) infection due to multiresistant Acinetobacter baumannii after a car crash. To treat such a severe disease we used a combination therapy of colistin (2 millions Units twice/day), rifampicin (600 mg/day), meropenem (1 g 3 times a day) after a synergistic activity test was performed (checkerboard method on Mueller-Hinton broth and 5x10(5) cfu/mL inoculum). After 24 days, when a significant clinical improvement was gained, the 3-drugs combination therapy was replaced with i.v. levofloxacin 500 mg twice/day but, after 10 days of quinolones therapy, fever started again and the same multidrug resistant (MDR) A. baumannii was isolated from the skin grafts, central venous catheter tip and bronchial alveolar lavage. A combination therapy with colistin and meropenem was therefore started and definitive defervescence was obtained after 10 days. This therapy was continued for 70 days even if the patient was apyretic because A. baumannii was still present in the skin secretions. After 109 days of hospitalization in our intensive care unit, the patient was transferred to a rehabilitative unit. This case shows how useful is, in selected cases, rediscovering old antibiotic drugs, specially when they are adopted as a combination therapy, and highlights the importance of the clinical microbiological laboratory as it may help clinicians in choosing the best drugs combination.

Topics: Accidents, Traffic; Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Amputation, Traumatic; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Meropenem; Microbial Sensitivity Tests; Rifampin; Thienamycins

The effect of colistin on bacterial eradication and survival was tested in experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh infection model was applied in 86 neutropenic Wistar rats. Six rats were used for the induction of neutropenia and for the selection of the dose regimen of colistin; the remainder was equally divided into four groups: A, controls; B, rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after bacterial challenge; 5mg/kg of rifampicin was administered intravenously and 3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4h after therapy; blood and tissue samples were sampled. Median survival of animals of groups A, B, C and D was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100, 100, 100 and 70%, respectively (P=0.018 between groups). Statistically significant decreases of bacteria were found in blood, liver, lung and spleen of group B compared with A; in lung of group C compared with A; and in blood and liver of group D compared with A. Colistin was effective in prolonging survival in an experimental thigh infection by multidrug-resistant A. baumannii in neutropenic rats. Its activity was enhanced after co-administration with rifampicin. These results mandate the application of colistin in the event of infections by multidrug-resistant pathogens and the need for its co-administration with rifampicin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Blood; Colistin; Cyclophosphamide; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Injections, Intramuscular; Injections, Intravenous; Liver; Lung; Male; Rats; Rats, Wistar; Rifampin; Spleen; Survival Analysis; Survival Rate; Treatment Outcome

Post-surgical meningitis and/or ventriculitis caused by Gram-negative bacteria may be difficult to treat due to the emergence of multiresistant strains. Two patients with multiresistant Acinetobacter baumannii central nervous system infection, successfully treated with either intravenous and/or intraventricular colistin are presented. Unresolved issues such as dose and duration of intraventricular colistin are discussed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aneurysm, Ruptured; Anti-Bacterial Agents; Colistin; Craniocerebral Trauma; Cross Infection; Device Removal; Drug Resistance, Multiple, Bacterial; Female; Humans; Hydrocephalus; Injections, Intraventricular; Intracranial Aneurysm; Male; Postoperative Complications; Ventriculoperitoneal Shunt

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Topics: Acinetobacter Infections; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Retrospective Studies; Risk Factors; Thienamycins; Ventilators, Mechanical

Our study aimed to determine the efficacy and safety of colistin in the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug-resistant Pseudomonas aeruginosa or Acinetobacter baumanii.. Pairwise, retrospective exposed-unexposed study.. Combined medical and surgical intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia).. Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P. aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa susceptible to imipenem. All patients had normal renal function at the onset of antibiotic therapy.. Case patients were treated by colistin intravenously and control patients were treated by imipenem intravenously.. Baseline characteristics were similar between the colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was 9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20 days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious parameters after the initiation of antibiotic therapy was not statistically different between the two groups. During the antibiotic course, none of the patients in either group developed renal failure.. We conclude that colistin can be a safe and effective option in the treatments of VAP caused by pan-drug-resistant P. aeruginosa or A. baumanii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Injections, Intravenous; Intensive Care Units; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Retrospective Studies; Time Factors

We investigated an outbreak of Acinetobacter baumannii in the intensive care unit (ICU) of a hospital in Rome, Italy. The outbreak involved 14 patients whose isolates were most frequently recovered from bronchoalveolar lavage. All isolates were multidrug-resistant and showed diminished susceptibility or resistance to carbapenems. A. baumannii strains with a similar antibiotic susceptibility pattern were isolated from the environment. Pulsed-field gel electrophoresis identified a single clone from both the patients' and environmental isolates. Because of the lack of a single source of infection, the eradication of the epidemic required a broad approach, including contact isolation and cohorting, aggressive environmental disinfection, and close monitoring of the ward staff's performance. Infected patients were successfully treated with combined therapy. Although considered of low virulence, A. baumannii can be particularly aggressive and difficult to treat in ICU patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Disinfection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Isolation; Rifampin; Rome; Sulbactam

The study investigated the effect of colistin and minocycline when tested singly and in combination against Acinetobacter baumannii.. Thirteen unrelated imipenem-resistant A. baumannii clinical isolates were included in the study. MICs of colistin sulphate and minocycline were determined by broth macrodilution and Etest. Organisms were also tested against the two antibiotics singly and in combination using time-kill methods and an Etest-based method.. Neither colistin nor minocycline when tested alone demonstrated bactericidal activity. However, the combination of colistin and minocycline demonstrated bactericidal activity against most of the isolates tested. At 24 h, the combination of antibiotics demonstrated synergy in 12 of the 13 isolates by time-kill methods. None of the isolates demonstrated synergy by Etest methods.. The combination of colistin and minocycline was found to be bactericidal and synergistic against A. baumannii by time-kill methods. There was no agreement between time-kill and Etest methods for synergy testing.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline

To determine the in vitro activities and interactions of imipenem, colistin and tigecycline with old antibacterial agents against carbapenem-resistant Acinetobacter baumannii.. Forty-three carbapenem-resistant A. baumannii isolates from the intensive care unit of a university hospital were collected and their MICs of imipenem, colistin and tigecycline were determined. With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill study was performed for the evaluation of antibacterial activity of colistin, tigecycline, imipenem/sulbactam and colistin/rifampicin.. The time-kill study of colistin demonstrated bactericidal activity against A. baumannii at concentrations of 4xMIC and 8xMIC, whereas tigecycline showed bacteriostatic activity at all concentrations. The combination regimens of imipenem/sulbactam and colistin/rifampicin were synergistic and bactericidal at 1xMIC.. Imipenem/sulbactam combination, colistin and tigecycline showed good in vitro activities against carbapenem-resistant A. baumannii isolates. Even though colistin is bactericidal against carbapenem-resistant A. baumannii, the colistin/rifampicin combination is more warranted in order to be certain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Sulbactam; Tigecycline

Increasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest on MH and Isosensitest agar, broth microdilution, and VITEK 2) on 102 clinical isolates collected from patient materials during a selective digestive decontamination or selective oral decontamination trial in an intensive-care unit. Disk diffusion is an unreliable method to measure susceptibility to colistin. High error rates and low levels of reproducibility were observed in the disk diffusion test. The colistin Etest, agar dilution, and the VITEK 2 showed a high level of agreement with the broth microdilution reference method. Heteroresistance for colistin was observed in six Enterobacter cloacae isolates and in one Acinetobacter baumannii isolate. This is the first report of heteroresistance to colistin in E. cloacae isolates. Resistance to colistin in these isolates seemed to be induced upon exposure to colistin rather than being caused by stable mutations. Heteroresistant isolates could be detected in the broth microdilution, agar dilution, Etest, or disk diffusion test. The VITEK 2 displayed low sensitivity in the detection of heteroresistant subpopulations of E. cloacae. The VITEK 2 colistin susceptibility test can therefore be considered to be a reliable tool to determine susceptibility to colistin in isolates of genera that are known not to exhibit resistant subpopulations. In isolates of genera known to (occasionally) exhibit heteroresistance, an alternative susceptibility testing method capable of detecting heteroresistance should be used.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Agar; Anti-Bacterial Agents; Bacterial Infections; Colistin; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymyxin B

Multidrug-resistant Acinetobacter baumannii infection has presented a global medical challenge. The antibiograms of paired colistin-susceptible and -resistant strains revealed increased susceptibility of colistin-resistant strains to most tested antibiotics, including those that are active against only gram-positive bacteria. Synergy between colistin and rifampicin was observed in the colistin-susceptible strains. The ability to form biofilm in the colistin-resistant strains was significantly lower (P<.001) than in the parent strains. Our study provides valuable information for potential expansion of our current therapeutic options against colistin-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Rifampin

To investigate antimicrobial resistance in clinical isolates of Acinetobacter spp. from two Korean hospitals.. Two hundred and sixty-five isolates of Acinetobacter spp. from two Korean hospitals were collected and were identified to species level using partial rpoB gene sequences. Antimicrobial susceptibility testing was performed using a broth microdilution method.. rpoB gene sequences indicated that 214 isolates (80.8%) were Acinetobacter baumannii, and allowed these to be classified into three subgroups (I, II and III); 142 isolates (53.6%) belonged to subgroup I, 54 (20.4%) to subgroup II and 18 (6.8%) to subgroup III. Forty-eight isolates (18.1%) and 74 isolates (27.9%) were resistant to polymyxin B and colistin, respectively. However, antimicrobial resistance rates varied markedly between subgroups. While A. baumannii subgroup I showed low resistance rates to polymyxin B and colistin (2.1% and 7.0%, respectively), subgroups II and III showed high resistance rates to these antibiotics (38.9% and 64.8% in subgroup II and 72.2% and 88.9%, in subgroup III, respectively). Multidrug resistance was also significantly more frequent in subgroup I (45.1%) than in subgroups II and III (13.0% and 16.7%, respectively).. Our data indicate that subgroup identification of A. baumannii may aid selection of appropriate antimicrobial agents for the treatment of Acinetobacter infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Korea; Phylogeny; Polymyxin B

Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Blotting, Southern; Carbapenems; China; Chloramphenicol; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Rifampin; Sequence Analysis, DNA

This study evaluated the activity of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against nine epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemase in Naples, Italy. The isolates were susceptible to colistin but differed in their resistance to imipenem and rifampicin. Time-kill studies showed a bactericidal effect for colistin but not for imipenem, rifampicin or sulbactam/ampicillin used as single agents. Synergism was observed with combinations of rifampicin+imipenem or sulbactam/ampicillin for all isolates and with colistin+rifampicin for isolates showing higher minimum inhibitory concentrations for rifampicin. Combined use of the antimicrobials tested may provide good therapeutic options for OXA-58 carbapenemase-producing A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Drug Synergism; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Italy; Microbial Sensitivity Tests; Rifampin; Sulbactam

In this study, we explored risk factors associated with bacteraemia caused by colistin-susceptible/carbapenem-resistant (Co(S)/Ca(R)) Acinetobacter baumannii. A retrospective cohort study of hospitalised patients with A. baumannii bacteraemia was performed at a tertiary care hospital over a 44-month period. Thirty-nine patients with bacteraemia due to A. baumannii (35 Intensive Care Unit and 4 ward patients) were included in the analysis. Twenty-five patients (64%) had bacteraemia due to Co(S)/Ca(R)A. baumannii and 14 patients (36%) had bacteraemia due to colistin-susceptible/carbapenem-susceptible A. baumannii. Mortality was 56% (14/25) and 35.7% (5/14) for patients in the two groups, respectively (P=0.22). Bivariate analysis showed that prior exposure to fluoroquinolones (P=0.01) and antipseudomonal penicillins (P=0.004) as well as a higher number of antibiotics in use on the day of bacteraemia (P=0.02) were associated with isolation of a Co(S)/Ca(R) strain among patients with A. baumannii bacteraemia. Multivariate analysis using a backward logistic regression model showed that only exposure to fluoroquinolones was associated with development of Co(S)/Ca(R)A. baumannii bacteraemia (odds ratio=11.6; 95% confidence interval 2.4-55.9; P=0.02). The appearance of Co(S)/Ca(R)A. baumannii infections represents a major threat to critically ill hospitalised patients. Exposure to fluoroquinolones is an independent risk factor for development of Co(S)/Ca(R)A. baumannii bacteraemia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Blood; Carbapenems; Cohort Studies; Colistin; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Penicillins; Quinolones; Retrospective Studies; Risk Factors

Multi-drug resistant (MDR) organisms in intensive care units (ICUs) are a growing concern. The emergence of several infections with MDR Acinetobacter baumannii prompted a review of cases and evaluation of the efficacy of intervention.. To determine the rate of clinical cure, the incidence of drug resistance, and the mortality rate associated with A. baumannii infection.. Retrospective review of A. baumannii infections in three surgical ICUs between January, 2004 and November, 2005. Infection was identified in 291 patients, 20 of whom were excluded because of incomplete documentation. Of the remaining 271 patients, 71% were male, and the mean age was 47 +/- 18 years (range 13-90 years).. Patients had a mean length of stay in the ICU of 14 days (range 0-136 days) before infection. The initial positive cultures were from bronchoalveolar lavage fluid (BAL) in 72.3%, blood in 16.2%, a catheter tip in 6.3%, urine in 1.8%, wound in 2.2%, and abscess in 1.1%. In 46.9% of patients, the first culture was polymicrobial. The Acinetobacter isolates were resistant or intermediate-resistant to imipenem-cilastatin in 81.2% of cases; 19.9% were resistant to all drugs except colistin, and two were resistant to all tested drugs. Colistin was used in 75.6% of patients (intravenous 61.5%, nebulized 38.5%). The mean duration of treatment was 13 +/- 8.9 days (range 0-56 days), and clinical cure was achieved in 73.8% of patients. Recurrent infection after initial cure was found in 19.2% of patients. There was no significant difference in clinical cure rates between patients treated with colistin and those treated with other culture-directed drugs (75.1% vs. 69.7%), or between patients treated with intravenous vs. nebulized colistin (72.4% vs. 79.5%). The mortality rate was 26.2% for the entire group and was significantly higher in the subgroup of transplant patients (n = 31) (64.5% vs. 21.4%; p < 0.001).. The majority of A. baumannii isolates were MDR, and a significant proportion were sensitive only to colistin. Treatment of A. baumannii infection with colistin is effective by both intravenous and nebulized routes of administration. However, infection with A. baumannii in critically ill surgical patients is associated with a high mortality rate, particularly in transplant patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Florida; Hospital Mortality; Humans; Immunosuppression Therapy; Incidence; Intensive Care Units; Male; Middle Aged; Organ Transplantation; Retrospective Studies

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections

Emergence of panresistant gram negative bacilli has lead to the progressive reintroduction of intravenous colistin.. To describe the clinical experience observed with this compound.. A retrospective analysis was performed for all treatments lasting >/= 48 hours. Medical records were analyzed to obtain clinical parameters and microbiological data, evaluate clinical response and evolution until discharge.. 24 treatments lasting >/= 48 hours were applied between June 2005 and September 2006. Intravenous colistin was indicated to treat cases of ventilator-associated (VA) pneumonia (n = 10; 41.7%), abscess or collections (12.5%), bloodstream infections, non-VA pneumonia or urinary tract infections (4.2% each one, respectively). Treatment was initiated on average at 3.2 days (+/- 2.85) from diagnosis of infection. All courses were microbiologically-guided, and involved P. aeruginosa or A. baumannii isolates. Susceptibility was evaluated by E-test in 11 isolates (MIC90 3.6 nicrog/mL, range 0.38 to 4 microg/mL). One isolate was resistant to colistin (9%). A favorable response was observed in 12 treatments (50%) with a relapse in 5 cases (41.7%). Being treated for pneumonia was the only factor associated to failure, (p = 0.04) Eradication was documented in 8 cases (33.3%) and persistence in 11 (45.8%). In 5 cases a microbiological follow-up was not available. Survival at time of discharge was 45.5%. (n = 10) None of the treatment courses was associated with nefrotoxicity.. Intravenous colistin is a safe compound useful to treat various nosocomial infections due to pan-resistant gram negative bacilli. Nonetheless, its clinical efficacy is limited, especially among patients treated for nosocomial pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Multidrug-resistant Acinetobacter baumannii is an emergent nosocomial pathogen. A 61-year-old woman developed meningitis caused by MDRAB 27 days after receiving a surgical intervention for invasive meningioma. The patient failed to respond to high doses of meropenem and sulbactam treatment and the organism persisted in the cerebrospinal fluids for two months. The regimen was changed to intravenous and intrathecal colistin for 28 days and the patient responded well. Administration of colistin both intravenously and intrathecally could be a suitable option as a salvage therapy for meningitis due to multidrug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Cerebrospinal Fluid; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Injections, Spinal; Meningeal Neoplasms; Meningioma; Meningitis, Bacterial; Middle Aged; Postoperative Complications

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Craniocerebral Trauma; Cross Infection; Drug Resistance, Bacterial; Humans; Injections, Spinal; Male; Meningitis, Bacterial

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Rifampin

Reported here is the case of a patient with septic shock due to multidrug-resistant Acinetobacter baumannii, which developed after complicated acute pancreatitis with intra-abdominal abscess. Treatment with colistin methanesulphonate and high doses of meropenem were initiated, but since shock persisted, tigecycline was added to the regimen, resulting in successful resolution of the infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Minocycline; Pancreatitis, Acute Necrotizing; Shock, Septic; Thienamycins; Tigecycline; Treatment Outcome

CNS infections due to multiresistant Acinetobacter baumannii (MRAB) are an emerging problem in neurosurgical patients. Colistin remains one of the few remaining treatment options for MRAB but has poor CNS penetration. We describe our experience with intraventricular or intrathecal colistin for this infection.. Cases known to have received intraventricular or intrathecal colistin for CNS infections due to MRAB were retrospectively reviewed regarding colistin treatment, colistin efficacy and adverse events.. Five patients were identified. All were admissions to the neurosurgical ICU and all were cured of their CNS infections. Three cases were complicated by drug-induced aseptic meningitis or ventriculitis.. This largest case series to date shows that direct instillation of colistin into the CNS may cause chemical meningitis or ventriculitis but it is an effective treatment option for MRAB CNS infection. Further study of dosing regimens is needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Central Nervous System Bacterial Infections; Child, Preschool; Colistin; Drug Resistance; Female; Humans; Injections, Intraventricular; Injections, Spinal; Male; Middle Aged

Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as "salvage" therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 microg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10(8) to 10(9) CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 microg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 microg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 microg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in "colistin-susceptible" clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Microbial Sensitivity Tests

The prospective case series study presented here was conducted to assess the outcome of patients with infections caused by polymyxin-only-susceptible (POS) gram-negative bacteria managed with intravenous colistin. Between July 2003 and April 2005 a total of 27 patients were infected with a POS gram-negative bacterium and received intravenous colistin at a dose of 2 million international units (MIU) (160 mg or 66.7 mg colistin base) every 8 h for a mean (+/-SD) duration of 13.9 (+/-7.5) days. Nine patients had ventilator-associated pneumonia and received, in addition to the intravenous colistin therapy, 1 MIU (80 mg or 33.3 mg colistin base) aerosolized colistin every 12 h for a mean (+/-SD) duration of 13 (+/-6.5) days. The predominant pathogens were Pseudomonas aeruginosa (n = 17) and Acinetobacter baumannii (n = 12); in two patients both pathogens were isolated from one clinical specimen. In-hospital mortality and clinical response were 15% and 85%, respectively. Colistin-associated nephrotoxicity was observed in two of the 27 patients. POS gram-negative pathogens represent a major threat for hospitalized patients. Colistin appears to be an effective and safe treatment, even in patients with severe underlying diseases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Treatment Outcome

The objective of this study was to determine the efficacy of systemic colistin therapy in the treatment of nosocomial infections caused by multidrug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa and to study related adverse events. We prospectively studied 78 infections caused by multidrug-resistant A. baumannii or P. aeruginosa that were treated with colistin. The sites of infection were pulmonary infection (78.2%), urinary tract infection (7.7%), primary bloodstream infection (11.5%) and meningitis (2.6%). The mean daily dose of colistin was 5.5+/-1.1 MU/day (range 2-9 MU/day) and the mean duration of colistin therapy was 9.3+/-3.8 days (range 5-21 days). A favourable clinical response to colistin occurred in 60 cases (76.9%). Renal failure occurred in only seven cases. We conclude that colistin can be a safe and effective salvage therapeutic option for nosocomial infections caused by multidrug-resistant A. baumannii or P. aeruginosa.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Prospective Studies; Pseudomonas Infections; Salvage Therapy; Treatment Outcome

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Biomedical Research; Colistin; Critical Care; Databases, Bibliographic; Decision Making; Drug Resistance, Multiple, Bacterial; Humans; Information Storage and Retrieval; Pneumonia, Bacterial

The use of colistin for the treatment of infections caused by multiple-drug-resistant (MDR) gram-negative microorganisms was studied.. The efficacy of colistin for treating infections caused by MDR gram-negative microorganisms and the development of renal toxicity were studied in hospitalized adult patients in Spain. Patients treated between January 2001 and October 2001 were included.. Over the study period, 71 courses of inhaled colistin, 12 courses of i.v. or intramuscular (i.m.) colistin, and 2 courses of intrathecal colistin were administered to 80 patients. All were infected by MDR organisms: 69 (86%) by Acinetobacter baumannii and 11 (14%) by Pseudomonas aeruginosa. In 41 patients (51%), the episodes were caused by A. baumannii strains susceptible exclusively to colistin. The causative organisms were cleared in 92% of the patients from whom posttreatment repeat specimens were obtained. The in-hospital mortality rate was 18% (14 patients). There were no significant changes in mean serum urea or creatinine concentrations in patients receiving i.v. or i.m. therapy.. Colistin was used in 80 patients infected with A. baumannii or P. aeruginosa and appeared to be efficacious and safe.

Topics: Acinetobacter Infections; Colistin; Drug Administration Routes; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Inpatients; Length of Stay; Male; Middle Aged; Pseudomonas Infections; Retrospective Studies; Spain; Treatment Outcome

We compared the E-test to the broth microdilution method for testing the susceptibility of 115 clinical isolates of Acinetobacter baumannii to colistin. Twenty-two (19.1%) strains were resistant to colistin and 93 (80.8%) strains were susceptible according to the reference broth microdilution method. A categorical agreement of 98.2% was found, with only two (1.7%) very major errors. Agreement within 1 twofold dilution between the E-test and the broth microdilution was 16.5%. Complete agreement was found for the strains for which MICs fell within the range of 0.25 to 1 microg of colistin/ml. However, there was poor concordance, particularly in extreme dilutions with higher MICs by the E-test method.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests

Continuous intravenous colistin (2,000,000 units per 24 h) was administered in a 41-y-old patient with Acinetobacter baumannii bacteraemia, which led to the cure of the infection. The isolated microorganism was a multi-resistant strain (it was sensitive only to colistin). In addition, the patient had developed allergic reactions to previously administered antimicrobial agents of several classes during his hospitalization. Continuous intravenous infusion of colistin proved to be a salvage regimen, which led to cure of a bacteraemia due to a multi-resistant isolate, without showing any allergic cross-reactivity with other antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Bacteremia; Colistin; Diagnosis, Differential; Drug Resistance, Bacterial; Humans; Infusions, Intravenous; Male

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Infusions, Intravenous; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

We report a case of serious nosocomial meningitis due to a multidrug-resistant Acinetobacter baumannii in a 23-year-old woman who had a posterior fossa craniotomy with upper cervical laminectomy for excision of a meningioma at the level of foramen magnum. Post-operatively, she had neck pain with continuous fever and deterioration in the level of consciousness and convulsions. The CSF was turbid and had neutrophil pleocytosis. A multidrug-resistant Acinetobacter baumannii was isolated from the blood and CSF. The patient failed high doses of imipenem, ciprofloxacin and systemic colistin but responded well to intraventricular injections of colistin 125,000 units twice daily for 3 weeks. No apparent side effects were noticed. We have reviewed other similar cases reported in the literature.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Microbial; Female; Humans; Injections, Intraventricular; Meningitis, Bacterial; Treatment Outcome

We report a case of a 52-year-old man with post-surgical meningitis due to a multi-drug resistant Acinetobacter baumannii. Despite therapy with intravenous amikacin and imipenem the meningitis progressed. Upon institution of combination therapy with amikacin by the intravenous and intrathecal (IT) routes, and intravenous colistin the patient experienced successful clinical and microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Humans; Infusions, Intravenous; Injections, Spinal; Male; Meningitis, Bacterial; Middle Aged; Treatment Failure

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Rifampin; Treatment Outcome

Twenty-one patients with multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia were treated with nebulized polymyxin E (colistin). Overall clinical and microbiological response rates were 57.1% and 85.7%, respectively. Nebulized colistin may be reasonably efficacious and safe for treatment of MDR pneumonia. Its role in therapy warrants further investigation in comparative studies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Anti-Bacterial Agents; Central Nervous System Bacterial Infections; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Meningitis, Bacterial; Middle Aged; Treatment Outcome

Topics: Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Spinal; Treatment Outcome

We report our experience with two cases of fixation device-related orthopedic infections due to multidrug-resistant Acinetobacter baumannii strains. Both patients were successfully treated with intravenous administration of colistin, despite the reported poor penetration of this medication to these tissues, in the old literature. No serious colistin-associated toxicity developed and no recurrence of the infection occurred on follow up.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Infusions, Intravenous; Male; Middle Aged; Prostheses and Implants

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex includes some of the most clinically relevant species of the genus Acinetobacter due to their capacity to cause epidemic nosocomial outbreaks as well as their increasing resistance to antibiotics. Susceptibility of Acinetobacter strains varies greatly depending on origin, thus highlighting the importance of local analyses of susceptibility profiles. Two hundred twenty-one strains of the A. calcoaceticus-A. baumannii complex were identified using biochemical tests and were biotyped. Strain susceptibility to imipenem, meropenem, colistin and sulbactam was studied using agar dilution. Eight different biotypes were found, type 1 accounting for 69.2% of the strains. MIC(50) and MIC(90) to imipenem, meropenem, colistin and sulbactam were 4 and 8 mg/l, 16 and 32 mg/l, 0.5 and 1mg/l, and 8 and 16 mg/l, with susceptibility rates of 64.3, 22.6, 98.2 and 73.8%, respectively. Biotype 1 was the most resistant. A statistically significant difference was observed for the mean MIC of the four predominant biotypes to imipenem, meropenem and sulbactam but not to colistin.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; Drug Resistance, Microbial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Sulbactam; Thienamycins

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Female; Humans; Injections, Spinal; Meningioma; Meningitis, Bacterial; Middle Aged; Neurosurgical Procedures; Postoperative Complications

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Colony Count, Microbial; Disease Models, Animal; Endocarditis, Bacterial; Heart Valves; Humans; Microbial Sensitivity Tests; Rabbits; Treatment Outcome

Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model.. We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively.. In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone.. Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rifampin; Tobramycin

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Kidney Diseases

We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Female; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged; Pneumonia; Prospective Studies; Renal Insufficiency; Ventilators, Mechanical

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Pneumonia, Bacterial; Respiration, Artificial

A total of 287 Acinetobacter isolates belonging to DNA groups 2 (A. baumannii) and 13TU was collected consecutively from 46 hospitals and typed by randomly amplified polymorphic DNA fingerprinting with primers DAF-4 and ERIC-2. With a similarity coefficient of >/=72% as a cut-off value, 37 clusters of genotypically similar isolates (genotypes) were recognised. Four major clusters, found in 15, 12, 12 and 8 hospitals respectively, accounted for 42% of isolates, but only three of these predominant clusters were associated with outbreaks of infection in individual hospitals. Many of the isolates were resistant to multiple antibiotics, including expanded-spectrum beta-lactam agents, aminoglycosides, tetracyclines and fluoroquinolones, but >98% remained susceptible to carbapenems and colistin. Overall, the study demonstrated that a heterogeneous population of Acinetobacter DNA group 2 and 13TU isolates, frequently showing multiple resistance to antibiotics, was causing infections in UK hospitals, and that four predominant genotypes appeared to have disseminated among geographically distinct locations.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cluster Analysis; Colistin; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Random Amplified Polymorphic DNA Technique; United Kingdom

The effect of a selective decontamination of the digestive tract (SDD) regimen including polymyxin and tobramycin on several body site reservoirs was compared between a test group and a control group in intensive care unit (ICU) patients with faecal multi-resistant Acinetobacter baumannii colonization. SDD significantly reduced faecal and pharyngeal carriage when compared with the control group at the end of ICU stay (48% versus 91%, P = 0.001, and 38.5% versus 78%, P = 0.01, respectively), but failed to reduce axillary colonization (75% versus 78%, P = 0.6). In addition, the isolation of A. baumannii from new clinical samples was lower in patients with SDD (45.5% versus 81%, P = 0.05). No resistance to polymyxin was observed. We conclude that the digestive tract reservoir of A. baumannii in ICU patients may be decreased by a SDD regimen.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Colistin; Digestive System; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Middle Aged; Pilot Projects; Prospective Studies; Tobramycin

Described here is a case of meningitis caused by multidrug-resistant Acinetobacter baumannii susceptible only to colistin, which was treated successfully with intravenous colistin sulfomethate sodium (5 mg/kg/day). The levels of colistin in serum and cerebrospinal fluid and the pharmacokinetic/pharmacodynamic parameters of colistin were determined. In this case, intravenously administered colistin penetrated cerebrospinal fluid (25% of serum levels) at levels sustaining bactericidal concentrations.

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Humans; Injections, Intravenous; Male; Meningitis, Bacterial; Microbial Sensitivity Tests

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Female; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rifampin; Survival Analysis

The increased incidence of nosocomial infections by multidrug-resistant Acinetobacter spp creates demand on the application of some combinations of older antimicrobials on that species. The in vitro activities of colistin and of rifampin and of their interaction were tested on 39 nosocomial isolates of Acinetobacter baumannii. All isolates were resistant to ampicillin/sulbactam, to 3(rd) and 4(th) generation cephalosporins, to amikacin and to ciprofloxacin. MICs were determined by a microdilution technique and interactive studies between 1x or 4x MIC of colistin and rifampin were performed by the time-kill assay. Rifampin was applied at a concentration of 2 microg/mL which is equal to its mean serum level. All isolates were inhibited by colistin and only 15.2% by rifampin. Synergy between 1x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 51.3% of isolates at 24 h of growth. Synergy between 4x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 66.7% of isolates at 24 h of growth. It is concluded that colistin is highly active on multidrug-resistant Acinetobacter spp and its activity on A.baumannii is increased in the presence of rifampin, so that their administration might be proposed for nosocomial infections by these isolates.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Synergism; Humans; Microbial Sensitivity Tests; Rifampin

Acinetobacter baumannii is an opportunistic pathogen associated with numerous nosocomial infections. In recent years it has shown extraordinary ease in developing resistance to most antimicrobial agents, which is a serious problem as it makes these infections difficult to treat. We determined the in vitro activity of eight quinolones, five betalactam agents and colistin in 160 clinical isolates of A. baumannii. In general, we observed a high rate of resistance to the quinolones (90%), excluding clinafloxacin (25%), and to ampicillin-sulbactam (61.25%) and imipenem (50%). Colistin is the agent with least resistance (13.125%), although its toxicity limits its therapeutic use. Clinafloxacin may be a good option to treat A. baumannii infections, especially in cases of therapeutic failure with other antimicrobial agents.

Topics: Acinetobacter; Acinetobacter Infections; Ampicillin; Anti-Infective Agents; Aza Compounds; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Fluoroquinolones; Gatifloxacin; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Moxifloxacin; Nalidixic Acid; Naphthyridines; Norfloxacin; Ofloxacin; Opportunistic Infections; Quinolines; Sulbactam; Thienamycins

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Drug Resistance, Multiple; Female; Humans; Meningitis, Bacterial; Middle Aged; Treatment Outcome

Topics: Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Critical Care; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Erythromycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Patient Isolation; Risk Factors

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Adult; Anti-Bacterial Agents; Brain Diseases; Carbapenems; Central Nervous System Bacterial Infections; Cerebral Ventricles; Colistin; Drug Resistance, Microbial; Encephalitis; Female; Humans; Injections, Intraventricular; Male; Middle Aged; Treatment Outcome