colistin and Klebsiella-Infections

We aimed to describe the effect of aminoglycosides and tigecycline to reduce the mortality in colistin- and carbapenem-resistant Klebsiella pneumoniae (ColR-CR-Kp) infections. We included the studies with defined outcomes after active or non-active antibiotic treatment of ColR-CR-Kp infections. The active treatment was defined as adequate antibiotic use for at least 3 days (72 h) after the diagnosis of ColR-CR-Kp infection by culture. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the checklist of PRISMA 2020 was applied. Crude and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated and pooled in the random effects model. Adding aminoglycosides to the existing treatment regimen reduced overall mortality significantly (OR 0.34, 95% CI 0.20-0.58). Overall mortality was 34% in patients treated with aminoglycoside-combined regimens and was 60% in patients treated with non-aminoglycoside regimens. Treatment with tigecycline is not found to reduce mortality (OR: 0.76, 95% CI: 0.47-1.23). Our results suggest that aminoglycoside addition to the existing regimen of colistin- and carbapenem-resistant Klebsiella pneumoniae infections reduces mortality significantly.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sepsis; Tigecycline

OXA-48 and NDM are amongst the most prevalent carbapenemase types associated with. We reviewed studies looking at the antibiotic treatment and outcome of OXA-48-like and/or NDM-producing CRKP.. The best available treatment option for OXA-48 producers is ceftazidime-avibactam, where available and when the price permits its use. Colistin remains as the second-line option if

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Cefiderocol; Colistin; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mutation; Permeability

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

Several recent cases associating cleaned and high-level disinfected duodenoscopes with outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs) may cause bronchoscopists, pulmonologists, and other stakeholders to inquire about the effectiveness of today's practices for reprocessing flexible bronchoscopes. The primary objectives of this study were to address this question and investigate the risk of bronchoscopes transmitting infections of CRE and related MDROs. The published literature and the US Food and Drug Administration's medical device database of adverse events were searched beginning in 2012, when endoscopy first emerged as a recognized risk factor for transmission of CRE. The Internet was also searched during this same time frame to identify other relevant cases. Several cases associating reprocessed bronchoscopes with infections of CRE or a related MDRO were identified. This study's findings suggest that bronchoscopes may pose an underrecognized potential for transmission of CRE and related MDROs, warranting greater public awareness, enhanced preventive measures, and updated reprocessing guidance. This study's data also suggest that the cleaning and high-level disinfection of bronchoscopes performed in accordance with published guidelines and manufacturer instructions may not always be sufficiently effective to eliminate this risk. Several factors were identified that can adversely affect a bronchoscope's reprocessing and pose a risk of transmission of these multidrug-resistant bacteria, including use of a damaged or inadequately serviced bronchoscope, and formation of an inaccessible biofilm. Recommendations are provided to improve the safety of flexible bronchoscopes, including supplementing their reprocessing with an enhanced measure such as sterilization when warranted, and strict adherence to a periodic servicing and maintenance schedule consistent with the bronchoscope manufacturer's instructions.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Bronchoscopes; Bronchoscopy; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cross Infection; Disinfection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Equipment Contamination; Equipment Reuse; Humans; Klebsiella Infections; Klebsiella pneumoniae; Pseudomonas aeruginosa; Pseudomonas Infections

Carbapenem-resistant Enterobacteriaceae infections have spread globally, leaving polymyxins, including colistin, as 'last-resort treatments'. Emerging colistin resistance raises the spectre of untreatable infections. Despite this threat, data remain limited for much of the world, including Southeast Asia where only 3 of 11 nations submitted data on carbapenem and colistin resistance for recent World Health Organization (WHO) reports. To improve our understanding of the challenge, we utilised broad strategies to search for and analyse data on carbapenem and colistin resistance among Escherichia coli and Klebsiella in Southeast Asia. We found 258 studies containing 526 unique reports and document carbapenem-resistant E. coli and Klebsiella in 8 and 9 of 11 nations, respectively. We estimated carbapenem resistance proportions through meta-analysis of extracted data for nations with ≥100 representative isolates. Estimated resistance among Klebsiella was high (>5%) in four nations (Indonesia, Philippines, Thailand and Vietnam), moderate (1-5%) in two nations (Malaysia and Singapore) and low (<1%) in two nations (Cambodia and Brunei). For E. coli, resistance was generally lower but was high in two of seven nations with ≥100 isolates (Indonesia and Myanmar). The most common carbapenemases were NDM metallo-β-lactamases and OXA β-lactamases. Despite sparse data, polymyxin resistance was documented in 8 of 11 nations, with mcr-1 being the predominant genotype. Widespread presence of carbapenem and polymyxin resistance, including their overlap in eight nations, represents a continuing risk and increases the threat of infections resistant to both classes. These findings, and remaining data gaps, highlight the urgent need for sufficiently-resourced robust antimicrobial resistance surveillance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asia, Southeastern; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Genotype; Humans; Infant; Infant, Newborn; Klebsiella Infections; Male; Middle Aged; Young Adult

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 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

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).. Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B; Polymyxins; Tigecycline; Treatment Outcome; Urinary Tract Infections

The wide dissemination of carbapenemase producing K. pneumoniae (KPC-Kp) has caused a public health crisis of global dimensions, due to the serious infections in hospitalized patients associated with high mortality. In 2014, we aim to review clinical data on KPC-Kp at a time when a pro-active strategy (combating the problem before it is established) is no longer useful, focusing on epidemiology, patient risk profile, infection control, digestive tract colonization and treatment issues such as the role of carbapenems or carbapenem sparing strategies, colistin and resistance, dual carbapenem administration and the role of tigecycline. All these issues are illustrated prospectively to provide a forum for a Consensus strategy when not only intensive care units but also medical and surgical wards are affected by the epidemics.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Drug Therapy, Computer-Assisted; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Risk Factors; Tigecycline

Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial infection at a high mortality rate. Nosocomial pneumonia in particular is associated with high mortality, likely due to the unfavorable pulmonary pharmacokinetics of the antibiotics used against this agent. Therefore, early and accurate microbiological identification and susceptibility evaluation are crucial in order to optimize antibiotic therapy. We report a case of ventilator-associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC-type carbapenemase treated using a carbapenem-sparing therapy and tailored according to the serum procalcitonin concentration in order to limit the duration of antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Calcitonin; Calcitonin Gene-Related Peptide; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Equipment Contamination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Pneumonia, Bacterial; Protein Precursors; Tigecycline; Treatment Outcome; Ventilators, Mechanical

Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two antibiotics were previously regarded to be largely equivalent, due to similarities in their chemical structure and spectrum of activity. In recent years, several pertinent differences, especially in terms of potency and disposition, have been revealed between polymyxin B and colistin. These differences are mainly attributed to the fact that polymyxin B is administered parenterally in its active form, while colistin is administered parenterally as an inactive pro-drug, colistimethate. In this review, we summarize the similarities and differences between polymyxin B and colistin. We also discuss the potential clinical implications of these findings, and provide our perspectives on how polymyxins should be employed to preserve their utility in this era of multi-drug resistance.

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxin B

Increasing use of colistin for multidrug-resistant Gram-negative bacterial infections has led to the emergence of colistin resistance in Klebsiella pneumoniae in several countries worldwide, including Europe (especially Greece), and colistin resistance rates are continually increasing. Heteroresistance rates, which were significantly higher than resistance rates, were found to be important. Although the mechanism underlying resistance is unclear, it has been suggested that it is related to lipopolysaccharide modification via diverse routes. Several factors have been reported as being associated with colistin resistance, with improper use and patient-to-patient transmission being most often cited. Total infections and infection-related mortality from colistin-resistant K. pneumoniae are high, but currently there are no established treatment regimens. However, several combination regimens that are mainly colistin-based have been found to be successful for treating such infections.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Cross Infection; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Microbial Sensitivity Tests; Treatment Outcome

The increasing incidence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) fundamentally alters the management of patients at risk to be colonized or infected by such microorganisms. Owing to the limitation in efficacy and potential for toxicity of the alternative agents, many experts recommend using combination therapy instead of monotherapy in CR-KP-infected patients. However, in the absence of well-designed comparative studies, the best combination for each infection type, the continued role for carbapenems in combination therapy and when combination therapy should be started remain open questions. Herein, the authors revise current microbiological and clinical evidences supporting combination therapy for CR-KP infections to address some of these issues.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Therapy, Combination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Rifampin; Risk Factors; Tigecycline

Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA in 1996. Since then, these versatile β-lactamases have spread internationally among Gram-negative bacteria, especially K pneumoniae, although their precise epidemiology is diverse across countries and regions. The mortality described among patients infected with organisms positive for KPC is high, perhaps as a result of the limited antibiotic options remaining (often colistin, tigecycline, or aminoglycosides). Triple drug combinations using colistin, tigecycline, and imipenem have recently been associated with improved survival among patients with bacteraemia. In this Review, we summarise the epidemiology of KPCs across continents, and discuss issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control. In view of the limitations of present treatments and the paucity of new drugs in the pipeline, infection control must be our primary defence for now.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Communicable Disease Control; Geography; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Tigecycline; Treatment Outcome

'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

A novel type of carbapenemase, New Delhi metallo beta-lactamase 1 (NDM 1), was first identified in 2008 in two Enterobacteriacea isolates, both recovered from a Swedish patient transferred from India. The emergence of NDM 1 is now reported from all continents, often in patients with a history of travel or hospitalization in the Indian subcontinent. The NDM 1 producing Gram-negative bacteria are mainly Enterobacteriaceae, which can cause colonization or fatal infections, with worrying antimicrobial susceptibility profiles: some isolates have developed resistance to practically all available antibiotics. Is the NDM-1 the super-bug? Are we in the post-antibiotic era? This review is a summary of currently available knowledge of NDM-1 that draws attention to future antimicrobial resistance scenarios.

Topics: Abscess; Anti-Bacterial Agents; beta-Lactamases; Buttocks; Colistin; Diabetes Complications; Drug Resistance, Multiple, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Sweden; Travel; Treatment Outcome

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

Topics: Adolescent; Adult; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Female; Hematopoietic Stem Cell Transplantation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies

Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients.. Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849).. The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9).. Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.

Topics: Administration, Oral; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; beta-Lactamases; Carrier State; Colistin; Decontamination; Drug Resistance, Bacterial; Female; Follow-Up Studies; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Risk Assessment; Survival Analysis; Treatment Outcome

To assess the effectiveness of selective digestive decontamination (SDD) for eradicating carbapenem-resistant Klebsiella pneumoniae (CRKP) oropharyngeal and gastrointestinal carriage.. A randomized, double-blind, placebo-controlled trial with 7 weeks of follow-up per patient.. A 1,000-bed tertiary-care university hospital.. Adults with CRKP-positive rectal swab cultures.. Patients were blindly randomized (1 :1) over a 20-month period. The SDD arm received oral gentamicin and polymyxin E gel (0.5 g 4 times per day) and oral solutions of gentamicin (80 mg 4 times per day) and polymyxin E (1 x 10(6) units 4 times per day for 7 days). The placebo arm received oral placebo gel 4 times per day and 2 placebo oral solutions 4 times per day for 7 days. Strict contact precautions were applied. Samples obtained from the throat, groin, and urine were also cultured.. Forty patients (mean age ± standard deviation, 71 ± 16 years; 65% male) were included. At screening, greater than or equal to 30% of oropharyngeal, greater than or equal to 60% of skin, and greater than or equal to 35% of urine cultures yielded CRKP isolates. All throat cultures became negative in the SDD arm after 3 days (P < .0001). The percentages of rectal cultures that were positive for CRKP were significantly reduced at 2 weeks. At that time, 16.1% of rectal cultures in the placebo arm and 61.1% in the SDD arm were negative (odds ratio, 0.13; 95% confidence interval, 0.02-0.74; P < .0016). A difference between the percentages in the 2 arms was still maintained at 6 weeks (33.3% vs 58.5%). Groin colonization prevalence did not change in either arm, and the prevalence of urine colonization increased in the placebo arm.. This SDD regimen could be a suitable decolonization therapy for selected patients colonized with CRKP, such as transplant recipients or immunocompromised patients pending chemotherapy and patients who require major intestinal or oropharyngeal surgery. Moreover, in outbreaks caused by CRKP infections that are uncontrolled by routine infection control measures, SDD could provide additional infection containment.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Carrier State; Colistin; Digestive System; Double-Blind Method; Drug Therapy, Combination; Female; Gentamicins; Groin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Pharynx; Rectum; Urine

Topics: Adolescent; Adult; Aged; Ampicillin; Carbenicillin; Child; Child, Preschool; Clinical Trials as Topic; Colistin; Escherichia coli Infections; Female; Humans; Injections, Intravenous; Klebsiella Infections; Male; Middle Aged; Nalidixic Acid; Penicillins; Pseudomonas Infections; Sulfonamides; Tetracycline; Urinary Tract Infections; Urine

Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis.. KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×10. In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination.. CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Ceftazidime; Colistin; Drug Combinations; Fosfomycin; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Osteomyelitis; Rabbits

The aim of this study was to understand the prevalence of antibiotic resistance in Klebsiella pneumoniae present in the population in Bergen city, Norway using city-scale sewage-based surveillance, as well as the potential spread of K. pneumoniae into the marine environment through treated sewage. From a total of 30 sewage samples collected from five different sewage treatment plants (STPs), 563 presumptive K. pneumoniae isolates were obtained on Simmons Citrate Agar with myo-Inositol (SCAI) plates, and 44 presumptive K. pneumoniae isolates on SCAI plates with cefotaxime. Colistin resistance was observed in 35 isolates, while cefotaxime resistance and tigecycline resistance was observed in only five isolates each, out of 563 presumptive K. pneumoniae isolates. All 44 isolates obtained on cefotaxime-containing plates were multidrug-resistant, with 25% (n = 11) showing resistance against tigecycline. Clinically important acquired antibiotic resistance genes (ARGs), like bla

Topics: Anti-Bacterial Agents; Cefotaxime; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sewage; Tigecycline; Wastewater-Based Epidemiological Monitoring

Emerging mobile colistin resistance (

Topics: Anti-Bacterial Agents; Colistin; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Phylogeny; Plasmids; Sepsis

Colistin resistance is acquired by different lipopolysaccharide (LPS) modifications. We proposed to evaluate the of effect

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Cytokines; Drug Resistance, Bacterial; Humans; Immunity, Innate; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Microbial Sensitivity Tests

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) has become a great threat to public health. This study reported an hv-CRKp-associated fatal infection and revealed its mechanisms of antimicrobial resistance and within-host evolution.. A carbapenem-susceptible K. pneumoniae (CSKp) and 11 KPC-producing CRKp strains were isolated from a lung transplant recipient receiving continual antimicrobial therapy for 1.5 years. Pulsed-field gel electrophoresis (PFGE) separated two clusters between CSKp and CRKp.. This study depicted a rapid and diverse within-host evolution of resistance in hv-CRKp of ST11-KL64 clone.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae

In Chinese zoos, there are usually specially designed bird parks, similar to petting zoos, that allow children and adults to interact with diverse birds. However, such behaviors present a risk for the transmission of zoonotic pathogens. Recently, we isolated eight strains of Klebsiella pneumoniae and identified two

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Birds; Colistin; Drug Resistance, Multiple, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Tigecycline

Infections caused by multi-drug resistant

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Disease Outbreaks; Humans; India; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Tertiary Care Centers

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant clinical problem, given the lack of therapeutic options. The CRKP strains have emerged as an essential worldwide healthcare issue during the last 10 years. Global expansion of the CRKP has made it a significant public health hazard. We must consider to novel therapeutic techniques. Bacteriophages are potent restorative cases against infections with multiple drug-resistant bacteria. The Phages offer promising prospects for the treatment of CRKP infections.. In this study, a novel K. pneumoniae phage vB_KshKPC-M was isolated, characterized, and sequenced, which was able to infect and lyse Carbapenem-resistant K. pneumoniae host specifically.. One hundred clinical isolates of K. pneumoniae were collected from patients with COVID-19 associated with ventilator-associated acute pneumonia hospitalized at Shahid Beheshti Hospital, Kashan, Iran, from 2020 to 2021. Initially, all samples were cultured, and bacterial isolates identified by conventional biochemical tests, and then the ureD gene was used by PCR to confirm the isolates. The Antibiotic susceptibility test in the disc diffusion method and Minimum inhibitory concentrations for Colistin was done and interpreted according to guidelines. Phenotypic and molecular methods determined the Carbapenem resistance of isolates. The blaKPC, blaNDM, and blaOXA-23 genes were amplified for this detection. Biofilm determination of CRKP isolates was performed using a quantitative microtiter plate (MTP) method. The phage was isolated from wastewater during the summer season at a specific position from Beheshti Hospital (Kashan, Iran). The sample was processed and purified against the bacterial host, a CRKP strain isolated from a patient suffering from COVID-19 pneumoniae and resistance to Colistin with high potency for biofilm production. This isolate is called Kp100. The separated phages were diluted and titration by the double overlay agar plaque assay. The separate Phage is concentrated with 10% PEG and stored at -80 °C until use. The phage host range was identified by the spot test method. The purified phage morphology was determined using a transmission electron microscope. The phage stability tests (pH and temperature) were analyzed. The effect of cationic ions on phage adsorption was evaluated. The optimal titer of bacteriophage was determined to reduce the concentration of the CRKP strain. One-step growth assays were performed to identify the purified phage burst's latent cycle and size. The SDS-PAGE was used for phage proteins analysis. Phage DNA was extracted by chloroform technique, and the whole genome of lytic phage was sequenced using Illumina HiSeq technology (Illumina, San Diego, CA). For quality assurance and preprocessing, such as trimming, Geneious Prime 2021.2.2 and Spades 3.9.0. The whole genome sequence of the lytic phage is linked to the GenBank database accession number. RASTtk-v1.073 was used to predict and annotate the ORFs. Prediction of ORF was performed using PHASTER software. ResFinder is used to assess the presence of antimicrobial resistance and virulence genes in the genome. The tRNAs can-SE v2.0.6 is used to determine the pres. Phage vB_KshKPC-M is assigned to the Siphoviridae, order Caudovirales. It was identified as a linear double-stranded DNA phage of 54,378 bp with 50.08% G + C content, had a relatively broad host range (97.7%), a short latency of 20 min, and a high burst size of 260 PFU/cell, and was maintained stable at different pH (3-11) and temperature (45-65 °C). The vB_KshKPC-M genome contains 91 open-reading frames. No tRNA, antibiotic resistance, toxin, virulence-related genes, or lysogen-forming gene clusters were detected in the phage genome. Comparative genomic analysis revealed that phage vB_KshKPC-M has sequence similarity to the Klebsiella phages, phage 13 (NC_049844.1), phage Sushi (NC_028774.1), phage vB_KpnD_PeteCarol (OL539448.1) and phage PWKp14 (MZ634345.1).. The broad host range and antibacterial activity make it a promising candidate for future phage therapy applications. The isolated phage was able to lyse most of the antibiotic-resistant clinical isolates. Therefore, this phage can be used alone or as a phage mixture in future studies to control and inhibit respiratory infections caused by these bacteria, especially in treating respiratory infections caused by resistant strains in sick patients.

Topics: Anti-Bacterial Agents; Bacteriophages; Carbapenems; Colistin; COVID-19; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Phylogeny; Ventilators, Mechanical

The extracellular capsule is a virulence factor present in many facultative pathogens, but its role in antimicrobial resistance remains controversial. To shed light on this debate, we tested six antibiotics on four Klebsiella pneumoniae species complex strains. Noncapsulated strains exhibited increased tolerance to polymyxins, but not to other antibiotics, as measured using the MIC. Our results urge caution on the use of therapeutic agents that target the capsule and may result in selection for its inactivation.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxins; Virulence Factors

The treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains is difficult due to the limited antimicrobial options and high mortality. There are many reports on intracranial infections caused by CR-Kp, but only a few on brain abscesses caused by CR-Kp. Here, we present a case of brain abscess caused by CR-Kp successfully treated with combined antibiotics. A 26-year-old male patient was admitted to our hospital due to high fever and headache. His past medical history includes a surgical intervention due to an acute subdural hematoma, performed at an external healthcare center. After the current diagnosis of cerebral abscess, he underwent two surgeries. During the procedure, multiple cerebral abscesses were drained and capsulotomies were performed under ultrasound guidance. The combination of meropenem and vancomycin was started. The contents of the abscesses were sent to the microbiology and pathology laboratory. On the 3 rd day of treatment, the medical team was informed that CR-Kp grew in an abscess culture. The patient's treatment was changed to meropenem + colistin + tigecycline. The patient developed electrolyte disturbances during the follow-up and this was considered an adverse effect of colistin. On the 41 st day of treatment, colistin was discontinued, fosfomycin was added, and meropenem and tigecycline were maintained. Treatment was discontinued on the 68 th day, when the patient was discharged. The general condition of the patient, who has been followed up for two years, is satisfactory. The treatment of CR-Kp infections should be individualized, and the pharmacokinetics and pharmacodynamics of antibiotics should be considered in each case.

Topics: Adult; Anti-Bacterial Agents; Brain Abscess; Carbapenem-Resistant Enterobacteriaceae; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Tigecycline

We investigated the therapeutic capacity of the isolated Klebsiella bacteriophage NK20 against pandrug-resistant strains. Moreover, we assessed the impact of resistance development on the overall therapeutic outcome both in vitro and in vivo.. The pandrug-resistant K. pneumoniae Kp20 is used as a host strain for the isolation of bacteriophages using sewage samples. Spot assay was then used to compare the spectra of the isolated phages, while kinetic and genomic analysis of the phage with the broadest spectrum was assessed. Antibacterial potential of the phage was assessed using turbidimetric assay and MIC with and without colistin. Finally, the therapeutic efficacy was evaluated in vivo using a rat respiratory infection model.. The isolated lytic bacteriophage (NK20) showed a relatively broad spectrum and an acceptable genomic profile. In vitro antibacterial assay revealed bacterial resistance development after 12 h. Colistin inhibited bacterial regrowth and reduced pandrug-resistant strains' colistin MICs. Despite the isolation of resistant clones, intranasal administration of NK20 significantly (p < 0.05) reduced the bacterial load in both the pulmonary and blood compartments and rescued 100 % of challenged rats. Histological and immunological analysis of treated animals' lung tissue revealed less inflammation and lower TNF-α and caspase-3 expression.. NK20 is a promising candidate that rescued rats from untreatable, pan-drug-resistant K. pneumoniae Kp20. Moreover, it steers the evolution of resistant mutants with higher sensitivity to colistin and less virulence, opening the door for using phages as sensitizing and anti-virulence entities rather than direct killer.

Topics: Animals; Anti-Bacterial Agents; Bacteriophages; Colistin; Genomics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Rats; Respiratory Tract Infections

The objective of this study was to develop a rapid prediction method for carbapenem-resistant Klebsiella pneumoniae (CRKP) and colistin-resistant K. pneumoniae (ColRKP) based on routine MALDI-TOF mass spectrometry (MS) results in order to formulate a suitable and rapid treatment strategy. A total of 830 CRKP and 1462 carbapenem-susceptible K. pneumoniae (CSKP) isolates were collected; 54 ColRKP isolates and 1592 colistin-intermediate K. pneumoniae (ColIKP) isolates were also included. Routine MALDI-TOF MS, antimicrobial susceptibility testing, NG-Test CARBA 5, and resistance gene detection were followed by machine learning (ML). Using the ML model, the accuracy and area under the curve for differentiating CRKP and CSKP were 0.8869 and 0.9551, respectively, and those for ColRKP and ColIKP were 0.8361 and 0.8447, respectively. The most important MS features of CRKP and ColRKP were m/z 4520-4529 and m/z 4170-4179, respectively. Of the CRKP isolates, MS m/z 4520-4529 was a potential biomarker for distinguishing KPC from OXA, NDM, IMP, and VIM. Of the 34 patients who received preliminary CRKP ML prediction results (by texting), 24 (70.6%) were confirmed to have CRKP infection. The mortality rate was lower in patients who received antibiotic regimen adjustment based on the preliminary ML prediction (4/14, 28.6%). In conclusion, the proposed model can provide rapid results for differentiating CRKP and CSKP, as well as ColRKP and ColIKP. The combination of ML-based CRKP with preliminary reporting of results can help physicians alter the regimen approximately 24 h earlier, resulting in improved survival of patients with timely antibiotic intervention.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The coinfection process producing multiple species of pathogens provides a specific ecological niche for the exchange of genetic materials between pathogens, in which plasmids play a vital role in horizontal gene transfer, especially for drug resistance, but the underlying transfer pathway remains unclear. Interspecies communication of the plasmids associated with the transfer of third-generation cephalosporins, quinolones, and colistin resistance has been observed in simultaneously isolated Escherichia coli and Klebsiella pneumoniae from abdominal drainage following surgery. The MICs of antimicrobial agents were determined by the broth microdilution method. The complete chromosome and plasmid sequences were obtained by combining Illumina paired-end short reads and MinION long reads. S1-PFGE, southern blot analysis and conjugation assay confirmed the transferability of the

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Coinfection; Colistin; Communication; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Quinolones

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and is difficult to treat, causing increased morbidity and mortality rates in critically ill patients. We conducted a multicenter cross-sectional study of intensive care unit (ICU) inpatients in 78 hospitals to investigate the prevalence and molecular characteristics of CRKP in Henan Province, China, a hyperepidemic region. A total of 327 isolates were collected and downsampled to 189 for whole-genome sequencing. Molecular typing revealed that sequence type 11 (ST11) of clonal group 258 (CG258) was predominant (88.9%,

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Cross-Sectional Studies; Genomics; Humans; Inpatients; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Microbial Sensitivity Tests

Klebsiella pneumoniae, a pathogen of critical clinical concern, urgently demands effective therapeutic options owing to its drug resistance. Polymyxins are increasingly regarded as a last-line therapeutic option for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, polymyxin resistance in K. pneumoniae is an emerging issue. Here, we report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates. To further confirm this, we investigated the efficacy of combined GaNt and colistin

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antioxidants; Colistin; Drug Resistance, Multiple, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Polymyxins; Reactive Oxygen Species

Colistin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses health challenges. To investigate the prevalence and molecular characteristics of colistin-resistant CRKP, 708 isolates were collected consecutively from 28 tertiary hospitals in China from 2018 to 2019, and 14 colistin-resistant CRKP were identified. Two-component systems (TCSs) related to colistin resistance (PmrA/B, PhoP/Q, and CrrA/B), the negative regulator mgrB gene and mcr genes, were analysed using genomic sequencing. The relative expression of TCSs genes along with their downstream pmrC and pmrK genes was determined using quantitative real-time PCR (qRT‒PCR). A novel point mutation in PhoQ was confirmed by site-directed mutagenesis, and the subsequent transcriptome changes were analysed by RNA sequencing (RNA-Seq). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to detect modifications in lipid A. The results showed that only one isolate carried the mcr-8.1 gene, nine exhibited MgrB inactivation or absence, and three exhibited mutations in PmrB. One novel point mutation, L247P, in PhoQ was found to lead to a 64-fold increase in the minimum inhibitory concentration (MIC) of colistin. qRT‒PCR revealed overexpression of phoP/Q and pmrK in isolates with or without MgrB inactivation, and pmrB mutation resulted in overexpression of pmrA and pmrC. Furthermore, transcriptome analysis revealed that the PhoQ L247P novel point mutation caused upregulated expression of phoP/Q and its downstream operon pmrHFIJKLM. Meanwhile, the pmrA/B regulatory pathway did not evolve colistin resistance. Mass spectrometry analysis showed the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) to lipid A in colistin-resistant isolates with absence of MgrB. These findings illustrate that the molecular mechanisms of colistin resistance in CRKP isolates are complex, and that MgrB inactivation or absence is the predominant molecular mechanism. Interventions should be initiated to monitor and control colistin resistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Microbial Sensitivity Tests; Prevalence

The management of severe neurologic infections due to multidrug-resistant (MDR)

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

Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a ≥8-fold decrease in colistin MIC in the presence of carbonyl cyanide

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) represents an urgent threat to global public health due to the limited therapeutic options available to control this pathogen. This study aims to analyze the molecular epidemiology, antimicrobial resistance and virulence profile of CRKP isolated from patients at hospitals in Southeastern Brazil. KPC and other beta-lactamase genes were detected in all strains, which were also multidrug-resistant (MDR). In addition, 11 strains showed resistance to last-resort antimicrobials, such as colistin and tigecycline. MLST analysis revealed eight different sequence types (ST11, ST37, ST147, ST340, ST384, ST394, ST437, and ST628), being two (ST628 and ST394) reported for the first time in Brazil. Strains belonging to the clonal complex 258 (CC258) "high-risk clones" were prevalent in this study. The Galleria mellonella model showed the emergence of virulent CRKP strains in the healthcare environment and, suggests that colistin-resistant strains were associated with higher virulence. This study shows the presence of virulent CRKP-MDR strains in hospitals across Southeastern Brazil, and draws attention to the presence of highly virulent emerging CRKP-MDR ST628 strains, showing that virulent and resistant clones can emerge quickly, requiring constant monitoring.

Topics: Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Multilocus Sequence Typing

The study aimed to investigate prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) blood culture isolates and their susceptibility to two new antibiotics, imipenem/relebactam and ceftazidime/avibactam. Out of 765 isolates recovered from blood cultures in a tertiary care hospital in Serbia between 2020 and 2023, 143 non-repetitive K. pneumoniae strains were included in this study. Minimum inhibitory concentration (MIC) values of the examined antimicrobial drugs was determined by VITEK 2 system, MIC test strip (imipenem/relebactam and ceftazidime/avibactam), and broth microdilution method (tigecycline and colistin). Carbapenemase-encoding genes (blaKPC, blaOXA-48-like, blaNDM, blaVIM, blaIMP) were detected using a multiplex-PCR assay, the BioFire-Blood Culture Identification 2-panel. This closed molecular assay is designed for the BioFire® FilmArray® system, enabling automated sample preparation, amplification, detection, and analysis (bioMérieux, France). Results revealed that K. pneumoniae was the most common isolate from blood cultures in 2022. The prevalence of K. pneumoniae was about 11.6% in 2020 and 2021, while in 2022 it raised to over 30%. Also, the frequency of CRKP increased from 11.76% in 2020, through 15.29% in 2021 to 72.94% in 2022. The majority of CRKP carried blaOXA-48-like (60.0%), followed by blaKPC (16.47%), and blaNDM (8.24%) genes, while 14.12% harboured both blaOXA-48-like and blaNDM genes. Only 25.88% of CRKP isolates were resistant to ceftazidime/avibactam, while 51.76% were resistant to imipenem/relebactam and colistin. The rapid spread of CRKP is particularly concerning because therapeutic options are limited to a few antibiotics. While imipenem/relebactam and colistin showed similar antimicrobial activity against CRKP clinical isolates, ceftazidime/avibactam proved to be the most effective antibiotic.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Blood Culture; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Ceftazidime; Colistin; Drug Combinations; Hospitals, University; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Serbia

Due to multi-drug resistance, physicians increasingly use the last-resort antibiotic colistin to treat infections with the Gram-negative bacterium Klebsiella pneumoniae. Unfortunately, K. pneumoniae can also develop colistin resistance. Interestingly, colistin resistance has dual effects on bacterial clearance by the immune system. While it increases resistance to antimicrobial peptides, colistin resistance has been reported to sensitize certain bacteria for killing by human serum. Here we investigate the mechanisms underlying this increased serum sensitivity, focusing on human complement which kills Gram-negatives via membrane attack complex (MAC) pores. Using in vitro evolved colistin resistant strains and a fluorescent MAC-mediated permeabilization assay, we showed that two of the three tested colistin resistant strains, Kp209_CSTR and Kp257_CSTR, were sensitized to MAC. Transcriptomic and mechanistic analyses focusing on Kp209_CSTR revealed that a mutation in the phoQ gene locked PhoQ in an active state, making Kp209_CSTR colistin resistant and MAC sensitive. Detailed immunological assays showed that complement activation on Kp209_CSTR in human serum required specific IgM antibodies that bound Kp209_CSTR but did not recognize the wild-type strain. Together, our results show that developing colistin resistance affected recognition of Kp209_CSTR and its killing by the immune system.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Immunoglobulin M; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation

To date, limited data exist on demonstrating the usefulness of machine learning (ML) algorithms applied to MALDI-TOF in determining colistin resistance among Klebsiella pneumoniae. We aimed to detect colistin resistance in K. pneumoniae using MATLAB on MALDI-TOF database.. A total of 260 K. pneumoniae isolates were collected. Three ML models, namely, linear discriminant analysis (LDA), support vector machine, and Ensemble were used as ML algorithms and applied to training data set.. The accuracies for the training phase with 200 isolates were found to be 99.3%, 93.1%, and 88.3% for LDA, support vector machine, and Ensemble models, respectively. Accuracy, sensitivity, specificity, and precision values for LDA in the application test set with 60 K. pneumoniae isolates were 81.6%, 66.7%, 91.7%, and 84.2%, respectively.. This study provides a rapid and accurate MALDI-TOF MS screening assay for clinical practice in identifying colistin resistance in K. pneumoniae.

Topics: Algorithms; Anti-Bacterial Agents; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Machine Learning; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To investigate the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae, and characterize the underlying molecular mechanisms.. The population analysis profiles (PAPs) method was used to detect colistin heteroresistance. The time-killing assay was used to examine the effect of colistin on carbapenem-resistant Klebsiella pneumoniae (CRKP) in vitro. Galleria mellonella larvae infection model was used to test the potential virulence. qRT-PCR assay was conducted to compare the expression levels of efflux pump genes. Next and third-generation sequencing were conducted to analyse the genomic features.. Two colistin-heteroresistant isolates were detected from a multi-center carbapenem-resistant Enterobacterales (CRE) surveillance study in China, which exhibited similar survival rates as the K2 hypervirulent reference strain ATCC 43816 in a G. mellonella larvae model. The two isolates belonged to ST11, harbouring the iucABCD, iutA, iroBCD, and rpmA. This study showed the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae. AcrAB-TolC and OqxAB efflux overexpression were involved in mediating colistin heteroresistance.

Topics: Animals; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Larva

Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP.. All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy.. The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Colistin; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated

This study aimed to evaluate antibiotic resistance genes and virulence genes and the clonal relationship of the carbapenem-nonsusceptible Klebsiella pneumoniae strains by molecular methods which are isolated from various clinical specimens from patients treated in tertiary care hospital in Turkey.. Identification of 32 carbapenem non-susceptible K. pneumoniae were determined by VITEK-2 (BioMérieux, France) automated system. Thirteen colistin-resistant strains were tested with the broth microdilution method. Various antibiotic resistance genes and virulence genes frequently seen in carbapenem-resistant strains were screened by PCR. Immunochromatographic tests used in the rapid diagnosis of carbapenemases were compared with PCR results. In addition, PFGE, MLST and MALDI-TOF MS methods were used to determine the clonal relationship among these strains.. PCR demonstrated that 31 of the strains carried at least one of the carbapenemase genes. In one strain, the coexistence of bla. In addition to OXA-48, which is endemic in our country, it has been determined that KPC, which is more common in the world, is becoming increasingly common in our region. ST101 type was determined as the most common type between the strains. To the best of our knowledge, this is the first study that compares these three methods in our country. There may be differences between bacterial identifications made with VITEK-2 and MALDI-TOF MS. In this study, it was observed that MALDI-TOF MS analyses were not compatible with the typing of strains according to PFGE and MLST analysis results.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Klebsiella pneumonia causes serious infections in hospitalized patients. In recent years, carbapenem-resistant infections increased in the world. The molecular epidemiological investigation of carbapenem-resistant K. pneumoniae isolates was aimed in this study.. Fifty carbapenem-resistant K. pneumoniae isolates from six geographical regions of Turkey between September 2019-2020 were included in the study. The disk diffusion method was used for the antibiotic susceptibility testing. The microdilution confirmed colistin susceptibility. Genetic diversity was investigated by MLST (Multi-Locus Sequence Typing).. The resistance rates were as follows: 49 (98%) for meropenem, 47 (94%) imipenem, 50 (100%) ertapenem, 30 (60%) colistin and amoxicillin-clavulanate, 49 (98%) ceftriaxone, 48 (96%) cefepime, 50 (100%) piperacillin-tazobactam, 47 (94%) ciprofloxacin, 40 (80%) amikacin, 37 (74%) gentamicin. An isolate resistant to colistin by disk diffusion was found as susceptible to microdilution. ST 2096 was the most common (n:16) sequence type by MLST. ST 101 (n:7), ST14 (n:6), ST 147 and ST 15 (n:4), ST391 (n:3), ST 377 and ST16 (n:2), ST22, ST 307, ST 985, ST 336, ST 345, and ST 3681 (n:1) were classified in other isolates. In İstanbul and Ankara ST2096 was common. Among Turkey isolates, the most common clonal complexes (CC) were CC14 (n:26) and CC11 (n = 7).. In Turkey, a polyclonal population of CC14 throughout the country and inter-hospital spread were indicated. The use of molecular typing tools will highlight understanding the transmission dynamics.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Turkey

Isolation of colistin- and carbapenem-resistant Klebsiella pneumoniae (CCR-Kp) is increasing in hospital settings worldwide, which is related to increased morbidity, mortality and healthcare costs. The aim of this work was to perform whole-genome sequencing (WGS), genomic and phylogenetic analysis, and conjugation assays of an extensively drug-resistant (XDR) CCR-Kp isolate from Argentina.. WGS of strain KpS26 isolated from a bloodstream infection was performed using Illumina MiSeq-I, and de novo assembly was achieved using SPAdes v.3.11. A maximum likelihood tree was created using MEGA7 based on core genome single nucleotide polymorphisms from whole-genome alignment of K. pneumoniae isolates identified in silico as sequence type 15 (ST15). The resistome, plasmids and integrons were analysed using ResFinder, AMRFinderPlus, ISfinder, plasmidSPAdes, PlasmidFinder and IntegronFinder. Standard conjugation was performed.. KpS26 belonged to ST15, which is less common than ST258, ST25 and ST11 that are globally reported as responsible for CCR-Kp outbreaks. Fourteen transferable antimicrobial resistance genes (ARGs), including bla. The XDR CCR-Kp isolate analysed here shows that ST15 is also disseminating bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Multilocus Sequence Typing; Phylogeny

Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Retrospective Studies

Colistin is one of the few antibiotics that exhibit bactericidal effect on carbapenemase-producing

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests

Due to its high transmissibility, Klebsiella pneumoniae is one of the leading causes of nosocomial infections. Here, we studied the biological cost of colistin resistance, an antibiotic of last resort, in this opportunistic pathogen using a murine model of gut colonization and transmission. Colistin resistance in K. pneumoniae is commonly the result of the inactivation of the small regulatory protein MgrB. Without a functional MgrB, the two-component system PhoPQ is constitutively active, leading to an increase in lipid A modifications and subsequent colistin resistance. Using an isogenic

Topics: Animals; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Mice

Increased use of colistin in healthcare necessitates studies on the trend of colistin resistance and the underlying mechanisms.. To understand the susceptibility trend and molecular mechanisms of colistin resistance in neonatal isolates over a 12 year period.. Colistin susceptibility, mRNA expression, whole genome sequence and mutational analysis was performed. Phylogenomic comparison with a global collection of colistin-resistant Klebsiella pneumoniae strains (n = 70) was done.. Of 319 Enterobacterales (K. pneumoniae and Escherichia coli) studied, colistin resistance was found in 9 K. pneumoniae (2.8%). The transmissible colistin resistance gene, mcr, was absent. Colistin-resistant K. pneumoniae belonged to diverse sequence types (ST14/37/101/147/716) and exhibited multiple mechanisms of colistin resistance including overexpression of the two-component systems (TCS) (phoP/Q, pmrA/B), and AcrAB-TolC pump and its regulators. Mutations in TCS, mgrB, pumps, repressors, and lipopolysaccharide-modifying genes were detected. Phylogenomic comparison revealed that this global collection of colistin-resistant K. pneumoniae was diverse, with the presence of epidemic and international clones. Mutations in mgrB and TCS noted in global strains were comparable to the study strains. Co-occurrence of carbapenem resistance (n = 61, 87%) was observed in global strains. Co-existence of dual carbapenemases (blaNDM-5 with blaOXA-48/181) in multiple lineages within different replicons was found in neonatal colistin-resistant study isolates only.. Colistin resistance both in study and global strains is multifaceted and attributed to mutations in chromosomal genes leading to lipopolysaccharide modification or efflux of colistin through pumps. With no transmissible mcr, prevalence of colistin-resistant strains was low in this unit. Colistin-resistant strains with dual carbapenemases causing sepsis are alarming as they are practically untreatable.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Escherichia coli; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Microbial Sensitivity Tests; Neonatal Sepsis; Phylogeny

The emergence of carbapenemase-producing Klebsiella pneumoniae strains has triggered the use of old antibiotics such as colistin. This is driving the emergence of colistin resistance in multidrug-resistant strains that underlie life-threatening infections. This study analyses the mutational diversity of 22 genes associated with colistin resistance in 140 K. pneumoniae clinical isolates integrated in a high-resolution phylogenetic scenario. Colistin susceptibility was accessed by broth microdilution. A total of 98 isolates were susceptible and 16 were resistant, 10 of which were carbapenemase producers. Across the 22 genes examined, 171 non-synonymous mutations and 9 mutations associated with promoter regions were found. Eighty-five isolates had a truncation and/or deletion in at least one of the 22 genes. However, only seven mutations, the complete deletion of mgrB or insertion sequence (IS)-mediated disruption, were exclusively observed in resistant isolates. Four of these (mgrB

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Phylogeny

CrrAB two-component regulatory system is associated with colistin resistance in Klebsiella pneumoniae. Recently, some K. pneumoniae isolates lacking crrAB genes have been identified. In this study, we investigated the distribution and structural variation of the crrBAC-kexD cluster. To evaluate the structural variation of the crrBAC-kexD cluster, we explored 59 clinical K. pneumoniae isolates from Korea, and 508 whole genomes of K. pneumoniae and other strains of Klebsiella sp. Significant structural variations in crrBAC-kexD and its surrounding regions were identified among K. pneumoniae genomes. Within the genus Klebsiella, the cluster was identified only in K. pneumoniae, K. variicola, and K. quasipneumoniae, which form the K. pneumoniae complex. Among the 304 available K. pneumoniae genomes, an intact crrBAC-kexD cluster was identified in 178 isolates (58.6%), while the cluster was absent in 90 isolates (29.6%). Partial deletions within the cluster were identified in 22 genomes (7.2%). The most diverse structural patterns of the crrBAC-kexD cluster were observed in ST11 strains. Some clades lacked the crrBAC-kexD cluster. The crrBAC-kexD cluster was identified in the genomes of other bacterial species, including Citrobacter freundii and Enterobacter ludwigii. The crrBAC-kexD cluster is proposed to have been acquired by the ancestor of the K. pneumoniae complex from other bacterial species and the cluster may have been lost and re-acquired repeatedly in K. pneumoniae strains according to the phylogenetic analysis. The dynamic evolution of the crrBAC-kexD cluster suggests that it may have other roles, in addition to colistin resistance, in bacterial physiology.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multigene Family; Phylogeny

The accelerating rate of carbapenems resistance in Klebseilla pneumoniae isolates has put the treatment option worrisome. The effective strategy to ameliorate this alarming situation is possible through enhancing the combination therapy and appropriate laboratory diagnosis. Hence, the study was focused on identifying carbapenemase-producing K. pneumoniae and their antibiogram pattern.. A total of 944 clinical samples from patients attending Sahid Gangalal National Heart Center were processed from September 2019 to March 2020 to identify the possible bacterial pathogens following the standard microbiological procedures. K. pneumonaie isolates were further subjected to antibiotic susceptibility testing by the modified Kirby Bauer disc diffusion technique. Phenotypic confirmation of carbapenemase production was done by the modified carbapenemase inactivation method. The minimum inhibitory concentration of colistin was determined by the broth microdilution method.. Of the total 944 samples, 15.47% (146) samples showed bacterial growth, among which 23.97% (35) were K. pneumoniae. Out of 35 K. pneumoniae isolates, 45.71% (16) were multidrug-resistant followed by 42.86% (15) extensively drug-resistant. Fourteen isolates of K. pneumoniae were carbapenemase producers among which 20% (7) were serine carbapenemase while 20% (7) showed metallo-?-lactamase production. All the carbapenemase-producing K. pneumoniae were susceptible to colistin with <0.125µg/ml. Carbapenemase activity showed statistically significant with multidrug resistance (p=<0.05).. An increasing resistance to the carbapenem drugs showed a great problem in the management of K. pneumoniae infections among immunocompromised patients especially cardiac patients however, colistin can be still an ultimate choice of drug for disease management.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Nepal

Carbapenem-resistant Klebsiella pneumoniae is associated with high morbidity and mortality, and capsule serotypes make treatment difficult. The aim of this study is to investigate the relationship between colistin resistance and capsule types in carbapenem-resistant K. pneumoniae isolates. In 2018- 2020, we conducted our study with 115 carbapenem-resistant K. pneumoniae strains diagnosed by matrix-mediated laser desorption ionization time-of-flight mass spectrometry method (MALDI-TOF MS; Bruker Daltonics, Germany). Colistin sensitivities were determined by using DxM MicroScan WalkAway System (Beckman Coulter, ABD) automated system and were then verified by liquid microdilution (MIC). Capsule serotypes were investigated by conventional polymerase chain reaction (PCR) method. Among the carbapenem resistant K. pneumoniae isolates, 42% (48) were resistant to colistin and 58% (67) were susceptible to colistin. In the K. pneumoniae isolates with colistin resistance 33% (16) K5, 13% (6) K2, 8% (4) K20 4% (2) K1 and 2% (1) K54 and K57 capsule serotypes were found, while in the K. pneumoniae isolates with colistin susceptible 12% (8) K5, 4% (3) K2, 3% (2) K20, 1.5% (1) K1 and K54 capsule serotypes were found. Serotype K5 was very frequent in isolates collected from patients with urinary tract diseases. The resistance profile data obtained from the present study can serve as an information base to understand the infection pattern prevailing in the hospital.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Serogroup

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

Topics: Anti-Bacterial Agents; Azithromycin; Biofilms; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mesylates; Microbial Sensitivity Tests; Pneumonia; Polymyxin B

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a huge health challenge worldwide. The aim of this study was to evaluate the incidence of polymyxin resistance in clinical CRKP isolates in China and to characterize the molecular mechanisms underlying these polymyxin-resistant CRKP (PR-CRKP) isolates.. A total of 493 CRKP clinical isolates from patients were collected from six tertiary-care hospitals in China during 2017-2018. Minimum inhibitory concentrations of polymyxin B and colistin were determined using the broth microdilution method. PR-CRKP isolates were identified and subjected to whole-genome sequencing. Quantitative real-time PCR and structural modelling analysis were also performed.. We observed a 2.2% (11/493) polymyxin resistance rate in this multicentre cohort. Polymyxin B MICs ranged from 4 to 64 μg/mL and colistin MICs ranged from 8 to 128 μg/mL in 11 PR-CRKP isolates. Key genetic variations identified in PR-CRKP isolates involved eight disruptions (seven insertional inactivation by an insertion sequence [IS] element, one frameshift deletion) in mgrB, and three missense mutations in pmrA, pmrB, and phoP. ISKpn26 was the predominant IS (4/7), and three of these occurred in nucleotide position 74 in the mgrB gene. In addition, we reported a novel mutation S62R in pmrB that may confer polymyxin resistance in K. pneumoniae.. Our findings highlight the multifaceted molecular mechanisms of polymyxin resistance in CRKP.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; DNA Transposable Elements; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxin B; Polymyxins

There is an increase of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the pediatric population and epidemiological data are limited.. To calculate the frequency of CRKP in pediatric patients, to determine the in vitro activity of colistin and to detect the presence of mcr-1 gene in said isolates.. 220 isolates of K. pneumoniae were studied in a pediatric hospital between January 2018 and December 2019. Antimicrobial susceptibility was determined by microdilution in broth according to guidelines of CLSI and EUCAST. The genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 and mcr-1 were detected by polymerase chain reaction (PCR).. 9.5% (n: 21) of the isolates were characterized as CRKP, where was observed a resistance to colistin of 47.6% (10/21) with values of MIC50 of 2 μg/mL and MIC90 of ≥ 4 μg/mL. In 100% of CRKP strains the blaKPC gene was detected and the mcr-1 gene was not found. The resistance profile to other antimicrobials was as follow: gentamicin 100% (n: 21), trimethoprim/sulfamethoxazole 100% (n: 21), ciprofloxacin 100% (n: 21), amikacin 19% (n: 4). All of the isolates were sensitive to ceftazidime/avibactam and tigecycline.. This study demonstrates a significant value of resistance to colistin in pediatric patients compared to other last line antimicrobial such as ceftazidime/avibactam and tigecycline.

Topics: Anti-Bacterial Agents; Argentina; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Ceftazidime; Child; Colistin; Hospitals, Pediatric; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Tigecycline

Antimicrobial resistance (AMR) is a global threat that requires serious attention, particularly when it is developed against colistin, which is considered one of the 'last-resort' antibiotics for curing an infection. This study aimed to investigate the AMR profile of the Klebsiella (K.) pneumoniae clinical isolates and to obtain the comprehensive characteristics of the carbapenemases among the carbapenem-resistant K. pneumoniae (CR-KP) when isolated. In addition, to detect the colistin resistance and investigate the MCR genes in the clinical K. pneumoniae isolates for the first time in Jordan.. A total of 179 K. pneumoniae isolates were cultured and they were confirmed using the VITEK 2 system and PCR. The antibiotic susceptibilities, extended-spectrum beta-lactamase (ESβL), multidrug-resistant (MDR), and CR-KP were determined by using the VITEK 2 system, disc diffusion, and the minimum inhibitory concentration (MIC) test. PCR was performed to detect the MCR and carbapenemase genes.. The rates of ESβL, MDR, and CR-KP were 48 %, 62 %, and 12.8 %, respectively. High colistin resistance of 49.7 % (89/179) was found. Only one MCR-1 (1.1 %) out of the 89 colistin resistance isolates was detected. Many of the isolates harbored the ESβL genes. In particular, the carbapenem genes were detected in 26 isolates, with 46 % KPC enzyme genes (12/26), 23 % IMP genes (6/26), 19 % OXA-48 genes (5/26), 11.5 % NDM-1 genes (3/26) but no VIM gene was found. The statistical analyses revealed a significant association between colistin resistance and MDR (P ≤ 0.05, Chi-square test). An association between colistin resistance and the Piperacillin, Ceftazidime, Cefpodoxime, Imipenem, Aztreonam, and Tobramycin resistance was noted.. The study's findings demonstrated the presence of the MCR-1 gene in the K. pneumoniae clinical isolates for the first time in Jordan and indicated that the KPC and IMP encoded carbapenemases were the most prevalent K. pneumoniae carbapenemases in Jordan patients.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Jordan; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

The more frequent usage of colistin resulted in an increase of colistin resistance due to lipopolysaccharide modifications. The aim of this study was to reveal the prevalence and mechanisms of colistin resistance among multidrug-resistant Klebsiella pneumoniae isolates collected in Bulgaria. One hundred multidrug resistant K. pneumoniae isolates were collected in a period between 2017 and 2018. Among them, 29 colistin resistant and 8 heteroresistant isolates were observed and further investigated. Clonal relatedness was detected by RAPD and MLST. Сarbapenemases, two component system phoQ/phoP, pmrA/B, and mgrB were investigated by PCR amplification and Sanger sequencing. Among 37 colistin nonsusceptible isolates, we detected 25 NDM-1 producers. The isolates belonged mainly to ST11 (80%), and also to ST147, ST35, ST340, ST219 (1-2 members per clone). Nine colistin resistant isolates showed changes in mgrB. IS903B-like elements truncated mgrB in five isolates. In two isolates, premature stopcodon (Q30stopcodon) was observed and another two isolates did not amplify mgrB, possibly due to bigger deletion or insertion. No isolates showed phoQ/phoP and pmrA/B mutations except for pmrB (four isolates had R256G). All isolates with IS903B insertions belonged to ST11 clone. The mgrB alterations play major role in colistin resistance in K. pneumoniae isolates studied in the current work. We report truncation of mgrB by IS903 like element in colistin resistant NDM-1 producing K. pneumoniae ST11 clone in Bulgaria.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Bulgaria; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Random Amplified Polymorphic DNA Technique

Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study.Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-meropenem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as ≥3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as ≥2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, blaKPC and blaCTX-M-1 genes was screened by PCR using specific primers.The blaOXA-48 gene was identified together with blaCTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indifferent effect on the strains.Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ciprofloxacin; Colistin; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tobramycin

The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Edetic Acid; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Prevalence

The spread of multidrug-resistant (MDR) K. pneumoniae carbapenemase-producing bacteria (KPC) is one of the most serious threats to global public health. Due to the limited antibiotic options, colis- tin often represents a therapeutic choice. In this study, we performed Whole-Genome Sequencing (WGS) by Illumina and Nanopore platforms on four colistin-resistant K. pneumoniae isolates (CoRKp) to explore the resistance profile and the mutations involved in colistin resistance. Mapping reads with reference sequence of the most com- mon genes involved in colistin resistance did not show the presence of mobile colistin resistance (mcr) genes in all CoRKp. Complete or partial deletions of mgrB gene were observed in three out of four CoRKp, while in one CoRKp the mutation V24G on phoQ was identified. Complementation assay with proper wild type genes restored colistin susceptibility, validating the role of the amino acid substitution V24G and, as already described in the literature, confirming the key role of mgrB alterations in colistin resistance. In conclusion, this study allowed the identification of the novel mutation on phoQ gene involved in colistin resistance phenotype.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation

Colistin-resistant Klebsiella pneumoniae (ColR-Kp) causes high mortality rates since colistin is used as the last-line antibiotic against multi-drug resistant Gram-negative bacteria. To reduce infections and mortality rates caused by ColR-Kp fast and reliable detection techniques are vital. In this study, we used a label-free surface-enhanced Raman scattering (SERS)-based sensor with machine learning algorithms to discriminate colistin-resistant and susceptible strains of K. pneumoniae. A total of 16 K. pneumoniae strains were incubated in tryptic soy broth (TSB) for 4 h. Collected SERS spectra of ColR-Kp and colistin susceptible K. pneumoniae (ColS-Kp) have shown some spectral differences that hard to discriminate by the naked eye. To extract discriminative features from the dataset, autoencoder and principal component analysis (PCA) that extract features in a non-linear and linear manner, respectively were performed. Extracted features were fed into the support vector machine (SVM) classifier to discriminate K. pneumoniae strains. Classifier performance was evaluated by using features extracted by each feature extraction techniques. Classification results of SVM classifier with extracted features by an autoencoder (autoencoder-SVM) has shown better performance than SVM classifier with extracted features by PCA (PCA-SVM). The accuracy, sensitivity, specificity, and area under curve (AUC) value of the autoencoder-SVM model were found as 94%, 94.2%, 93.8%, and 0.98, respectively. Furthermore, the autoencoder-SVM model has demonstrated statistically significantly better classifier performance than PCA-SVM in terms of accuracy and AUC values. These results illustrate that non-linear features can be more discriminative than linear ones to determine SERS spectral data of antibiotic-resistant and susceptible bacteria. Our methodological approach enables rapid and high accuracy detection of ColR-Kp and ColS-Kp, suggesting that this can be a promising tool to limit colistin resistance.

Topics: Anti-Bacterial Agents; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Machine Learning; Microbial Sensitivity Tests

Klebsiella pneumoniae is a significant infectious pathogen that causes bloodstream infections. This study aimed to genetically characterize a novel sequence type 4523 (ST4523) multidrug-resistant (MDR) K. pneumoniae strain recovered from the blood of a 79-year-old Chinese female patient with severe pneumonia and chronic obstructive pulmonary disease who ultimately died of the infection. The susceptibility testing results showed that strain 18SHX180 is nonsusceptible to cephalosporin, carbapenems, combinations of β-lactam and β-lactamase inhibitors, levofloxacin, and colistin and is only susceptible to amikacin. The phylogenetic structure showed that strain 18SHX180 belongs to a novel sequence type, ST4523, and capsule serotype K111. ST4523 is closely related to ST11, the most dominant clone of clinical carbapenem-resistant K. pneumoniae in China. ST4523 has 2 single-base variants in

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cephalosporins; Colistin; Female; Formaldehyde; Humans; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Plasmids; Sepsis

Colistin is considered as the last-line antibiotic for the treatment of infections caused by extensively drug-resistant Gram-negative pathogens belonging to the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) group. The present study aimed to explore the colistin resistance mechanisms of a Klebsiella aerogenes (formerly Enterobacter aerogenes) isolate (Kae1177-1bg) obtained from a Bulgarian critically ill patient with septic shock in 2020. Antimicrobial susceptibility testing and whole-genome sequencing using DNA nanoball technology were performed. The resulting read pairs were used for draft genome assembly, MLST analysis and mutation screening in the pmrA/B, phoP/Q, and mgrB genes. Kae1177-1bg demonstrated high-level resistance to colistin, resistance to 3rd generation cephalosporins and susceptibility to all other antibiotics tested. In our strain a CMY-2-type class C cephalosporinase was the only β-lactamase identified. No mobile colistin resistance (mcr) genes were detected. A total of three missense variants in the genes for the two-component PmrA/PmrB system were identified. Two of them were located in the pmrB (pR57K and pN275K) and one in the pmrA gene (pL162M). The pN275K variant emerged as the most likely cause for colistin resistance because it affected a highly conservative position and was the only nonconservative amino acid substitution. In conclusion, to the best of our knowledge, this is the first documented clinical case of a high-level colistin-resistant K. aerogenes in Bulgaria and the first identification of the nonconservative amino acid substitution pN275K worldwide. Colistin-resistant Gram-negative pathogens of ESKAPE group are serious threat to public health and should be subjected to infection control stewardship practices.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bulgaria; Colistin; Critical Illness; Drug Resistance, Bacterial; Enterobacter aerogenes; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Shock, Septic

Extensively drug-resistant and hypervirulent

Topics: Aminoglycosides; Anti-Bacterial Agents; beta-Lactams; China; Colistin; Disease Outbreaks; Hospitals, Teaching; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Quinolones; Tigecycline; Virulence; Virulence Factors

K. pneumoniae isolates often harbor various antibiotic resistance determinants including extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases (p-Amp-C) and carbapenemases. In this study we analyzed 65 K. pneumoniae isolates obtained from urinary tract infections in the outpatients setting, with regard to antibiotic susceptibility, β-lactamase production, virulence traits and plasmid content.Antibiotic susceptibility was determined by broth microdilution method. PCR was applied to detect genes encoding ESBLs, p-Amp-C and carbapenemases and plasmid incompatibility groups. Phenotypic methods were applied to characterize virulence determinants. Increasing resistance trend was observed for amoxicillin/clavulanate, imipenem, meropenem and ciprofloxacin. The study showed that ESBLs belonging to the CTX-M family, conferring high level of resistance to expanded-spectrum cephalosporins (ESC) were the dominant resistance trait among early isolates (2013 to 2016) whereas OXA-48 carbapenemase, belonging to class D, emerged in significant numbers after 2017. OXA-48 producing organisms coharbored ESBLs. KPC-2 was dominant among isolates from Dubrovnik in the recent years. Colistin resistance was reported in three isolates. Inc L/M was the dominant plasmid in the later period, encoding OXA-48. Hyperviscosity was linked to KPC positivity and emerged in the later period. This report describes evolution of antibiotic resistance in K. pneumoniae from ESBLs to carbapenemases and colistin resistance. The study demonstrated the ability of K. pneumoniae to acquire various resistance determinants, over time. The striking diversity of the UTI isolates could result from introduction of the isolates from the hospitals, transfer of plasmids and multidirectional evolution.

Topics: Amoxicillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cephalosporins; Ciprofloxacin; Clavulanic Acid; Colistin; Croatia; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Multidrug resistant Klebsiella pneumoniae is associated with nosocomial infections in both outbreak and non-outbreak situations. The study intends to evaluate the potential of enterobacterial repetitive intergenic consensus- polymerase chain reaction (ERIC-PCR), a genomic based typing and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) proteomic-based typing techniques for clonal relatedness among multidrug resistant Klebsiella pneumoniae isolates.. Multidrug resistant clinical isolates of Klebsiella pneumoniae (n = 137) were collected from March 2019 to February 2020. Identification and protein-based phylogenetic analysis were performed by MALDI-TOF MS. Genomic typing was done by ERIC-PCR and analyzed by an online data analysis service (PyElph). Dice method with unweighted pair group method with arithmetic mean (UPGMA) program was used to compare the ERIC profiles. The samples were also evaluated by PCR for the presence of genes encoding carbapenemases, extended spectrum beta lactamases (ESBLs) and mobile colistin resistance-1 (mcr1).. The study presents ERIC-PCR as more robust and better discriminatory typing tool in comparison to MALDI-TOF for clonal relatedness in multidrug resistant K. pneumoniae clinical isolates. Isolates were typed into 40 ERIC types, and six groups by MALDI-TOF-MS. PCR-based analysis revealed that all the strains harbored two or more ESBL and carbapenemase genes. None of the isolates revealed the presence of the plasmid mediated mcr-1 gene for colistin resistance.

Topics: Colistin; Enterobacteriaceae; Humans; Klebsiella Infections; Klebsiella pneumoniae; Phylogeny; Polymerase Chain Reaction; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tertiary Care Centers

The determination of clonal interactions between microorganisms is very important in epidemiological studies. In the present study, we aimed to evaluate the resistance mechanisms and genetic relationships of carbapenem and colistin resistant Klebsiella pneumoniae (K. pneumoniae) strains isolated from inpatients at two university hospitals in Turkey.. A total of 38 K. pneumoniae clinical isolates were included in the study. Identification of isolates was confirmed by 16S rRNA sequencing. Antimicrobial susceptibility testing was performed with VITEK-2 system (bio-Mérieux, France). Modified Hodge test was used for the detection of carbapenemase activity in isolates. Carbapenem resistance genes (blaOXA-48, blaNDM, blaKPC, blaIMP, blaVIM) and colistin resistance genes (mcr-1, mcr-2 and mcr-3) were investigated by PCR. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and multilocus sequence typing (MLST) analysis were used to determine the genetic relatedness among the isolates.. We detected that 58% of isolates were positive for only blaOXA-48, 5% were only positive for blaNDM, and 34% were positive for both blaOXA-48 and blaNDM. blaKPC, blaIMP, blaVIM, mcr-1, mcr-2, and mcr-3 were not detected among the isolates. Only one carbapenem resistant isolate was negative for the carbapenemase genes tested. A total of nine profiles were found by ERIC-PCR, and MLST results showed seven different sequence types-ST14, ST16, ST79, ST101, ST1543, ST2096, and ST2832. The seven STs were grouped by PHYLOVIZ Online into four clonal complexes. The most common ST was ST14 (81%) in Center 1 and ST2096 (94%) in Center 2.. We determined MLST types of carbapenem and colistin resistant K. pneumoniae isolates from two different centers. Although the most common ST types were different in these centers, both ST types were clustered in CC14. To the best of our knowledge this is the first report of ST14 and ST2096 outbreaks in Turkey.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; RNA, Ribosomal, 16S; Turkey

Carbapenemase-producing Klebsiella pneumoniae (CP-KP) is becoming extensively disseminated in Iranian medical centers. Colistin is among the few agents that retains its activity against CP-KP. However, the administration of colistin for treatment of carbapenem-resistant infections has increased resistance against this antibiotic. Therefore, the identification of genetic background of co-carbapenem, colistin-resistance K. pneumoniae (Co-CCRKp) is urgent for implementation of serious infection control strategies.. Fourteen Co-CCRKp strains obtained from routine microbiological examinations were subjected to molecular analysis of antimicrobial resistance (AMR) using whole genome sequencing (WGS).. In our study, different genetic modifications in chromosomal coding regions of some regulator genes resulted in phenotypic resistance to colistin. However, the extra-chromosomal colistin resistance through mcr genes was not detected. Continuous genomic investigations need to be conducted to accurately depict the status of colistin resistance in clinical settings.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Hospitals; Humans; Iran; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Whole Genome Sequencing

Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenem-cilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacteremia; beta-Lactamase Inhibitors; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Cilastatin; Colistin; Drug Combinations; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tetracyclines

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Catheter-Related Infections; Catheters; Colistin; Drug Combinations; Drug Resistance, Bacterial; Edetic Acid; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Virulence

Five

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Clone Cells; Colistin; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Middle Aged

Genomic surveillance can inform effective public health responses to pathogen outbreaks. However, integration of non-local data is rarely done. We investigate two large hospital outbreaks of a carbapenemase-carrying

Topics: Bacterial Proteins; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Epidemiological Monitoring; Germany; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Transport Proteins; Models, Molecular; Phylogeny; Protein Conformation

Ineffectiveness of carbapenems against multidrug resistant pathogens led to the increased use of colistin (polymyxin E) as a last resort antibiotic. A gene belonging to the DedA family encoding conserved membrane proteins was previously identified by screening a transposon library of K. pneumoniae ST258 for sensitivity to colistin. We have renamed this gene dkcA (dedA of Klebsiella required for colistin resistance). DedA family proteins are likely membrane transporters required for viability of Escherichia coli and Burkholderia spp. at alkaline pH and for resistance to colistin in a number of bacterial species. Colistin resistance is often conferred via modification of the lipid A component of bacterial lipopolysaccharide with aminoarabinose (Ara4N) and/or phosphoethanolamine. Mass spectrometry analysis of lipid A of the ∆dkcA mutant shows a near absence of Ara4N in the lipid A, suggesting a requirement for DkcA for lipid A modification with Ara4N. Mutation of K. pneumoniae dkcA resulted in a reduction of the colistin minimal inhibitory concentration to approximately what is found with a ΔarnT strain. We also identify a requirement of DkcA for colistin resistance that is independent of lipid A modification, instead requiring maintenance of optimal membrane potential. K. pneumoniae ΔdkcA displays reduced virulence in Galleria mellonella suggesting colistin sensitivity can cause loss of virulence.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Larva; Membrane Proteins; Moths; Virulence

Topics: Adolescent; Aged; Anti-Bacterial Agents; Bacterial Proteins; Child; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Middle Aged; Taiwan

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

This study aimed to characterise insertional mutations disturbing themgrB gene in carbapenem-resistant Klebsiella pneumoniae (CRKp).. A total of 118 clinical CRKp isolates were surveyed for polymyxin resistance and insertion sequence (IS) elements disruptingmgrB.. Of the 118 isolates, 78 (66.1%) displayed polymyxin resistance, of which 54% (42/78) hadmgrB::IS inserts. Sequencing analyses showed 13 insertion sites in mgrB. mgrB::ISSen4(IS3) was observed for the first time in CRKp.. Ten different IS elements disruptedmgrB, with a predominance (76%) of IS5 sequences.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Brazil; Carbapenems; Colistin; DNA Transposable Elements; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Colistin provides in vitro activity against numerous ESBL-producing and carbapenem-resistant bacteria. However, clinical information with respect to its utilization in infection caused by ESBL producers is limited. The aim of this study was a comparison of mortality rates of loading dose (LD) colistin and carbapenems as definitive therapies in a cohort of patients with infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. A retrospective cohort study in 396 patients with ESBL-producing E.coli and K.pneumoniae infection at a university-affiliated hospital was conducted between 1 January 2005 and 30 June 2015 to compare outcomes of infected patients who received LD colistin (95 patients) with carbapenems (301 patients). The three primary outcomes were 30-day mortality, clinical response and microbiological response. The most common infection types were urinary tract infection (49.49%), followed by pneumonia (40.66%), bacteremia (13.64%), skin and soft tissue infections (4.80%) and intra-abdominal infection (3.03%). LD colistin group provided higher 30-day mortality when compared with carbapenems group (HR 7.97; 95% CI 3.68 to 17.25; P = 0.001). LD colistin was also independently associated with clinical failure (HR 4.30; 95% CI 1.93 to 9.57; P = 0.001) and bacteriological failure (HR 9.49; 95% CI 3.76 to 23.96; P = 0.001) when compared with those who received carbapenems. LD colistin treatment was associated with poorer outcomes, i.e. mortality rate, clinical response and microbiological response. Moreover, when adjusted confounding factors, LD colistin was still less effective than carbapenems. It should be noted that, however, the use of Vitek-2 to assess colistin susceptibility could provide inaccurate results. Also, the difference in baseline characteristics could still remain in retrospective study although compensation by hazard ratio adjustment was performed. Therefore, clinical utilization of LD colistin should be recommended as an alternative for treatment ESBL-producing Enterobacteriaceae only in the circumstances where carbapenems cannot be utilized, but this recommendation must be considered carefully.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cohort Studies; Colistin; Escherichia coli; Escherichia coli Infections; Female; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Plasmids; Sequence Deletion

Topics: Colistin; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids

Topics: Animals; Colistin; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Pets

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

The Klebsiella pneumoniae (K. pneumoniae) bacterium is responsible for many opportunistic infections such as sepsis, and a multidrug-resistant (MDR) clone sequence type (ST) 307 has recently begun to spread. The objective of this study was to report the first occurrence of this virulent genotype, which was found in the context of a urinary infection in a domestic feline in Brazil. The K. pneumoniae isolate was identified from the urine of a 6-month-old male crossbreed cat using 16S rRNA sequencing. It was then subjected to antimicrobial susceptibility testing, followed by multilocus sequence typing analysis, and PCR detection of virulence and resistance genes. The antimicrobial susceptibility profile demonstrated that the isolate was MDR and associated with the presence of the colistin resistance gene (mcr-1). Genotyping allowed us to classify the isolate as K. pneumoniae ST307 with the presence of wabG, uge, and entB genes. MDR K. pneumoniae is important in human and veterinary medicine because it causes many types of infections. Clonal propagation of virulent or MDR genotypes such as K. pneumoniae ST307 is a global concern. This report of ST307 isolation from a urine sample in a domestic feline is the first in Brazil.

Topics: Animals; Anti-Bacterial Agents; Brazil; Cat Diseases; Cats; Colistin; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genotype; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Urinary Tract Infections

Limited clinical studies describe the pharmacodynamics of fosfomycin (FOS), tigecycline (TGC) and colistin methanesulfonate (CMS) in combination against KPC-producing Klebsiella pneumoniae (KPC-Kp). Population pharmacokinetic models were used in our study. Monte Carlo simulation was conducted to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR) of each agent alone and in combination against KPC-Kp in patients with normal or decreased renal function.. The simulated regimen of FOS 6 g q8h reached ≥90% PTA against a MIC of 64 mg/L in patients with normal renal function. For patients with renal impairment, FOS 4 g q8h could provide sufficient antimicrobial coverage against a MIC of 128 mg/L. And increasing the daily dose could result to the cut-off value to 256 mg/L in decreased renal function. For TGC, conventional dosing regimens failed to reach 90% PTA against a MIC of 2 mg/L. Higher loading and daily doses (TGC 200/400 mg loading doses followed by 100 mg q12h/200 mg q24h) were needed. For CMS, none achieved 90% PTA against a MIC of 2 mg/L in normal renal function. Against KPC-Kp, the regimens of 200/400 mg loading dose followed by 100 q12h /200 mg q24h achieved > 80% CFRs regardless of renal function, followed by CMS 9 million IU loading dose followed by 4.5/3 million IU q12h in combination with FOS 8 g q8h (CFR 75-91%).. The use of a loading dose and high daily dose of TGC and CMS in combination with FOS can provide sufficient antimicrobial coverage against critically ill patients infected with KPC-Kp.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Critical Illness; Female; Fosfomycin; Humans; Kidney; Kidney Function Tests; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Plasmids

Although colistin is frequently regarded as the antibiotic of last resort in treating carbapenem-resistant Klebsiella pneumoniae, colistin heteroresistance may in part be associated with antibiotic treatment failure. However, we do not know how widespread the colistin heteroresistance is in carbapenem-resistant K. pneumoniae isolates. In this study, we performed colistin disc diffusion assays, E-tests, and population analysis profiling for KPC-2-producing K. pneumoniae isolates to identify colistin heteroresistance. Although no colistin-resistant colonies were detected by the disc diffusion test and E-test, a colistin-resistant subpopulation was identified in population analysis profiling in all colistin-susceptible, KPC-2-producing K. pneumoniae isolates. Colistin-resistant subpopulations were also identified even when isolates had no colistin exposure. The ratio of colistin-resistant subpopulations to the total population increased as the exposure concentration of colistin increased. In in vitro time-kill assays, regrowth was observed in all isolates after 2 h upon exposure to colistin. We identified common amino acid alterations in PhoQ, PhoP, and PmrB in colistin-resistant subpopulations from some isolates, but no substitutions were found in most resistant subpopulations from other isolates. In all colistin-resistant subpopulations, overexpression of PhoQ and PbgP was observed. In this study, we demonstrated that colistin heteroresistance may be common in KPC-2-producing K. pneumoniae isolates, which could not be detected in the disc diffusion method and E-test. Colistin heteroresistance may cause colistin treatment failure in part and may evolve into resistance. Thus, development of more reliable diagnostic methods is required to detect colistin heteroresistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Colistin resistance in Gram negative bacteria is mainly attributed to chromosomal mutations in Two Component Systems(TCS) PhoPQ and PmrAB and plasmid-borne genes(mcr and its variants). The aim of this study was to understand the molecular basis of colistin resistance in Klebsiella pneumoniae and determine clonal transmission, in a North Indian tertiary care hospital over a 2.5 year period. Antimicrobial susceptibility was determined by Vitek and colistin resistance was confirmed by broth microdilution. Carbapenemases(bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Phylogeny; Tertiary Care Centers; Transcription Factors

Colistin is one of the last-resort antibiotics for treating carbapenem-resistant Klebsiella pneumoniae (CRKP). However, colistin resistance in CRKP poses a global antimicrobial crisis, as therapeutic options are limited. We investigated risk factors for in vivo emergence of colistin resistance in CRKP and explored the underlying resistance mechanisms. We conducted this matched case-control study of patients with sequential CRKP clinical strains at a medical centre in Taiwan between October 2016 and June 2019. The case group included patients with an index colistin-resistant CRKP (ColR-CRKP) strain and a previous colistin-susceptible CRKP (ColS-CRKP) counterpart. The control group encompassed patients with both an index and previous ColS-CRKP strains. Cases and controls were matched according to the time at risk, and conditional logistic regression was used to evaluate potential risk factors. Alterations in genes associated with resistance were compared between ColR-CRKP and ColS-CRKP strains. We identified 24 CRKP cases with in vivo-emergent colistin resistance, matched in a 1:2 ratio with controls. Multivariate analysis showed that colistin exposure is the only independent risk factor predisposing to colistin resistance (adjusted odds ratio = 19.09, 95% confidence interval 1.26-290.45; P = 0.034). Alteration in the mgrB gene was the predominant mechanism for emergent colistin resistance (17/24; 71%). In conclusion, colistin use is a risk factor for in vivo emergence of colistin resistance in CRKP. Given the lack of a rapid and reliable method to detect colistin resistance in daily practice, physicians should be vigilant for the emergence of resistance during colistin treatment.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Membrane Proteins; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Taiwan; Tertiary Care Centers

Klebsiella pneumoniae is an opportunistic pathogen commonly associated with nosocomial infections. In our previous study, we have demonstrated that colistin-resistant K. pneumoniae is more susceptible to killing by lytic tailed phages than the colistin-sensitive parent strain, including T1-like ФNJS1. This fitness cost associated with colistin resistance is due to the alteration of the surface charge that promotes phage adherence and infection. However, the receptor for phage adsorption has not been identified. In this study, we found that ФNJS1 specifically infected nonmucoid K. pneumoniae isolates, and the accelerated phage adsorption to colistin-resistant nonmucoid K. pneumoniae cells is reversible. Further research suggested that bacteria lipopolysaccharide may be involved in phage reversible adsorption, while capsule polysaccharide may block the receptors on cell surface from phage attachment. Transposon mutagenesis of colistin-resistant K. pneumoniae revealed that mutation in wecA and wecG, two genes involved in lipopolysaccharide O-antigen biosynthesis, significantly deceased phage adsorption capacity and infection efficiency. Inactivation of wzyE, which leaded to the shorten of O-antigen chain length, enhanced phage infectivity. Moreover, mutation of the outer membrane protein FepA slowed the phage lysis rate, suggesting that FepA may be an irreversible receptor for ФNJS1. In summary, our results show a delicate balance between ФNJS1 and its hosts, where the lipopolysaccharide O-antigen may serve as an essential reversible receptor for phage NJS1, while the long O-antigen chain hinders the bacteriophage infection.

Topics: Bacteriophages; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mutagenesis; O Antigens

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with "carbapenem-resistant K. pneumoniae (CRKp)" bacteremia between 2014 and 2018 were divided into two groups as "colistin susceptible (ColS)" and "colistin resistant (ColR)" based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Proportional Hazards Models; Retrospective Studies; Sepsis

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Thailand

BackgroundFrance is a low prevalence country for colistin resistance. Molecular and epidemiological events contributing to the emergence of resistance to colistin, one of the 'last-resort' antibiotics to treat multidrug-resistant Gram-negative infections, are important to investigate.AimThis retrospective (2014 to 2017) observational study aimed to identify risk factors associated with acquisition of colistin-resistant

Topics: Anti-Bacterial Agents; Bacterial Proteins; Clone Cells; Colistin; Cross Infection; Drug Resistance, Bacterial; Epidemics; France; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors

Although in vitro data suggest that tigecycline is active against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), experimental and clinical data are limited. We studied the effect of tigecycline alone or in combination for experimental infections by KPC-Kp. A total of 540 male C57BL/6 mice were infected with three genetically diverse KPC-Kp isolates susceptible to tigecycline with meropenem minimum inhibitory concentrations (MICs) of 4, 16 and 256 μg/mL, respectively. Mice were randomly treated with water for injection, tigecycline, meropenem and colistin alone, and double or triple combinations of tigecycline, colistin and meropenem. Mouse survival was recorded for 14 days. In separate experiments, mice were sacrificed 6 h and 24 h after bacterial challenge for quantitative culture of tissues and serological analysis. Time-kill curves were performed. Tigecycline, colistin and meropenem concentrations were measured in tissues and serum by high-performance liquid chromatography (HPLC). Survival was significantly prolonged when mice were treated with tigecycline alone and tigecycline-containing regimens compared with control mice and mice treated with tigecycline-sparing regimens. Tigecycline-sparing regimens were active only against the isolate with a meropenem MIC of 4 μg/mL. Mortality was associated with progression to multiple organ failure. Tigecycline and tigecycline-containing regimens achieved a rapid decrease of bacterial loads both in tissues and in vitro. Tigecycline concentrations in tissues were negatively correlated with tissue bacterial load. Tigecycline alone or in combination with meropenem and/or colistin achieves effective treatment of experimental KPC-Kp infections irrespective of the meropenem MIC.

Topics: Animals; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Disease Models, Animal; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Mice; Tigecycline

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Increasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (. Twenty-two colistin resistant. Colistin resistance in

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids

The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a serious public-health issue as colistin is the last line of defence against infections caused by multidrug-resistant Gram-negative bacteria. In this study, we generated a draft genome sequence for CoRKp strain P094-1 isolated from a sputum sample of an infected patient.. Whole genomic DNA of strain P094-1 was sequenced using a PacBio sequencing platform. Generated reads were de novo assembled using Hierarchical Genome Assembly Process (HGAP) v.3.0. Colistin resistance-related genes were predicted from the genome sequence and were validated experimentally.. The genome of strain P094-1 lacked a 20.3-kb region, including complete deletion of the mgrB gene. Molecular and genome sequencing-based analyses revealed that the observed colistin resistance of P094-1 could not be attributed to plasmid-borne genes mcr-1 to mcr-9 or to alteration of the pmr and pho operons (deletions, insertions or substitutions), but was conferred by an insertion sequence 1 (IS1)-induced total deletion of mgrB.. This is the first reported whole-genome sequence of an unusual CoRKp isolate containing an IS1-induced deletion of mgrB.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae

Treatment of infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) frequently involves combination therapy with various antimicrobial agents in the hope of achieving synergistic effects. Routine laboratory antimicrobial synergy testing is a service that is currently unavailable owing to the laborious nature of the reference time-kill assay (TKA) as well as the widely used chequerboard method. In this study, we explored whether easier methods, based on the Etest technique, might offer a suitable alternative.. In vitro interactions of tigecycline combination with colistin, gentamicin, fosfomycin or meropenem against 26 CPKP isolates were evaluated employing the TKA, chequerboard method and three Etest methodologies (the MIC/MIC ratio, the cross formation and the agar/Etest method). Rates of consequent synergy and concordance of the studied methods were determined.. All antimicrobial combinations demonstrated some degree of synergy against the CPKP isolates tested. No antagonism was observed for any of the combinations. All methods showed poor synergy concordance with the TKA, producing non-significant kappa (κ) results. Etest methods (MIC/MIC ratio and agar/Etest) exhibited fair agreement (κ=0.29 and 0.38, respectively) with the chequerboard method.. There is a poor correlation between synergy testing methods of tigecycline combinations, which may be associated with their different endpoints. To elucidate method comparability and reliability, their correlation with clinical outcomes appears important.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gentamicins; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tigecycline

We aimed to develop here a specific real-time PCR assay with TaqMan® probe to detect efficiently bacterial strains harboring the new plasmid mediated-colistin resistance mcr-8 gene.. Specific primers and probe for mcr-8 gene were designed from sequences alignment of all mcr genes variants. Specificity of the designed primers and probe were first checked par BlastN analysis and by in silico PCR. The analytical sensitivity and specificity tests were performed in vitro on a panel of 290 genomic DNA of Gram-negative bacteria and 250 metagenomic DNA from human stool samples. Whole genome sequencing (WGS) was performed here using MiSeq technology.. To the best of our knowledge, we propose here, the first real-time PCR assay targeting mcr-8 gene with high specificity and sensitivity, able to detect mcr-8 gene in less than 2 h from any DNA sample. This real-time PCR assay allowed the first description of a clinical K. pneumoniae strain harboring the mcr-8 gene in Algeria.

Topics: Algeria; Bacterial Proteins; Colistin; Computer Simulation; Drug Resistance, Bacterial; Feces; High-Throughput Nucleotide Sequencing; Humans; Klebsiella Infections; Klebsiella pneumoniae; Limit of Detection; Microbial Sensitivity Tests; Plasmids; Real-Time Polymerase Chain Reaction; Whole Genome Sequencing

Polymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versus transmission in PR emergence.. We included 88 patients with PR K. pneumoniae from 2011-2018 and collected demographic, antimicrobial exposure, and infection data. Whole-genome sequencing was performed on 388 isolates, including 164 PR isolates. Variant calling and insertion sequence detection were performed, focusing on key genes associated with PR (mgrB, crrAB, phoPQ, and pmrAB). We conducted phylogenetic analyses of key K. pneumoniae multi-locus sequence types (ST258, ST17, ST307, and ST392).. Polymyxin exposure was documented in 53/88 (60%) patients prior to PR detection. Through an analysis of key PR genes, we detected 129 individual variants and 72 unique variant combinations in PR isolates. This included multiple, distinct changes in 36% of patients with serial PR isolates. Insertion sequence disruption was limited to mgrB (P < .001). Polymyxin minimum inhibitory concentrations showed stepwise increases with the number of PR genes affected (P < .001). When clusters containing PR isolates in ≥2 patients were analyzed, 10/14 had multiple genetic events leading to PR.. Molecular mechanisms leading to PR in clinical K. pneumoniae isolates are remarkably heterogenous, even within clusters or individual patients. Polymyxin exposure with de novo PR emergence led to PR in the majority of patients, rather than transmission. Optimizing polymyxin use should be a key strategy in stopping the spread of PR.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phylogeny; Polymyxins; Retrospective Studies

Topics: Anti-Bacterial Agents; Base Sequence; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Feces; Fluoroquinolones; Genes, Bacterial; Genomics; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutagenesis, Insertional; Plasmids; Virulence; Whole Genome Sequencing

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing K. pneumoniae has rapidly expanded and is associated with severe nosocomial infections. Last-line antibiotics, such as colistin and tigecycline, remain the only treatment option. This study described the genetic background of a novel pan-resistant KPC-producing K. pneumoniae isolate from Tokyo, Japan.. The antibiotic susceptibility of clinical isolates from a patient hospitalised in 2016 was tested using a MicroScan WalkAway instrument and the broth microdilution method. Susceptibility was defined according to breakpoints provided by the Clinical and Laboratory Standards Institute. Whole-genome sequencing was performed to detect acquired resistance genes and gene mutations.. This study identified molecular resistance markers in a pan-resistant isolate and provided a genomic description of the pan-resistance and origins of the isolate and plasmid. The isolate is closely related to a recent highly pathogenic carbapenem-resistant K. pneumoniae identified in China; however, it lacks a virulence plasmid (but it could still act as a reservoir for a virulence plasmid). This K. pneumoniae isolate is of concern in hospital and community care settings.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Japan; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Whole Genome Sequencing

Carbapenem resistance among multidrug resistant organism is a growing global concern with high rates being reported from South Asia and Mediterranean countries. It is associated not only with high morbidity and mortality, but also pose a grave health hazard. Among various studies, it has been found that among the gram-negative bacteria Klebsiella species is found to have a high resistance. The aim of the study was to evaluate the prevalence and pattern of colistin resistance in Klebsiella species (spp.) in a tertiary care hospital in India.. An audit of microbiological data of all Klebsiella spp. isolates from blood, urine, sputum and pus was collected from patients admitted to intensive care unit (ICUs) between 1st January 2015 to 31st December 2017 and the prevalence of Colistin resistance in Klebsiella spp. was calculated.. Over a period of thirty six months, 2499 isolates were identified from culture positive specimen of blood, urine, sputum, broncho-alveolar lavage (BAL) fluid and pus from patients admitted to ICU. Among the total isolates 21.32% (n=533) of Klebsiella spp. were isolated and 1.28% (n=30) of isolates were colistin resistant. In patients admitted to ICU, colistin resistant Klebsiella spp. was identified in 8.75% (n=14) of the total blood samples, 4.26% (n=7) in urine samples and 4.4% (n=8) in sputum and BAL samples.. The prevalence of Colistin resistant Klebsiella spp. was estimated to be 5.6% in our ICU. Colistin resistant Klebsiella is becoming an emerging threat in ICU settings limiting further treatment options. Stringent surveillance and robust antibiotic stewardship program to tide over this crisis is need of the hour.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Female; Humans; India; Intensive Care Units; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Tertiary Care Centers

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Europe; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Cancer Care Facilities; Child; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged

Increasing colistin consumption is leading to expanding colistin resistance in Klebsiella pneumoniae worldwide, but particularly in Asia. Epidemiological studies indicate a link between specific insertion sequences (ISs) and colistin resistance; however, proof of a colistin-IS correlation is lacking.. Colistin-resistant mechanisms, and in vitro and in vivo efficacies of colistin against K. pneumoniae with ISs were investigated.. Colistin-resistant genes, including mcr-1 gene, were detected in 49 colistin- and carbapenem-resistant K. pneumoniae isolates. crrCAB genetic environments were analysed using whole-genome sequencing and polymerase chain reaction (PCR) mapping. Identified ISs were cloned into pRK415 vectors and investigated for potential contributions to colistin resistance. A Caenorhabditis elegans model was employed for in vivo analysis.. mgrB gene alterations (32/49, 65.3%) were identified as the major colistin-resistant mechanism, followed by variations in crrB (57.1%), pmrB (32.7%), phoQ (20.9%), pmrA (16.3%) and phoP (8.2%) genes. Furthermore, 21 of the 49 tested isolates (42.9%) contained the IS elements, ISKpn26, ISEcp1, IS10R, IS903B or ISKpn14 in mgrB or in the surrounding region of crrCAB, indicating an association between these ISs and colistin resistance. The frequencies of colistin resistance significantly increased in colistin-susceptible K. pneumoniae laboratory strains, with plasmids carrying different ISs from clinical strains. In vivo analysis revealed that K. pneumoniae harboring ISKpn26 was associated with decreased lifespan during colistin treatment, leading to an increased risk for colistin treatment failure.. These findings indicate a correlation between diverse ISs and colistin resistance in K. pneumoniae and confirm a role for ISs in colistin treatment.

Topics: Anti-Bacterial Agents; Asia; Colistin; DNA Transposable Elements; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae

We present an updated picture (1/1/2017-31/08/2019) of the frequency of carbapenemase producing Klebsiella pneumoniae (CPKP) in surveillance rectal swabs (SRS) and in clinical samples (CS) of patients admitted to a tertiary level hospital, focusing on longitudinal evolution of CPKP detected in SRS and on colistin resistant strains.. Retrospective longitudinal analysis. Only the first positive CPKP strain isolated from each patient was included.. 638 CPKP strains were identified (471 in SRS and 167 in CS). SRS frequency increased over time in the medical department, remained high in the surgical department (SD) and decreased in the intensive care department. Most SRS-71.3%-and 49.1% of CS had nosocomial origin; about half of the SRS were identified in the SD. Regarding SRS evolution, carriage was confirmed in 39.5% of patients, no more testing in 25.5%, clinical involvement in 24.8 %, and negative result in 10.2%. Rates of colistin resistance were 20.1% in 2017, 31.2% in 2018 and 26.9% in 2019.. CPKP diffusion is still an important issue despite the surveillance program. It is vital to enhance medical staff's awareness on this because most CPKP first detections in SRS occurred during hospital stay due to a nosocomial acquisition with a comparable picture over time. Colistin resistance is increasing.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Drug Resistance, Bacterial; Epidemiological Monitoring; Female; Hospitals, Teaching; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Longitudinal Studies; Male; Middle Aged; Rectum; Retrospective Studies; Tertiary Care Centers

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carrier Proteins; Colistin; Drug Resistance, Bacterial; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae

In Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece.. From 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing.. Among the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated.. This study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Thailand

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Chickens; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Transport Proteins; Microbial Sensitivity Tests; Phylogeny; Plasmids; Whole Genome Sequencing

The emergence and outbreak of colistin-resistant CRKP (carbapenem-resistant Klebsiella pneumoniae) have been the major global public threat in recent years. Present study emphasized the genome-wide distribution, characterization of drug resistance virulence genes in an extremely drug-resistant (XDR) Klebsiella pneumoniae strain isolated from a patient with drug-induced hepatitis, hospitalized in a tertiary care facility in India.. The total genomic DNA was sequenced using the Illumina Hiseq platform. De novo assembly of reads was done using CLC genomics workbench. Genome annotation was performed using PROKKA. Sequence typing (ST), virulence-related genes and antimicrobial resistance genes were predicted from genome sequences. Phenotypic evaluation of efflux pump function was done in presence of colistin and efflux pump inhibitor (EPI).. Antibiogram analysis confirmed the isolate to be XDR. The number of contigs in assembly file was found to be 867 with a total of 6,060,836 bases and a total of 5547 coding sequences. The isolate exhibited high resistance to colistin due to mutations in two-component systems and predicted to be efflux mediated. The sequence typing of Klebsiella pneumoniae SDL79 is assigned to ST147.. This is the first whole genome analysis of XDR Klebsiella pneumoniae ST147 from a hospital conferring co-resistance to last resort drugs. However, the detailed molecular mechanism behind the drug resistance will be carried out in our future endeavors.

Topics: Carbapenems; Colistin; Genomics; Humans; India; Klebsiella Infections; Klebsiella pneumoniae

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

We investigated the colistin resistance of Klebsiella pneumoniae blood isolates from South Korea. Among 252 K. pneumoniae isolates, only 11 (4.4%) demonstrated colistin resistance, of which, one was resistant to all antibiotics but tigecycline. Multilocus sequence typing analysis revealed ten sequence types among the 11 colistin-resistant isolates, indicating independent occurrence of colistin resistance in K. pneumoniae. To understand the mechanism of colistin resistance, amino acid variations in PmrAB, PmrD, PhoPQ, and MgrB were investigated. Amino acid substitutions were identified in all the colistin-resistant K. pneumoniae isolates. Particularly, extensive alterations in the genes associated with colistin resistance were shared in four colistin-resistant isolates, suggesting recombination between these genes of unrelated isolates. Our results suggest that genetic recombination is responsible for colistin resistance in some K. pneumoniae isolates.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Genetic Variation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Republic of Korea

Colistin is considered as a last resort treatment for infections caused by multidrug-resistant Enterobacteriaceae. Plasmid-mediated mobile colistin resistance (mcr) genes contributed to the global spread of colistin resistance. This is the first report of plasmid-mediated colistin resistance mcr-8 gene from a clinical Klebsiella pneumoniae K9 isolate recovered from Lebanon. The isolate was characterized phenotypically and genotypically through both short and long read whole-genome sequencing, plasmid typing and conjugation assays. k9 belonged to sequence type 15 and harbored 31 antimicrobial resistance genes. The mcr-8.1 variant was carried on a novel ~ 300 kb multireplicon plasmid having IncFIA, IncR and IncHI1B. The plasmid was conjugative and carried a plethora of antimicrobial resistance determinants. The introduction of novel mcr variants in Lebanon poses an alarming health concern. Surveillance and screening for colistin resistant Enterobacteriaceae and mcr in livestock, animal farms, imported meat and poultry is highly recommended along with monitoring antibiotic use.

Topics: Bacterial Proteins; Colistin; Female; Genome Size; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lebanon; Microbial Sensitivity Tests; Middle Aged; Plasmids; Whole Genome Sequencing

We evaluated different susceptibility testing media against 200 Klebsiella pneumoniae isolates that have been genetically characterized for the presence of polymyxin resistance mechanisms. The media evaluated included calcium enriched media that was described to promote separation of mcr-carrying Enterobacterales isolates and standard cation-adjusted Mueller-Hinton broth with and without polysorbate 80. The testing conditions evaluated did not show improvement in the separation of isolates carrying MgrB alterations and other mutation-driven polymyxin resistance mechanisms.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Culture Media; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Polymyxins

The increased incidence of polymyxin-resistant MDR Klebsiella pneumoniae has become a major global health concern.. To characterize the lipid A profiles and metabolome differences between paired polymyxin-susceptible and -resistant MDR K. pneumoniae clinical isolates.. Three pairs of K. pneumoniae clinical isolates from the same patients were examined [ATH 7 (polymyxin B MIC 0.25 mg/L) versus ATH 8 (64 mg/L); ATH 15 (0.5 mg/L) versus ATH 16 (32 mg/L); and ATH 17 (0.5 mg/L) versus ATH 18 (64 mg/L)]. Lipid A and metabolomes were analysed using LC-MS and bioinformatic analysis was conducted.. The predominant species of lipid A in all three paired isolates were hexa-acylated and 4-amino-4-deoxy-l-arabinose-modified lipid A species were detected in the three polymyxin-resistant isolates. Significant metabolic differences were evident between the paired isolates. Compared with their corresponding polymyxin-susceptible isolates, the levels of metabolites in amino sugar metabolism (UDP-N-acetyl-α-d-glucosamine and UDP-N-α-acetyl-d-mannosaminuronate) and central carbon metabolism (e.g. pentose phosphate pathway and tricarboxylic acid cycle) were significantly reduced in all polymyxin-resistant isolates [fold change (FC) > 1.5, P < 0.05]. Similarly, nucleotides, amino acids and key metabolites in glycerophospholipid metabolism, namely sn-glycerol-3-phosphate and sn-glycero-3-phosphoethanolamine, were significantly reduced across all polymyxin-resistant isolates (FC > 1.5, P < 0.05) compared with polymyxin-susceptible isolates. However, higher glycerophospholipid levels were evident in polymyxin-resistant ATH 8 and ATH 16 (FC > 1.5, P < 0.05) compared with their corresponding susceptible isolates.. To our knowledge, this study is the first to reveal significant metabolic perturbations associated with polymyxin resistance in K. pneumoniae.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Metabolomics; Microbial Sensitivity Tests; Polymyxins

Topics: Animals; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Drugs, Generic; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Therapeutic Equivalency

Colistin (CST) is a last-resort therapeutic option for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections in critically ill patients. The effect of subinhibitory CST concentrations (sub-MICs) on biofilm formation is organism-dependent. We investigated the interactions between CST and innate immune cells against CR-Kp biofilms (CR-KpBF) by studying the effect of biofilm sub-MICs of CST on (i) damage induced by human polymorphonuclear neutrophils (PMNs) on CR-KpBF and (ii) the immunomodulatory potential on human mononuclear cells (MNCs) exposed to CR-KpBF. The impact of CST on PMN-induced biofilm damage was assessed by XTT reduction assay. Signal transduction and gene expression profiles in response to CST sub-MICs of MNCs exposed to CR-KpBF were studied by RT-PCR and multiplex ELISA. Pre-exposure of CR-Kp to 0.06 mg/L CST led to subsequent increased PMN-mediated biofilm damage against CR-KpBF in the presence of CST biofilm sub-MICs: there was an additive effect at 2, 4, 8 and 16 mg/L. However, the overall biofilm damage was not >52%. MNCs responded to CR-KpBF through Toll-like receptor 2 (TLR2) by 2.5-fold upregulation and NLRP3 inflammasome activation. CR-KpBF stimulated increased production of interleukin 1-beta (IL-1β), tumour necrosis factor-alpha (TNFα), IL-8 and IL-6. In the combination treatment, 0.5 mg/L CST reduced IL-1β, TNFα and IL-8 levels, whereas at 2 mg/L and 8 mg/L it increased the anti-inflammatory cytokine IL-10 (P < 0.05). Biofilm sub-MICs of CST enhance PMN killing capacity and attenuate production of inflammatory cytokines by MNCs exposed to CR-KpBF, playing a potentially important immunotherapeutic role especially for patients with cytokine deregulation.

Topics: Anti-Bacterial Agents; Biofilms; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cytokines; Humans; Immunomodulation; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cathelicidins; Colistin; Klebsiella Infections; Klebsiella pneumoniae; Lizards; Microbial Sensitivity Tests; Moths

The prevalence of polymyxin-resistant Enterobacteriaceae is increasing worldwide. Their emergence is worrisome and limits therapeutic options for severely ill patients. We aimed to investigate the molecular and epidemiological characteristics of polymyxin-resistant Klebsiella pneumoniae circulating in Brazilian hospitals. Polymyxin-resistant K. pneumoniae isolates from two Brazilian healthcare facilities were characterized phenotypically and subjected to whole genome sequencing (WGS). Using the WGS data we determined their sequence type, resistance gene content (resistome), their composition of virulence genes and plasmids. ST11 was the most common (80 %) sequence type among the isolates followed by ST345, ST15 and ST258. A resistome analysis revealed the common presence of bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Mutation; Polymyxins

Klebsiella pneumoniae is a leading cause of intractable hospital-acquired multidrug-resistant infections and carbapenemase-producing K. pneumoniae (CPKp) are particularly feared. Most of the clinical isolates produce capsule as a major virulence factor. Recombination events at the capsule locus are frequent and responsible for capsule diversity within Klebsiella spp. Capsule diversity may also occur within clonal bacterial populations generating differences in colony aspect. However, little is known about this phenomenon of phenotypic variation in CPKp and its consequences.. Here, we explored the genetic causes of in vitro switching from capsulated, mucoid to non-mucoid, non-capsulated phenotype in eight clinical CPKp isolates. We compared capsulated, mucoid colony variants with one of their non-capsulated, non-mucoid isogenic variant. The two colony variants were distinguished by their appearance on solid medium. Whole genome comparison was used to infer mutations causing phenotypic differences. The frequency of phenotypic switch was strain-dependent and increased along with colony development on plate. We observed, for 72 non-capsulated variants that the loss of the mucoid phenotype correlates with capsule deficiency and diverse genetic events, including transposition of insertion sequences or point mutations, affecting genes belonging to the capsule operon. Reduced or loss of capsular production was associated with various in vitro phenotypic changes, affecting susceptibility to carbapenem but not to colistin, in vitro biofilm formation and autoaggregation.. The different impact of the phenotypic variation among the eight isolates in terms of capsule content, biofilm production and carbapenem susceptibility suggested heterogeneous selective advantage for capsular loss according to the strain and the mutation. Based on our results, we believe that attention should be paid in the phenotypic characterization of CPKp clinical isolates, particularly of traits related to virulence and carbapenem resistance.

Topics: Animals; Anti-Bacterial Agents; Bacterial Capsules; Bacterial Proteins; beta-Lactamases; Biofilms; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phenotype; Virulence; Virulence Factors

The increasing prevalence of multidrug-resistant

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Virulence

Carbapenemase-producing and colistin resistant Klebsiella pneumoniae has become a worldwide healthcare problem. This study describes molecular characterization of carbapenemase-producing and colistin resistant clinical K. pneumoniae isolates.A total of 93 non-replicate carbapenem and colistin resistant K. pneumoniae were recovered from clinical specimens in a university hospital during 2017-2019. Detection of blaOXA-48, blaKPC, blaNDM-1, blaIMP, blaVIM-1 and mcr-1, -2, -3, -4, -5, -6, -7, and -8 genes was performed by PCR. The bacterial isolates were assigned to clonal lineages by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).All isolates harbored blaOXA-48 and only two isolates harbored blaOXA-48, and blaNDM-1 genes together. In colistin resistant K. pneumoniae, mcr-1 was detected in two (2.1%) isolates. Ninety three isolates of K. pneumoniae were categorized into three clusters and five pulsotypes. MLST revealed two different sequence types, ST101 (89/93) and ST147 (4/93).In our study ST101 was found to be a significantly dominant clone carrying blaOXA-48 and among our strains a low frequency of mcr-1 gene was determined. The emergence of colistin resistance was observed in K. pneumoniae ST101 isolates. ST101 may become a global threat in the dissemination of carbapenem and colistin resistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Turkey

The aim of this study was to determine the effect of colistin resistance and other predictors on fatality among patients with Klebsiella pneumoniae bloodstream infections (Kp-BSI) and to describe the effect of amikacin and tigecycline on the outcome in an OXA-48 dominant country.. This was a retrospective study performed among patients >16 years of age in a tertiary hospital with 465 beds. All cases had ≥1 positive blood culture for K. pneumoniae 48 h after admission.. Among 210 patients with Kp-BSI, the 30-day mortality rate after isolation of the microorganism was 58%. The rate of carbapenem resistance was higher (64% vs. 38%, p < 0.001) and the colistin minimum inhibitory concentration (MIC) was elevated (7 vs. 4, p < 0.029) among the patients who died. Among the colistin-resistant K. pneumoniae, the rates of OXA-48, ST101, and NDM-1 were 78%, 67%, and 35%, respectively. Amikacin was added to the treatment of 13 patients with carbapenem and colistin-resistant Kp-BSI and 77% survived (p < 0.001). Tigecycline was added to the treatment of 24 patients with carbapenem and colistin-resistant Kp-BSI, and the 30-day mortality rate was 71% (p = 0.576). In the multivariate analysis, carbapenem resistance (odds ratio (OR) 5.2, 95% confidence interval (CI) 2.47-10.9, p < 0.001) and increasing APACHE II score (OR 1.19, 95% CI 1.12-1.26, p < 0.001) were significantly associated with 30-day mortality. The addition of amikacin to the treatment regimen (OR 0.05, 95% CI 0.01-0.23, p < 0.001) was significantly beneficial.. Carbapenem resistance, increasing MIC of colistin, and the lungs as the source of the infection were significantly associated with 30-day mortality. The empirical use of combined active aminoglycosides was found to be beneficial in the treatment of colistin-resistant K. pneumoniae infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Tertiary Care Centers; Tigecycline; Young Adult

Klebsiella pneumoniae has emerged worldwide as a major cause of severe infections owing to the rising prevalence of multidrug-resistant strains in clinical settings. This study aimed to investigate the genomic features of pandrug-resistant K. pneumoniae strain KP2 with high colistin and tigecycline resistance isolated from a patient in China.. The antimicrobial susceptibility of K. pneumoniae KP2 was determined by microdilution broth assay. Whole genomic DNA was extracted and was sequenced using an Illumina HiSeq X10 platform. De novo genome assembly was performed using Unicycler, and the draft genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). The sequence type (ST), capsular type, antimicrobial resistance and virulence-related genes were identified from the genome sequence. Core genome multilocus sequence typing (cgMLST) analysis was performed by BacWGSTdb server.. Klebsiella pneumoniae KP2 was resistant to all antimicrobial agents tested, including colistin and tigecycline. The genome size was calculated as 5 729 339bp, with 5772 protein-coding sequences and a G+C content of 57.0%. The isolate was assigned to ST11 with capsular serotype KL64. Several antimicrobial resistance genes and virulence genes as well as genomic islands and multiple insertion sequences were identified in the genome sequence. The closest relative of K. pneumoniae KP2 was another isolate from Hangzhou that differed by only 45 cgMLST loci.. The genome sequence data presented in this study can serve as an important reference sequence for further understanding of the antimicrobial resistance mechanisms and virulence potential of this bacterial species.

Topics: Anti-Bacterial Agents; Base Composition; beta-Lactamases; China; Colistin; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Prevalence; Sequence Analysis, DNA; Serogroup; Tigecycline; Virulence; Whole Genome Sequencing

Topics: Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Chlorhexidine; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae

Klebsiella pneumoniae is an important human pathogen, able to accumulate and disseminate a variety of antimicrobial resistance genes. Resistance to colistin, one of the last therapeutic options for multi-drug-resistant bacteria, has been reported increasingly. Colistin-resistant K. pneumoniae (ColRKp) emerged in two hospitals in Rio de Janeiro state, Brazil in 2016. The aim of this study was to investigate if these ColRKp isolates were clonally related when compared between hospitals, to identify the molecular mechanisms of colistin resistance, and to describe other antimicrobial resistance genes carried by isolates. Twenty-three isolates were successively recovered, and the whole-genome sequence was analysed for 10, each of a different pulsed-field gel electrophoresis (PFGE) type. Although some PFGE clusters were found, none of them included isolates from both hospitals. Half of the isolates were assigned to CC258, three to ST152 and two to ST15. One isolate was pandrug resistant, one was extensively drug resistant, and the others were multi-drug resistant. Colistin resistance was related to mutations in mgrB, pmrB, phoQ and crrB. Eleven new mutations were found in these genes, including two nucleotide deletions in mgrB. All isolates were carbapenem resistant, and seven were associated with carbapenemase carriage (bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Transcription Factors; Whole Genome Sequencing

Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.. Retrospective observational study.. Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.. Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).. Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Typing Techniques; Colistin; Cross Infection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Multilocus Sequence Typing; Retrospective Studies; Young Adult

In the present study, we provide the results of a detailed genomic analysis and the growth characteristics of a colistin-resistant KPC-3-producing

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Ethanolaminephosphotransferase; Genetic Fitness; Hospitals; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Mutant Proteins; Sequence Deletion; Transcription Factors; Whole Genome Sequencing

The management of Klebsiella pneumoniae carbapenemase producing (KPC) infections represents a major challenge. Several safety and efficacy concerns are shared by available antibiotics used in KPC infections, leading to the occurrence of serious adverse drug reactions (ADRs), with ceftazidime-avibactam possibly showing a more favourable risk-benefit profile. We investigated the potential impact of resistance on ADR reports in countries with different prevalence of KPC isolates (Italy vs. United Kingdom [UK]), and described safety profile of newer and older antibiotics used in KPC infections.. Three spontaneous reporting systems (SRSs) with different features (Italy, UK and worldwide FAERS) were used to describe safety profiles of colistin, meropenem, tigecycline, gentamicin and ceftazidime-avibactam in terms of System Organ Class and Preferred Term level. ADRs were plotted with prevalence of KPC isolates in Italy and UK. A comparison between before-after the KPC outbreak period (1999-2008 vs. 2009-2018) of overall and serious ADRs for selected antibiotics in each SRS was performed. Relationship between total and serious number of ADR reports per year and KPC isolates per year after KPC outbreak (2009-2017) was investigated for both Italy and UK.. A total of 16,329 ADR reports were collected in the three SRSs, with meropenem (42.6%) and gentamicin (36.9%) having the highest number of reports. Significant increase in total and serious ADR reports after the KPC outbreak compared to previous 10 years was found for colistin, meropenem and gentamicin (p < 0.01). No significant increase in tigecycline ADRs was reported in FAERS and UK database. Unexpected safety signals involving selected antibiotics were not detected. Significant positive relationship between overall and serious ADR reports and KPC isolates per year for both Italy (p < 0.01; p = 0.005) and UK (p = 0.032; p = 0.013) was found.. KPC outbreak led to significant increase in ADRs to selected antibiotics, and a close relationship with antimicrobial resistance was found, both in countries with high and low resistance rate. New safety signals were not detected for selected agents. Active surveillance should be maintained to promptly identify unexpected safety issues.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Ceftazidime; Child; Child, Preschool; Colistin; Disease Outbreaks; Drug Combinations; Female; Gentamicins; Humans; Infant; Infant, Newborn; Italy; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Pharmacovigilance; Tigecycline; United Kingdom; Young Adult

In recent years, colistin has been the drug of choice for treatment of nosocomial infections, especially in bloodstream infections, lower respiratory tract infections, or urinary tract infections. In this study, 65 multidrug-resistant Klebsiella pneumoniae isolated from different clinical samples were included. Minimum inhibitory concentration (MIC) of colistin was detected by broth microdilution method in three different ways. For selected K. pneumoniae strains, eazyplex SuperBug mcr-1 test was performed. This test detects mcr-1 gene, which encodes a colistin-resistance determinant. Most of the analyzed K. pneumoniae strains were resistant to colistin in all applied methods. The exception was two strains, where MIC of colistin was 2 mg/L in SensiTest Colistin and MIC-Strip Colistin tests. In MIC COL test, MIC for these strains was 4 mg/L. All analyzed strains produced extended-spectrum beta-lactamases and 11 (16.9%) metallo-beta-lactamases. Eleven (16.9%) K. pneumoniae strains were resistant to all antibiotics, whereas 17 (26.1%) were susceptible to only one drug. Colistin MIC values varied from 2 to >64 mg/L in MIC-Strip Colistin test; from 2 to >16 mg/L in SensiTest Colistin and from 4 to >16 mg/L in MIC COL test. None of the analyzed K. pneumoniae strains carried mcr-1 gene. Data of this work suggest that resistance to colistin emerged among multidrug-resistant K. pneumoniae strains. The tests allowed for reliable estimation of susceptibility to colistin and could be used in microbiological diagnostics.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phenotype; Poland

Carbapenem-resistant Klebsiella pneumoniae are a major problem. We aimed to investigate carbapenemase-encoding genes and transferable mcr-1 genes among 57 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from hospitalized patients.. Antibiotic susceptibility tests were performed by Phoenix (BD). Results for ertapenem and colistin were confirmed by gradient diffusion and microdilution methods. Carbapenemase and mcr-1 genes were investigated by Polymerase Chain Reaction (PCR).. Thirty-two (56.14%) isolates were from intensive care units (ICU). Antibiotic resistance rates by Phoenix: 52.63% for amikacin; 73.69% trimethoprim sulfamethoxazole; 91.23% cefepime; 82.46% tigecycline; 59.65% colistin. Carbapenemases positivity: 82.45% (47) for blaOXA-48, 40.35% (23) blaOXA-55, 3.50% (2) blaOXA-51, 1.75% (1) blaOXA-23, 1.75% (1) blaOXA-24, 1.75% (1) blaIMP. blaOXA-58, blaKPC, blaNDM-1, and blaVIM were not detected. Twenty (35.08%) isolates had both blaOXA-48 and blaOXA-55. Three isolates were mcr-1 (+) and blaOXA-48 (+). One mcr-1 (+) isolates was blaOXA-51 (+). One colistin sensitive isolate determined by Phoenix, was found colistin resistant by microdilution.. OXA-48 and OXA-55 co-harboring isolates and mcr-1 gene (+) isolates were spreading. Automated colistin susceptibility results should be confirmed by microdilution method. Resistance mechanisms in Enterobacteriaceae should be determined and the isolates should be monitored by molecular epidemiological methods. Effective infection control measures will contribute to reduce risk of antibiotic resistant bacterial infections and dissemination of antibiotic resistance.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Ertapenem; Ethanolaminephosphotransferase; Female; Hospitals; Humans; Inpatients; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Turkey

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a formidable health challenge in recent years owing to the shortage of effective antibiotics. Colistin is the last and sometimes the only therapeutic option for CRKP infections. Unfortunately, resistance to colistin monotherapy is likely to develop. CRKP in China reportedly exhibit low rates of resistance to trimethoprim-sulfamethoxazole. The aim of this study was to evaluate the in vitro efficacy of trimethoprim-sulfamethoxazole in combination with colistin against four CRKP clinical isolates. The trimethoprim-sulfamethoxazole/colistin combination rapidly killed all four of the tested isolates after 2 h up to 24 h. Trimethoprim-sulfamethoxazole is one of the few remaining antimicrobials with some activity against CRKP. In particular, combined with colistin, trimethoprim-sulfamethoxazole might be promising for the treatment of CRKP infections.

Topics: Anti-Bacterial Agents; Carbapenems; China; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Algeria; Amino Acid Substitution; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Dissemination of multidrug-resistant Klebsiella pneumoniae in the hospital environment represents a primary target of resistance containment and stewardship programs. At present, polymyxins, mostly in combination, exemplify a last-resort alternative. Colistin-resistant K. pneumoniae isolates harboring OXA-48 plus CTX-M-15 (n = 21) with the simultaneous colistin-susceptible counterparts (n = 9) were recovered from 14 hospitalized patients (January 2014-January 2015) admitted in different wards. In most cases, patients had not previously received colistin. Genetic relatedness experiments demonstrated that 93% (28/30) of isolates belonged to the ST11 high-risk clone. Heteroresistance and the fitness cost of colistin resistance were addressed in susceptible and resistant isolates as well as in in vitro-obtained stable mutants, and results appeared to be strain dependent. Whole genome sequencing demonstrated molecular changes in pmrA, pmrB, and mgrB genes. Plasmid-mediated colistin resistance genes were not found. Colistin resistance in multidrug-resistant K. pneumoniae isolates should be continuously monitored to detect its potential emergence, even in patients not previously exposed to colistin.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Spain

The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates and their involvement in several nosocomial outbreaks are of high concern. This study was conducted to investigate the genetic relatedness and molecular determinants of carbapenem resistance in 100 CRKP isolates. Susceptibility to carbapenems as well as other antibiotics was determined by using disk diffusion method. The Modified Hodge test was performed for detection of carbapenemase production. The minimum inhibitory concentrations of selected antibiotics were determined by broth microdilution method. The presence of bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance; Humans; Iran; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Coinfection; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Eye Neoplasms; Febrile Neutropenia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Male; Melanoma; Meropenem; Middle Aged; Neoplasms, Second Primary; Pseudomonas Infections; Tigecycline

Topics: Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; India; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Sequence Analysis, DNA; Whole Genome Sequencing

Polymyxin B and E (colistin) have been pivotal in the treatment of XDR Gram-negative bacterial infections; however, resistance has emerged. A structurally related lipopeptide, octapeptin C4, has shown significant potency against XDR bacteria, including polymyxin-resistant strains, but its mode of action remains undefined.. We sought to compare and contrast the acquisition of resistance in an XDR Klebsiella pneumoniae (ST258) clinical isolate in vitro with all three lipopeptides to potentially unveil variations in their mode of action.. The isolate was exposed to increasing concentrations of polymyxins and octapeptin C4 over 20 days. Day 20 strains underwent WGS, complementation assays, antimicrobial susceptibility testing and lipid A analysis.. Twenty days of exposure to the polymyxins resulted in a 1000-fold increase in the MIC, whereas for octapeptin C4 a 4-fold increase was observed. There was no cross-resistance observed between the polymyxin- and octapeptin-resistant strains. Sequencing of polymyxin-resistant isolates revealed mutations in previously known resistance-associated genes, including crrB, mgrB, pmrB, phoPQ and yciM, along with novel mutations in qseC. Octapeptin C4-resistant isolates had mutations in mlaDF and pqiB, genes related to phospholipid transport. These genetic variations were reflected in distinct phenotypic changes to lipid A. Polymyxin-resistant isolates increased 4-amino-4-deoxyarabinose fortification of lipid A phosphate groups, whereas the lipid A of octapeptin C4-resistant strains harboured a higher abundance of hydroxymyristate and palmitoylate.. Octapeptin C4 has a distinct mode of action compared with the polymyxins, highlighting its potential as a future therapeutic agent to combat the increasing threat of XDR bacteria.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipopeptides; Microbial Sensitivity Tests; Mutation; Peptides, Cyclic; Polymyxin B; Whole Genome Sequencing

Carbapenemases represent a public health threat, as they can spread through horizontal gene transfer and cause outbreaks. New Delhi metallo-ß-lactamase-1 (NDM-1) is a metallo-ß-lactamase that has spread rapidly in the last decade, causing worldwide alarm. This study aimed to describe the first isolate of NDM-1-producing and extensively drug resistant Klebsiella pneumoniae in Albania, its clinical context and genetic characterization.. Strain was isolated from both oral and rectal intensive care unit admission screening swabs of a 70-year-old male patient with no history of international travel in the previous 6 months. Sequencing was performed by Illumina NextSeq500 platform, with a paired-end run of 2 by 150bp, after Nextera XT paired-end library preparation. Sequencing reads were assembled using SPAdes Genome (version 3.6.1) with accurate de novo settings. The assembled contigs were uploaded into the online tools: BIGSdb-Kp, ResFinder and PlasmidFinder.. NDM-1-producing Enterobacteriaceae are spreading in the Balkans. Identification of NDM-1-producing and extensively drug resistant K. pneumoniae ST15 in Albania is a cause for serious concern. There should be a continuous national and Balkan multinational surveillance of bla

Topics: Aged; Albania; Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Gastrointestinal Tract; Humans; Klebsiella Infections; Klebsiella pneumoniae; Longitudinal Studies; Male; Microbial Sensitivity Tests; Mouth; Multilocus Sequence Typing; Plasmids; Rectum; Sequence Analysis, DNA

Colistin is the last line of therapy for infections caused by multidrug-resistant Gram-negative bacteria. The objective of this study was to determine the phenotypic and genotypic characteristics of colistin-resistant Klebsiella pneumoniae (K. pneumoniae) isolated from swine samples in Malaysia.. A total of 46 swine K. pneumoniae strains isolated from 2013-2015 in Malaysia were analysed for the production of extended-spectrum β-lactamases and carbapenemase. The resistance traits and genetic diversity of these strains were characterised by polymerase chain reaction, conjugation, plasmid analysis, and pulsed-field gel electrophoresis.. Nineteen of 46 strains were multidrug resistant while 13 were resistant to colistin. The majority of colistin-resistant strains harboured bla. It is believed that this is the first report of colistin-resistant K. pneumoniae among swine strains associated with mcr-1 plasmid in Malaysia. Due to the emergence of β-lactam, carbapenem and colistin resistance, the use of colistin in animal husbandry and agriculture should be avoided to prevent treatment failure.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Conjugation, Genetic; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genetic Variation; Genotype; Genotyping Techniques; Klebsiella Infections; Klebsiella pneumoniae; Malaysia; Microbial Sensitivity Tests; Plasmids; Swine; Swine Diseases

BACKGROUND We investigated the factors affecting antibiotic resistance in the intensive care unit (ICU)-related hospital-acquired infections caused by Klebsiella pneumoniae (KP-HAI) and the effects of antibiotics used for high-level antibiotic resistance on patient survival. MATERIAL AND METHODS This retrospective study was performed at the adult ICU of Bezmialem Vakif University Hospital. Patients who were followed up between 01 January 2012 and 31 May 2017 were evaluated. Each KP strain was categorized according to resistance patterns and analyzed. The efficiency of antibiotic therapy for highly-resistant KP-HAI was determined by patients' lifespans. RESULTS We evaluated 208 patients. With the prior use of carbapenem, antibiotics against resistant Gram-positives, and tigecycline, it was observed that the resistance rate of the infectious agents had a significant increase. As the resistance category increases, a significant decrease was seen in the survival time. We observed that if the treatment combination included trimethoprim-sulfamethoxazole, the survival time became significantly longer, and tigecycline-carbapenem-colistin and tigecycline-carbapenem combination patients showed significantly shorter survival times. CONCLUSIONS When the resistance increases, delays will occur in starting suitable and effective antibiotic treatment, with increased sepsis frequency and higher mortality rates. Trimethoprim-sulfamethoxazole can be an efficient alternative to extend survival time in trimethoprim-sulfamethoxazole-susceptible KP infections that have extensive drug resistance.

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Microbial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia; Retrospective Studies; Risk Factors; Survival Rate; Tigecycline; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

New antibiotics are urgently needed to treat multi-drug resistant infections; however, production of novel antibiotics is diminishing. Synergistic combination drug therapy to enhance the activity of available antibiotics may improve management of patients with resistant infections.. Colistin-resistant Klebsiella pneumoniae isolates were collected from inpatients in 10 Greek hospitals and used to study combination activity of colistin plus azidothymidine. Combination activity was evaluated with the sum of fractional inhibitory concentrations (ΣFIC) using the mini checkerboard broth microdilution method.. A hundred individual strains were tested. Synergistic activity was noted in 79% (79/100) of isolates and additive activity in the remaining 21% (21/100). ΣFIC. Colistin with azidothymidine exhibited promising synergistic activity against colistin-resistant Klebsiella pneumoniae isolates warranting further investigation of the combination.

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Greece; Hospitals; Humans; Inpatients; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Zidovudine

A 60-year-old woman received meropenem/colistin treatment for bilateral pneumonia caused by a ST15 carbapenemase producing Klebsiella pneumoniae. The patient recovered but re-infection with the same (ST15), but now colistin-resistant K. pneumoniae, occurred. The molecular mechanism of the emerged colistin resistance was identified as mgrB gene modification by insertion element (IS) IS903B.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Recurrence

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Genetic Variation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Prevalence

Multidrug-resistant (MDR) Klebsiella pneumoniae isolates with colistin resistance are a major concern in healthcare settings. This study aimed to evaluate the genome-wide distribution of antimicrobial resistance genes in K. pneumoniae CRKP I with high colistin resistance isolated from a patient in India.. The whole genome of K. pneumoniae CRKP I was sequenced on an Illumina MiSeq platform. De novo genome assembly was performed using SPAdes v.3.0.0, and the genome sequence was analysed using bioinformatics tools available from the Center for Genomic Epidemiology.. The genome of K. pneumoniae CRKP I is 5.1 Mb in size and contains different classes of antimicrobial resistance genes. The isolate is highly resistant to colistin owing to a point mutation in mgrB gene, encoding a negative regulator of the PhoP/PhoQ two-component system. Multilocus sequence typing (MLST) showed that K. pneumoniae CRKP I belongs to ST78.. These data provide useful information for comparative genomic analysis regarding the dissemination of antimicrobial resistance genes in K. pneumoniae. To our knowledge, this is the first report of a MDR K. pneumoniae with high colistin resistance belonging to ST78 causing infection in a human.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genome, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Point Mutation; Whole Genome Sequencing

The last few years have seen the emergence of multi-drug resistant (MDR) Gram-negative infections, which are associated with high morbidity and mortality. The indiscriminate use of colistin has led to the development of resistance, which can be diagnosed effectively by broth microdilution. Studies from India are limited, and this study was conducted in order to determine the prevalence and risk factors associated with colistin resistance.. Urine samples from patients admitted with urinary tract infection (UTI), growing MDR Escherichia coli and Klebsiella pneumoniae, were tested for the minimum inhibitory concentration (MIC) of colistin by broth microdilution. Isolates with an MIC >2 µg ml. Two hundred and fifty MDR isolates (E. coli=142/2319 and K.pneumoniae=108/775) from 216 patients were selected from the 25 046 isolates screened. Twenty-five isolates (20 K.pneumoniae and 5 E. coli) were resistant to colistin, with a prevalence of 3.52  % in E. coli and 18.5  % in K. pneumoniae among the MDR isolates. PCR for the mcr1 and mcr2 genes was negative. Multivariate regression showed that multiple episodes of hospitalization, hospital stay >2 weeks, exposure to >three antibiotic classes and abnormality/surgery of the lower urinary tract were the significant risk factors for colistin resistance. Previous use of colistin and colistin resistance had a significant effect on all outcomes.. K. pneumoniae show six times higher prevalence of colistin resistance than E. coli, and the emergence of resistant organisms has led to an increase in morbidity in infected patients.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prevalence; Risk Factors; Urinary Tract Infections; Young Adult

The emergence and spread of metallo-beta-lactamase-producing multidrug-resistant (MDR)

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Egypt; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phenotype

To assess the epidemiological features of 76 Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) isolates recovered from three hospitals in Buenos Aires, Argentina, during 2015-2017.. Antimicrobial susceptibilities were determined according to CLSI Clinical and Laboratoy Standards guidelines. Molecular typing of KPC-Kp was performed by pulsed-field gel electrophoresis (PFGE)-Xbal and multilocus sequence typing. Plasmid encoded genes involved in carbapenem, fosfomycin and colistin resistance were detected by polymerase chain reaction (PCR) and sequencing. Also, mgrB inactivation was investigated in those colistin-resistant isolates. Genetic platforms involved in horizontal spread of bla. Besides β-lactams, high resistance rates were observed for gentamycin, quinolones and trimethoprim-sulfamethoxazole. KPC-Kp sequence type (ST)258 corresponded to 26% of the isolates, while 42% corresponded to ST25. The other isolates were distributed in a diversity of lineages such as ST11 (10.5%), ST392 (10.5%), ST307, ST13, ST101, ST15 and ST551. bla. Despite previous reports in Argentina, ST258 is no longer the absolute clone among KPC-Kp isolates. In the present study, dissemination of more virulent lineages such as the hypermucoviscous ST25 was detected. The emergence of the high-risk clone ST307 and occurrence of bla

Topics: Argentina; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; beta-Lactams; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Multilocus Sequence Typing; Plasmids

We tested extended-spectrum β-lactamase producing bacteria from wild gulls (Larus spp.) sampled in 2009 for the presence of mcr-1. We report the detection of mcr-1 and describe genome characteristics of four Escherichia coli and one Klebsiella pneumoniae isolate from Spain and Portugal that also exhibited colistin resistance. Results represent the earliest evidence for colistin-resistant bacteria in European wildlife.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Bird Diseases; Charadriiformes; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Portugal; Spain

Klebsiella pneumoniae (KP), a common cause of invasive infections, is often extensively drug resistant in India. At present, studies on resistance mechanism and clonal relationship of KP from India are limited. The present study was undertaken to determine the resistance mechanism and clonal relationship of colistin-resistant isolates obtained from various specimens. Carbapenemases were also determined since the isolates were carbapenem resistant.. Sixty five isolates from blood, exudates and respiratory specimens collected between 2016 and 2017 were studied. Colistin minimum inhibitory concentration (MIC) was performed by broth-micro dilution method. Multiplex PCR was carried out to determine carbapenemases. Targeted sequencing was performed to determine mutations in mgrB, phoP, phoQ and multilocus sequence typing was performed to determine the prevalent clones.. Colistin MIC ranged from 4 to 256 μg/ml. SHV, TEM and CTX-M were co-produced in 60 per cent and OXA48-like in 71 per cent. Thirteen isolates had mutations in mgrB. Mutations included a premature stop codon at 21. This study revealed the changing trend of carbapenem resistance mechanism predominantly to OXA48-like from NDM. Known mgrB mutations and novel mutations in phoP and phoQ were detected. There was no plasmid-mediated colistin resistance. ST14 and ST231 were international clones associated with carbapenem resistance. Colistin-resistant KP was of diverse clones with predominantly ST231, ST14 and ST2096.

Topics: Bacterial Proteins; beta-Lactamases; Colistin; DNA Transposable Elements; Drug Resistance, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Mutation; Plasmids

In a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).. KPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time-kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin.. In vitro, colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P < 0.001) and the addition of gentamicin enhanced the efficacy of colistin + meropenem (P = 0.025). Tigecycline reduced the efficacy of colistin (P = 0.007). Colistin-resistant strains emerged in all groups except colistin + fosfomycin and two strains showed cross-resistance to HDP LL-37.. In this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.

Topics: Animals; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Osteomyelitis; Rabbits

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Chromatography, Liquid; Colistin; Critical Illness; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Serum; Tandem Mass Spectrometry; Tigecycline

The increasing rate of infections caused by multiple drug resistant gram-negative bacteria has led to resuscitation of colistin. As a result, colistin resistance, mainly among Klebsiella pneumoniae strains has also been increased. The aim of this study was to investigate molecular mechanisms behind colistin resistance.. Twenty colistin-resistant K. pneumoniae strains isolated from clinical samples of different patients were involved in this study. VITEK2 automated ID/AST system (Biomeriux, France) was used for the identification and also the susceptibility testing for antibiotics other than colistin. Colistin susceptibility was determined by broth microdilution method. To identify the mechanisms of resistance, mutations on mgrB genes, expression levels of pmrA, pmrB, pmrC, pmrD, pmrE, pmrK, phoQ, and phoP genes, and the presence of plasmid mediated colistin resistance genes, mcr-1 and mcr-2 were investigated.. As a result of the study, increased expression levels of the pmrA, pmrB, pmrD, pmrK, phoP, and phoQ genes were observed. All colistin resistant strains were found wild type for the mgrB gene which is thought to be esponsible for colistin resistance. Also, no mcr-1 or mcr-2 genes which are the causes of plasmid mediated colistin resistance have been detected in any of the strains.. Among the colistin resistant K. pneumoniae strains included in our study, increased expression Levels of the genes responsible for cell membrane modifications related with colistin resistance were the most common mechanisms.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation

Topics: Aminoglycosides; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Colistin; Drug Combinations; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Drug Synergism; Fluoroquinolones; Fusidic Acid; Gene Expression; Glycopeptides; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lincosamides; Macrolides; Microbial Sensitivity Tests

Topics: Animals; Anti-Bacterial Agents; Arthritis; Carbapenem-Resistant Enterobacteriaceae; Colistin; Debridement; Disease Models, Animal; Female; Injections, Intra-Articular; Injections, Intramuscular; Klebsiella Infections; Klebsiella pneumoniae; Prosthesis-Related Infections; Rabbits; Treatment Outcome

Polymyxins (i.e., polymyxin B and colistin) are used as a last-line therapy to combat multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance in K. pneumoniae is increasingly reported worldwide. This study identified the genetic variations responsible for high-level colistin resistance in MDR K. pneumoniae clinical isolates.. Sixteen MDR K. pneumoniae isolates were obtained from stool samples of 8 patients before and after colistin treatment. Their genomes were sequenced on Illumina MiSeq to determine genetic variations.. Fifteen of 16 isolates harboured ISKpn26-like element insertion at nucleotide position 75 of mgrB, abolishing its negative regulation on phoPQ; while colistin-susceptible ATH7 contained intact mgrB and phoQ. Interestingly, each of the 7 mgrB-disrupted, colistin-susceptible isolates contained a nonsynonymous substitution in PhoQ (G39S, L239P, N253T or V446G), potentially impairing its function and intergenically suppressing the effect caused by mgrB inactivation. Additionally, three of the 7 corresponding mgrB-disrupted, colistin-resistant isolates harboured a secondary nonsynonymous substitution in PhoQ (N253P, D438H or T439P).. This is the first report of phoQ mutations in mgrB-disrupted, colistin-susceptible K. pneumoniae clinical isolates. We also discovered multiple phoQ mutations in mgrB-disrupted, colistin-resistant strains. Our findings highlight the multifaceted molecular mechanisms of colistin resistance in K. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Clinical Decision Rules; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prognosis; ROC Curve; Survival Analysis

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Gastrointestinal Tract; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Microbial Sensitivity Tests; Middle Aged

To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).. Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.. 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20-1.43, P <0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19-4.50, P <0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02-2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25-0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43-0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L.. In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.

Topics: Aged; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Propensity Score; Tertiary Care Centers; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Proteins; Chromosomes; Colistin; Drug Resistance, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; beta-Lactamase Inhibitors; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Colistin; Colombia; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; France; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Turkey

We identified one clinical isolate of K. pneumoniae harboring the mcr 1 (plasmid of IncX4 family) and bla

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

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Female; Hematopoietic Stem Cell Transplantation; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Oncology Service, Hospital; Pediatrics

Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem- and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae.

Topics: Bacterial Proteins; Carbapenems; Colistin; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Hospitals, Pediatric; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Point Mutation; Vietnam

The emergence of colistin-resistant

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Genomics; Hospitals, Teaching; Humans; Klebsiella Infections; Klebsiella pneumoniae; Operon; Sequence Alignment; Tunisia; Whole Genome Sequencing

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Hospitals, Pediatric; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Vietnam; Whole Genome Sequencing

Colistin resistance causes substantial problems in the treatment of serious infections with carbapenem-resistant (CR) gram-negative bacteria. In this study, we report a fatal hospital outbreak from the spread of a pandrug-resistant Klebsiella pneumoniae clone. An outbreak investigation was conducted after consecutive isolation of nine CR-K. pneumoniae (CR-Kp) strains from eight patients in two intensive care units of a university hospital within 2 weeks. Carbapenem and colistin resistance genes were investigated with PCR, clonal relationships of isolates were studied with pulse-field gel electrophoresis, and multilocus sequence types were determined. The outcomes of the affected patients were analyzed. Genotyping showed a predominant CR-Kp clone consisting of seven strains from six patients. These strains were in ST11 type, an international high-risk clone. They were resistant to all antimicrobials, including colistin, and positive for NDM-1 and OXA-48 carbapenemases, but negative for plasmid-borne colistin resistance genes. One patient had colonization and the remaining five died due to the infection within mean 12 days. No environmental or staff links could be established, and the outbreak was stopped by augmenting infection-control measures. Colistin-resistant K. pneumoniae could clonally expand in the hospital setting, and this spread might be associated with high mortality due to the lack of an appropriate treatment option. Immediate implementation of infection-control measures may be the best way to limit fatal consequences of the spread of such incurable pathogens.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Escherichia coli Proteins; Female; Hospitals; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Young Adult

Plasmid-borne colistin resistance mediated by mcr-1 may contribute to the dissemination of pan-resistant Gram-negative bacteria. Here, we show that mcr-1 confers resistance to colistin-induced lysis and bacterial cell death, but provides minimal protection from the ability of colistin to disrupt the Gram-negative outer membrane. Indeed, for colistin-resistant strains of Enterobacteriaceae expressing plasmid-borne mcr-1, clinically relevant concentrations of colistin potentiate the action of antibiotics that, by themselves, are not active against Gram-negative bacteria. The result is that several antibiotics, in combination with colistin, display growth-inhibition at levels below their corresponding clinical breakpoints. Furthermore, colistin and clarithromycin combination therapy displays efficacy against mcr-1-positive Klebsiella pneumoniae in murine thigh and bacteremia infection models at clinically relevant doses. Altogether, these data suggest that the use of colistin in combination with antibiotics that are typically active against Gram-positive bacteria poses a viable therapeutic alternative for highly drug-resistant Gram-negative pathogens expressing mcr-1.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Ethanolaminephosphotransferase; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Japan; Jaw Fractures; Klebsiella Infections; Klebsiella pneumoniae; Male

We describe the molecular characteristics of colistin resistance and its impact on patient mortality.. A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR.. A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates.. Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Female; Gene Expression Profiling; Genotype; Hospitals; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Multilocus Sequence Typing; Polymerase Chain Reaction; Prospective Studies; Sequence Analysis, DNA; Survival Analysis; Turkey; Young Adult

Topics: Aged, 80 and over; Bacterial Proteins; Clone Cells; Colistin; Contact Tracing; Cross Infection; Drug Contamination; Drug Resistance, Multiple, Bacterial; Ethanolaminephosphotransferase; Female; France; Genes, Bacterial; Hand Hygiene; Hand Sanitizers; Humans; Infectious Disease Transmission, Patient-to-Professional; Infectious Disease Transmission, Professional-to-Patient; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; R Factors

Topics: Bacterial Proteins; beta-Lactamases; Brazil; Cephalosporins; Colistin; DNA Transposable Elements; Drug Resistance, Bacterial; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae

Colistin and polymyxin B MICs were determined for 106 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates using Sensititre Research Use Only GNX2F plates (Thermo Fisher) and compared to CLSI broth macrodilution (BMD) as the reference method. For colistin, EUCAST breakpoints were applied and testing of isolates with very major (VM) errors was repeated in duplicate by both methods to determine a majority result. Essential agreement (MIC ± one dilution) of GNX2F with the reference method was 97.1% for polymyxin B and 92.5% for colistin (7 VM errors, 22.6%). After discrepancy testing, there were 28 colistin resistant isolates by BMD and essential agreement was 94.3% with 4 VM errors (14.3%). Colistin and polymyxin B GNX2F results showed acceptable essential agreement with BMD for MICS without interpretation. Colistin VM errors with EUCAST breakpoints were due to MIC variability in the 2 to 4 μg/mL range that could be addressed by establishing an intermediate category.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxin B

Colistin is one of the last-resort antibiotics used to treat carbapenem-resistant Klebsiella pneumoniae infection. Our previous studies indicated that clinical strains encoding CrrB with amino acid substitutions exhibited higher colistin resistance (MICs ≥512 mg/L) than did colistin-resistant strains encoding mutant MgrB, PmrB or PhoQ.. CrrAB may regulate another unknown mechanism(s) contributing to colistin resistance, besides modifications of LPS with 4-amino-4-deoxy-l-arabinose and phosphoethanolamine.. To identify these potential unknown mechanism(s), a transposon mutant library of A4528 crrB(N141I) was constructed. Loci that might contribute to colistin resistance and were regulated by crrB were confirmed by deletion and complementation experiments.. Screening of 2976 transposon mutants identified 47 mutants in which the MICs of colistin were significantly decreased compared with that for the parent. Besides crrAB, crrC and pmrHFIJKLM operons, these 47 transposon insertion mutants included another 13 loci. Notably, transcript levels of one of these insertion targets, H239_3064 (encoding a putative RND-type efflux pump), were significantly increased in A4528 crrB(N141I) compared with the A4528 parent strain. Deletion of H239_3064 in the A4528 crrB(N141I) background resulted in an 8-fold decrease in the MIC of colistin; complementation of the deletion mutant with H239_3064 restored resistance to colistin. Susceptibilities of A4528-derived strains to other antibiotics were also tested. Mutations of crrB resulted in decreased susceptibility to tetracycline and tigecycline, and deletion of H239_3064 in A4528 crrB(N141I) attenuated this phenomenon.. This study demonstrated that missense mutations of K. pneumoniae crrB lead to increased expression of H239_3064, leading in turn to decreased susceptibility to colistin, tetracycline and tigecycline.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation, Missense; Operon; Tetracycline

Antibiotic resistance is a growing crisis and a grave threat to human health. It is projected that antibiotic-resistant infections will lead to 10 million annual deaths worldwide by the year 2050. Among the most significant threats are carbapenem-resistant

Topics: Animals; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Enterobacteriaceae; Klebsiella Infections; Klebsiella pneumoniae; Mice; Polymyxins

We describe colistin-resistant KPC-2-producing Klebsiella pneumoniae isolates from cerebrospinal fluid, belonging to ST423, selected during treatment for neuroinfection. Colistin resistance was related to mgrB gene interruption by an IS5-like.

Topics: beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutagenesis, Insertional

A significant cause of mortality in the intensive care unit (ICU) is multidrug-resistant (MDR) Gram-negative bacteria, such as MDR

Topics: Acinetobacter baumannii; Aged; Bacterial Proteins; beta-Lactamases; Colistin; Critical Care; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Shock, Septic

We report a case of a 35-year-old male with a pancreatic pseudocyst, who developed bilateral endogenous endophthalmitis, 4 days after surgical drainage of the pseudocyst. Bacterial cultures of the pancreatic drain fluid and the vitreous tap showed the growth of Klebsiella pneumoniae. The cultured organism was resistant to all the tested antibiotics except colistin. Intravenous colistin was instituted and three injections of intravitreal colistin were given in the left eye of the patient. Complete resolution of infection was seen and visual acuity of 6/6 was regained in both eyes, which was maintained at 4-month follow-up.

Topics: Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Endophthalmitis; Eye Infections, Bacterial; Follow-Up Studies; Humans; Injections, Intravenous; Intravitreal Injections; Klebsiella Infections; Klebsiella pneumoniae; Male; Pancreatic Pseudocyst; Visual Acuity; Vitreous Body

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) has emerged globally over the last decade as a major nosocomial pathogen that threatens patient care. These highly resistant bacteria are mostly associated with a single Kp clonal group, CG258, but the reasons for its host and hospital adaptation remain largely unknown.. We analyzed the in vivo evolution of a colistin-resistant KPC-Kp CG258 strain that contaminated a patient following an endoscopy and was responsible for a fatal bacteremia 4.5 years later. Whole-genome sequencing was performed on 17 KPC-Kp isolates from this patient; single-nucleotide polymorphisms were analyzed and their implication in antimicrobial resistance and bacterial host adaptation investigated.. The patient KPC-Kp strain diversified over 4.5 years at a rate of 7.5 substitutions per genome per year, resulting in broad phenotypic modifications. After 2 years of carriage, all isolates restored susceptibility to colistin. Higher expression of the fimbriae conferred the ability to produce more biofilm, and the isolate responsible for a bacteremia grew in human serum. The convergent mutations occurring in specific pathways, such as the respiratory chain and the cell envelope, revealed a complex long-term adaptation of KPC-Kp.. Broad genomic and phenotypic diversification and the parallel selection of pathoadaptive mutations might contribute to long-term carriage and virulence of KPC-Kp CG258 strains and to the dissemination of this clone.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Biofilms; Carrier State; Colistin; Drug Resistance, Bacterial; Endoscopy; Equipment Contamination; Evolution, Molecular; Fatal Outcome; Fimbriae, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Mutation; Polymorphism, Single Nucleotide; Whole Genome Sequencing

The inactivated mgrB gene and the mcr-1 gene are important mechanisms of colistin resistance in Klebsiella pneumoniae and they are threats to the clinical use of colistin. In this study, mcr-1 gene was cloned into K. pneumoniae strains (XH209 and KP10) and their derived strains (XH209 M and KP10 M), which showed high-level resistance to colistin. The acquisition of the mcr-1 gene led to colistin resistance in XH209 and KP10, but the addition of mcr-1 gene did not cause change of colistin minimum inhibitory concentrations in the XH209 M and KP10 M. In addition, the impact of mcr-1 gene on growth rate showed strain specific in K. pneumoniae. In conclusion, the mcr-1 gene does not cause the same level of colistin resistance as the inactivated mgrB gene in K. pneumoniae. The mcr-1 gene has no effect on colisitin resistance when it coexists with inactivated mgrB gene in K. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests

Topics: Adult; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Proteins; beta-Lactamases; Biofilms; Brazil; Colistin; Colony Count, Microbial; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Carbapenemase-producing Klebsiella pneumoniae causes high mortality owing to the limited therapeutic options available. Here, we investigated an emergent carbapenem-resistant K. pneumoniae strain with hypervirulence found among KPC-2-producing strains in Taiwan.. KPC-producing K. pneumoniae strains were collected consecutively from clinical specimens at the Taipei Veterans General Hospital between January 2012 and December 2014. Capsular types and the presence of rmpA/rmpA2 were analysed, and PFGE and MLST performed using these strains. The strain positive for rmpA/rmpA2 was tested in an in vivo mouse lethality study to verify its virulence and subjected to WGS to delineate its genomic features.. A total of 62 KPC-2-producing K. pneumoniae strains were identified; all of these belonged to ST11 and capsular genotype K47. One strain isolated from a fatal case with intra-abdominal abscess (TVGHCRE225) harboured rmpA and rmpA2 genes. This strain was resistant to tigecycline and colistin, in addition to carbapenems, and did not belong to the major cluster in PFGE. TVGHCRE225 exhibited high in vivo virulence in the mouse lethality experiment. WGS showed that TVGHCRE225 acquired a novel hybrid virulence plasmid harbouring a set of virulence genes (iroBCDN, iucABCD, rmpA and rmpA2, and iutA) compared with the classic ST11 KPC-2-producing strain.. We identified an XDR ST11 KPC-2-producing K. pneumoniae strain carrying a hybrid virulent plasmid in Taiwan. Active surveillance focusing on carbapenem-resistant hypervirulent K. pneumoniae strains is necessary, as the threat to human health is imminent.

Topics: Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred C57BL; Multilocus Sequence Typing; Phylogeny; Plasmids; Polymorphism, Single Nucleotide; Taiwan; Tigecycline; Virulence

The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant Klebsiella pneumoniae isolates from Pakistan. These clinical isolates represented five sequence types: ST11 (n = 3 isolates), ST14 (n = 3), ST15 (n = 1), ST101 (n = 2), and ST307 (n = 1). Resistance profiles against 25 clinically-relevant antimicrobials were determined by broth microdilution; resistant phenotypes were observed for at least 15 of the 25 antibiotics tested in all isolates except one. Specifically, 8/10 isolates were carbapenem-resistant and 7/10 isolates were colistin-resistant. The blaNDM-1 and blaOXA-48 carbapenemase genes were present in 7/10 and 5/10 isolates, respectively; including 2 isolates carrying both genes. No plasmid-mediated determinants for colistin resistance (e.g. mcr) were detected, but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were observed. A blaOXA-48-carrying IncL/M-type plasmid was found in all blaOXA-48-positive isolates. The application of WGS to molecular epidemiology and surveillance studies, as exemplified here, will provide both a more complete understanding of the global distribution of MDR isolates and a robust surveillance tool useful for detecting emerging threats to public health.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Colistin; DNA Restriction Enzymes; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Typing; Plasmids; Whole Genome Sequencing

To evaluate the prevalence of clinical mcr-1-positive Escherichia coli and Klebsiella pneumoniae and characterize the antimicrobial resistance profiles of mcr-1-positive E. coli and mcr-1-negative E. coli in China.. A total of 6264 clinical E. coli (n = 3854) and K. pneumoniae (n = 2410) were collected from hospitalized patients from 18 to 20 hospitals as part of the China Antimicrobial Resistance Surveillance Trial (CARST) between January 2007 and June 2016. PCR was used to screen for the mcr-1 gene among all isolates. Antibiotic susceptibility testing was performed using the broth microdilution method. mcr-1-positive pathogens were then characterized by MLST and minimum spanning tree analysis using the BURST algorithm for related STs.. We examined 39 (0.62%) clinical isolates of mcr-1-positive E. coli and K. pneumoniae over a 10 year period. Resistance to antimicrobial agents was significantly more severe in mcr-1-positive isolates than mcr-1-negative isolates, particularly piperacillin (P = 0.008), amikacin (P < 0.0001), nitrofurantoin (P < 0.004) and fosfomycin (P < 0.0001). Among mcr-1-carrying isolates, ESBL production was as high as 84.6% (33 of 39) and 92.3% (36 of 39) of them displayed an MDR phenotype. STs suggested ubiquitous dissemination of mcr-1-carrying pathogens.. mcr-1-carrying E. coli and K. pneumoniae displayed a lower prevalence and abundant phylogenetic diversity in mainland China. mcr-1-positive E. coli showed significant differences in antimicrobial resistance profiles compared with mcr-1-negative E. coli strains, suggesting physicians may consider prescribing different antibiotics when faced with infections caused by mcr-1-positive pathogens.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; China; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Retrospective Studies

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cross Infection; Drug Resistance, Bacterial; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Time Factors

The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene bla

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Colistin; Conjugation, Genetic; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Molecular; Phylogeny; Position-Specific Scoring Matrices; Protein Conformation

Emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that also exhibit resistance to tigecycline and colistin have become a major clinical concern, as these two agents are the last-resort antibiotics used for treatment of CRKP infections. A leukemia patient infected with CRKP was subjected to follow-up analysis of variation in phenotypic and genotypic characteristics of CRKP strains isolated from various specimens at different stages of treatment over a period of 3 years. Our data showed that (1) carbapenem treatment led to the emergence of CRKP in the gastrointestinal (GI) tract of the patient, which subsequently caused infections at other body sites as well as septicemia; (2) treatment with tigecycline led to the emergence of tigecycline-resistant CRKP, possibly through induction of the expression of a variant tet(A) gene located in a conjugative plasmid; (3) colistin treatment was effective in clearing CRKP from the bloodstream but led to the emergence of mcr-1-positive Enterobacteriaceae strains as well as colistin-resistant CRKP in the GI tract due to inactivation of the mgrB gene; and (4) tigecycline- and colistin-resistant CRKP could persist in the human GI tract for a prolonged period even without antibiotic selection pressure. In conclusion, clinical CRKP strains carrying a conjugative plasmid that harbors the bla

Topics: Adult; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Carbapenems; Caspofungin; Colistin; Diarrhea; Drug Resistance, Bacterial; Echinocandins; Feces; Gastrointestinal Tract; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leukemia, Monocytic, Acute; Lipopeptides; Male; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

Carbapenem resistance in. We analysed 2011-2016 data from the German Antimicrobial Resistance Surveillance (ARS) System, which contains routine data of antimicrobial susceptibility testing from voluntarily participating German laboratories.. We included 154,734 isolates from 655 hospitals in the analysis. Carbapenem non-susceptibility in. Carbapenem non-susceptibility in

Topics: Adult; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gentamicins; Germany; Hospitals; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Tertiary Care Centers; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Algeria; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Gene Silencing; Hospitalization; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Transcription Factors

Colistin has been used for therapy of carbapenem-resistant Gram-negative infections in Thailand, especially carbapenem-resistant. A prospective observational study was performed in adult hospitalized patients at Siriraj Hospital who received colistin for treatment of infections during December 2016 and November 2017. The surveillance culture samples were collected from the stool and the site of infection of each patient who received colistin at the study enrollment, days 3 and 7 after the study enrollment, and once a week thereafter for determination of CoR EC and CoR KP. CoR EC and CoR KP were also tested for a presence of mcr-1 gene.. One hundred thirty-nine patients were included. Overall prevalence of CoR EC or CoR KP colonization was 47.5% among 139 subjects. Prevalence of CoR EC or CoR KP colonization was 17.3% of subjects at study enrollment, and 30.2% after study enrollment. Use of fluoroquinolones, aminoglycosides, and colistin was found to be significantly associated with CoR EC or CoR KP colonization. The mcr-1 gene was detected in 13.0% of CoR EC or CoR KP isolates, and in 27.3% of subjects with CoR EC or CoR KP colonization. CoR EC or CoR KP colonization persisted in 65.2% of the subjects at the end of the study. Five patients with CoR KP infections received combination antibiotics and they were alive at hospital discharge.. Prevalence of CoR EC or CoR KP colonization in hospitalized patients receiving colistin was high and it was associated with the use of colistin. Therefore, patients who receive colistin are at risk of developing CoR EC or CoR KP colonization and infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Communicable Diseases, Emerging; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Female; Hospitalization; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Thailand

ComASP™ Colistin showed high levels of overall/evaluable essential agreement (94.9%/93.6%) and categorical agreement (97.2%), with very major errors in 0.7% (1/141 colistin-resistant), and met the current acceptance criteria proposed by the CLSI. Ten major errors were observed [4.0% (10/251) colistin-susceptible], three of which were within essential agreement.. ComASP™ Colistin is a commercial BMD method that reliably determined colistin MICs in a large collection of carbapenem-resistant K. pneumoniae isolates.

Topics: Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

A colistin-resistant mucoid Klebsiella strain was recovered from the blood of a patient in China. Hypervirulence has been reported in Klebsiella pneumoniae, but not in other Klebsiella spp. The strain was suspected to be hypervirulent and was therefore characterized.. The strain was subjected to genome sequencing using both the short-read Illumina HiSeq X10 Sequencer and the long-read MinION sequencer. Precise species identification was established using average nucleotide identity based on genome sequences. Virulence and antimicrobial resistance genes were identified using ResFinder and the bigsdb database. Conjugation experiments were performed. Virulence was assessed using wax moth (Galleria mellonella) larvae with control Klebsiella strains of low virulence and hypervirulence.. The strain had a 5 553 341 bp circular chromosome and a 236 355 bp large plasmid. It was identified as Klebsiella variicola. The strain had multiple virulence genes encoding mucoid phenotype regulator (rmpA and rmpA2), aerobactin (iucABCD-iutA), salmochelin (iroBCDN) and yersiniabactin (irp1-2 and ybtAEPQSTUX) on the plasmid, which was not self-transmissible. It exhibited enhanced virulence in the larvae model, suggesting that the strain was hypervirulent. It was resistant to colistin (MIC = 8 mg/L) but was susceptible to amikacin, aztreonam, cefotaxime, ceftazidime, gentamicin, imipenem, meropenem, moxifloxacin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole and tigecycline. The D150G substitution in PhoP, part of the PhoP-Q two-component system, which is known to mediate colistin resistance, was present in the strain.. Hypervirulence is not restricted to K. pneumoniae; it is also seen in other Klebsiella spp. The convergence of colistin resistance and hypervirulence in K. variicola represents a new challenge for health.

Topics: Animals; Bacterial Proteins; China; Colistin; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Klebsiella; Klebsiella Infections; Larva; Moths; Phenotype; Plasmids; Virulence; Virulence Factors; Whole Genome Sequencing

A matched 1:2 case-control study was conducted among critically ill patients in order to identify the risk factors of colistin or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae (ColR-Kp, TigR-Kp) bacteraemia. MIC to colistin and tigecycline were determined by Etest. From 224 bacteraemic patients, 46.4% and 29.5% were resistant to colistin and tigecycline, respectively. PCR revealed that 199 isolates carried the bla

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Case-Control Studies; Colistin; Comorbidity; Critical Care; Critical Illness; Drug Resistance, Bacterial; Female; Genotype; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Tigecycline

"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: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Disease Outbreaks; Evolution, Molecular; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Multilocus Sequence Typing; Plasmids; Virulence

Nine Klebsiella pneumoniae isolates coproducing NDM-1 and OXA-232 carbapenemases were successively isolated from a single patient. Although they were isolated simultaneously and were isogenic, they presented different colony phenotypes (matt and mucoid). All nine isolates were resistant to most antibiotics except colistin and fosfomycin. In addition, matt-type isolates were resistant to tigecycline. No differences were detected in the cps cluster sequences, except for the insertion of IS5 in the wzb gene of two matt-type isolates. In vitro virulence assays based on production of capsular polysaccharide, biofilm formation, and resistance to human serum indicated that the mucoid-type isolates were significantly more virulent than the matt-type. In addition, mucoid-type isolates showed higher survival rates than the matt-type ones in infection experiments in the fruit fly, suggesting a higher virulence of K. pneumoniae isolates with a mucoid phenotype. To our knowledge, this is the first report of K. pneumoniae colonies with different phenotypes being isolated from the same sample. In addition, we show that virulence varies with colony phenotype. Dissemination of K. pneumoniae isolates expressing both antibiotic resistance and high virulence would constitute a great threat.

Topics: Animals; Anti-Bacterial Agents; Bacterial Capsules; Bacterial Proteins; beta-Lactamases; Biofilms; Colistin; Drosophila melanogaster; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Phenotype; Serotyping; Survival Rate; Tigecycline; Virulence; Virulence Factors

The efficiency of Rapid Polymyxin NP test for detection of colistin-resistant isolates was tested against a collection of 131 non-repetitive Klebsiella pneumoniae, including 98 colistin-resistant and 33 colistin-susceptible isolates. In addition, the performance of this test was compared with those of the automated systems, BD Phoenix™ and VITEK®2, and the Etest. Determination of imipenem and meropenem MICs showed that 95 of colistin-resistant (Col-R) isolates were also resistant to at least one carbapenem. Characterization of colistin resistance mechanisms showed that 75 out of 98 Col-R isolates were associated with the presence of alterations in the mgrB gene, while no mcr genes were detected among our isolates. Rapid Polymyxin NP correctly detected 97 out of 98 colistin-resistant isolates (Geometric mean MIC value 9.89 mg/L), except one ST147 K. pneumoniae harboring a wild-type mgrB gene (MIC: 8 mg/L), yielding a sensitivity 99%. The other methods gave more false-negative results with colistin-resistant strains; BD Phoenix™,VITEK®2, and the gradient Etest missed five, two and three colistin-resistant, respectively (95%, 98% and 97%). The Rapid Polymyxin NP test gave false positive results with six isolates, for which colistin MICs were 1-2 mg/L (specificity 82%). Despite the fact that Rapid Polymyxin exhibited lower specificity than other methods (82% versus 94%, 88% and 85%), it is easy-to-perform and rapid. Thus, these findings indicate that the Rapid Polymyxin NP test can be an initial tool for the detection of colistin-resistant isolates.

Topics: Anti-Bacterial Agents; Automation, Laboratory; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; False Positive Reactions; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxins; Sensitivity and Specificity; Tertiary Care Centers

The mcr-1 gene encodes a phosphoethanolamine transferase that confers resistance to colistin by transferring phosphoethanolamine to lipid A. A 33-kb IncX4 plasmid harboring mcr-1 was detected in a Klebsiella pneumoniae isolate and two Escherichia coli isolates, and a 66-kb IncI2 plasmid was detected in three E. coli isolates in hospitals in Okinawa, Japan.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Humans; Japan; Klebsiella Infections; Klebsiella pneumoniae; Methyltransferases; Plasmids

Since KPC-2-producing Klebsiella pneumoniae are associated with successful dissemination of a major clone, defined as sequence type 258 (ST258), the aim of this study was to perform whole-genome sequencing (WGS) of the first colistin-resistant K. pneumoniae strain (Kpn666) carrying bla. WGS of strain Kpn666 isolated from an asymptomatic urinary tract infection was performed using Illumina MiSeq, and de novo assembly was performed using SPADES v.3.11. Contigs were re-ordered using the ST258 reference genome NJST258_1 (GenBank CP006923) and were oriented with the MAUVE Contig Mover. Twenty complete genomes of K. pneumoniae identified as ST258 using the Pasteur MLST site were downloaded from GenBank (May 2017). A maximum-likelihood tree was created using MEGA7 based on core single nucleotide polymorphisms (SNPs) from whole-genome alignment obtained with SNP sites (https://github.com/sanger-pathogens/snp-sites).. WGS analysis revealed a genome of 5448179bp (5232 CDS, 108 RNAs). Phylogenetic analysis identified that Kpn666 belonged to clade I lineage of ST258. Further studies also identified IncR, IncFIB(K) and IncFII(K) plasmid replicons and 11 transferable associated antimicrobial resistance genes (ARGs) comprising four drug classes. The mgrB gene involved in colistin resistance was shown to be disrupted by insertion of an IS5-like element.. The first isolate of KPC-2-producing K. pneumoniae detected in Uruguay was sequenced and the results confirm the ability of this bacterium to capture several ARGs. The KPC-2 carbapenemase in Uruguay is likely to have been introduced by the high-risk clone ST258.

Topics: beta-Lactamases; Colistin; Genome, Bacterial; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Multilocus Sequence Typing; Phylogeny; Urinary Tract Infections; Uruguay

Mutations in mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC regulatory systems have been found responsible for colistin resistance. The aim of our study was to investigate the role of alteration in mgrB gene and plasmid mediate mcr-1 and mcr-2 genes as a source of colistin resistance in 17 non duplicate Klebsiella pneumoniae clinical isolates.. All isolates classified as resistant to colistin by VITEK 2 system (BioMerieux, Marcy I' Etoile, France) were included. Susceptibility to colistin was also determined by broth microdilution using breakpoints recommended by EUCAST (>2mg/L resistant; and ≤2mg/L susceptible). PCR amplification of mgrB gene was performed and sequenced using specific primers. Presence of mcr-1 and mcr-2 was also investigated using PCR.. PCR amplification of the mgrB gene of the 17 K.pneumoniae isolates revealed a larger (~1000bp) amplicon in three isolates when compared with the wild type mgrB ampiclon (250 bp). Sequencing of these amplicons showed that mgrB was disrupted by the insertion of ISKpn14, a IS element belonging to the IS1 family. Sequencing, of the 250 bp mgrB gene in the remaining 14 isolates revealed frame shift mutation after the second codon leading to a premature stop codon in only one isolate.. The study showed that colistin resistance in 20% of the K. pneumoniae isolates was due to loss of function of mgrB. We describe for the first-time from India, insertional inactivation of mgrB by ISKpn14 inserted at different sites, responsible for colistin resistance.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; Codon; Colistin; Drug Resistance, Bacterial; Female; Frameshift Mutation; Genes, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Mutagenesis, Insertional; Polymerase Chain Reaction

In the present report we characterized the outer membrane proteome, genomic, and lipid A remodelling changes following the evolution of a colistin-susceptible K. pneumoniae ATCC 13883 strain into an extremely colistin-resistant strain. Lipid A profiling revealed the outer membrane of the colistin-susceptible strain is decorated primarily by hexa- and hepta-acylated lipid A species and a minor tetra-acylated species. In the lipid A profile of the extremely colistin-resistant strain, in addition to the aforementioned lipid A species, the obligatory 4-amino-4-deoxy-l-arabinose modification of the hexa-acylated lipid A was detected. Comparative genomic analysis revealed that the mgrB gene of the colistin-resistant strain is inactivated by a single nucleotide insertion which produces a frame-shift, resulting in premature termination. We also detected two synonymous mutations in the two-component system genes phoP and phoQ. Comparative profiling of the outer membrane proteome of each strain revealed that outer membrane proteins from bacterial stress response, glutamine degradation, pyruvate, aspartate, and asparagine metabolic pathways were over-represented in the extremely colistin-resistant K. pneumoniae ATCC 13883 strain. In comparison, in the sensitive strain, outer membrane proteins from carbohydrate metabolism, H

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Microbial Sensitivity Tests; Proteome

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

Carbapenemase-producing Klebsiella pneumoniae has become a worldwide recognized cause of nosocomial infections and requires urgent public health attention. The main reason of this concern is the increasing resistance to all the last-resort antibiotics, including colistin. The ideal methodology for colistin susceptibility testing still remains undefined. However, the emergence of colistin as one of the last-option treatments requires a reliable method to determine the susceptibility profile of resistant isolates. The aim of the present study was to evaluate the impact of detecting colistin resistance in Klebsiella pneumoniae isolates using MALDI-TOF MS in clinical routine practice. For this reason, 139 isolates of K. pneumoniae were collected during 2015-2017 from patients hospitalized at Pisa University Hospital. Colonies suspected to be colistin resistant were identified using MALDI-TOF MS (Bruker Daltonik GmbH, Bremen, Germany) following a protein extraction protocol. Strains were previously wholly genome sequenced. To create a customized database entry and to generate classifying algorithm models, 1.112 mass spectra were collected. In relation to their mass signals and intensities, a two dimensional peak distribution was created. The recognition capability of the algorithm based on two manually selected mass peaks was 91,8%, while cross validation was 87,6%. The proportion of correctly classified colistin-resistant K. pneumoniae was 91% and colistin-susceptible was 73%. The emergence of colistin-resistant Gram-negative organisms has a dramatic impact on patient outcomes. Our study, based on MALDI-TOF MS technology, offers rapid preliminary results on colistin resistance profile coupled with bacteria identification.

Topics: Algorithms; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To evaluate whether acquired resistance to cationic antimicrobial peptide (CAMP) group molecules, being normal components of the human immune system, may select co-resistance to antibiotic peptides such as polymyxins, considering they share the same mechanism of action. We aimed to evaluate strains producing the recently identified plasmid-encoded polymyxin resistance determinant MCR-1, which is a phosphoethanolamine transferase that modifies the lipopolysaccharide structure of Gram-negative bacteria.. In vitro susceptibility studies were performed using human CAMPs, namely cathelicidin LL-37, α-defensin 5 (HD5), and β-defensin 3 (HDB3), towards MCR-1-producing and colistin-resistant Escherichia coli or Klebsiella pneumoniae.. Cross-resistance to CAMPs and colistin mediated by MCR-1 or chromosomal mechanisms was neither observed in E. coli nor in K. pneumoniae.. Future therapeutic development of human CAMPs is not likely to be impeded by the spread of MCR-1 plasmid-mediated resistance to polymyxins, at least in E. coli.

Topics: Antimicrobial Cationic Peptides; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxins

We evaluated the in vitro activity of different antimicrobial combinations with and without colistin against 39 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains (colistin + meropenem/doripenem, colistin + tigecycline, colistin + rifampicin, gentamicin + meropenem, gentamicin + tigecycline and the double-carbapenem regimen meropenem + ertapenem) using the chequerboard method. The triple combination colistin + meropenem + tigecycline was also tested. In addition, killing studies were performed for meropenem + ertapenem.. Gentamicin-based combinations showed a high level of synergy. Meropenem + ertapenem was synergic in 12/39 (30.7%) of the strains, whereas based on killing studies 1 × MIC meropenem + 1 × MIC ertapenem and 2 × MIC meropenem + 1 × MIC ertapenem combinations were bactericidal and synergic at 24 h [mean area under the bactericidal curve (AUBC) 54.9 ± 26.1 and 44.2 ± 15.3 compared with 1 × MIC meropenem (134.5 ± 40.1) and 2 × MIC meropenem (126.4 ± 5.4), respectively, P  <   0.0001]. When the results were stratified according to meropenem MIC, we found that the degree of synergy significantly increased for isolates with lower meropenem (and not ertapenem) MICs, up to an MIC of 128 mg/L. Among colistin-containing combinations, synergy was observed in 18/39 (46.1%), 33/34 (97%), 24/39 (61.5%) and 17/39 (43.5%) of the strains for colistin + meropenem, colistin + rifampicin, colistin + tigecycline and colistin + doripenem, respectively, including colistin-resistant strains. Colistin + meropenem + tigecycline at subinhibitory concentrations resulted in the absence of growth of 37/39 strains (94.8%).. Our in vitro data suggest that colistin might be a valid therapeutic option against CR-Kp, even in the presence of colistin resistance, whereas the double-carbapenem regimen represents a viable option when colistin is not recommended, especially if the meropenem MIC is ≤ 128 mg/L. Since traditional antimicrobial susceptibility reports are not sufficiently informative for clinicians, synergy testing as well as actual meropenem MIC evaluation should always be performed in the case of CR-Kp infections.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

We report intestinal carriage of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L) in a patient in France who had been hospitalized for fungal meningitis. The strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are associated with colistin resistance.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; France; Genes, Bacterial; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Plasmids; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactamases; Brazil; Colistin; Drug Resistance, Bacterial; Escherichia coli Proteins; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Plasmids

KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined the combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin, in time-kill experiments and hollow-fibre infection models (HFIM).. Two KPC-2-producing K. pneumoniae isolates were used: one susceptible to both colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin ≤8 mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A: MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L). Time-kill experiments assessed an array of colistin and fosfomycin concentrations against both isolates. Colistin and fosfomycin pharmacokinetics from critically ill patients were simulated in the HFIM to define the pharmacodynamic activity of humanized regimens over 5 days against KPC 9A.. In time-kill experiments, synergy was demonstrated for all colistin/fosfomycin combinations containing >8 mg/L fosfomycin against the double-susceptible KPC strain, 9A. Synergy versus KPC strain 5A was only achieved at the highest concentrations of colistin (4 mg/L) and fosfomycin (512 mg/L) at 48 h. In the HFIM, colistin or fosfomycin monotherapies resulted in rapid proliferation of resistant subpopulations; KPC 9A regrew by 24 h. In contrast to the monotherapies, the colistin/fosfomycin combination resulted in a rapid 6.15 log 10  cfu/mL reduction of KPC 9A by 6 h and complete suppression of resistant subpopulations until 120 h.. Colistin and fosfomycin may represent an important treatment option for KPC-producing K. pneumoniae otherwise resistant to traditional antibiotics.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological

The spread of

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; France; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Plasmids; Portugal

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.

Topics: Bacterial Outer Membrane Proteins; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains.. The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively.. The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

Colistin resistance is increasingly recognized among carbapenemase-producing Klebsiella pneumoniae isolates in several European regions. The current study documents the appearance of colistin resistance among KPC-2 and SHV-5-produning K. pneumoniae strains in Bulgaria.. Four colistin-resistant K. pneumoniae isolates were recovered from 2 patients hospitalized in the anesthesiology and resuscitation clinic of a tertiary care university hospital in Sofia, Bulgaria. Microbial identification and antimicrobial susceptibility testing was performed by Vitek 2 (Biomerieux, France). β-Lactamase genes were amplified using a panel of primers for detection of all MBL-types, KPCs, plasmid-mediated AmpCs in single PCR reactions, OXA-type carbapenemases, extended-spectrum β-lactamases (ESBLs) and TEM enzymes. The colistin-resistant mcr-1 gene was also investigated using previously described primers and conditions. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to investigate clonality.. The 4 K. pneumoniae isolates exhibited colistin MICs >16 mg/L and showed multidrug-resistant phenotypes, remaining intermediately susceptible only to gentamicin. They were clustered into a single PFGE clonal type and MLST assigned them to sequence type 258. All isolates possessed KPC-2 carbapenemase and SHV-5 ESBL. They were negative for the plasmid-mediated colistin-resistant mcr-1 gene, possibly implying an intrinsic mechanism of resistance.. Although colistin use in Bulgaria only started moderately during 2014, the findings of the current study notify the appearance of colistin resistance among carbapenemase-producing Klebsiella species in another European region.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Bulgaria; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Multilocus Sequence Typing; Tertiary Care Centers

This study aimed to understand the impact on virulence and fitness of mutations in specific genes found after adaptation of Klebsiella pneumoniae to colistin. Isolates with an increase in their inhibitory concentration (MIC) to colistin of 32- to >128-fold were shown to have mutations in mgrB, phoPQ and pmrAB, all known regulators of pathways affecting membrane lipid content. When these strains were used in studies in Galleria mellonella there was no clear correlation between mutations in specific genes per se and loss of virulence. Strains which showed sequence duplication in the HAMP-domain of PmrB showed reduced virulence but strains with point mutations in pmrAB showed no decrease in virulence. Similarly, specific mutations in mgrB in individual strains showed either loss of virulence or no effect/increased virulence. This study suggests that the impact on virulence may be independent of the colistin resistance mechanism and reflects differences in individual strain backgrounds.

Topics: Adaptation, Biological; Animals; Anti-Bacterial Agents; Biological Assay; Colistin; Drug Resistance, Bacterial; Genes, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Larva; Lepidoptera; Microbial Sensitivity Tests; Mutation; Survival Analysis; Virulence

In this study, we retrospectively evaluated clinical outcomes of 75 patients with dual colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections over a 5-year period in a single tertiary care hospital in India. We observed a high in-hospital mortality rate of 69.3%. Our findings indicate the urgent need for new antibiotics to treat these infections.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Dog Diseases; Dogs; Drug Resistance, Multiple, Bacterial; Female; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pets; Tigecycline

Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.. To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.. The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.. All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.. The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.

Topics: Adult; Aged; Amino Sugars; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Chromosomes, Bacterial; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Lipopolysaccharides; Male; Membrane Proteins; Microbial Sensitivity Tests; Middle Aged; Mutagenesis, Insertional

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging worldwide, limiting therapeutic options. Mutational and plasmid-mediated mechanisms of colistin resistance have both been reported. The emergence and clonal spread of colistin resistance was analysed in 40 epidemiologically-related NDM-1 carbapenemase producing Klebsiella pneumoniae isolates identified during an outbreak in a group of London hospitals. Isolates from July 2014 to October 2015 were tested for colistin susceptibility using agar dilution, and characterised by whole genome sequencing (WGS). Colistin resistance was detected in 25/38 (65.8%) cases for which colistin susceptibility was tested. WGS found that three potential mechanisms of colistin resistance had emerged separately, two due to different mutations in mgrB, and one due to a mutation in phoQ, with onward transmission of two distinct colistin-resistant variants, resulting in two sub-clones associated with transmission at separate hospitals. A high rate of colistin resistance (66%) emerged over a 10 month period. WGS demonstrated that mutational colistin resistance emerged three times during the outbreak, with transmission of two colistin-resistant variants.

Topics: Aged; Aged, 80 and over; Bacterial Proteins; beta-Lactamases; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Female; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; London; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Whole Genome Sequencing

Topics: Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae

The emergence of carbapenem-resistant Klebsiella pneumoniae strains is threatening antimicrobial treatment.. Sixty-eight carbapenemase-producing K. pneumoniae strains isolated at Luigi Sacco University Hospital-ASST Fatebenefratelli Sacco (Milan, Italy) between 2012 and 2014 were characterised microbiologically and molecularly. They were tested for drug susceptibility and carbapenemase phenotypes, investigated by means of repetitive extra-genic palindromic polymerase chain reaction (REP-PCR), and fully sequenced by means of next-generation sequencing for the in silico analysis of multi-locus sequence typing (MLST), their resistome, virulome and plasmid content, and their core single nucleotide polymorphism (SNP) genotypes.. All of the samples were resistant to carbapenems, other β-lactams and ciprofloxacin; many were resistant to aminoglycosides and tigecycline; and seven were resistant to colistin. Resistome analysis revealed the presence of blaKPC genes and, less frequently blaSHV, blaTEM, blaCTX-M and blaOXA, which are related to resistance to carbapenem and other β-lactams. Other genes conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulphonamide, tetracycline, trimethoprim and macrolide-lincosamide-streptogramin were also detected. Genes related to AcrAB-TolC efflux pump-dependent and pump-independent tigecycline resistance mechanisms were investigated, but it was not possible to clearly correlate the genomic features with tigecycline resistance because of the presence of a common mutation in susceptible, intermediate and resistant strains. Concerning colistin resistance, the mgrB gene was disrupted by an IS5-like element, and the mobile mcr-1 and mcr-2 genes were not detected in two cases. The virulome profile revealed type-3 fimbriae and iron uptake system genes, which are important during the colonisation stage in the mammalian host environment. The in silico detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), ColRNAI, IncX1, IncX3, IncFII(K), IncN, IncL/M(pMU407) and IncFIA(HI1). REP-PCR showed five major clusters, and MLST revealed six different sequence types: 512, 258, 307, 1519, 745 and 101. Core SNP genotyping, which led to four clusters, correlated with the MLST data. Isolates of the same sequencing type often had common genetic traits, but the SNP analysis allowed greater strain tracking and discrimination than either the REP-PCR or MLST analysis.. Our findings support the importance of implementing bacterial genomics in clinical medicine in order to complement traditional methods and overcome their limited resolution.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Fluoroquinolones; Genome, Bacterial; Genotype; Hospitals; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Multilocus Sequence Typing; Polymorphism, Single Nucleotide; Whole Genome Sequencing

The mcr-1 (mobile colistin resistance 1) gene, which encodes phosphoethanolamine transferase, has been recently identified as a source of acquired resistance to polymyxins in Escherichia coli. Using the SuperPolymyxin selective medium, we prospectively screened 100 pigs at 2 farms in Portugal for polymyxin-resistant Enterobacteriaceae and recovered 98 plasmid-mediated MCR-1-producing isolates. Most isolates corresponded to nonclonally related E. coli belonging to many sequence types; we also found 2 Klebsiella pneumoniae sequence types. The mcr-1 gene was carried on IncHI2 or IncP plasmid backbones. Our finding of a high rate of MCR-1 producers on 2 pig farms in Portugal highlights the diffusion of that colistin-resistance determinant at the farm level. The fact that the pigs received colistin as metaphylaxis in their feed during the 6 weeks before sampling suggests selective pressure.

Topics: Animals; Anti-Bacterial Agents; Colistin; Conjugation, Genetic; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Farms; Gene Dosage; Gene Expression; Gene Transfer, Horizontal; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Plasmids; Portugal; Swine

The objective of this study was to assess the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem (MEM) in critically-ill patients with bloodstream infections (BSI) due to Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) with MEM minimum inhibitory concentrations (MICs) ≥16 mg/L. Nineteen critically-ill patients with KPC-Kp BSI were given combination therapy including MEM, tigecycline, plus colistin or gentamicin (according to susceptibility testing). MEM was administered as an extended 3-hour infusion of 2 g every 8 hours, or adjusted according to renal function. MEM plasma concentrations were determined by high-performance liquid chromatography. PK/PD targets for MEM were defined as T > 40% 1×MIC and T > 40% 4×MIC. Possible synergisms between MEM and coadministered agents were assessed by time-kill assays based on plasma levels for MEM and on fixed plasma concentrations for the other agents. In none of 19 patients MEM reached any PK/PD target. The actual MEM MICs were 256, 512, and 1024 mg/L in 1, 3, and 15 isolates, respectively. However, theoretically, the PK/PD target of T > 40% 1×MIC could have been achieved in 95%, 68%, 32% and 0% of the isolates for MIC equal to 8, 16, 32, and 64 mg/L, respectively. No synergisms were observed between MEM and coadministered agents. In conclusion, high-dose MEM failed to reach PK/PD targets in 19 patients with BSI due to KPC-Kp with very high MEM MICs. On a theoretical basis, our results suggest a possible usefulness of MEM against resistant blood isolates with MICs up to 32 mg/L.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline

Resistance determinants of a colistin susceptible and five colistin resistant Klebsiella pneumoniae ST258 from a Hungarian outbreak were investigated. A novel MgrB variant in colistin susceptible strain was found. Elevated phoP and arn gene expressions and wild-type PmrB in all colistin resistant K. pneumoniae were detected. All strains lacked mcr-1.

Topics: Bacterial Proteins; Base Sequence; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Hungary; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Sequence Analysis

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae

In this study, we have attempted to report the first clonal spread of colistin-resistant Klebsiella pneumoniae coproducing KPC and VIM carbapenemases in the neonatal unit of Rabta Teaching Hospital of Tunis (Tunisia). This retrospective study was performed from January 1, 2014 to December 31, 2014 in the Microbiology Laboratory at the Rabta University Hospital of Tunis. Twenty-one nonreplicate colistin-resistant K. pneumoniae were isolated from 19 patients hospitalized in the neonatal unit and 2 patients in the adult intensive care unit (ICU). Most of the strains were isolated from invasive specimens. Pulsed-field gel electrophoresis (PFGE) and PCR analysis and nucleotide sequencing of the blaKPC and blaVIM genes were performed. Mortality was reported in 92% of cases. All the strains were resistant to colistin (minimum inhibitory concentration [MICs] ranged from 8 to 12 mg/L). The MICs for imipenem of K. pneumoniae isolates ranged from 3 to 256 mg/L for 13 strains that were characterized as intermediate or resistant. The MICs for ertapenem were higher than 32 mg/L for the 19 resistant strains. All the isolates were sensitive to tigecycline and chloramphenicol. PFGE analysis revealed two clones (I and II). Twenty of the 21 colistin-resistant, carbapenem-resistant K. pneumoniae isolates belonged to clone I. Only one strain was related to clone II. PCR analysis and nucleotide sequencing revealed that the 20 isolates belonged to clone I, coproduced the blaKPC and blaVIM genes. A single strain (clone II), which was isolated in the ICU, did not produce KPC and VIM carbapenemases. All strains did not produce OXA-48.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; beta-Lactams; Chloramphenicol; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Ertapenem; Female; Gene Expression; Hospitals, University; Humans; Imipenem; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Retrospective Studies; Survival Analysis; Tigecycline; Tunisia

NDM-producing Enterobacteriaceae are considered emergent on the African continent and have been increasingly reported in recent years. In contrast, strains producing NDM-type enzymes have been rarely reported in Italy, usually associated with sporadic cases or small outbreaks. Here we report two cases of infection caused by NDM-1-producing Klebsiella pneumoniae (NDM-KP) in two unrelated patients returned from travel to Egypt.. The two patients had been previously hospitalised for a short period in two different Egyptian hospitals. In our institution in Italy, NDM-KP isolates were detected from surgical wound drainage (patient #1) and respiratory secretions and blood cultures (patient #2). Rectal swabs of both patients were persistently positive for NDM-KP. In both cases, NDM-1-producing isolates exhibited a multidrug-resistant phenotype, being susceptible only to tigecycline and colistin. Analysis by multilocus sequence typing (MLST) revealed that the two K. pneumoniae isolates were not clonally related, belonging to different sequence types (STs), namely ST15 from patient #1 and ST11 from patient #2.. To the best of our knowledge, this is the first report of NDM-producing isolates imported from Africa to Italy, with no obvious link to the Indian subcontinent. Our experience confirms that Egypt is an emergent source of NDM-producing Enterobacteriaceae, thus representing a cause of concern for Mediterranean countries. Owing to its geographical position, Italy is a first-line European checkpoint with respect to African countries and plays a pivotal role in limiting the dissemination of high-risk clones, especially considering the latest strong migration flows.

Topics: Africa; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Egypt; Enterobacteriaceae; Genotype; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Longitudinal Studies; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Multilocus Sequence Typing; Surgical Wound; Tigecycline

Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide.. A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling.. In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73-6.57; P < .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp.. In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Comorbidity; Female; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Proportional Hazards Models

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

A carbapenemase-producing colistin-resistant Klebsiella oxytoca isolate was recovered from a blood culture of a female patient without previous report of risk factors to obtain multidrug-resistant Gram-negative bacilli. A combination of biochemical and molecular methods was used to identify the resistance mechanism of this isolate. Carbapenemase production was mediated by Verona integron-encoded metallo-β-lactamase (VIM)-2. Colistin resistance was not due to plasmid- borne mcr-1 gene, but we found an integration of IS5-like sequence in the mgrB gene of K. oxytoca. This gene is known to be an important regulator of the PhoPQ two-component system, and the disruption of this gene is most likely the cause of lipid A modification resulting in colistin resistance of our isolate. To the best of our knowledge this constitutes the first report of a carbapenemase-producing K. oxytoca with colistin resistance, a case that demonstrates the limited treatment options for infections with multidrug-resistant organisms.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Blood Culture; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella oxytoca; Membrane Proteins; Mutagenesis, Insertional; Plasmids

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Colistin; Humans; Internal Fixators; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Load; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lepidoptera; Lipid A; Lung; Membrane Proteins; Mice, Inbred C57BL; Polymyxins; Survival Analysis; Virulence

Twenty-seven colistin-resistant, carbapenemase-producing

Topics: Bacterial Proteins; beta-Lactamases; Child, Preschool; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Serbia

Topics: Aged; Anti-Bacterial Agents; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lebanon; Male; Middle Aged; Multilocus Sequence Typing; Polymerase Chain Reaction

Infection by bacteria carrying New Delhi metallo-β-lactamase 1 (NDM-1) is becoming a global health problem. We report a case of meningitis caused by NDM-1-producing Klebsiella pneumoniae, for which intrathecal administration of colistin was curative. A previously healthy 38-year-old Japanese man, who lived in Hyderabad, India, suddenly collapsed and was brought to a local hospital. He was diagnosed with subarachnoid hemorrhage and underwent emergency surgery which included partial skull removal. Approximately 1 month after surgery, he was repatriated to Japan and was admitted to our institution with information that he had been treated for multi-drug resistant Acinetobacter infection with colistin. A week after admission, he developed aspiration pneumonia due to NDM-1-producing K. pneumoniae, which was successfully treated by intravenous (IV) administration of colistin. Subsequently, he underwent a surgical procedure to repair his skull defect. He developed high-grade fever and altered mental status on postoperative day 2. NDM-1-producing K. pneumoniae was identified in the cerebrospinal fluid, establishing the diagnosis of meningitis. Although IV colistin was only partially effective, intrathecal colistin (10 mg daily by lumbar puncture for 14 days) successfully eradicated the meningitis. Because of economic globalization, NDM-1-producing bacteria may be brought to Japan by those who are repatriated after sustaining critical illnesses and being treated in foreign countries. This report may provide useful information on the treatment of central nervous system infection by NDM-1-producing bacteria.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; India; Injections, Spinal; Japan; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Microbial Sensitivity Tests

The emergence of colistin resistance may further contribute to treatment failure of infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae. The colistin resistance rates were determined and colistin-resistant carbapenemase-producing K. pneumoniae (COL-R CP-Kp) were characterized over an 18-month period in a Greek hospital. Out of 135 carbapenemase producers, 19 isolates (14%) were categorized as resistant to colistin. Phenotypic and molecular characterization of the COL-R CP-Kp isolates revealed that all were MDR blaKPC producers and, excluding one isolate of MLST ST383, belonged to the international clonal lineage ST258. Furthermore, PCR amplification and sequencing of the mgrB locus revealed nucleotide sequences of different sizes and insertions of IS1- and IS5-like mobile elements. The majority (63%) of the COL-R blaKPC producers was recovered from patients in the intensive care unit (ICU) and clinical data indicated that all patients should have acquired these isolates in the ICU. The findings of the present study underscore a concerning evolution of colistin resistance in a setting of high K. pneumoniae carbapenemase (KPC)-Kp endemicity, such as Greece. Thus, continuous surveillance, molecular characterization, prudent use of antibiotics, and implementation of infection control measures for K. pneumoniae are urgent.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Female; Gene Expression; Greece; Hospitals; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Membrane Proteins; Microbial Sensitivity Tests; Middle Aged; Mutagenesis, Insertional; Sequence Analysis, DNA

The lack of treatment for multidrug-resistant (MDR) Enterobacteriaceae often leads to the use of double or triple antibiotic combinations to increase the option of clinical success. This study analyzes multiple combination bactericidal testing (MCBT) to screen double and triple antibiotic combinations, at standard peak serum concentration, for bactericidal activity against 21 MDR Klebsiella pneumoniae isolates. This method was compared with time-killing curves. The full bactericidal activity against all strains was obtained only by adding colistin. MCBT has a potential to become a rapid method for testing multiple antibiotic combinations for MDR microorganisms when colistin is used, providing clinicians with in vitro cidal data within 48 hr of strain isolation.

Topics: Anti-Bacterial Agents; beta-Lactams; Colistin; Culture Media; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Predictive Value of Tests; Rifampin; Thienamycins; Tigecycline

Infections caused by carbapenemase-producing Klebsiella pneumoniae resistant to tigecycline, colistin, or aminoglycosides are a growing health concern. In our retrospective chart review, we noted increased resistance to colistin compared with tigecycline, despite limited prior use of colistin. This may affect the choice of presumptive antibiotics used in these hard to treat infections. Improved infection control and antimicrobial stewardship practices are essential to prevent the spread of these multidrug-resistant organisms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Young Adult

In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistin-resistant derivatives. However, pmrB was significantly upregulated in only two colistin-resistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ- and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistin-resisant K. pneumoniae.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Gene Deletion; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Operon

A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Child; China; Colistin; Drug Resistance, Bacterial; Escherichia coli; Estonia; Genetic Variation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Plasmids; South Africa

Donor-derived infections with multidrug-resistant gram-negative bacteria are associated with poor outcomes, in part because of limited treatment options. Here, we describe a case of donor-derived, disseminated infection with colistin-resistant, carbapenemase-producing Klebsiella pneumoniae in a liver transplant recipient that was cured with addition of intravenous fosfomycin to a multidrug regimen, in conjunction with aggressive surgical source control. Intravenous fosfomycin represents a promising adjunctive agent for use in treatment of extensively drug-resistant infections in immunocompromised hosts.

Topics: Aged; Allografts; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fibrosis; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Microbial Sensitivity Tests; Minocycline; Tigecycline

Klebsiella pneumoniae New Delhi metallo-beta-lactamase-1 (NDM-1) strains have recently become a new threat in kidney transplant recipients due to the strains' resistance to almost all antibiotics, including carbapenems.. We present a case series of 3 patients with urinary tract infections (UTIs) caused by multiresistant K pneumoniae NDM-1 strains who were treated with the same protocol. Genotyping sequencing with pulsed-field gel electrophoresis was performed in all cases.. All patients were male and had undergone kidney transplantation 4, 7, and 8 months, respectively, before the admission. Combined antibiotic therapy consisting of imipenem/cilastatin in maximal doses, gentamicin and/or colistin for 21 to 27 days, followed by oral fosfomycin, was used in all cases. There were no further UTI episodes in 2 patients at the 12-month visit. Three months after initial treatment, the third patient presented with leukocyturia with no clinical symptoms and a urine culture positive for K pneumonia NDM-1 strain. Interestingly, the strain was susceptible to trimethoprim/sulfamethoxazole despite resistance in previous urine culture samples. The patient was successfully treated with trimethoprim/sulfamethoxazole 2 × 960 mg/d for 3 weeks followed by 480 mg/d and 3 doses of fosfomycin. Genotyping sequencing revealed identical DNA restriction fragments in bacterial strains from 2 patients. In the third case, although a difference in 2 restriction fragments was observed, the strain was considered related to the others.. In cases of UTI caused by K pneumoniae NDM-1 strains, prolong combined treatment followed by oral fosfomycin prophylaxis can be successful. Strain genotyping should be performed to optimize further treatment protocols in such cases.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Drug Combinations; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Fosfomycin; Genotype; Gentamicins; Humans; Imipenem; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Klebsiella pneumoniae is emerging as an important nosocomial pathogen due to its rapidly increasing multidrug resistance, which has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort. However, heteroresistance (i.e., the presence of a subpopulation of resistant bacteria in an otherwise susceptible culture) may hamper the effectiveness of colistin treatment in patients. In a previous study, we showed that colistin resistance among extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates emerged after the introduction of selective digestive tract decontamination (SDD) in an intensive care unit (ICU). In this study, we investigated heteroresistance to colistin among ESBL-producing K. pneumoniae isolates by using population analysis profiles (PAPs). We used whole-genome sequencing (WGS) to identify the mutations that were associated with the emergence of colistin resistance in these K. pneumoniae isolates. We found five heteroresistant subpopulations, with colistin MICs ranging from 8 to 64 mg/liter, which were derived from five clonally related, colistin-susceptible clinical isolates. WGS revealed the presence of mutations in the lpxM, mgrB, phoQ, and yciM genes in colistin-resistant K. pneumoniae isolates. In two strains, mgrB was inactivated by an IS3-like or ISKpn14 insertion sequence element. Complementation in trans with the wild-type mgrB gene resulted in these strains reverting to colistin susceptibility. The MICs for colistin-susceptible strains increased 2- to 4-fold in the presence of the mutated phoQ, lpxM, and yciM alleles. In conclusion, the present study indicates that heteroresistant K. pneumoniae subpopulations may be selected for upon exposure to colistin. Mutations in mgrB and phoQ have previously been associated with colistin resistance, but we provide experimental evidence for roles of mutations in the yciM and lpxM genes in the emergence of colistin resistance in K. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Phylogeny; Polymorphism, Single Nucleotide

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Klebsiella Infections; Klebsiella pneumoniae; Plasmids

Bacteria resistant to colistin, a last resort antibiotic reflect the pre-antibiotic era. In this study, colistin resistance carbapenem-resistant K. pneumoniae (COL

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cluster Analysis; Colistin; Cross Infection; Drug Resistance, Bacterial; Genotype; Humans; India; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Molecular Typing

Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to the limited treatment options.. To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin-susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC).. Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for bla. In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions.. Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Colistin; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals, University; Humans; Infant; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Young Adult

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Biomarkers; Brazil; Colistin; Cross Infection; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Prevalence; Retrospective Studies

A 62-year-old man presented with fever, abdominal pain, and malaise 13 months after emergency endovascular aortic repair. Computed tomographic angiograms showed a periprosthetic fluid and gas collection, so infection was diagnosed. Open conversion was performed, involving endograft explantation and in situ aortic reconstruction. Cultures and the explanted prosthesis were positive for carbapenemase-producing Klebsiella pneumoniae, resistant to colistin. Because of the sparse data on endograft infections caused by this pathogen, we placed the patient on an empiric double-carbapenem regimen for 4 weeks. Symptomatic recovery occurred after 21 days. On the 30th day, we deployed a stent to treat a new pseudoaneurysm. Three years later, the patient had no signs of persistent or recurrent infection. We think that this is the first report of aortic endograft infection caused by colistin-resistant, carbapenemase-producing K. pneumoniae.

Topics: Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Aortography; Bacterial Proteins; beta-Lactamases; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Carbapenems; Colistin; Computed Tomography Angiography; Device Removal; Drug Resistance, Bacterial; Endovascular Procedures; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Prosthesis-Related Infections; Treatment Outcome

In this prospective study, consecutive isolates of Klebsiella pneumoniae were tested for different mechanisms of carbapenem resistance using the modified Hodge test (MHT), Rosco Neo-Sensitabs (ROSCO). Phenylalanine arginine beta-naphthylamide assay (PABN) inhibitor-based test was done on isolates in which the mechanism of resistance was not identifiable by the ROSCO. Among 105 selected isolates, carbapenemase production was noted in 100 (95%) by MHT and ROSCO showed 97 (92·4%) inhibition with dipicolinic acid signifying the production of MBL. PCR amplification was positive in 90 (86%) isolates for bla(NDM-1) and 46 (44%) isolates for bla(OXA-48). 54 (51%) isolates were positive for bla(CTX-M) and all belonged to bla(CTX-M) group 1. Isolates co produced bla(OXA-48) (31/105, 30%) and bla(CTX-M) (40/105, 38%) in combination with the carbapenemase (bla(NDM-1)) gene. Five colistin-resistant isolates were positive for bla(OXA-48). Eight isolates did not show inhibition with any of the inhibitor containing disks and found to be positive for bla(OXA-48). Isolates were tested for colistin-meropenem synergy and detection rate was higher by the checkerboard (48%) than E-test method (35%). Our study necessitates continuous surveillance to recognize the predominant machinery of resistance in a particular geographical region to formulate effective control measures.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Thienamycins

Alterations in the PhoPQ two-component regulatory system may be associated with colistin resistance in Klebsiella pneumoniae. MgrB is a small transmembrane protein produced upon activation of the PhoPQ signalling system, and acts as a negative regulator on this system. We investigated the role of the MgrB protein as a source of colistin resistance in a series of K. pneumoniae.. Colistin-resistant K. pneumoniae isolates were recovered from hospitalized patients worldwide (France, Turkey, Colombia and South Africa). The mgrB gene was amplified and sequenced. A wild-type mgrB gene was cloned and the corresponding recombinant plasmid was used for complementation assays. Clonal diversity was evaluated by MLST and Diversilab analysis.. Of 47 colistin-resistant isolates, 12 were identified as having a mutated mgrB gene. Five clonally unrelated isolates had an mgrB gene truncated by an IS5-like IS, while one clone also harboured an insertional inactivation at the exact same position of the mgrB gene, but with ISKpn13. Another clone harboured an insertional inactivation due to ISKpn14 at another location of the mgrB gene. Two clonally related isolates harboured an IS (IS10R) in the promoter region of mgrB. Finally, three clonally unrelated isolates harboured substitutions leading to anticipated stop codon in the MgrB protein. Complementation assays with a wild-type MgrB protein restored full susceptibility to colistin for all colistin-resistant isolates identified with qualitative or quantitative MgrB modifications.. The inactivation or down-regulation of the mgrB gene was shown to be a source of colistin resistance in K. pneumoniae. Interestingly, identical genetic events were identified among clonally unrelated isolates.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Genetic Complementation Test; Genetic Variation; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Molecular Sequence Data; Multilocus Sequence Typing

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymerase Chain Reaction

Topics: Amikacin; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Female; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Rectum; Treatment Failure

Antimicrobial therapy for sepsis caused by carbapenem- and colistin-resistant Klebsiella pneumoniae is not well established. We hypothesized that the early use of gentamicin in cases due to susceptible organisms would decrease the crude mortality rate of this infection.. This retrospective cohort study examined 50 cases of sepsis caused by carbapenem-resistant K. pneumoniae occurring between June 2012 and February 2013 during an outbreak of K. pneumoniae ST512 producing KPC-3, SHV-11 and TEM-1. Survival curves categorized by the use of gentamicin were constructed using the Kaplan-Meier method and compared using the log-rank test. Eight multivariate models using Cox regression were designed to study the risk factors for mortality and test the hypothesis.. The 30 day crude mortality rate was 38%. The use of targeted gentamicin was associated with reduced mortality (20.7% versus 61.9%, P = 0.02). In all multivariate regression models, the use of gentamicin was independently associated with lower mortality until Day 30 (HR 0.17-0.29, P = 0.03-0.002 depending on the model) after controlling for other potential confounding variables such as age, optimal treatment, renal function, severity of infection, underlying disease, use of tigecycline and previous hospitalization.. Gentamicin reduced the mortality from sepsis caused by this K. pneumoniae ST512 clone producing KPC-3, SHV-11 and TEM-1.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Cohort Studies; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis; Survival Analysis; Treatment Outcome; Young Adult

Topics: Animals; Anti-Bacterial Agents; Cattle; Colistin; Drug Resistance, Bacterial; France; Genes, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Mastitis, Bovine; Microbial Sensitivity Tests; Polymerase Chain Reaction

Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 μg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Therapy, Combination; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Porins; Retrospective Studies

Infections due to carbapenemase-producing Klebsiella pneumoniae represent an emerging threat due to the high mortality rate and lack of valid antimicrobial combinations, especially when the strain is colistin-resistant. We report a case of bloodstream infection due to pandrug-resistant K. pneumoniae treated successfully with an innovative regimen comprising a combination of colistin plus double carbapenem, along with an in vitro analysis showing the synergistic and bactericidal effect.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

We first describe two novel variants of blaKPC, blaKPC-16 and blaKPC-17, which were identified in three Klebsiella pneumoniae isolates from a patient in Taiwan. KPC-16 and KPC-17 differed from KPC-2 by two (P202S and F207L) and a single (F207L) amino acid substitutions, respectively. All three isolates with identical pulsotype belonged to sequence type 11. The MICs of the three isolates for colistin and tigecycline were 0.5 μg/mL and 2 μg/mL, respectively. Moreover, an outbreak of at least 39 blaKPC-17-containing K. pneumoniae isolates is ongoing in southern Taiwan in 2014. Physicians should know that blaKPC-17-containing isolates can substantially threaten public health.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Taiwan; Tigecycline

The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae continues to increase, and the possible development of KPC-producing K. pneumoniae infections in cystic fibrosis (CF) patients is a matter of concern. Here, we describe the establishment of a chronic lung infection due to a colistin-resistant KPC-producing K. pneumoniae isolate in an Italian CF patient.

Topics: Anti-Bacterial Agents; Chronic Disease; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Underage Drinking

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross-Sectional Studies; Gentamicins; Hospitals; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

Gene modifications in the PmrAB and PhoPQ two-component regulatory systems, as well as inactivation of the mgrB gene, are known to be causes of colistin resistance in Klebsiella pneumoniae. The objective of this study was to characterise the mechanism involved in colistin resistance in a Klebsiella oxytoca isolate. A K. oxytoca clinical isolate showing resistance to colistin was recovered in Cali, Colombia. The pmrA, pmrB, phoP, phoQ and mgrB genes were amplified and sequenced. Wild-type mgrB genes from K. pneumoniae and K. oxytoca were cloned, and corresponding recombinant plasmids were used for complementation assays. By analysing the mgrB gene of the K. oxytoca isolate and its flanking sequences, an insertion sequence (IS) of 1196bp was identified in its promoter region. The insertion was located between nucleotides -39 and -38 when referring to the start codon of the mgrB gene, thus negatively interfering with expression of the mgrB gene by modifying its promoter structure. This IS was very similar to ISKpn26 (99% nucleotide identity) belonging to the IS5 family. Complementation assays with mgrB genes from wild-type K. pneumoniae or K. oxytoca restored full susceptibility to colistin. In conclusion, here we identified the mechanism involved in colistin resistance in a K. oxytoca isolate. Modulation of mgrB gene expression was the key factor for this acquired resistance to colistin.

Topics: Aged; Anti-Bacterial Agents; Cloning, Molecular; Colistin; Colombia; DNA Transposable Elements; DNA, Bacterial; Drug Resistance, Bacterial; Gene Expression; Genetic Complementation Test; Humans; Klebsiella Infections; Klebsiella oxytoca; Male; Membrane Proteins; Molecular Sequence Data; Mutagenesis, Insertional; Plasmids; Polymerase Chain Reaction; Promoter Regions, Genetic; Sequence Analysis, DNA

We investigated the synergism of colistin and imipenem against a multidrug-resistant K. pneumoniae isolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the common β-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. The bla SHV-31, bla CMY-2, and bla DHA-1 were detected. Outer membrane porin genes analysis revealed loss of ompK36 and frame-shift mutation of ompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistant K. pneumoniae infections.

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Hip; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Porins

Frequent use of carbapenems has contributed to the increase to K. pneumoniae strains resistant to this class of antibiotics (CRKP), causing a problem in the clinical treatment of patients. This investigation reports the epidemiology, genetic diversity, and clinical implication of the resistance to drugs mediated by CRKP in our hospital. A total of 280 K. pneumoniae strains were collected; in particular 98/280 (35%) were CRKP. Sequencing analysis of CRKP isolated strains showed that 9/98 of MBL-producing strains carried the bla VIM-1 gene and 89/98 of the isolates were positive for bla KPC-2. Antimicrobial susceptibility tests revealed a complete resistance to third-generation cephalosporins and a moderate resistance to tigecycline, gentamicin, and fluoroquinolones with percentages of resistance of 61%, 64%, and 98%, respectively. A resistance of 31% was shown towards trimethoprim-sulfamethoxazole. Colistin was the most active agent against CRKP with 99% of susceptibility. Clonality was evaluated by PFGE and MLST: MLST showed the same clonal type, ST258, while PFGE analysis indicated the presence of a major clone, namely, pulsotype A. This finding indicates that the prevalent resistant isolates were genetically related, suggesting that the spread of these genes could be due to clonal dissemination as well as to genetic exchange between different clones.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Lactamases; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Female; High-Throughput Nucleotide Sequencing; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged

We describe an outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-KP) ST258 that occurred in two institutions (a hospital and a nursing home) in the Netherlands between July and December 2013. In total, six patients were found to be positive for KPC-KP. All isolates were resistant to colistin and exhibited reduced susceptibility to gentamicin and tigecycline. In all settings, extensive environmental contamination was found. Whole genome sequencing revealed the presence of bla KPC-2 and bla SHV-12 genes, as well as the close relatedness of patient and environmental isolates. In the hospital setting, one transmission was detected, despite contact precautions. After upgrading to strict isolation, no further spread was found. After the transfer of the index patient to a nursing home in the same region, four further transmissions occurred. The outbreak in the nursing home was controlled by transferring all KPC-KP-positive residents to a separate location outside the nursing home, where a dedicated nursing team cared for patients. This outbreak illustrates that the spread of pan-resistant Enterobacteriaceae can be controlled, but may be difficult, particularly in long-term care facilities. It, therefore, poses a major threat to patient safety. Clear guidelines to control reservoirs in and outside the hospitals are urgently needed.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Environmental Microbiology; Female; Genome, Bacterial; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Epidemiology; Netherlands; Patient Safety; Practice Guidelines as Topic; Prospective Studies; Sequence Analysis, DNA; Sequence Homology

The aim of this study was to characterize the spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) in a tertiary level hospital using ongoing active surveillance with rectal swab cultures. Furthermore, this study analyzed the presence of CPKP in the clinical samples (CS) of a single patient as well as the evolution of Colistin-sensitive strains (CoS) to Colistin-resistant strains (CoR).. This study was performed from January 1, 2012 to December 31, 2014. In 2012, a survey was conducted in the Intensive Care Department. In autumn 2013, active monitoring was extended to the Surgery Department, and since mid-2014, the surveillance has included the Medical Department as well. Only the first isolated strain from each patient was included. Antimicrobial susceptibility testing was performed on CPKP isolates: Klebsiella pneumoniae carbapenemase, oxacillinase-48, Verona integron-encoded metallo-β-lactamase and New Delhi metallo-β-lactamase were detected using a validated in-house PCR method, and multilocus sequence typing (MLST) was used to investigate the clonal transmission of strains.. A total of 15,104 patients were included in the study, and 496 consecutive non-replicated strains of CPKP were collected: 149 strains were collected in 2012 (39 [26.2 %] from surveillance rectal swabs [SRS]), 133 strains were collected in 2013 (70 [52.6 %] from SRS) and 214 strains were collected in 2014 (164 [76.6 %] from SRS). We observed a significant increase in the percentage of positive SRS cases in 2014 relative to 2013 and 2012 (p = 0.0001 and p = 0.0172, respectively) and in the proportion of CPKP first isolated by SRS relative to those identified by CS (p < 0.0001). Among all available samples, the number of CoR isolated from SRS was higher in 2013 and 2014 compared with 2012 (p = 0.0019 and p = 0.008, respectively). ST-258 and ST-512 were more prevalent in the tested specimens, and a new single locus variant (SLV) of ST-512 (ST-745) was isolated.. The results of this 3-year study of 15,104 patients highlight the clinical relevance of antimicrobial resistance as well as the drug-selection pressure of colistin therapy. The active surveillance in the three different departments increased the level of CPKP cases isolated by SRS.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biological Evolution; Colistin; Drug Resistance, Bacterial; Hospitals, Teaching; Humans; Intensive Care Units; Italy; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Polymerase Chain Reaction; Prevalence

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

In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy.. Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates.. Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Epidemiological Monitoring; Fluoroquinolones; Gene Expression; Hospitals; Humans; Incidence; Italy; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Multilocus Sequence Typing; Mutation; Plasmids

Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae carbapenemase (KPC) have spread globally in the last decade. Colistin is a key agent in treating infections caused by this pathogen. In this issue of the Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli, V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini, P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341-3344, 2015, http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin-resistant KPC-producing K. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae

We describe a large hospital outbreak (93 bloodstream infections) of colistin-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates which was mirrored by increased colistin consumption. The outbreak was mostly traced to the clonal expansion of an mgrB deletion mutant of an ST512 strain that produced KPC-3.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Molecular Typing; Sequence Deletion

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

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.

Topics: Aged; Bacteremia; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospitalization; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Risk Factors

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Topics: Anti-Bacterial Agents; Antiviral Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Ceftazidime; Colectomy; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Ganciclovir; Humans; Immunosuppressive Agents; Intestine, Small; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir

In this study susceptibility to different antimicrobial peptides was investigated on colistin-susceptible and colistin-resistant identical pulsotype strains of KPC-2 producing Klebsiella pneumoniae ST258 as well as colistin-susceptible and colistin-resistant Enterobacter asburiae strains isolated from clinical samples. In our test, bacteria were exposed to 50 mg/ml lactoferrin, lysozyme and protamine - cationic antimicrobial peptides belonging to innate immune system and having structural similarity to polymyxins - in separate reactions. After 18 hours incubation of colonies were counted. 40% of colistin-resistant K. pneumoniae strains and 97% of colistin-susceptible counterpart strains were lysed by protamine whereas 87% and 100% colony forming unit decrease by lysozyme was seen, respectively. In the case of colistin-resistant E. asburiae strains 1 log10 cell count increase were observed after treatment with lysozyme and 1.56 log10 after lactoferrin exposure compared to the initial number whereas the colistin-susceptible showed no relevant cell count increase. Our findings suggest that acquired colistin-resistance in Enterobacteriaceae is associated with tolerance against antimicrobial peptides.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

This study examines the interaction of polymyxin B and colistin with the surface and outer membrane components of a susceptible and resistant strain of Klebsiella pneumoniae. The interaction between polymyxins and bacterial membrane and isolated LPS from paired wild type and polymyxin-resistant strains of K. pneumoniae were examined with N-phenyl-1-naphthylamine (NPN) uptake, fluorometric binding and thermal shift assays, lysozyme and deoxycholate sensitivity assays, and by (1)H NMR. LPS from the polymyxin-resistant strain displayed a reduced binding affinity for polymyxins B and colistin in comparison with the wild type LPS. The outer membrane NPN permeability of the resistant strain was greater compared with the susceptible strain. Polymyxin exposure enhanced the permeability of the outer membrane of the wild type strain to lysozyme and deoxycholate, whereas polymyxin concentrations up to 32 mg/ml failed to permeabilize the outer membrane of the resistant strain. Zeta potential measurements revealed that mid-logarithmic phase wild type cells exhibited a greater negative charge than the mid-logarithmic phase-resistant cells. Taken together, our findings suggest that the resistant derivative of K. pneumoniae can block the electrostatically driven first stage of polymyxin action, which thereby renders the hydrophobically driven second tier of polymyxin action on the outer membrane inconsequential.

Topics: 1-Naphthylamine; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Cell Membrane; Cell Membrane Permeability; Colistin; Deoxycholic Acid; Drug Interactions; Drug Resistance; Hydrophobic and Hydrophilic Interactions; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Membrane Potentials; Microbial Sensitivity Tests; Muramidase; Polymyxin B; Protein Binding; Species Specificity; Static Electricity

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

To characterize at the genomic level the evolution of multiresistance during an outbreak of Klebsiella pneumoniae in a burns intensive care unit. The outbreak involved a DHA-1 β-lactamase-producing strain that later acquired carbapenem and fosfomycin resistance, and in one case colistin resistance.. The genomes of two isolates were sequenced and compared with a previously sequenced genome. The role of hypermutability was investigated by measuring the mutation frequencies of the isolates and comparison with a collection of control strains.. Sequence comparison identified four single-nucleotide variants and two transposon insertions. Analysis of the variants in the whole collection related carbapenem and fosfomycin resistance to a nonsense mutation in the ompK36 porin gene and colistin resistance to an IS1 insertion in the mgrB gene. The plasmid carrying the blaDHA-1 gene was unstable in the absence of antibiotics, and analysis of isolates that had lost the plasmid showed that the porin mutation alone was not sufficient to generate carbapenem resistance. The mutation frequencies were similar among all the strains analysed.. Carbapenem resistance required production of the DHA-1 β-lactamase and decreased permeability, but fosfomycin resistance depended only on permeability. Resistance to colistin might be related to an alteration in the regulation of the phoPQ system. Hypermutation is not related to the selection of porin mutants. Plasmid instability might be due to the high number of mobile elements and suggests a major role for antibiotic selection pressure in the emergence and evolution of this outbreak.

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple; Evolution, Molecular; Female; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Sequence Data; Mutation Rate; Sequence Analysis, DNA

Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline; Treatment Outcome

To report a case of Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae ventriculitis successfully treated with dual intraventricular plus systemic antibiotic therapy.. A 43-year-old woman with a ventriculoperitoneal shunt was transferred from a nursing home with fever, altered mental status, and leukocytosis. She was found to have KPC-producing K pneumoniae ventriculitis. Combination intraventricular antibiotic therapy with colistin and gentamicin plus systemic colistin and amikacin led to the resolution of infection.. Utilization of intraventricular or intrathecal antibiotics has been described in the literature for multidrug resistant (MDR) Gram-negative central nervous system (CNS) infections; however, none of the cases were caused by a KPC-producing organism. Given the pathogenicity and limited treatment options for this resistant organism, we utilized intraventricular colistin 10 mg and intraventricular gentamicin 10 mg in combination with systemic colistin and amikacin. An extensive literature search revealed several case reports and case series of documented MDR Acinetobacter baumanii CNS infections successfully treated with intraventricular colistin or aminoglycoside therapy with good tolerability. Additionally, recent pharmacokinetic analyses suggest improved cerebrospinal fluid (CSF) concentrations with direct CNS antimicrobial administration in combination with systemic therapy. Although our patient's cerebral spinal fluid cultures were cleared with dual intraventricular plus systemic therapy, she continued to deteriorate clinically because of her comorbid conditions and required hospice admission.. This describes the first reported case of KPC-producing K pneumoniae ventriculitis microbiologically cured based on negative blood and CSF cultures with a combination of intraventricular and systemic therapy.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cerebral Ventriculitis; Colistin; Female; Gentamicins; Humans; Infusions, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae

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

We report the epidemiological and clinical features of the first outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) type 2 in Switzerland. The outbreak took place in the medical intensive care unit (MICU) of our tertiary care hospital and affected three severely ill patients. After the implementation of strict infection control measures, no further patients colonised with KPC-KP could be detected by the screening of exposed patients. Successful treatment of patients infected with KPC-KP consisted of a combination therapy of meropenem, colistin and tigecycline.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Infection Control; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Molecular Typing; Switzerland; Tertiary Care Centers; Thienamycins; Tigecycline; Treatment Outcome

Five carbapenem-resistant strains (three Klebsiella pneumoniae, one Escherichia coli, and one Enterobacter aerogenes) were isolated between 2009 and 2012 at the Verona University Hospital, Italy, during an epidemiological analysis of antibiotic resistance determinants and plasmid profiles in Enterobacteriaceae. Two out of the five strains, K. pneumoniae E530 and E. coli E558, were cultured from bile and abdominal drainage, respectively, of a single patient. The strains were resistant to beta-lactams and fluoroquinolones, and susceptible to tigecycline and colistin. All the strains harboured bla(KPC-3), bla(TEM-1), and bla(OXA-9), and the three K. pneumoniae additionally carried blaSHV-11 and aac(6')Ib. The bla(KPC-3) was inserted in transposon Tn4401a. All the strains hosted an FIIk-type plasmid, and the three K. pneumoniae coharboured an colE-type plasmid. Transconjugants, besides bla(KPC-3), harboured bla(TEM-1) and bla(OXA-9) genes on FIIk-type plasmid. K. pneumoniae E301 was ST258, while strain E530 and C525 belonged to the ST512, and E. coli E558 was ST43. To our best knowledge, this is the first report that strongly supports the transmission of bla(KPC-3) from ST512 K. pneumoniae to E. coli ST43 in a single patient, a phenomenon of both clinical and microbiological importance.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Bile; Colistin; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Enterobacter aerogenes; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Plasmids; Tigecycline

Combination therapy is recommended for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal regimen for colistin-resistant strains is unknown. We compared the synergistic activity and post-antibiotic effect (PAE) of colistin in combination with other antimicrobials against colistin-susceptible and -resistant KPC-Kp bloodstream isolates.. The genotypes of nine colistin-susceptible and eight colistin-resistant KPC-Kp bloodstream isolates were analysed using PCR and amplicon sequencing. Combinations of colistin, meropenem, tigecycline, rifampicin and teicoplanin were then screened using the Etest, a chequerboard assay and time-kill studies. Synergistic combinations were also analysed with respect to the PAE in time-kill curves and the PAE at clinically achievable concentrations.. Insertional inactivation of the PhoQ/PhoB two-component regulatory system by mgrB-IS5 was identified in 6/8 (75%) colistin-resistant KPC-Kp. Colistin/rifampicin combinations resulted in no interactions [fractional inhibitory concentration (FIC) indices 1.5-2] for colistin-susceptible strains, but were uniformly synergistic (FIC indices 0.1-0.4) against colistin-resistant KPC-Kp. Time-kill kinetic analysis, at clinically achievable fixed concentrations of rifampicin and colistin, confirmed synergy and produced persistent growth inhibition (3 h) of colistin-resistant KPC-Kp strains exposed to colistin/rifampicin or colistin/rifampicin/tigecycline combinations.. Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Drug Synergism; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; Tigecycline

Colistin is a key drug for the treatment of infections caused by extensively drug-resistant strains of Enterobacteriaceae producing carbapenemases. However, the emergence of colistin resistance is being increasingly reported, especially among Klebsiella pneumoniae strains producing KPC-type carbapenemases (KPC-KP). In this work, we investigated colistin-susceptible (KPB-1) and colistin-resistant (KPB-2) sequential isolates obtained from a patient with a KPC-KP infection before and after low-dosage colistin treatment, respectively. By using a next-generation sequencing approach and comparative genomic analysis of the two isolates, we detected in KPB-2 a nonsynonymous nucleotide substitution in the gene encoding the PmrB sensor kinase, resulting in a leucine-to-arginine substitution at amino acid position 82. Compared with KPB-1, KPB-2 exhibited upregulated transcription of pmrA and of pmrK, which is part of the pmrHFIJKLM operon responsible for modification of the colistin lipopolysaccharide target. Complementation with wild-type pmrB in KPB-2 restored colistin susceptibility and reduced the transcription of pmrA and pmrK to basal levels, while expression of PmrB(L82R) in KPB-1 did not alter colistin susceptibility or upregulate pmrA and pmrK expression, confirming the dominance of wild-type PmrB versus the PmrB(L82R) mutant. The present results indicated that PmrB mutations mediating colistin resistance may be selected during low-dosage colistin treatment. The colistin-resistant phenotype of KPB-2 was stable for up to 50 generations in the absence of selective pressure and was not associated with a significant fitness cost in a competition experiment.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Clone Cells; Colistin; Drug Dosage Calculations; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Microbial Sensitivity Tests; Mutation; Operon; Transcription Factors

A series of colistin-resistant Klebsiella pneumoniae isolates recovered from different countries was investigated in order to evaluate the involvement of the PmrA/PmrB two-component system in this resistance. Six isolates possessed a mutated PmrB protein, which is encoded by the pmrB gene, part of the pmrCAB operon involved in lipopolysaccharide modification. The same amino acid substitution (Thr157Pro) in PmrB was identified in the six isolates. The six isolates belonged to four distinct clonal groups, recovered in South Africa (sequence type 14 [ST14]), Turkey (ST101), and Colombia (ST258 and ST15). Three out of the four clones produced a carbapenemase, OXA-181, OXA-48, or KPC-3, while a single isolate did not produce any carbapenemase. Expression assays revealed an overexpression of the pmrA (70-fold), pmrB (70-fold), pmrC (170-fold), and pmrK (40-fold) genes in the pmrB-mutated isolate compared to expression of the pmrB wild-type isogenic K. pneumoniae isolate, confirming that the PmrB substitution was responsible for increased expression levels of those genes. Complementation assays leading to the expression of a wild-type PmrB protein restored the susceptibility to colistin in all isolates, confirming that the substitution in PmrB was responsible for the resistance phenotype. This study identified a key amino acid located in the PmrB protein as being responsible for the overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to colistin.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Colombia; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multigene Family; Mutation; Operon; South Africa; Transcription Factors; Turkey

To identify the risk factors for incident enteric colonization by KPC-producing Klebsiella pneumoniae (KPC-Kp) resistant to colistin or tigecycline during Intensive Care Unit (ICU) stay.. A prospective observational study of patients admitted to the ICU was conducted during a 27-month period. Rectal samples taken upon admission and weekly afterwards were inoculated on selective chromogenic agar. K. pneumoniae isolates were characterized by standard methodology. Mean inhibitory concentration (MIC) to colistin and tigecycline were determined by E-test. The presence of bla KPC gene was confirmed by PCR.. Among 254 patients, 62 (24.4%) became colonized by colistin- resistant KPC-Kp during their stay. Multivariate analysis revealed that corticosteroid, colistin administration and number of colonized patients in nearby beds per day were significantly associated with colonization. Among 257 patients, 39 (17.9%) became colonized by tigecycline resistant KPC-Kp during their stay. Risk factors identified by multivariate analysis were: days at risk, obesity, number of colonized patients treated in nearby beds per day and administration of tigecycline.. The high prevalence of colistin or tigecycline resistant KPC-Kp enteric carriage in ICU patients indicate that dissemination is due to their transfer from patient to patient via the personnel and indicates the importance of strict infection control protocols.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Greece; Hospitalization; Hospitals, University; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prospective Studies; Risk Factors; Tertiary Care Centers; Tigecycline

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Oncology Service, Hospital

The emergence of colistin-resistant Klebsiella pneumoniae (CRKP) is a major public health concern worldwide. In this study, the prevalence and molecular basis of colistin resistance in CRKP isolated from healthy individuals and patients in Lao PDR, Thailand, Nigeria and France were investigated. Stool samples were screened by culture for the presence of colistin-resistant Klebsiella spp. Whole-genome sequence analysis was used to decipher the molecular mechanism of colistin resistance in a blaNDM-1-positive in vitro-selected CRKP mutant. PCR amplification and sequencing of the mgrB genetic environment was performed for all CRKP isolates as well as control colistin-susceptible K. pneumoniae (CSKP) isolates recovered from the same stools. A total of 869 stool samples were screened for colistin-resistant Klebsiella spp., yielding 32 CRKP and 2 colistin-resistant Klebsiella oxytoca. Comparative whole-genome sequence analysis revealed that an in vitro-selected CRKP mutant had an insertion sequence in its mgrB gene, as well as missense mutations in other selected clones. Of the 34 colistin-resistant Klebsiella spp. isolates, 14 (41.2%; 13 CRKP and 1 K. oxytoca) from the four countries also had various defects in their mgrB genes, but no such defects were found in the CSKP controls (P<10(-4)). Few mutations were observed in pmrAB compared with mgrB among the CRKP isolates. The worldwide emergence of CRKP is a major public health concern. Detection and surveillance of such strains are warranted to prevent an uncontrollable pandemic. Inactivation of the PhoP/PhoQ regulator gene mgrB is associated with ≥40% of colistin resistance among the CRKP isolates observed in this study.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Feces; France; Genome, Bacterial; Humans; Israel; Klebsiella Infections; Klebsiella pneumoniae; Laos; Male; Molecular Sequence Data; Nigeria; Sequence Alignment; Sequence Analysis, DNA; Thailand

Consecutive non-replicate clinical isolates (n=191) of carbapenem non-susceptible Enterobacteriaceae were collected from 21 hospital laboratories across Italy from November 2013 to April 2014 as part of the European Survey on Carbapenemase-producing Enterobacteriaceae (EuSCAPE) project. Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) represented 178 (93%) isolates with 76 (43%) respectively resistant to colistin, a key drug for treating carbapenamase-producing Enterobacteriaceae. KPC-KP colistin-resistant isolates were detected in all participating laboratories. This underscores a concerning evolution of colistin resistance in a setting of high KPC-KP endemicity.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Endemic Diseases; Health Surveys; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Laboratories, Hospital; Microbial Sensitivity Tests; Polymerase Chain Reaction; Sentinel Surveillance

Solid organ transplantation (SOT) is a risk factor for the acquisition of carbapenem-resistant Klebsiella pneumoniae. This infection is associated with a high mortality rate given the limited armamentarium of antibiotics for multidrug-resistant organisms along with continued immunosuppression to prevent graft rejection. We report a case of carbapenem-resistant K. pneumoniae pneumonia, bacteraemia and intra-abdominal infection in a newly transplanted liver recipient. The patient was successfully treated with a long course of high-dose tigecycline and colistin, along with surgical drainage. We discuss SOT-relevant epidemiology, therapeutic options and the rationale for our treatment choice.

Topics: Anti-Bacterial Agents; Colistin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Male; Middle Aged; Minocycline; Opportunistic Infections; 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

Colistin, tigecycline, levofloxacin, tobramycin, and rifampin alone and in combination with doripenem were investigated for their in vitro activities and postantibiotic effects (PAEs) on Klebsiella pneumoniae. The in vitro activities of tested antibiotics in combination with doripenem were determined using a microbroth checkerboard technique. To determine the PAEs, K. pneumoniae 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. Colistin, tobramycin, and levofloxacin produced strong PAEs ranging from 2.71 to 4.23 h, from 1.31 to 3.82 h, and from 1.35 to 4.72, respectively, in a concentration-dependent manner. Tigecycline and rifampin displayed modest PAEs ranging from 1.18 h to 1.55 h and 0.92 to 1.19, respectively. Because it is a beta-lactam, PAEs were not exactly induced by doripenem (ranging from 0.10 to 0.18 h). In combination, doripenem scarcely changed the duration of PAE of each tested antibiotic alone. The findings of this study may have important implications for the timing of doses during K. pneumoniae therapy with tested antibiotics.

Topics: Carbapenems; Colistin; Doripenem; Dose-Response Relationship, Drug; Drug Combinations; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Minocycline; Rifampin; Tigecycline; Tobramycin

We characterized carbapenem resistance mechanisms among 12 Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (referred to here as KPC K. pneumoniae) clinical isolates and evaluated their effects on the activity of 2- and 3-drug combinations of colistin, doripenem, and ertapenem. All isolates were resistant to ertapenem and doripenem; 75% (9/12) were resistant to colistin. Isolates belonged to the ST258 clonal group and harbored blaKPC-2, blaSHV-12, and blaTEM-1. As determined by time-kill assays, doripenem (8 μg/ml) and ertapenem (2 μg/ml) were inactive against 92% (11/12) and 100% (12/12) of isolates, respectively. Colistin (2.5 μg/ml) exerted some activity (range, 0.39 to 2.5 log10) against 78% (7/9) of colistin-resistant isolates. Colistin-ertapenem, colistin-doripenem, and colistin-doripenem-ertapenem exhibited synergy against 42% (5/12), 50% (6/12), and 67% (8/12) of isolates, respectively. Expression of ompK35 and ompK36 porins correlated with each other (R(2) = 0.80). Levels of porin expression did not correlate with colistin-doripenem or colistin-ertapenem synergy. However, synergy with colistin-doripenem-ertapenem was more likely against isolates with high porin expression than those with low expression (100% [8/8] versus 0% [0/4]; P = 0.002). Moreover, bactericidal activity (area under the bacterial killing curve) against isolates with high porin expression was greater for colistin-doripenem-ertapenem than colistin-doripenem or colistin-ertapenem (P ≤ 0.049). In conclusion, colistin-carbapenem combinations may provide optimal activity against KPC K. pneumoniae, including colistin-resistant isolates. Screening for porin expression may identify isolates that are most likely to respond to a triple combination of colistin-doripenem-ertapenem. In the future, molecular characterization of KPC K. pneumoniae isolates may be a practical tool for identifying effective combination regimens.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biomarkers, Pharmacological; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Porins

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Carbapenems; Colistin; Doripenem; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Ventilator-Associated; Treatment Outcome

Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Cross Infection; Decontamination; Disease Outbreaks; Drug Resistance, Bacterial; Gastrointestinal Tract; Humans; Infection Control; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Tobramycin

Carbapenem resistance due to OXA-48 enzymes in Klebsiella pneumoniae is increasing particularly in the Middle Eastern and European regions. Treatment options are limited. The aim of this study was to evaluate the in vitro synergistic activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA-48 producing K. pneumoniae strains. Twelve carbapenem-resistant OXA-48 producing K. pneumoniae isolates were enrolled in this study. Synergistic activity of fosfomycin combined with imipenem, meropenem, colistin, and tigecycline was assessed by chequerboard method. The combination of fosfomycin was synergistic with imipenem, meropenem and tigecycline with the ratios of 42%, 33%, and 33%, respectively. Whilst the combination of fosfomycin with colistin was fully antagonistic against all of the strains, there was no statistically significant difference between the in vitro synergistic activities of fosfomycin in combination with imipenem, meropenem and tigecycline combinations (P > 0.05). Fosfomycin in combination with other agents can be preferred against multidrug resistant K. pneumoniae strains.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Colistin; Disk Diffusion Antimicrobial Tests; Drug Synergism; Fosfomycin; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Minocycline; Molecular Typing; Real-Time Polymerase Chain Reaction; Thienamycins; Tigecycline

In this study antibiotic combinations for multidrug-resistant Klebsiella pneumoniae strains were investigated. The study included a colistin-susceptible and a colistin-resistant KPC-2 producing K. pneumoniae ST258 strains isolated in 2008 and 2009 during an outbreak in Hungary. Antibiotic combinations were analyzed by checkerboard technique and fractional inhibitory concentration indices were calculated. The following antibiotics were tested: ceftazidime, cefotaxime, ceftriaxone, ampicillin, imipenem, ertapenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, polymyxin B and colistin. Combinations including 0.25 μg/ml colistin plus 1 μg/ml rifampicin, 0.25 μg/ml polymyxin B plus 1 μg/ml rifampicin, 1 μg/ml imipenem plus 2 μg/ml tobramycin, were found synergistic.These in vitro synergistic combinations suggest potential therapeutical options against infections caused by KPC-2 producing, multidrug-resistant K. pneumoniae ST258.

Topics: Anti-Bacterial Agents; Ceftazidime; Colistin; Drug Resistance, Bacterial; Drug Synergism; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Tobramycin

Doripenem-colistin exerts synergy against some, but not all, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains in vitro. We determined if doripenem MICs and/or ompK36 porin gene mutations impacted the responses of 23 sequence type 258 (ST258), KPC-2-producing strains to the combination of doripenem (8 μg/ml) and colistin (2 μg/ml) during time-kill assays. The median doripenem and colistin MICs were 32 and 4 μg/ml. Doripenem MICs did not correlate with KPC-2 expression levels. Five and 18 strains had wild-type and mutant ompK36, respectively. The most common mutations were IS5 promoter insertions (n = 7) and insertions encoding glycine and aspartic acid at amino acid (aa) positions 134 and 135 (ins aa134-135 GD; n = 8), which were associated with higher doripenem MICs than other mutations or wild-type ompK36 (all P values ≤ 0.04). Bactericidal activity (24 h) was achieved by doripenem-colistin against 12%, 43%, and 75% of ins aa134-135 GD, IS5, and wild-type/other mutants, respectively (P = 0.04). Doripenem-colistin was more active in time-kill studies than colistin at 12 and 24 h if the doripenem MIC was ≤8 μg/ml (P = 0.0007 and 0.09, respectively), but not if the MIC was >8 μg/ml (P = 0.10 and 0.16). Likewise, doripenem-colistin was more active at 12 and 24 h against the wild type/other mutants than ins aa134-135 GD or IS5 mutants (P = 0.007 and 0.0007). By multivariate analysis, the absence of ins aa134-135 GD or IS5 mutations was the only independent predictor of doripenem-colistin responses at 24 h (P = 0.002). In conclusion, ompK36 genotypes identified ST258 KPC-K. pneumoniae strains that were most likely to respond to doripenem-colistin.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Multivariate Analysis; Mutation; Porins; Promoter Regions, Genetic

Colistin is one of the few agents that retain activity against extensively drug-resistant strains of Klebsiella pneumoniae producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the mgrB gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of mgrB inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type mgrB, which restored colistin susceptibility in KKBO-4, and by construction of an mgrB deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional mgrB inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1 in vitro, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the mgrB gene, upregulated transcription of phoP, phoQ, and pmrK (which is part of the pmrHFIJKLM operon) was detected. These findings confirmed the MgrB regulatory role in K. pneumoniae and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the pmrHFIJKLM operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genes, Regulator; Humans; Klebsiella Infections; Klebsiella pneumoniae; Membrane Proteins; Mutagenesis, Insertional; Operon; Signal Transduction; Transcription, Genetic

After a single patient was transferred to Leipzig University Hospital from a hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in Germany. Ninety patients hospitalised between July 2010 and October 2012 were affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14 consecutive patients (16%) were treated with a short course (7 days) of selective digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP carrier status was followed in all 14 SDD patients by submitting stool samples to KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days). Successful elimination of KPC-2-KP was defined as a minimum of three consecutive negative PCR test results separated by ≥48 h each. Decolonisation of KPC-2-KP was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days), but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD treatment resulted in the development of secondary resistance to colistin (19% increase in resistance rate) and gentamicin (45% increase) in post-treatment isolates. In the control group, no secondary resistance occurred. We conclude that the SDD protocol applied in this study was not sufficiently effective for decolonisation and was associated with resistance development.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Feces; Female; Gentamicins; Germany; Greece; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Time Factors

The impact of under-acylation of lipid A on the interaction between Klebsiella pneumoniae LPS and polymyxins B and E was examined with fluorometric and calorimetric methods, and by (1)H NMR, using a paired wild type (WT) and the ΔlpxM mutant strains B5055 and B5055ΔlpxM, which predominantly express LPS with hexa- and penta-acylated lipid A structures respectively. LPS from B5055ΔlpxM displayed a fourfold increased binding affinity for polymyxins B and E compared with the B5055 WT LPS. EC50 values were consistent with polymyxin minimum inhibitory concentration (MIC) values for each strain. Accordingly, polymyxin exposure considerably enhanced the permeability of the B5055ΔlpxM OM. Analysis of the melting profiles of isolated LPS aggregates suggested that bactericidal polymyxin activity may relate to the acyl chains' phase of the outer membrane (OM). The enhanced polymyxin susceptibility of B5055ΔlpxM may be attributable to the favorable insertion of polymyxins into the more fluid OM compared with B5055. Molecular models of the polymyxin B-lipid A complex illuminate the key role of the lipid A acyl chains for complexation of polymyxin. The data provide important insight into the molecular basis for the increased polymyxin susceptibility of K. pneumoniae strains with under-acylated lipid A. Under-acylation appears to facilitate the integration of the N-terminal fatty-acyl chain of polymyxin into the OM resulting in an increased susceptibility to its antimicrobial activity/activities.

Topics: Acylation; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Cell Membrane Permeability; Colistin; Computer Simulation; Fatty Acids; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipid A; Mutation; Polymyxin B; Structure-Activity Relationship

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of healthcare-associated infection in Italy, with high morbidity and mortality. Prevalent CR-KP clones and resistance mechanisms vary between regions and over time. Therapeutic approaches and their impact on mortality have to be investigated. We performed a prospective study of patients with CR-KP isolation, hospitalized in nine hospitals of Rome, Italy, from December 2010 to May 2011, to describe the molecular epidemiology, antibiotic treatment and risk factors for mortality. Overall, 97 patients (60% male, median age 69 years) were enrolled. Strains producing blaKPC-3 were identified in 89 patients, blaVIM in three patients and blaCTX-M-15 plus porin defects in the remaining five patients. Inter-hospital spread of two major clones, ST512 and ST258, was found. Overall, 36.1% and 20.4% of strains were also resistant to colistin and tigecycline, respectively. Infection was diagnosed in 91 patients who received appropriate antibiotic treatment, combination therapy and removal of the infectious source in 73.6%, 59.3% and 28.5% of cases, respectively. Overall, 23 different antibiotic regimens were prescribed. In-hospital mortality was 25.8%. Multivariate analysis adjusted for appropriate treatment, combination therapy and infectious-source removal, showed that Charlson comorbidity score, intensive-care unit onset of infection, bacteraemia and infection due to a colistin-resistant CR-KP strain were independent risk factors for mortality. The spread of clones producing K. pneumoniae carbapenemases, mainly ST258, is currently the major cause of CR-KP infection in central Italy. We observed a high rate of resistance to colistin that is independently associated with worse outcome.

Topics: Aged; Analysis of Variance; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospital Mortality; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Typing; Prospective Studies; Risk Factors

A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens were considered appropriate in 12% of episodes according to the Vitek 2 System and in 100% based on E-test.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Therapy, Combination; Female; Gentamicins; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

The objective of this study was to evaluate the mortality of and risk factors for bacteriuria due to carbapenem-resistant Klebsiella pneumoniae (CRKp) versus carbapenem-susceptible K. pneumoniae (CSKp) producing extended spectrum β lactamase (ESBL).. This was a retrospective case-control study in which 135 case-patients with bacteriuria due to CRKp were compared with 127 control patients with CSKp producing ESBL. In a first step, multivariate Cox regression and Kaplan-Meier survival analysis models were used to determine the difference in mortality between the two groups and risk factors for mortality. In a second step, a univariate analysis was used to identify risk factors for CRKp colonization.. There were no significant demographic or clinical differences between the groups. In-hospital mortality in the study and control groups was 29 and 25 %, respectively (non-significant difference). Multivariate analysis revealed that the most important risk factor for mortality in both groups was being bed ridden [hazard ratio 2.2, 95 % confidence interval (CI) 1.23-3.93; P = 0.008]. Patients with CRKp bacteriuria had a longer hospitalization time with a mean ± standard deviation of 28 ± 33 days compared to 22 ± 28 days in the control group (P < 0.05). Several univariate risk factors for acquiring CRKp bacteriuria were identified: antibiotic use [odds ratio (OR) 1.93, 95 % CI 1.18-3.17, p = 0.008], especially colistin (OR 2.04, 95 % CI 1.04-4.02; P = 0.036), presence of a urinary catheter (OR 2.09, 95 % CI 1.2-3.63; P = 0.008), surgery (OR 3.94, 95 % CI 1.85-8.37; P = 0.0002), invasive procedures (OR 3.06, 95 % CI 1.61-5.8; P = 0.0004), and intensive care unit admission (OR 2.49, 95 % CI 1.18-5.37; P = 0.015).. Bacteriuria caused by CRKp as compared that caused by CSKp was not found to be a risk factor for death.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteriuria; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Colistin; Confidence Intervals; Female; Hospital Mortality; Humans; Intensive Care Units; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Retrospective Studies; Risk Factors; Treatment Outcome; Urinary Catheters; Young Adult

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Mauritius; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Phylogeography; Tigecycline

To describe the treatment and outcomes of patients with carbapenemase-producing Enterobacteriaceae and evaluate whether these cases represented active infection requiring antibiotic therapy or colonization.. Adult inpatients with carbapenemase-producing Enterobacteriaceae were retrospectively evaluated. Cases were classified as colonization versus infection by 2 infectious diseases physicians. Multiple cultures that grew in the same patient within a 2-week period were evaluated as a single case.. A total of 42 cases among 35 patients were identified. The mean age of the cohort was 67.7 ± 13.7 y, mean APACHE II score was 17.9 ± 8.6, and 77% of patients were in the intensive care unit when the carbapenem-producing Enterobacteriaceae was isolated. Klebsiella pneumoniae (84%) was the predominant organism; urine (36%), tissue/wound/drainage (25%), and blood (20%) were the most common sites of collection. Though 43% of cases were classified as colonization, 56% of these cases were treated with antibiotics. Only 1 patient characterized as colonized subsequently developed infection, 29 days later. Among infected cases, colistin (55%), meropenem (41%), aminoglycosides (32%), and tigecycline (27%) were used for treatment, and combination antimicrobial therapy was common (55%). Clinical and microbiological success was higher in patients receiving combination therapy (83% vs 60%, p = 0.35). Colistin monotherapy was only successful in urinary infections. All-cause hospital mortality was 29%.. Nearly half of cases represented colonization, yet the majority were treated with broad-spectrum antibiotics. Determining infection versus colonization is a critical first step in managing patients with carbapenemase-producing Enterobacteriaceae. The risk of not treating apparent colonization appears low.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins; Treatment Outcome

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactamases; Colistin; Fatal Outcome; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Teicoplanin; Thienamycins; Treatment Failure; 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

We describe polyclonal spread of colistin-resistant Klebsiella pneumoniae in an acute general hospital in Italy. Between June and December 2011, 58 colistin-resistant K. pneumoniae isolates were recovered from 28 patients admitted to different wards, but mainly in the intensive care units. All isolates were tested for drug susceptibility and the presence of beta-lactamase (bla) genes. Clonality was investigated by repetitive extragenic palindromic (rep)-PCR and multilocus sequence typing (MLST). Fifty-two isolates had minimum inhibitory concentrations (MICs) for colistin of 6-128 mg/L, carried bla(KPC3) and were attributed to sequence type ST258. The remaining six isolates were susceptible to carbapenems, exhibited MICs for colistin of 3-32 mg/L, and belonged to two different types, ST15 and ST273. Rep-PCR included all isolates in three clusters, one containing all ST258 KPC-3-producing isolates and two containing ST15 and ST273 isolates.Cross-transmission containment measures and intensification of staff and environmental hygiene could not stop the outbreak. Selective pressure and horizontal transmission probably contributed to emergence and spread of three different strains of colistin-resistant K. pneumoniae in the hospital. Strict implementation of the above measures and a wider awareness of the antimicrobial resistance threat are crucial to preserve the last therapeutic options of the multidrug-resistant Gram-negative infections.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Hospitals, General; Humans; Intensive Care Units; Italy; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Patients' Rooms; Polymerase Chain Reaction

The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U.S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.

Topics: Adult; Aged; Carbapenems; Colistin; Contact Tracing; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Female; Genome, Bacterial; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Sequence Data; Mutation; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; United States; Young Adult

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older (P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem (P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Genotype; Hospitals, University; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Michigan; Microbial Sensitivity Tests; Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; Colistin; Humans; Klebsiella; Klebsiella Infections; Microbial Sensitivity Tests; Polymyxin B

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is an emerging multidrug-resistant nosocomial pathogen. This is a retrospective chart review describing the outcomes and treatment of 60 cases of CR-Kp bloodstream infections. All CR-Kp isolated from blood cultures were identified retrospectively from the microbiology laboratory from January 2007 to May 2009. Clinical information was collected from the electronic medical record. Patients with 14-day hospital mortality were compared to those who survived 14 days. The all-cause in-hospital and 14-day mortality for all 60 CR-Kp bloodstream infections were 58.3% and 41.7%, respectively. In this collection, 98% of tested isolates were susceptible in vitro to tigecycline compared to 86% to colistimethate, 45% to amikacin, and 22% to gentamicin. Nine patients died before cultures were finalized and received no therapy active against CR-Kp. In the remaining 51 patients, those who survived to day 14 (n = 35) were compared to nonsurvivors at day 14 (n=16). These patients were characterized by both chronic disease and acute illness. The 90-day readmission rate for hospital survivors was 72%. Time to active therapy was not significantly different between survivors and nonsurvivors, and hospital mortality was also similar regardless of therapy chosen. Pitt bacteremia score was the only significant factor associated with mortality in Cox regression analysis. In summary, CR-Kp bloodstream infections occur in patients who are chronically and acutely ill. They are associated with high 14-day mortality and poor outcomes regardless of tigecycline or other treatment regimens selected.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prognosis; Retrospective Studies; Tigecycline; Treatment Outcome

We report the first outbreak caused by colistin-resistant Klebsiella pneumoniae producing KPC-3 carbapenamase in two Italian hospitals. This spread occurred in 1 month, and was caused by eight colistin-resistant and carbapenem-resistant Klebsiella pneumoniae isolates from eight patients. A further three isolates were obtained from the intestinal tract and pharyngeal colonization. All isolates were multidrug-resistant (MDR), including being resistant to colistin, but they were susceptible to gentamicin and tigecycline. PCR detection showed that all isolates harboured the bla(KPC-3) gene associated with bla(SHV-11) , bla(TEM-1) and bla(OXA-9) . All K. pneumoniae isolates, genotyped by pulsed-field gel electrophoresis and multilocus sequence typing, belonged to the same sequence type (ST)258 clone. From our data and a review of the international literature, K. pneumoniae ST258 seems to be the most widespread genetic background for KPC dissemination in Europe.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Colistin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sicily

Five cases of infection due to colistin-resistant, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae belonging to the international epidemic clone ST258 occurred over a 4-month period. These cases likely represented both emergence of resistance and transmission of resistant organism. The colistin-resistant isolates were able to persist in the absence of selective pressure in vitro.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Epidemics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Bacteremia; beta-Lactamases; Calciphylaxis; Coinfection; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Minocycline; Tigecycline

Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of Klebsiella pneumoniae carbapenemase-producing bacteria is an emerging cause of abdominal infections.. We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by Klebsiella pneumoniae Sequence Type 258 producing K. pneumoniae carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV-negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR) pathogen.. Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Neoplasms; Middle Aged; Minocycline; Pancreatic Neoplasms; Pancreatitis, Chronic; Tigecycline

There has been an increase in recent years of antimicrobial resistance of Gram negative bacilli (GNB). Carbapenems, the mainstay for the treatment of multidrug resistant GNB infections, are no longer always effective leaving treatment options limited. We present the case of patient with recurrent, complicated urinary tract infections. The current episode was caused by carbapenem-resistant K. pneumoniae and P. aeruginosa and carbapenem-susceptible, but MDR E. cloacae. Resistance to carbapenems of K. pneumoniae was conferred by the production of the class B metallo-beta-lactamase, VIM1. Infection control measures were implemented and following a 2-week course of treatment with colistin, the infection resolved and the patient was discharged. We discuss the changes in the epidemiology, the mechanisms involved and the means of detecting carbapenem resistance in GNB. We would also like to stress the role of infection control measures in limiting patient-to-patient spread of MDR organisms which, are of paramount importance in cases when few treatment options are left available.

Topics: Aged; Anastomosis, Surgical; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Male; Nephrolithiasis; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Tract Infections

In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Population Surveillance; Republic of Korea

In vitro activity of fosfomycin was evaluated against 68 bla(KPC)-possessing Klebsiella pneumoniae (KpKPC) isolates, including 23 tigecycline- and/or colistin-nonsusceptible strains. By agar dilution, 93% of the overall KpKPC were susceptible (MIC(50/90) of 16/64 microg/ml, respectively). The subgroup of 23 tigecycline- and/or colistin-nonsusceptible strains showed susceptibility rates of 87% (MIC(50/90) of 32/128 microg/ml, respectively). Notably, 5 out of 6 extremely drug-resistant (tigecycline and colistin nonsusceptible) KpKPC were susceptible to fosfomycin. Compared to agar dilution, disk diffusion was more accurate than Etest.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Fosfomycin; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Phenotype; Tigecycline

A matched 1:3 case-control study investigated factors predicting colistin-resistant versus colistin-susceptible KPC-producing Klebsiella pneumoniae acquisition and its impact on patient outcomes. Case patients were more often admitted from other institutions (P = 0.019) and had longer therapy with beta-lactam/beta-lactamase inhibitors (P = 0.002) and higher overall mortality (P = 0.05). All 52 study isolates were clonally related, suggesting horizontal dissemination. None of these parameters independently predicted colistin resistance, which probably occurred in a susceptible KPC-KP strain that was subsequently disseminated horizontally.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Case-Control Studies; Cluster Analysis; Colistin; DNA Fingerprinting; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Risk Factors; Treatment Outcome

Nine Klebsiella pneumoniae isolates showing non-susceptibility to carbapenems were collected from three centres in the north-eastern region of Hungary. The minimum inhibitory concentrations (MICs) of antibiotics were determined by Etest. The putative production of a carbapenemase was tested by the modified Hodge test. The presence of bla (KPC) genes was verified by polymerase chain reaction (PCR) and sequencing. Furthermore, molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates showed extensively drug-resistant (XDR) phenotype, and of these, eight isolates were highly resistant to colistin. The isolates carried bla (KPC-2), bla (SHV-12), bla (TEM-1) and bla (SHV-11). PFGE analysis of the nine KPC-2-producing Hungarian ST258 K. pneumoniae isolates, two KPC-2-producing Norwegian ST258 isolates and 33 CTX-M-15-producing ST11 isolates revealed the existence of one genetic cluster at an 88% similarity level. The overall results of the PFGE clustering, MLST and the presence of SHV-11 in both ST11 and ST258 suggest that this is the first hyperepidemic clonal complex of multidrug-resistant K. pneumoniae, probably CC258/CC340, possibly undergoing worldwide spread.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Carbapenems; Cluster Analysis; Colistin; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Hungary; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

Klebsiella pneumoniae carbapenemase (KPC) 3-producing Escherichia coli was isolated from a carrier of KPC-3-producing K. pneumoniae. The KPC-3 plasmid was identical in isolates of both species. The patient's gut flora contained a carbapenem-susceptible E. coli strain isogenic with the KPC-3-producing isolate, which suggests horizontal interspecies plasmid transfer.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Colistin; Conjugation, Genetic; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Escherichia coli; Escherichia coli Infections; Gastrointestinal Tract; Humans; Israel; Klebsiella Infections; Klebsiella pneumoniae; Male; Metronidazole; Plasmids; Vancomycin

Within the last decade, human infections caused by enterobacteria which produce the Klebsiella pneumoniae carbapenemase (KPC) became a serious therapeutic and epidemiological problem worldwide. The KPC producing strains of K. pneumoniae broadly disseminated in the USA then spread to Europe. Recently, the KPC-2 was found in Poland. In the presented study we tested 11 ertapenem resistant isolates of K. pneumoniae. The isolates were obtained from 10 patients of a regular hospital (RH) and from one patient of a palliative care hospital (PH) in Warsaw, Poland. Expression of the KPC was confirmed in all the tested isolates by the positive result of phenotypic test with boronic acid. All the isolates were also shown to harbour the bla(KPC) gene by PCR with primers targeting the core 372 bp fragment of the gene, and all but two were resistant to imipenem and meropenem as determined by the disc-diffusion method. The DNA sequence analysis of the complete bla(KPC) gene from representative isolate DM0269 revealed variant 2 of KPC (KPC-2). Tested isolates were subjected to genotyping by the PFGE with XbaI. Dendrogram based on the PFGE profiles was composed of two main branches with 82,3% of similarity. Branch A encompassed 9 isolates (93,2%), including the one from the PH-patient, while the two remaining isolates (86,5%) were located in branch B. Five isolates of the branch A were indistinguishable by the PFGE. The high genetic similarity of the branch A isolates strongly suggests the intra-hospital dissemination of epidemic K. pneumoniae KPC+ sensu stricto strain. Most probably, the strain was also transferred to the palliative care hospital. In contrast, the branch B isolates appear to belong to the distinct sensu stricto strain, that has acquired the bla(KPC) gene via horizontal transfer. This is the first report on the intra-hospital dissemination of the KPC producing K. pneumoniae in Poland. It is noteworthy, all the tested strains were also resistant to cefotaxime, ceftazidime, aztreonam, ciprofloxacin and sulphonamides, but sensitive to colistin.

Topics: Adult; Aged; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Ciprofloxacin; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Poland; Species Specificity

Topics: Anti-Bacterial Agents; Colistin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests

The spread of antimicrobial resistance among members of the Enterobacteriaceae is a significant clinical threat. We report the treatment of pan-resistant Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a 49-year-old male and review available therapeutic options. Despite a poor prognosis, the patient recovered, but remains colonized with the pan-resistant isolate.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

We describe a hospital outbreak caused by colistin-resistant Klebsiella pneumoniae producing KPC-2 beta-lactamase in two distinct medical centres. Seven clinical isolates of K. pneumoniae exhibiting resistance to carbapenems were collected from patients with hospital-acquired infection. All isolates were phenotypically positive for carbapenemase activity but negative for metallo-beta-lactamase production. PCR analysis using specific primers for bla(KPC), bla(SHV), bla(TEM) and bla(CTX-M) demonstrated that all clinical strains of K. pneumoniae from hospital A and one isolate from hospital B were genetically related and carried bla(KPC-2) in addition to bla(SHV-12). In contrast, the remaining isolate carried bla(S)(HV-5) with bla(K)(PC-2) and yielded a different profile. These results indicate the clonal spread of KPC producers between hospitals as well as the acquisition of KPC genes by different K. pneumoniae strains. All isolates were resistant to carbapenems, beta-lactams, ciprofloxacin, aminoglycosides and colistin, but intermediately susceptible to tigecycline and susceptible to gentamicin. The infection was fatal in five cases. The emergence of colistin-resistant K. pneumoniae possessing bla(KPC)(-2) underscores the implementation of strict control measures to prevent their dissemination of these organisms in hospitals.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genotype; Greece; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymerase Chain Reaction

Due to its increased non-susceptibility rates, Klebsiella pneumoniae has emerged as one of the most problematic pathogens.. The level of resistance to 25 antimicrobials of K. pneumoniae isolates from a teaching hospital in Greece and the evolution trends during 2 decades were examined.. A statistically significant increase in non-susceptibility rates was found for almost all antimicrobials examined. During 2008, the isolates presented non-susceptibility rates to aminoglycosides >50% and to quinolones >60%. Nowadays, 1 out of 10 isolates is non-susceptible to colistin. Moreover, the isolates non-susceptible to imipenem were almost doubled between 2007 (29%) and 2008 (50%). Among the imipenem-resistant isolates, 1 out of 4 was also resistant to colistin.. The effectiveness of carbapenems has been compromised and the increase in resistance to colistin is rapid and steep.

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

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

Enterobacteriaceae are rarely the etiologic agents of endocarditis, with Klebsiella species being especially rare. From the end of 2005, isolates of carbapenem-resistant Klebsiella pneumoniae began to appear in various hospitals across Israel, sensitive only to colistin and gentamicin. We present a case of hospital-acquired endocarditis caused by carbapenem-resistant K. pneumoniae in a young adult.. An 18-year-old man with 40% full thickness burns developed acute bacterial endocarditis complicated by embolic myocardial infarction. Carbapenem-resistant K. pneumoniae carrying the blaKPC3 gene was isolated from multiple blood cultures. He recovered fully after antibiotic treatment with colistin and gentamicin.. To our knowledge, this is the first reported case of acute bacterial endocarditis caused by carbapenem-resistant K. pneumoniae. The combination of intravenous colistin and gentamicin was effective and resulted in the cure of this patient's endocarditis without the need for surgical intervention.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Treatment Outcome

Resistance to colistin is emerging in multidrug-resistant Gram-negative bacteria and no solid pharmacodynamic data are available for colistin against Klebsiella pneumoniae.. Twenty-one multidrug-resistant clinical K. pneumoniae isolates from 16 different clinical sites worldwide were employed. The genetic relatedness of these isolates was examined with PFGE. In vitro pharmacodynamic properties of colistin (sulphate) were investigated by studying the MICs, mutation prevention concentrations, time-kill kinetics, population analysis profiles and the post-antibiotic effect (PAE). Time-kill was studied with three clinical isolates plus ATCC 13883 at concentrations ranging from 0.5 to 64x MIC. The PAE was examined after 20 min of exposure of these isolates.. The 22 isolates belonged to 18 different PFGE groups. For susceptible isolates, colistin MICs ranged from 0.125 to 1 mg/L. Six isolates were colistin-resistant with MICs of >/=32 mg/L. Colistin heteroresistance was observed in 15 of 16 isolates considered colistin-susceptible based on MICs. For susceptible isolates, colistin showed extremely rapid killing; however, regrowth was observed as early as 2 h after treatment and substantial regrowth at 24 h even at concentrations up to 64x MIC for some isolates. Colistin exhibited no or very modest PAE against the isolates tested.. The data suggest that monotherapy with colistin methanesulfonate, the parenteral form of colistin, and long dosage intervals may be problematic for the treatment of infections caused by multidrug-resistant K. pneumoniae, particularly for colistin-heteroresistant strains. Further investigation on combination therapy of colistin with other antibiotics is warranted.

Topics: Anti-Bacterial Agents; Cluster Analysis; Colistin; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Microbial Viability; Mutation; Time Factors

We report the use of tigecycline, firstly with colistin and finally alone, in a patient with a persistent breakthrough bacteremia due to a Klebsiella pneumoniae isolate harboring a metallo-beta-lactamase (VIM-1) and an extended-spectrum beta-lactamase (SHV-12). Time-kill studies demonstrated that the combination of both compounds was synergistic along the first 12 h, suppressing the regrowth observed after 3 to 6 h when colistin was tested alone.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Drug Synergism; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Infections due to multidrug-resistant (MDR) Gram-negative pathogens in the ICU have prompted the use of colistin, an antibiotic forgotten for decades. The aim of this retrospective observational study was to record and present the emergence of colistin-resistant Klebsiella pneumoniae (CRKB) in a Greek ICU.. In a new university tertiary hospital, the first patients admitted in the ICU were already colonized or infected with MDR pathogens, and this led to frequent colistin use as part of empirical or microbiologically documented therapy. Colistin resistance was defined as MIC >4 mg/L by the Etest method. All CRKB isolated in surveillance cultures or clinical specimens in the ICU during the period 2004-5 were recorded along with patients' characteristics.. Eighteen CRKB were isolated from 13 patients over a 16 month period, representing either colonizing or infective isolates. Patients' mean age was 70 years, with a mean APACHE II score at admission of 22. They all had a long hospitalization (median 69 days) and a long administration of colistin (median 27 days). Colistin-resistant isolates were implicated as pathogens in two bacteraemias, a ventilator-associated pneumonia and two soft tissue infections. Repetitive extragenic palindromic PCR identified six distinct clones, and horizontal transmission was also documented.. Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.

Topics: Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Utilization; Female; Genes, Bacterial; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Multigene Family; Reverse Transcriptase Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Prostaglandins E

We suggest a novel approach to enhancing antimicrobial drug action by utilizing engineered peptide conjugates. Our most potent conjugates, [fMLF]PMBN and [fMLF]PMEN, are nonapeptides derived from polymyxin B's (PMB's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Phe-Leu-Dab-Dab-Thr], where Dab is 2,4-diaminobutyric acid) and polymyxin E's (PME's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Leu-Leu-Dab-Dab-Thr]), respectively, attached to a linear tail comprised of formyl-Met-Leu-Phe (fMLF). The cyclic part binds to gram-negative lipopolysaccharides, rendering the bacterial outer membrane permeable to hydrophobic antibiotics. The tail confers chemotactic and opsonic activities upon the conjugates. These two activities appear to be the basis for the conjugates' antibacterial activities. The conjugates are 8 to 10 times less toxic than the parent PMB or PME antibiotics. Fourteen of 18 mice lethally challenged with erythromycin-resistant Klebsiella pneumoniae survived following intraperitoneal administration of erythromycin and [fMLF]PMBN, whereas erythromycin or the peptide conjugate alone had no effect. Moreover, the clearance of Klebsiella from blood was markedly enhanced by intravenous injection of the [fMLF]PMEN peptide conjugate compared to the clearance of the organism from the mice treated with buffer alone as a control and was similar to that achieved by the PME antibiotic. Blood clearance was also significantly enhanced by administration of PMEN either alone or in a mixture with fMLF, although the effect was less than that produced by the peptide conjugate. Since resistance to polymyxins, the parent molecules of the synthetic cyclic peptides, is rare, the emergence of bacteria resistant to the antimicrobial properties of the peptide conjugates may be precluded as well.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Blood; Cell Membrane Permeability; Chemotaxis; Colistin; Drug Resistance, Bacterial; Erythromycin; Gram-Negative Bacteria; Humans; Klebsiella Infections; Klebsiella pneumoniae; Macrophages, Peritoneal; Mice; Microbial Sensitivity Tests; Opsonin Proteins; Peptides; Polymyxin B

Klebsiella pneumoniae that was resistant to all available antibiotics (minimum inhibitory concentration of imipenem, 32 microg/mL), including carbapenems, was isolated from blood samples obtained from a 48-year-old patient in the intensive care unit. The patient developed septic shock, which was successfully treated with colistin, the only antibiotic with activity against this multidrug-resistant strain.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Sepsis

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

An outbreak caused by a Klebsiella aerogenes resistant to ceftazidime, cefuroxime, cefotaxime, ampicillin and piperacillin and sensitive to aminoglycosides, imipenem and temocillin occurred in a teaching hospital's busy multi-disciplinary Intensive Care Unit over a 3-month period. Four patients had bacteraemia and a further four were colonized. Traditional infection control measures failed to eradicate the outbreak. The introduction of a selective gastrointestinal decontamination regimen consisting of tobramycin, amphotericin and colistin as a gel to the oropharynx, nose and rectum and a suspension via a nasogastric tube resulted in rapid disappearance of the outbreak strain with no new isolates being detected clinically or in surveillance specimens over an 8-week period.

Topics: Amphotericin B; Colistin; Cross Infection; Disease Outbreaks; Gastrointestinal Diseases; Hospitals, Teaching; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Tobramycin

The effect of antibiotic therapy on the intestinal flora was studied qualitatively and quantitatively in 41 infants. The results have been compared with 27 normal children of the same age and background. Antibiotics were responsible for the suppression of sensitive strains and for their replacement by resistant organisms but above all to a rapid multiplication of the intestinal flora. Colistin and pristinamycin caused these changes when given orally. Ampicillin when given both orally and parenterally but Colistin and the aminoglycosides when given parenterally did not have any effect. Fourteen cases of secondary septicaemia due to resistant organisms were observed but other factors were also important, namely the young age of the patients and intestinal problems (stasis and diarrhoea).

Topics: Age Factors; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Feces; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Intestines; Klebsiella Infections; Penicillin Resistance; Proteus Infections; Sepsis; Staphylococcal Infections

Three antibiotic-resistant strains of Klebsiella pneumoniae responsible for outbreaks of systemic infection in a hospital nursery were analyzed. Each organism emerged after prolonged use of a drug to which it was resistant. The first strain (RO16) produced neomycin phosphotransferase and contained three plasmids with molecular weights of 24, 25, and 30 X 10(6) daltons, respectively. Resistance to ampicillin, carbenicillin, neomycin, and kanamycin was transferred by conjugation at a frequency of 10(-6). The second strain of K. pneumoniae (RO106) produced gentamicin adenyltransferase and maintained aminoglycoside resistance only when propagated in antibiotic-containing medium. DNA analyses revealed eight species of plasmid DNA: one species with a molecular weight of 70 X 10(6) daltons apparently accounted for conjugal transfer of resistance to ampicillin, carbenicillin, chloramphenicol, and streptomycin. The third strain (RO180) was resistant primarily to colistin and lacked plasmids. Control of the outbreak due to this strain was achieved by aminoglycoside therapy.

Topics: Aminoglycosides; Colistin; DNA; Drug Resistance, Microbial; Electrophoresis, Polyacrylamide Gel; Genetics, Microbial; Gentamicins; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae

Topics: Aged; Amikacin; Colistin; Cross Infection; Disease Outbreaks; Drug Administration Schedule; Drug Resistance, Microbial; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Urinary Tract Infections

Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.

Topics: Adolescent; Cellulitis; Child; Child, Preschool; Colistin; Erythromycin; Female; Foot Injuries; Humans; Klebsiella Infections; Lincomycin; Male; Osteomyelitis; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Tetracyclines; Wounds, Penetrating

A myopathy caused by the activity of polymyxin E on the cell membrane was accompained by immunological manifestations. There were also disturbances of the central nervous system, contrasting with the absence of serious renal lesion.

Topics: Aged; Antigen-Antibody Reactions; Autoantibodies; Brain Diseases; Colistin; Electromyography; Fluorescent Antibody Technique; Frontal Lobe; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Muscles; Muscular Diseases; Neural Conduction; Osteomyelitis; Paralysis

Topics: Aged; Aniline Compounds; Biopsy, Needle; Carbuncle; Colistin; Humans; Kidney Diseases; Klebsiella Infections; Male; Sulfamethizole; Sulfathiazoles; Ultrasonography

During a serious epidemic of chest and urinary infections due to Klebsiella aerogenes in a neurosurgical unit, several patients developed klebsiella meningitis after trauma or surgery. Despite all attempts to control the epidemic and treat the meningitis with antibiotics, eight of the nine patients died. It was not until all antibiotics used to treat respiratory and urinary infections had been totally withdrawn that no further patients developed klebsiella meningitis.

Topics: Adult; Ampicillin; Child; Child, Preschool; Cloxacillin; Colistin; Cross Infection; Disease Outbreaks; Female; Gentamicins; Humans; Injections, Spinal; Klebsiella Infections; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Scotland; Surgical Wound Infection

Topics: Ampicillin; Cephalothin; Chloramphenicol; Colistin; Cross Infection; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Lung; Penicillin Resistance; Prognosis; Sepsis; Skin; Streptomycin; Sulfonamides; Surgical Wound Infection; Tetracycline; Urinary Tract

Topics: Acinetobacter; Adolescent; Adult; Alcaligenes; Arm Injuries; Bacillus subtilis; Blast Injuries; Blood; Cephalothin; Chloramphenicol; Colistin; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leg Injuries; Male; Penicillin Resistance; Penicillins; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Streptomycin; Warfare; Wound Infection

Topics: Animals; Anti-Bacterial Agents; Bacteria; Blood Proteins; Colistin; Culture Media; Drug Resistance, Microbial; Escherichia coli Infections; Gentamicins; Hydrogen-Ion Concentration; Kanamycin; Klebsiella Infections; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Protein Binding; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus; Streptomycin

Topics: Adolescent; Adult; Age Factors; Aged; Colistin; Cross Infection; Escherichia coli Infections; Female; Fever; Humans; Kanamycin; Klebsiella Infections; Leukocyte Count; Male; Microbial Sensitivity Tests; Middle Aged; Nitrogen; Penicillins; Proteus Infections; Pseudomonas Infections; Retrospective Studies; Sepsis; Sex Factors; Shock; Uremia

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Disease Outbreaks; Humans; Intensive Care Units; Klebsiella; Klebsiella Infections; Meningitis; Neurosurgery; Respiratory Tract Infections; Sputum; Urinary Tract Infections

Topics: Adult; Aged; Ampicillin; Anti-Bacterial Agents; Chloramphenicol; Chronic Disease; Colistin; Depression, Chemical; Drug Synergism; Erythromycin; Escherichia coli Infections; Female; Follow-Up Studies; Humans; Kanamycin; Klebsiella Infections; Male; Middle Aged; Nitrofurantoin; Oleandomycin; Oxacillin; Penicillins; Polymyxins; Proteus Infections; Pyelonephritis; Staphylococcal Infections; Stimulation, Chemical; Streptococcal Infections; Streptomycin; Sulfonamides; Tetracycline

Topics: Ampicillin; Cloxacillin; Colistin; Cross Infection; Humans; Intensive Care Units; Klebsiella Infections; Lung Diseases; Neurosurgery; Penicillin Resistance; Urinary Tract Infections

High doses of colistin were used in the treatment of severely ill patients with refractory klebsiella chest and urinary tract infections. At the same time renal function was monitored to determine possible nephrotoxicity. In all patients it produced acute renal failure and in some acute tubular necrosis. Though renal failure contributed to the final cause of death in some cases, in the majority death was due to the primary neurological illness.

Topics: Acute Kidney Injury; Adult; Aged; Colistin; Creatinine; Female; Humans; Kidney; Kidney Function Tests; Klebsiella Infections; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Tract Infections; Urea; Urinary Tract Infections

Topics: Adult; Aged; Alcoholism; Anti-Bacterial Agents; Cephalothin; Chloramphenicol; Colistin; Female; Humans; Kanamycin; Klebsiella; Klebsiella Infections; Lung; Male; Middle Aged; Penicillin Resistance; Penicillins; Pneumonia; Polymyxins; Radiography; Sputum; Streptomycin

Topics: Colistin; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Polymyxins; Pseudomonas Infections

Gentamicin was of value in the treatment of chronic urinary tract infections caused by multiresistant bacterial strains for which no atoxic antibiotic was available. The treatment was carried out after alkalinization of the patient's urine. With the dosage given, gentamicin gave a low serum and a relatively high urine concentration. Excretion of active gentamicin in the urine was high even in patients with impaired renal function. The results of treatment of complicated chronic urinary tract infections with initial gentamicin and following long-term therapy showed negative urinary cultures in 12 out of 24 patients within one to 14 months of follow-up time. To reduce the risk of toxic side effects the dosage was adjusted according to the patient's kidney function. No development of resistance was demonstrated in the bacteria.

Topics: Adult; Aged; Chronic Disease; Colistin; Drug Resistance, Microbial; Escherichia coli Infections; Female; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Male; Middle Aged; Proteus Infections; Urinary Tract Infections

Topics: Colistin; Cross Infection; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Kanamycin; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Meningitis; Ophthalmology; Oxytetracycline; Polymyxins