meropenem and Urinary-Tract-Infections

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

Plazomicin is a novel semisynthetic parenteral aminoglycoside that inhibits bacterial protein synthesis. It was approved by the United States Food and Drug Administration for use in adults with complicated urinary tract infections (cUTI), including pyelonephritis. Plazomicin displays potent in vitro activity against Enterobacteriaceae, including both extended-spectrum β-lactamase-producing and carbapenem-resistant isolates. Plazomicin's enhanced Enterobacteriaceae activity is due to its stability to commonly encountered aminoglycoside-modifying enzymes that compromise the activity of traditional aminoglycosides. Plazomicin resistance in Enterobacteriaceae is via modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases. Plazomicin does not display improved activity over traditional aminoglycosides against other problematic resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter baumannii. Plazomicin has been assessed in two phase III randomized controlled trials. The EPIC trial compared plazomicin and meropenem for the management of cUTI. In this trial, plazomicin demonstrated superiority in composite cure (81.7% vs 70.1%; difference 11.6%; 95% confidence interval [CI] 2.7-25.7) at the test-of-cure visit, which was driven by enhanced sustained microbiological eradication. The CARE trial compared plazomicin-based and colistin-based combinations in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE). In this analysis, plazomicin-based combinations were associated with numerically decreased mortality or serious disease-related complications when compared with colistin-based combinations (23.5% vs 50%, respectively; 90% CI -0.7 to 51.2). Furthermore, plazomicin was also associated with a lower incidence of nephrotoxicity than colistin. However, small sample sizes limit the interpretation of the findings in the CARE trial. Plazomicin is a novel aminoglycoside that offers clinicians an additional option for the management of CRE infections, with superior activity compared with traditional aminoglycosides and potentially improved efficacy and decreased toxicity compared with colistin.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Clinical Trials as Topic; Colistin; Dose-Response Relationship, Drug; Drug Approval; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Randomized Controlled Trials as Topic; Sisomicin; United States; United States Food and Drug Administration; Urinary Tract Infections

Vaborbactam (VAB; formerly RPX7009) is a novel beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta-lactamases. It has been co-formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug-resistant nonfermenting gram-negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa. The purpose of this article is to review existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro activity, and current progress in clinical trials of meropenem and VAB (MV). Phase 1 studies have demonstrated single and multiple doses of VAB up to 2000 mg, alone or in combination with meropenem 2000 mg administered as a prolonged infusion over 3 hours, are well tolerated with an adverse effect profile similar to that of meropenem monotherapy. The available data suggest preexisting resistance among KPC-producing isolates is rare. Strains with elevated MICs have been characterized by multiple resistance determinants including porin defects, increased drug efflux, and increased blaKPC expression. It remains uncertain whether multifactorial resistance will emerge during MV treatment and with more widespread use. Early data are positive for complicated urinary tract infections and MV compared with best available therapy in patients with serious carbapenem-resistant Enterobacteriaciae (CRE) infections. As clinicians contemplate how to incorporate MV into CRE treatment strategies, it will be important to track and understand resistance, discern the role, if any, of combination therapy in enhancing efficacy and/or preserving activity, and define the specific therapeutic niche of MV among the expanding anti-CRE armamentarium.

Topics: Anti-Bacterial Agents; Area Under Curve; Bacterial Proteins; beta-Lactamases; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Bacterial; Klebsiella Infections; Meropenem; Metabolic Clearance Rate; Microbial Sensitivity Tests; Porins; Urinary Tract Infections

Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.

Topics: Animals; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Drug Resistance, Bacterial; Humans; Meropenem; Randomized Controlled Trials as Topic; Thienamycins; Urinary Tract Infections

The global threat of the spread of carbapenem resistance in Enterobacteriaceae has led to the search for new antibacterials. Intravenous meropenem/vaborbactam (Vabomere™) is the first carbapenem/β-lactamase inhibitor combination approved in the USA for use in patients with complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a potent inhibitor of class A serine carbapenemases, which, when combined with the antibacterial meropenem, restores the activity of meropenem against β-lactamase producing Enterobacteriaceae, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem/vaborbactam demonstrated excellent in vitro activity against Gram-negative clinical isolates, including KPC- and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. In the phase 3, noninferiority TANGO I trial in patients with cUTIs, intravenous meropenem/vaborbactam was noninferior to intravenous piperacillin/tazobactam for overall success (composite of clinical cure and microbial eradication; FDA primary endpoint) and microbial eradication (EMA primary endpoint). In subsequent superiority testing, meropenem/vaborbactam was superior to piperacillin/tazobactam for overall success. Meropenem/vaborbactam was generally well tolerated, with a tolerability profile generally similar to that of piperacillin/tazobactam. TANGO I did not assess the efficacy of meropenem/vaborbactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and meropenem/vaborbactam is currently not indicated for these patients. Available evidence indicates that meropenem/vaborbactam is a useful treatment option for patients with cUTIs.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Boronic Acids; Drug Approval; Drug Combinations; Drug Resistance, Bacterial; Enterobacteriaceae; Humans; Meropenem; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; United States; Urinary Tract Infections

Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis. Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Boronic Acids; Ceftazidime; Drug Combinations; Enterobacteriaceae; Humans; Klebsiella pneumoniae; Meropenem; Pyelonephritis; Thienamycins; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Ceftazidime; Drug Combinations; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Urinary Tract Infections

Complicated urinary tract infections are increasingly caused by multidrug-resistant organisms. Carbapenem-resistant Enterobacteriaceae (CRE) constitute a rising threat among uropathogens with significant morbidity and mortality. Meropenem-vaborbactam is a novel carbapenem and cyclic boronic acid-based beta-lactamase inhibitor combination with potent activity against subtypes of CRE. Areas covered: This article reviews mechanisms of carbapenem resistance, existing treatment options for CRE, and the current evidence to support the use of meropenem-vaborbactam for the treatment of infections caused by subtypes of CRE including complicated urinary tract infections. Expert commentary: Meropenem-vaborbactam is a superior treatment option for infections secondary to Klebsiella pneumoniae carbapenemase (KPC)-producing CRE. It is associated with higher rates of treatment success and lower rates of toxicity than traditional agents and demonstrates a potentially higher barrier to acquired antimicrobial resistance than ceftazidime-avibactam. At present, meropenem-vaborbactam should be regarded as a preferred treatment option for invasive infections secondary to KPC-producing CRE.

Topics: Adult; Animals; Anti-Bacterial Agents; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Klebsiella pneumoniae; Meropenem; Urinary Tract Infections

On August 29, 2017, the United States Food and Drug Administration (FDA) approved meropenem/ vaborbactam fixed combination for the treatment of adults with complicated urinary tract infections (cUTI). The decision was based on substantial preclinical and clinical data, including two recent trials involving hundreds of adults with cUTI. Meropenem/ vaborbactam represents a powerful new treatment option to address antibiotic-resistant pathogens, including Klebsiella pneumoniae carbapenemase-producing bacteria. In this paper, we examine the work that led to FDA approval, with special emphasis on molecular pharmacology, pharmacokinetics, metabolism, efficacy and drug safety. We also look ahead, to explore how this promising new antimicrobial agent might be used in the near future to confront other drug-resistant infections..

Topics: Anti-Bacterial Agents; Boronic Acids; Clinical Trials as Topic; Drug Interactions; Heterocyclic Compounds, 1-Ring; Humans; Meropenem; Thienamycins; Urinary Tract Infections

The carbapenems are a group of broad-spectrum beta-lactam antibiotic agents of which there are three parenteral preparations currently available in South Africa, namely imimpenem/cilastatin, meropenem and ertapenem. Owing to the fact that imipenem/cilastatin and meropenem have a broad spectrum of activity that includes Pseudomonas and Acinetobacter species, they are ideal antibiotics for treatment of severe nosocomial infections. In contrast, ertapenem has limited in vitro activity against the latter non-fermentative gram-negative bacteria and is therefore more suitable for the treatment of certain severe community-acquired infections. This statement arises out of concerns about the general abuse of antibiotics such as the carbapenems, with the primary intention of highlighting the appropriate use of these agents.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Carbapenems; Cilastatin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Ertapenem; Humans; Imipenem; Lactams; Meropenem; Patient Selection; Pneumonia, Bacterial; Practice Patterns, Physicians'; Protease Inhibitors; South Africa; Surgical Wound Infection; Thienamycins; Urinary Tract Infections

A clinical, multicentre, randomised, comparative study in 283 adult hospitalized patients was carried out to assess efficacy of meropenem in the treatment of complicated and non-complicated urinary tract infections, in comparison to imipenem/cilastatin. Both antibiotics were administered intramuscularly, at a dose of 500 mg bid. The two groups were homogeneous, as regards the distribution between male and female, the mean age of the patients, the severity of infections and the mean duration of treatment. Clinical results were assessed at the end of therapy and follow-up (4-6 weeks). Bacteriological results were assessed at 5-9 days post-treatment and at follow-up. As regards clinical and bacteriological results patients showing a satisfactory response rate were compared, at the end of the treatments using a Chi square test. With both treatments high satisfactory clinical and bacteriological response rates were seen. As regards clinical satisfactory responses (97% of meropenem assessable patients versus 90% of imipenem/cilastatin assessable patients), there was a statistically significant difference in favor of meropenem. The bacteriological outcome was successful (eradication) for 75% of assessable patients in each group. Most failures were seen in the complicated infections, even when pathogens usually sensitives to carbapenemics were initially isolated. Safety was good with both drugs; no withdrawals in any group of treatment was seen because of side effects. The local tolerance of meropenem was globally rated as good.

Topics: Adult; Aged; Carbapenems; Chi-Square Distribution; Cilastatin; Cross Infection; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Urinary Tract Infections

Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.. This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.. The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.. Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant Gram-negative pathogens.

Topics: Adult; Anti-Bacterial Agents; Cephalosporins; Child; Escherichia coli; Humans; Infant, Newborn; Meropenem; Penicillanic Acid; Pyelonephritis; Tazobactam; Urinary Tract Infections

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

The increasing multidrug resistance among gram-negative uropathogens necessitates new treatments for serious infections. Plazomicin is an aminoglycoside with bactericidal activity against multidrug-resistant (including carbapenem-resistant) Enterobacteriaceae.. We randomly assigned 609 patients with complicated urinary tract infections (UTIs), including acute pyelonephritis, in a 1:1 ratio to receive intravenous plazomicin (15 mg per kilogram of body weight once daily) or meropenem (1 g every 8 hours), with optional oral step-down therapy after at least 4 days of intravenous therapy, for a total of 7 to 10 days of therapy. The primary objective was to show the noninferiority of plazomicin to meropenem in the treatment of complicated UTIs, including acute pyelonephritis, with a noninferiority margin of 15 percentage points. The primary end points were composite cure (clinical cure and microbiologic eradication) at day 5 and at the test-of-cure visit (15 to 19 days after initiation of therapy) in the microbiologic modified intention-to-treat population.. Plazomicin was noninferior to meropenem with respect to the primary efficacy end points. At day 5, composite cure was observed in 88.0% of the patients (168 of 191 patients) in the plazomicin group and in 91.4% (180 of 197 patients) in the meropenem group (difference, -3.4 percentage points; 95% confidence interval [CI], -10.0 to 3.1). At the test-of-cure visit, composite cure was observed in 81.7% (156 of 191 patients) and 70.1% (138 of 197 patients), respectively (difference, 11.6 percentage points; 95% CI, 2.7 to 20.3). At the test-of-cure visit, a higher percentage of patients in the plazomicin group than in the meropenem group were found to have microbiologic eradication, including eradication of Enterobacteriaceae that were not susceptible to aminoglycosides (78.8% vs. 68.6%) and Enterobacteriaceae that produce extended-spectrum β-lactamases (82.4% vs. 75.0%). At late follow-up (24 to 32 days after initiation of therapy), fewer patients in the plazomicin group than in the meropenem group had microbiologic recurrence (3.7% vs. 8.1%) or clinical relapse (1.6% vs. 7.1%). Increases in serum creatinine levels of 0.5 mg or more per deciliter (≥40 μmol per liter) above baseline occurred in 7.0% of patients in the plazomicin group and in 4.0% in the meropenem group.. Once-daily plazomicin was noninferior to meropenem for the treatment of complicated UTIs and acute pyelonephritis caused by Enterobacteriaceae, including multidrug-resistant strains. (Funded by Achaogen and the Biomedical Advanced Research and Development Authority; EPIC ClinicalTrials.gov number, NCT02486627.).

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Patient Acuity; Sisomicin; Urinary Tract Infections

Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.. To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.. Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.. Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.. Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.. Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.. Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.. clinicaltrials.gov Identifier: NCT02166476.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Pyelonephritis; Thienamycins; Urinary Tract Infections; Urine

The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI).. Trials were randomized and double blind. The ASPECT-cUTI regimen was 7 days of either intravenous ceftolozane/tazobactam (1.5 g) every 8 h or levofloxacin (750 mg) once daily. The ASPECT-cIAI regimen was 4-14 days of either intravenous ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) or meropenem (1 g) every 8 h. Baseline cultures were obtained in both indications. Enterobacteriaceae were selected for ESBL characterization based on predefined criteria and were verified genotypically. Outcomes were assessed at the test-of-cure visit 5-9 days post-therapy in ASPECT-cUTI and 24-32 days post-randomization in ASPECT-cIAI among microbiologically evaluable (ME) patients.. Of 2076 patients randomized, 1346 were included in the pooled ME population and 150 of 1346 (11.1%) had ESBL-ENT at baseline. At US FDA/EUCAST breakpoints of ≤2/≤1 mg/L, 81.8%/72.3% of ESBL-ENT (ESBL-Escherichia coli, 95%/88.1%; ESBL-Klebsiella pneumoniae, 56.7%/36.7%) were susceptible to ceftolozane/tazobactam versus 25.3%/24.1% susceptible to levofloxacin and 98.3%/98.3% susceptible to meropenem at CLSI/EUCAST breakpoints. Clinical cure rates for ME patients with ESBL-ENT were 97.4% (76/78) for ceftolozane/tazobactam [ESBL-E. coli, 98.0% (49 of 50); ESBL-K. pneumoniae, 94.4% (17 of 18)], 82.6% (38 of 46) for levofloxacin and 88.5% (23 of 26) for meropenem.. Randomized trial data demonstrated high clinical cure rates with ceftolozane/tazobactam treatment of cIAI and cUTI caused by ESBL-ENT.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; beta-Lactamase Inhibitors; beta-Lactamases; Cephalosporins; Double-Blind Method; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Male; Meropenem; Metronidazole; Middle Aged; Penicillanic Acid; Tazobactam; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.. This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.. The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.. NCT01732250 and 2012-004819-31; Pre-results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Greece; Humans; Israel; Italy; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future.. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli.. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals.. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy.. NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Topics: Administration, Intravenous; Anti-Bacterial Agents; beta-Lactamases; Clinical Protocols; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gastrointestinal Microbiome; Gram-Negative Bacteria; Humans; Intestines; Meropenem; Research Design; Thienamycins; Urinary Tract Infections

An analysis of subjects with concurrent bacteraemia and either nosocomial pneumonia, complicated intra-abdominal infection or complicated urinary tract infection from six phase 3 clinical trials demonstrated similar cure rates and clearance of bacteraemia in patients treated with doripenem and comparator agents.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Female; Humans; Imipenem; Intraabdominal Infections; Male; Meropenem; Ofloxacin; Pneumonia; Thienamycins; Treatment Outcome; Urinary Tract Infections

Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China.. Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed.. A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%).. Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.

Topics: Adult; Aged; Bacteria; Bacterial Infections; China; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

To evaluate the efficacy and safety of meropenem in Chinese patients, we conducted a study for the treatment of patients with lower respiratory tract infections, urinary tract infections and other infections.. A total of 182 hospitalized patients were enrolled in the study. 90 patients received 500 mg meropenem every 12 hours (or 1 g every 12 hours if necessary) and 92 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1 g every 12 hours if necessary) by intravenous infusion. The duration of treatment was 7 - 14 days for both groups.. Seventy of 90 cases receiving meropenem and 70 of 92 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rates were 90% for the meropenem group and 87% for the imipenem/cilastatin group, and the bacterial eradication rates were 86% in both groups. 93 (76%) of 123 strains isolated from patients produced beta-lactamases. Adverse drug reactions were evaluated in 72 cases in the meropenem group and 70 cases in the imipenem/cilastatin group. The adverse drug reaction rates were 9.7% and 8.6%, respectively. The results showed that there were no statistical differences between these two groups (P > 0.05).. Meropenem is effective and safe for the treatment of bacterial infections caused mainly by beta-lactamase-producing strains.

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Cilastatin; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

Meropenem is a new carbapenem antibiotic developed by Sumitomo Pharmaceuticals and shown to resist degradation by renal dehydropeptidase I (DPH-I), an enzyme which exists chiefly in the kidneys and decomposes carbapenem antibiotics. It has a powerful antibacterial activity with broad antibacterial spectrum. The objective of the study is to evaluate the efficacy and safety of meropenem.. A randomized, open-label, controlled study was conducted for treating patients with bacterial infections. A total of 112 hospitalized patients were enrolled in the study. 55 patients received meropenem 500 mg every 12 hours (or 1g every 12 hours if necessary) and 57 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1g/1g every 12 hours if necessary) intravenously. The duration of treatment was 7-14 days in both groups.. 42 of the 55 cases receiving meropenem and 41 of the 57 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rate was 88.1%(37/42) for the meropenem group and 85.4%(35/41) for the imipenem/cilastatin group, whereas the bacterial eradication rate was 81.1%(30/37) and 84.2%(32/38), respectively. 47(69.1%) of 68 strains isolated from patients produced beta-lactamase. Adverse drug reaction was evaluated in 44 cases of the meropenem group and 41 cases of the imipenem/cilastatin group. The adverse drug reaction rate was 13.6%(6/44) and 12.2%(5/41), respectively. The results showed that there were no statistical differences between these two groups (P > 0.05).. Meropenem and imipenem/cilastatin were effective and safe for the treatment of lower respiratory tract infections and urinary tract infections and other infections caused by beta-lactamase-producing strains.

Topics: Cilastatin; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Protease Inhibitors; Respiratory Tract Infections; Thienamycins; Treatment Outcome; Urinary Tract Infections

The clinical and bacteriological efficacies of meropenem in the treatment of 12 patients with urinary tract infection were studied. In 8 patients the drug was administered intravenously in a dose of 1 g every 8 hours and in 4 patients with the creatinine clearance below 50 ml/min it was administered in a dose of 1 g every 12 hours (the treatment course of 7 to 10 days). Meropenem was used in the monotherapy. Severe complicated urinary tract infections were mainly observed in the patients with long-term urolithiasis, subjected to repeated surgical interventions and isolating as a rule polyresistant strains of Pseudomonas aeruginosa and E.agglomerans as the pyelonephritis pathogens at a titre of 5 x 10(5)-5 x 10(8) microbial cells per 1 ml of the urine susceptible to meropenem in 80 to 96 per cent of the cases. The clinical efficacy of the drug was stated in all the patients while the bacteriological efficacy amounted to 88.9 per cent.

Topics: Adult; Aged; Aged, 80 and over; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins; Treatment Outcome; Urinary Tract Infections

In a multicenter, randomized, open comparison of meropenem to ceftazidime as empiric treatment of severe acute infections, 185 children (1 mo-15 years old, mean 65.4 mo) were enrolled. Meropenem (20 mg/kg t.i.d. i.v.) was given to 98 and ceftazidime (10-30 mg/kg t.i.d. i.v.) to 87 children, generally for 5 to 10 days (mean: 6.9 for meropenem and 7.5 for ceftazidime). Clinical response was evaluated at the beginning and at the end of therapy and 4 weeks later (follow-up). Clinical response was deemed satisfactory at the end of therapy in 96.7% of the patients treated with meropenem and in 95.3% of those who received ceftazidime without any statistically significant difference. One relapse occurred in a meropenem-treated patient at the follow-up clinical assessment. The baseline infecting organism was eradicated or presumed eradicated at the end of therapy in 14/16 patients treated with meropenem and in 14/15 treated with ceftazidime. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 9.2% in the meropenem group and 4.6% in the ceftazidime group. Our data show that meropenem is as effective as ceftazidime in the empiric treatment of severe infections in infants and children.

Topics: Adolescent; Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Drug Monitoring; Hospitalization; Humans; Infant; Infant, Newborn; Liver; Meropenem; Respiratory Tract Infections; Sepsis; Skin Diseases, Infectious; Thienamycins; Treatment Outcome; Urinary Tract Infections

Meropenem was compared with imipenem/cilastatin for the treatment of serious bacterial infections in a randomized, prospective multicentre study. Both study drugs were given intravenously 1 g every 8 h and no other antimicrobial agents were permitted concomitantly. Of the 204 patients enrolled, the treatment of 177 was evaluable for clinical efficacy and 115 for bacteriological efficacy. In the clinically evaluable treatment population, 75 (83%) of the 90 patients in the meropenem group and 78 (90%) of the 87 in the imipenem/cilastatin group had a single site of infection whereas the remainder had two or more sites of infection. Infections of the lower respiratory tract and peritoneal cavity predominated accounting for 95 and 75 cases respectively. Other infections included skin and soft tissue infections, complicated urinary tract infections, bacteraemia and a case of meningitis treated with meropenem and one of mediastinitis treated with imipenem/cilastatin. One hundred and nineteen (67%) patients were in an intensive care unit, 105 (59%) were receiving assisted ventilation and 93 (53%) of the patients had failed previous antibiotic therapy. One hundred and ten organisms were identified as pathogens in the meropenem group and 109 in the imipenem/cilastatin group. Overall, treatment with meropenem was clinically successful in 68 (76%) of 90 cases and imipenem/cilastatin in 67 (77%) of 87 cases and the corresponding eradication rates of bacteria were 85 of 110 (77%) and 90 of 109 (83%) respectively. Superinfections due to resistant bacteria occurred in two patients treated with meropenem and three cases given imipenem/cilastatin. No statistically significant differences in the clinical or bacteriological outcome were observed between the treatment groups for any of the infection sites analysed. Both drugs were well tolerated with adverse events considered to be related to therapy being recorded for 10 (9%) of 106 patients treated with meropenem and 12 (12%) of 98 of those who had been given imipenem/cilastatin. Empirical monotherapy with meropenem was therefore as effective and as well tolerated as that with imipenem/cilastatin for the treatment of serious bacterial infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Female; Hospitals; Humans; Imipenem; Infusions, Intravenous; Injections, Intravenous; Male; Meropenem; Middle Aged; Peritonitis; Protease Inhibitors; Respiratory Tract Infections; Thienamycins; Time Factors; Treatment Outcome; Urinary Tract Infections

The safety and efficacy of meropenem and imipenem/cilastatin were compared in the treatment of hospitalized patients with complicated urinary tract infections (UTIs) in a prospective, multicenter, open, parallel-group trial. Patients were randomized to receive 500-mg intravenous doses of either meropenem every 8 hours (n = 116) or imipenem/cilastatin every 6 hours (n = 119). Data from 95 patients given meropenem and 82 patients given imipenem/cilastatin were included in the evaluation of efficacy. Meropenem produced satisfactory clinical and bacteriologic responses in 99% and 90% of cases, respectively. These results were similar to those obtained with imipenem/cilastatin, which produced clinical improvement in 99% of cases and bacteriologic improvement in 81%. Two patients given meropenem and five patients given imipenem/cilastatin developed superinfections. The rate of relapse was similar in the two groups. Patients who received meropenem had fewer drug-related adverse reactions than did recipients of imipenem/cilastatin (8% vs. 19%). The results of this study demonstrate that meropenem is a safe and effective alternative to imipenem/cilastatin in the treatment of hospitalized patients with complicated UTIs.

Topics: Bacteria; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Protease Inhibitors; Thienamycins; Urinary Tract Infections

263 hospitalized patients were enrolled in a multicentre study to assess efficacy and safety of i. m. meropenem, compared to ceftazidime, in the treatment of lower respiratory tract infections and urinary infections as well. Meropenem, administered at a dose of 500 mg tid, was therapeutically equivalent to the reference agent (1000 mg tid in RTI's and 500 mg tid in UTI's) in both indications. The two treatments were well tolerated, without any serious local or systemic side effect.

Topics: Adult; Aged; Aged, 80 and over; Ceftazidime; Female; Humans; Male; Meropenem; Middle Aged; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

In three open, multicentre, prospective randomised studies, the efficacy and safety of meropenem were assessed and compared with ceftazidime (Study 1) and imipenem/cilastatin (Studies 2 and 3) in 864 patients; 417 with urinary tract infections (UTI) and 447 with community acquired lower respiratory tract infections (LRTI). All the antibiotics were administered by intramuscular injection. Clinical and bacteriological responses were assessed at the end of therapy and at follow-up (2-4 weeks for LRTI, 4-6 weeks for UTI). The clinical response rate in UTI at the end of therapy was 93-100% for meropenem 500 mg tds compared with 94-95% for ceftazidime 500 mg tds; for meropenem 500 mg bd it was 97%, significantly higher than that for imipenem/cilastatin 500 mg bd which was 90% (P = 0.03). At follow-up, the response rates were 90% for meropenem tds compared with 81-85% for ceftazidime 500 mg tds and 81% for meropenem bd compared with 78% for imipenem/cilastatin 500 mg bd. The clinical response rate in LRTI at end of therapy was 93% for meropenem 500 mg tds, compared with 92% for ceftazidime 1 g tds; for meropenem 500 mg bd the clinical response rate was 96%, compared with 91% for imipenem/cilastatin 500 mg bd (P = 0.054). At follow-up, the clinical response rates were 96%, 89%, 93% and 96%, respectively. The bacteriological response rates at 5-9 days post-therapy in UTI were 61-84% in patients treated with meropenem 500 mg tds, compared to 73-82% in patients treated with ceftazidime 500 mg tds; the rates for meropenem 500 mg bd and imipenem/cilastatin 500 mg bd were each 75%. At follow-up, the response rates were 40-72%, 57-70%, 51% and 49%, respectively. In LRTI, bacteriological response rates at the end of therapy were 91% for both meropenem 500 mg tds and ceftazidime 1 g tds, and 91% for meropenem 500 mg bd compared with 86% for imipenem/cilastatin 500 mg bd. At follow-up, the response rates were 87%, 77%, 84% and 79%, respectively. All treatments were well tolerated. In these studies, intramuscular meropenem proved to be an effective and well tolerated treatment for LRTI and UTI.

Topics: Bacterial Infections; Carbapenems; Ceftazidime; Cilastatin; Humans; Imipenem; Injections, Intramuscular; Meropenem; Respiratory Tract Infections; Thienamycins; Treatment Outcome; Urinary Tract Infections

A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.

Topics: Adolescent; Adult; Aged; Amikacin; Bacterial Infections; Carbapenems; Ceftazidime; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Meropenem; Middle Aged; Respiratory Tract Infections; Sepsis; Thienamycins; Time Factors; Treatment Outcome; Urinary Tract Infections

A clinical, multicentre, randomised, comparative study in 283 adult hospitalized patients was carried out to assess efficacy of meropenem in the treatment of complicated and non-complicated urinary tract infections, in comparison to imipenem/cilastatin. Both antibiotics were administered intramuscularly, at a dose of 500 mg bid. The two groups were homogeneous, as regards the distribution between male and female, the mean age of the patients, the severity of infections and the mean duration of treatment. Clinical results were assessed at the end of therapy and follow-up (4-6 weeks). Bacteriological results were assessed at 5-9 days post-treatment and at follow-up. As regards clinical and bacteriological results patients showing a satisfactory response rate were compared, at the end of the treatments using a Chi square test. With both treatments high satisfactory clinical and bacteriological response rates were seen. As regards clinical satisfactory responses (97% of meropenem assessable patients versus 90% of imipenem/cilastatin assessable patients), there was a statistically significant difference in favor of meropenem. The bacteriological outcome was successful (eradication) for 75% of assessable patients in each group. Most failures were seen in the complicated infections, even when pathogens usually sensitives to carbapenemics were initially isolated. Safety was good with both drugs; no withdrawals in any group of treatment was seen because of side effects. The local tolerance of meropenem was globally rated as good.

Topics: Adult; Aged; Carbapenems; Chi-Square Distribution; Cilastatin; Cross Infection; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Urinary Tract Infections

Physicians must leverage several factors when making antibiotic therapy decisions, including route of administration and duration of therapy. Oral administration provides several potential advantages including increased accessibility, prevention of hospitalizations and earlier discharges. Sulopenem-a broad-spectrum, synthetic penem β-lactam agent-uniquely possesses both oral and IV formulations along with noted stability among antimicrobial-resistant subsets. This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales and anaerobic clinical isolates predominantly from patients with bloodstream, intra-abdominal and urinary tract infections.. A contemporary collection of 1647 Enterobacterales and 559 anaerobic isolates was assembled from medical centres in Europe and the USA. Isolates were susceptibility tested using the CLSI reference methods: broth microdilution for Enterobacterales and agar dilution for anaerobes.. Sulopenem demonstrated potent in vitro antimicrobial activity (MIC50/90, 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 99.2% of isolates at ≤1 mg/L. This activity was conserved against resistant phenotypes including ESBL-phenotype Escherichia coli (MIC50/90, 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC50/90, 0.06/1 mg/L). Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin- and trimethoprim/sulfamethoxazole-non-susceptible subsets (MIC50/90, 0.03-0.06/0.12-0.5 mg/L). Against anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% susceptible (CLSI)] were the most active compounds tested.. The potent in vitro activity of sulopenem against this large collection of recent Enterobacterales and anaerobic clinical isolates from multiple infection types supports its further clinical evaluation in the treatment of intra-abdominal and urinary tract infections.

Topics: Anaerobiosis; Anti-Bacterial Agents; Escherichia coli; Humans; Lactams; Meropenem; Microbial Sensitivity Tests; Urinary Tract Infections

Antimicrobial resistance due to β-lactamase production is a worldwide issue, and β-lactamase inhibitors have been developed to overcome the growing problem. This study aimed to evaluate the in vitro activities of two recently introduced carbapenem/β-lactamase inhibitor combinations - imipenem/relebactam and meropenem/vaborbactam - and their comparators against Enterobacterales from patients with urinary tract infections (UTIs).. Enterobacterales isolates from patients with UTIs in Taiwan and participating in the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2020 were included. Minimum inhibitory concentrations (MICs) for various antibiotics were determined using the broth microdilution method. Susceptibility was interpreted based on the MIC breakpoints of the Clinical and Laboratory Standards Institute 2022. Genes encoding common β-lactamases, including extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases, were detected using multiplex polymerase chain reaction.. A total of 309 Enterobacterales isolates were included, against which both imipenem/relebactam and meropenem/vaborbactam exerted excellent efficacy (275 of 309, 95% and 288 of 309, 99.3%, respectively). Among imipenem non-susceptible isolates, 17 of 43 (39.5%) and 39 of 43 (90.7%) were susceptible to imipenem/relebactam and meropenem/vaborbactam, respectively.. Imipenem/relebactam and meropenem/vaborbactam may be appropriate choices for treating UTIs due to Enterobacterales resistant to commonly used antibiotics. Continuous monitoring of antimicrobial resistance is crucial.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Drug Combinations; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Taiwan; Urinary Tract Infections

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs.. A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae.. Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01).. In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Cefmetazole is active against extended-spectrum β-lactamase-producing

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefmetazole; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Urinary Tract Infections

It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients.. A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members.. Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole.. Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.. Il est bien établi que l’utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l’utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d’améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d’infections, sont rares. Nous avons entrepris d’élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients.. Un comité de 12 experts, composé de microbiologistes cliniques, d’intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d’anesthésistes, a collaboré à l’élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité.. Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole.. Les données issues d’une surveillance multicentrique de trois unités de soins intensifs, d’antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d’experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l’apprentissage, l’amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l’évolution des besoins en antibiotiques.. Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Clavulanic Acid; Community-Acquired Infections; Critical Illness; Cross Infection; Fluconazole; Humans; Meropenem; Microbial Sensitivity Tests; Nigeria; Piperacillin, Tazobactam Drug Combination; Pneumonia; Prospective Studies; Urinary Tract Infections

Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic

Topics: Anti-Bacterial Agents; Bacteria; Colistin; Escherichia coli Infections; Humans; Meropenem; Urinary Tract Infections; Uropathogenic Escherichia coli

The old antimicrobial nitroxoline is currently repurposed for oral treatment of uncomplicated urinary tract infections (UTIs).. To investigate the in vitro activity of nitroxoline against carbapenem-resistant Acinetobacter baumannii (CRAb).. From an international collection of previously well-characterized clinical A. baumannii isolates, 34 isolates from urinary tract sources with different carbapenem-resistance mechanisms were selected. Nitroxoline activity was analysed with broth microdilution (BMD), disc diffusion (DD) and within an in vitro biofilm model. MICs of meropenem and imipenem were assessed with BMD. Susceptibility to ciprofloxacin and trimethoprim/sulfamethoxazole was investigated using DD. Escherichia coli ATCC 25922 and A. baumannii NCTC 13304 were used for quality control.. All isolates were carbapenem resistant (MIC90 >32 mg/L for meropenem and imipenem) and most isolates were resistant to ciprofloxacin (33/34) and trimethoprim/sulfamethoxazole (31/34). Nitroxoline yielded MIC50/90 values of 2/2 mg/L (MIC range 1-2 mg/L) and inhibition zone diameters ranging from 20 to 26 mm. In contrast, for definite eradication of biofilm-associated CRAb in vitro, higher nitroxoline concentrations (≥16 to ≥128 mg/L) were necessary for all isolates.. Nitroxoline showed excellent in vitro activity against a collection of CRAb despite high resistance rates to other antimicrobials for parental and oral therapy of A. baumannii UTI. Currently, nitroxoline is recommended for the treatment of uncomplicated UTI in Germany with a EUCAST breakpoint limited to uncomplicated UTI and E. coli (S ≤16 mg/L). Nitroxoline could be a promising drug for oral treatment of lower UTI caused by CRAb. More data are warranted to correlate these findings with in vivo success rates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Ciprofloxacin; Escherichia coli; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Nitroquinolines; Sulfamethoxazole; Trimethoprim; Urinary Tract; Urinary Tract Infections

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a frequent pathogen of the urinary tract, but how CRKP adapts

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbon; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Phylogeny; Urinary Tract Infections

UTIs are majorly caused by species of bacteria in patients of almost all ages. The study was aimed to determine the prevalence rate of uropathogens, its antibiotic susceptibility pattern and associated risk factors. Urine samples were collected from n=470 participants using sterilized containers and were inoculated on culture media. The isolates were identified via gram-staining and biochemical characterization. A total of 43.20% samples were positive. Female contributed the highest prevalence rate, 78.82% as compared to male, 21.18%. The highest prevalence 40.90% was observed in the age-group 31-45, followed by 16-30 with 36.90%. Escherichia coli (47.80%) was the most prevalent, followed by Klebsiella pneumoniae (18.2%), Enterococcus faecalis (12.80%), Pseudomonas aeruginosa (10.30%) and Proteus mirabilis (7.40%). Staphylococcus aureus showed high sensitivity (100%) to amikacin, meropenem, imipenem, fosfomycin, vancomycin, clindamycin and linezolid while in case of E. faecalis, vancomycin and linezolid were highly potent. Amikacin and meropenem showed the highest (100%) potency followed by imipenem While Fosfomycin was highly potent to E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa with potency rate 89.97%, 92.31%, 100% and 100% respectively. In the current study, the positivity rate was highly observed in female. E. coli and K. pneumoniae were found the most ubiquitous for UTI.

Topics: Amikacin; Anti-Bacterial Agents; Escherichia coli; Female; Fosfomycin; Humans; Imipenem; Klebsiella pneumoniae; Linezolid; Male; Meropenem; Pseudomonas aeruginosa; Risk Factors; Tertiary Care Centers; Urinary Tract Infections; Vancomycin

Topics: Agar; Ampicillin; Animals; Anti-Bacterial Agents; Biofilms; Drug Resistance, Bacterial; Ertapenem; Escherichia coli Infections; Female; Imipenem; Meropenem; Norfloxacin; Saudi Arabia; Sheep; Urinary Tract Infections; Uropathogenic Escherichia coli; Virulence Factors

There are limited oral antimicrobial options for the treatment of urinary infections caused by ESBL-producing and MDR Enterobacterales. Sulopenem is an investigational thiopenem antimicrobial that is being developed as both an oral and IV formulation. The purpose of this study was to evaluate the in vitro activity of sulopenem versus bacterial pathogens recovered from the urine of patients admitted to or assessed at hospitals across Canada (CANWARD).. The in vitro activity of sulopenem and clinically relevant comparators was determined for 1880 Gram-negative and Gram-positive urinary isolates obtained as part of the CANWARD study (2014 to 2021) using the CLSI broth microdilution method.. Sulopenem demonstrated excellent in vitro activity versus members of the Enterobacterales, with MIC90 values ranging from 0.06 to 0.5 mg/L for all species tested. Over 90% of ESBL-producing, AmpC-producing and MDR (not susceptible to ≥1 antimicrobial from ≥3 classes) Escherichia coli were inhibited by ≤0.25 mg/L of sulopenem. Sulopenem had an identical MIC90 to meropenem for ESBL-producing and MDR E. coli. The MIC90 of sulopenem and meropenem versus MSSA was 0.25 mg/L. Sulopenem was not active in vitro versus Pseudomonas aeruginosa (similar to ertapenem), and it demonstrated poor activity versus Enterococcus faecalis (similar to meropenem).. Sulopenem demonstrated excellent in vitro activity versus bacterial pathogens recovered from the urine of Canadian patients. These data suggest that sulopenem may have a role in the treatment of urinary infections caused by antimicrobial-resistant Enterobacterales, but additional clinical studies are required.

Topics: Anti-Bacterial Agents; Canada; Escherichia coli; Humans; Meropenem; Microbial Sensitivity Tests; Urinary Tract Infections

Limited therapeutic options exist for treating severe infections caused by multidrug-resistant (MDR) and extensively drug-resistant Gram-negative bacteria (GNB). In this study, the activity of colistin (COL) as monotherapy and in combination with other antibiotics against Acinetobacter baumannii in vitro was investigated. In addition, the efficacy of intravenous colistimethate sodium (CMS) was evaluated in a murine model of urinary tract infection (UTI) induced by MDR Escherichia coli.. Minimum inhibitory concentration (MIC), Monte Carlo simulation, fractional inhibitory concentration index (FICI), time-kill study and erythrocyte lysis assay were applied to evaluate the effect and cytotoxicity of COL, meropenem, imipenem, doripenem (DOR) and sulbactam alone and in combination. For the in vivo experiment, determination of the bacterial burden and histopathological examination were performed to evaluate the efficacy of CMS against UTI.. Of 106 A. baumannii isolates, 104 (98.1%) were susceptible to COL. In the chequerboard assay, COL + DOR showed the highest rate of synergism (60%). No antagonism or cytotoxicity was observed. All COL-based combinations were able to inhibit or slow bacterial re-growth in a time-kill assay. In an in vivo activity study, intravenous CMS reduced not only the bacterial load but also inflammation and maintained structural integrity of infected bladders and kidneys.. The effectiveness of COL alone in vitro and in vivo suggested that intravenous CMS will be an effective and available therapeutic strategy for UTI due to MDR-GNB. In-depth in vitro tests demonstrated that COL + DOR could be an attractive option, especially when the COL MIC is ≥1 μg/mL.

Topics: Acinetobacter baumannii; Administration, Intravenous; Animals; Anti-Bacterial Agents; Biofilms; Colistin; Disease Models, Animal; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Monte Carlo Method; Sulbactam; Treatment Outcome; Urinary Tract Infections

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

Topics: Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Humans; Injections; Meropenem; Spectrophotometry, Ultraviolet; Urinary Tract Infections

The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Ceftazidime; Cohort Studies; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Topics: Adult; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gentamicins; Humans; Male; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Urinary Tract Infections

The continued evolution of bacterial resistance to the β-lactam class of antibiotics has necessitated countermeasures to ensure continued effectiveness in the treatment of infections caused by bacterial pathogens. One relatively successful approach has been the development of new β-lactam analogs with advantages over prior compounds in this class. The carbapenems are an example of such β-lactam analogs possessing improved stability against β-lactamase enzymes and, therefore, a wider spectrum of activity. However, all carbapenems currently marketed for adult patients are intravenous agents, and there is an unmet need for an oral agent to treat patients that otherwise do not require hospitalization. Tebipenem pivoxil hydrobromide (tebipenem-PI-HBr or SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing

Topics: Adult; Animals; Anti-Bacterial Agents; Carbapenems; Humans; Meropenem; Mice; Urinary Tract Infections

Escherichia coli ST131 clone and H30-R/H30-Rx subclones are the most common multidrug-resistant high-risk clones in UTIs. Antimicrobial susceptibility of fosfomycin was compared to five other agents in consecutively collected 299 urinary isolates using the agar dilution method. Prevalence of the ST131 clone and the occurrence of blaCTX-M were also investigated. Overall resistance to fosfomycin, cefuroxime, and ceftriaxone were 2.7%, 35.4%, and 30.1% respectively. fosA, fosA3, and fosC2 genes were not detected. In isolates resistant to ciprofloxacin (34.7%), the prevalence of ST131 clone was 31.7%, of which 81.8% belonged to H30-R and 66.7% to H30-Rx subclones. None of the isolates of the ST131 clone were resistant to fosfomycin. However, bla

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Cefuroxime; Ciprofloxacin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Urinary Tract Infections; Virulence Factors

We report a case of a 58-year-old renal transplant patient who developed a recurrent urinary tract infection with an extended-spectrum β-lactamase (ESBL)-positive

Topics: Anti-Bacterial Agents; beta-Lactamases; Chronic Disease; Drug Resistance, Multiple, Bacterial; Humans; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Netherlands; Phage Therapy; Recurrence; Urinary Tract Infections

Topics: Amikacin; Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Drug Synergism; Escherichia coli; Fosfomycin; Humans; Meropenem; Microbial Sensitivity Tests; Urinary Tract Infections

Urinary tract infections (UTIs) are one of the most common infections in humans. Studies have shown that antibiotics for UTIs are usually prescribed empirically before the results of urine culture are available. The aim of the study was to assess the antimicrobial resistance patterns of bacteria isolated from urine samples over 6 years in Ayder Comprehensive Specialized Hospital (ACSH), in Mekelle, Northern Ethiopia.. A retrospective study of culture results of UTI samples was conducted in ACSH from January 2012 to December 2017. Data were collected using a structured data sheet format and were analysed using SPSS v.20.0.. Among 1080 urine samples tested during the 6-year period, 308 (28.5%) were positive for bacterial isolates. The majority of participants were female (57.8%). The three most commonly isolated bacteria were Escherichia coli (48.1%), Klebsiella pneumoniae (16.2%) and Pseudomonas aeruginosa (6.5%). Escherichia coli was found to be most susceptible to imipenem (100%) and most resistant to ampicillin (94.9%). Similarly, K. pneumoniae was sensitive to meropenem (100%) but resistant to penicillin (100%). Multidrug resistance to two or more antimicrobials was observed in 267 isolates (86.7%), with a non-significantly higher prevalence in females (χ. This study revealed that most of the urine isolates showed high levels of antimicrobial resistance to commonly prescribed antibiotics although they remained susceptible to imipenem, nitrofurantoin and meropenem. The results call for continuous surveillance of antimicrobial resistance for better management of patients with UTIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Drug Resistance, Bacterial; Escherichia coli; Ethiopia; Female; Humans; Infant; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillins; Pseudomonas aeruginosa; Retrospective Studies; Sex Characteristics; Tertiary Care Centers; Urinary Tract Infections; Urine; Young Adult

The recently approved combination of meropenem and vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Disease Models, Animal; Drug Combinations; Escherichia coli; Humans; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Pyelonephritis; Urinary Tract Infections

Carbapenem-resistant

Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Coordination Complexes; Copper; Ertapenem; Escherichia coli; Humans; Ions; Meropenem; Microbial Sensitivity Tests; Urinary Tract Infections

Meropenem-vaborbactam is a fixed-dose combination product of a carbapenem and a cyclic boronic acid β-lactamase inhibitor with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE). The efficacy of meropenem-vaborbactam for the treatment of complicated urinary tract infections and acute pyelonephritis was demonstrated in a Phase III trial (TANGO I). Preliminary data from TANGO II, a separate Phase III study, support the efficacy of meropenem-vaborbactam for the treatment of infections caused by CRE. Overall, meropenem-vaborbactam appears to be safe and well tolerated. It has favorable toxicity, pharmacokinetic and pharmacodynamic profiles compared with other antibiotics with activity against CRE. Meropenem-vaborbactam is an important addition to the current armamentarium of antimicrobial agents with activity against K. pneumoniae carbapenemase-producing CRE.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Boronic Acids; Clinical Trials, Phase III as Topic; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Gram-Negative Bacterial Infections; Humans; Meropenem; Treatment Outcome; Urinary Tract Infections

Carbapenemase-producing Escherichia coli are a major clinical concern. The current study aimed to identify NDM-5-producing E. coli associated with community-acquired urinary tract infections (UTIs) co-harbouring extended-spectrum β-lactamases (ESBLs) and showing a phenomenon of imipenem minimum inhibitory concentration (MIC) creep.. A total of 973 urine samples were collected from females aged between 18-49 years diagnosed with UTI in Northeast India (June 2014-July 2016). Isolates were identified by standard microbiological methods. The presence of bla. This study observed a unique phenotype of NDM-producers that has not been reported previously. The observed phenomenon poses a global threat as these pathogens may evade phenotypic screening by routine laboratories.

Topics: Adult; beta-Lactamases; Community-Acquired Infections; Ertapenem; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Imipenem; India; Meropenem; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Plasmids; Urinary Tract Infections; Young Adult

Topics: Anti-Bacterial Agents; Drug Approval; Humans; Meropenem; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Thienamycins; United States; United States Food and Drug Administration; Urinary Tract Infections

In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring.. A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.. Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.. Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Cross Infection; Drug Monitoring; Female; Humans; Imipenem; Infant; Intensive Care Units; Male; Meropenem; Middle Aged; Piperacillin; Pneumonia; Prognosis; Tertiary Care Centers; Thienamycins; Urinary Tract Infections; Vancomycin; Young Adult

To identify frequency of uropathogenic Escherichia coli and its antibiotic susceptibility pattern.. This cross-sectional study was conducted at Khyber Teaching Hospital, Peshawar, Pakistan, from January 2014 to September 2015, and comprised urine specimens. Biochemical techniques were used to identify Escherichia coli and antibiotic susceptibility was determined by Kirby-Bauer disk diffusion and minimum inhibitory concentration methods. SPSS 23 was used for data analysis.. Of the 787 urine samples, 458(58.2%) grew significant positive growths. Escherichia coli growths were present in 351(76.6%) positive cultures of which 108(30.8%) came from males and 243(69.2%) from female patients. Resistance to fluoroquinolones tested was almost similar (p>0.05). Escherichia coli was highly sensitive to imipenem (98.6%), meropenem (97.8%), tazobactum (96.2%), cefoperazone+sulbactam (93.9%) and amikacin(92.5%).. Escherichia coli was a common pathogen causing urinary tract infections and was highly sensitive to imipenem, meropenem, tazobactum, cefoperazone+sulbactam and amikacin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Cefoperazone; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fluoroquinolones; Humans; Imipenem; Infant; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sulbactam; Tazobactam; Urinary Tract Infections; Young Adult

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nitrofurantoin; Urinary Tract Infections; Young Adult

Topics: Anti-Bacterial Agents; Drug Combinations; Enterobacter cloacae; Escherichia coli; Humans; Infusions, Intravenous; Klebsiella pneumoniae; Meropenem; Thienamycins; Urinary Tract Infections

Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia.. We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones.. Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae .. Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Catheter-Related Infections; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Indonesia; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Population Surveillance; Tertiary Care Centers; Thienamycins; Tigecycline; Urinary Tract Infections; Young Adult

We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Catheter-Related Infections; Female; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Prospective Studies; Salvage Therapy; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

Aerococcus urinae is an uncommon pathogen that was first identified in 1992. Herein, we report a case of bloodstream infection caused by A. urinae, which occurred in a 92-year-old Korean female patient with an underlying urologic infection who had altered consciousness. The blood culture yielded positive results for A. urinae; however, identifying A. urinae was challenging. Ultimately, we used 16S ribosomal RNA (rRNA) gene sequencing to identify the organism. The patient recovered after being treated with ertapenem and meropenem. To our knowledge, this is the first report of a case of A. urinae sepsis in South Korea.

Topics: Aerococcus; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Ertapenem; Female; Gram-Positive Bacterial Infections; Humans; Meropenem; Remission Induction; RNA, Ribosomal, 16S; Sepsis; Sequence Analysis, RNA; Thienamycins; Urinary Tract Infections

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Purple Urine Bag Syndrome (PUBS) refers to the purple discoloration of urine and is commonly observed in bed ridden patients with long-term urinary catheters. Although typically benign, the purple discoloration is alarming to both the patients and their attendants. This case report presents an uncommon case of PUBS in a 60-year-old lady with hypertension, type II diabetes, and chronic kidney disease stage 5, who presented to the emergency room with bilateral diabetic foot ulcers of 3 months duration, dry gangrene of ring finger and infected middle and little fingers with abscess over the palmar aspect of right hand of 20 days duration. PUBS is generally associated with alkaline urine as was observed in this patient, although it has also been reported in acidic urine. PUBS has long been documented in association with constipation and so has its association with diarrhea, a finding also observed in this case report.

Topics: Aged; Anti-Bacterial Agents; Catheters, Indwelling; Female; Humans; Hydrogen-Ion Concentration; Indoles; Meropenem; Thienamycins; Urinary Catheterization; Urinary Catheters; Urinary Tract Infections; Urine; Vancomycin

Topics: Aged, 80 and over; Anti-Infective Agents, Urinary; Delirium; Diagnosis, Differential; Humans; Male; Meropenem; Neurotoxicity Syndromes; Thienamycins; Treatment Outcome; Urinary Tract Infections

Eravacycline (formerly TP-434) was evaluated in vitro against pre-established biofilms formed by a uropathogenic Escherichia coli strain. Biofilms were eradicated by 0.5 μg/ml eravacycline, which was within 2-fold of the MIC for planktonic cells. In contrast, colistin and meropenem disrupted biofilms at 32 and 2 μg/ml, respectively, concentrations well above their respective MICs of 0.5 and 0.03 μg/ml. Gentamicin and levofloxacin eradicated biofilms at concentrations within 2-fold of their MICs.

Topics: Anti-Bacterial Agents; Biofilms; Colistin; Colony Count, Microbial; Escherichia coli Infections; Gentamicins; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Tetracyclines; Thienamycins; Urinary Tract Infections; Uropathogenic Escherichia coli

An increasing incidence of extended-spectrum β-lactamase (ESBL-) producing Escherihia Coli poses a difficult problem for clinicians to establish an optimal strategy for the effective antibiotic treatment of urinary tract infections (UTI).. (1) Fosfomycin/minocycline (FOM/MINO) or rifampicin/sulfamethoxazole-trimethoprim (RFP/ST) combinations and (2) levofloxacin (LVFX) alone were used as an internal medication, and (3) cefoperazone/sulbactam (CPZ/SBT) and (4) meropenem (MEPM) were administered through intravenous injection. The selection of antibiotics was done empirically, according to the history and severity of illness and urinary findings, and the presence of comobidities. The efficacy of the treatment was determined by the absence of any pathogenic bacteria from a urinary culture after treatment.. ESBL-producing and LVFX resistant non-ESBL producing E. coli were detected by an initial urinary culture in 33 and 10%, respectively, of the specimens before treatment. All the ESBL-producing E. Coli colonies were resistant against LVFX. The efficacy of the treatment was 9/11 (82%) in the FOM/MINO-RFP/ST group, 9/14 (64%) in the LVFX group, 9/16 (56%) in the CPZ/SBT group, and 19/27 (70%) in the MEPM group. In the FOM/MINO・RFP/ST group, ESBL-producing E. Coli were detected in the urine before treatment in 5 out of 16 patients and those E. coli disappeared after treatment in all 5 patients. In the LVFX group, the drug was changed to MEPM in 6 out of 15 patients soon after the presence of ESBL-producing/LVFX resistant E. Coli was identified by a urinary culture. In the CPZ/SBT group, ESBL-producing and/or LVFX-resistant E. coli disappeared in 4 out of 6 cases, while they were newly found in post-treatment urine cultures in 2 patients. In the MEPM group, 15 out of 28 patients initially had ESBL-producing/LVFX resistant E. Coli and those drug-resistant E. Coli disappeared from their urine after treatment in all patients. The drug susceptibility test of the urinary culture from all the patients with UTI showed CPZ/SBT-resistant colonies to be found in 19 out of 32 specimens, while AMPC/CVA-resistant ones were found in 9 out of 32 of ESBL-producing E. Coli.. Our present study demonstrates that FOM/MINO or ST combinations were effective in the treatment of ESBL-producing E. Coli in mild cases of UTI and MEPM in severe cases. When using β-lactam/β-lactamase inhibitor combinations, the effect should be ascertained by examining post-treatment urinary specimens, because of the presence of ESBL-producing E. Coli strains which are resistant to those antibiotics.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Meropenem; Middle Aged; Thienamycins; Urinary Tract Infections

This cross-sectional study was conducted at a tertiary care centre in Puducherry, south India, with the aim of finding the profile of the paediatric urinary tract infection (UTI), bacterial pathogens involved, and also to observe vesicoureteric reflux (VUR) and renal scarring in these patients.. A total of 524 paediatric patients ≤13 yr, suspected to have UTI, were included in the study. Urine samples were collected, processed for uropathogen isolation and antibiotic susceptibility test was performed as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Thirty two culture proven children with UTI underwent micturating cysto-urethrography (MCU) and dimercaptosuccinic acid (DMSA) scanning was done for 69 children.. o0 f the 524 children, 186 (35.4%) had culture proven UTI with 105 (56.4%) being infants, 50 (27.4%) between 1-5 yr, 30 (16.12%) between 5-13 yr and 129 (69.35%) males. Posterior urethral valve (PUV) was noted in three, hydronephrosis in one, VUR in 18 and renal scarring in 33. VUR as well as renal scarring were more in males >1 yr of age. A significant association (P=0.0054) was noted with a combined sensitivity and specificity of these investigations being 83 and 90 per cent, respectively of the MCU and DMSA scans for detecting VUR. Escherichia coli was the most common pathogen isolated, sensitive to nitrofurantoin, followed by cefoperazone-sulbactam, aminoglycosides and meropenem.. Our results indicate that UTI varies with age and gender and extensive evaluation is required in boys over one year of age with UTI. This study also highlights the better efficacy of aminoglycosides, cefoperazone-sulbactam and nitrofurantoin in vitro compared with meropenem in Gram-negative uropathogens.

Topics: Aminoglycosides; Cefoperazone; Child; Child, Preschool; Escherichia coli; Female; Humans; India; Infant; Infant, Newborn; Male; Meropenem; Nitrofurantoin; Thienamycins; Urinary Tract Infections; Vesico-Ureteral Reflux

In 2010, our hospital, in line with National guidance, changed advice on antibiotic prescribing for UTI to reduce use of cephalosporins in favour of penicillins. We hypothesized that this change in policy would have no impact on the pattern of antibiotic resistance of the organisms causing UTI.. Audit review of all urine samples sent to BWH from 2009 to 2013 and positive cultures showing Enterobacteriaceae were then tested for antibiotic susceptibility.. There has been an increase in the resistance of both Co-amoxiclav and Ciprofloxacin since 2009. Co-amoxiclav and trimethoprim now have similar resistance rates. Ciprofloxacin resistance has risen fairly quickly in the last four years from 1% to 8%. Resistance to nitrofurantoin has remained low. Gentamicin resistance remained stable and very low, second best to meroponem.. The results have been fed back to commissioners and internally and are being used as part of the guideline updating process.. Hospital protocols for treating infections should be reviewed and updated based on accurate local data. These data should be used for formulating regional specific protocols. Our results suggest that meroponem and ciprofloxacin should be reserved for microbiologically proven resistance to other antibiotics.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ciprofloxacin; Clinical Audit; Drug Resistance, Bacterial; England; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Gentamicins; Health Policy; Humans; Meropenem; Microbial Sensitivity Tests; Nitrofurantoin; Practice Guidelines as Topic; Thienamycins; Trimethoprim; Urinary Tract Infections

The purpose of this study is to investigate the prevalence of postoperative bacteriuria, pyuria and urine culture in patients with an orthotopic sigmoid colon neobladder replacement. Urine samples for bacteriuria, pyuria and urine culture, if necessary, were collected at 1, 3, 6, 9 and 12 months after surgery and the presence of blood culture and antibiotic-resistant strains, and their treatments on positive urine culture cases were investigated. Of 209 for bacteriuria and 207 for pyuria urine samples with evaluable data, 95 (45.5%) were positive for bacteriuria and 76 (36.7%) had pyuria (10 or more white blood cells per high-power field). Totally, 30 bacteria were isolated from urine culture of urinary tract infection (UTI) and Klebisiella pneumoniae, Escherichia coli, Staphylococcos aureus and Enterococcus spp. strains were representatively isolated. The incidence of pyuria significantly decreased over time (P=0.041) but that of bacteriuria did not (P=0.107). In them, there were six bacteria (20.7%) with antibiotic-resistant strains. The antibiotics used for their treatments representatively were levofloxacin in five cases, tazobactam/piperacillin in three cases and sulfamethoxazole/trimethoprim and cefepime, meropenem in two cases, respectively. In conclusion, these findings suggest that physicians taking care of sigmoid colon neobladder patients need to be aware of these high ratios of bacteriuria, pyuria and UTI, including bacteremia.

Topics: Aged; Anti-Bacterial Agents; Bacteriuria; Cefepime; Cephalosporins; Colon, Sigmoid; Cystectomy; Drug Resistance, Multiple, Bacterial; Enterococcus; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Leukocyte Count; Levofloxacin; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Postoperative Complications; Prevalence; Pyuria; Staphylococcus aureus; Sulfamethoxazole; Tazobactam; Thienamycins; Trimethoprim; Urinary Diversion; Urinary Tract Infections

Ertapenem plus doripenem or meropenem were given in three patients suffering from pandrug-resistant, KPC-2-positive Klebsiella pneumoniae bacteremia (2 patients) and urinary tract infection (1 patient), respectively. All responded successfully, without relapse at follow-up. The results obtained should probably be attributed to ertapenem's increased affinity for the carbapenemases hindering doripenem/meropenem degradation in the environment of the microorganism.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Doripenem; Drug Combinations; Drug Resistance, Bacterial; Ertapenem; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome; Urinary Tract Infections

Salmonella enterica serovar Minnesota is a rarely isolated organism in clinical samples mainly grown from stool cultures. Sepsis due to Salmonella is known in severely immunocompromised patients, but so far urosepsis due to S. enterica serovar Minnesota has not been described. We report a case of a 31-year-old patient suffering from Crohn's disease treated with infliximab and azathioprine, in whom was implanted a double-J ureteric catheter for urolithiasis. The patient presented with urinary tract infection and severe sepsis. S. enterica serovar Minnesota was grown from urine and blood cultures. After empiric antimicrobial treatment with meropenem and vancomycin, treatment was changed to ceftriaxone. Antimicrobial treatment was continued for a total of 3 weeks without evidence of Salmonella recurrence on follow-up visits. Salmonella spp. rarely cause urinary tract infection and sepsis. However, in immunocompromised patients, non-typhoidal salmonellosis merits a thorough clinical and microbiological evaluation.

Topics: Adult; Antibodies, Monoclonal; Ceftriaxone; Crohn Disease; Humans; Infliximab; Male; Meropenem; Recurrence; Salmonella enterica; Salmonella Infections; Sepsis; Thienamycins; Urinary Catheters; Urinary Tract Infections; Urolithiasis; Vancomycin

A strain of Klebsiella pneumoniae (K1) was isolated from a catheterized patient with a urinary tract infection. The patient was subsequently treated with meropenem, after which K. pneumoniae (K2) was once again isolated from the patient's urine. Susceptibility testing showed that strain K1 was fully susceptible to carbapenem antibiotics with the exception of ertapenem, to which it exhibited intermediate resistance, whilst K2 was resistant to ertapenem and meropenem. From pulsed-field gel electrophoresis profiling both strains exhibited identical banding patterns. Both contained CTX-M-15, OXA-1, SHV-1 and TEM-1 β-lactamase genes following PCR analyses. Outer membrane protein analysis demonstrated that K1 and K2 lacked an OMP of c. 40 kDa, with an additional OMP of c. 36 kDa missing from K2. Mutation studies showed that the K2 OMP phenotype could be selected by single-step carbapenem-resistant mutants of K1. Expression of transcriptional activator ramA and efflux pump component gene acrA were up-regulated in both strains by RT-PCR. Neither strain expressed ompK35, but ompK36 was found in both. Sequence analysis revealed gene sequences of ompK35, ompK36 and ramR in both strains; notably, ramR contained a mutation resulting in a premature stop codon. Transconjugation studies demonstrated transfer of a plasmid into E. coli encoding the CTX-M-15, TEM-1 and OXA-1 β-lactamases. We concluded that the carbapenem-resistant phenotype observed from this patient was attributable to a combination of CTX-M-15 β-lactamase, up-regulated efflux and altered outer membrane permeability, and that K2 arose from K1 as a direct result of meropenem therapy.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactam Resistance; beta-Lactams; Catheter-Related Infections; Conjugation, Genetic; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Ertapenem; Gene Expression Profiling; Gene Transfer, Horizontal; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Molecular Weight; Mutation; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Selection, Genetic; Thienamycins; Urinary Tract Infections; Urine

A case is presented of a breast-feeding mother receiving meropenem treatment for a postpartum urinary tract infection caused by extended-spectrum beta-lactamase producing Escherichia coli. Five milk samples were collected in a 48-hour period during meropenem therapy. The average and maximum meropenem concentrations in milk were 0.48 and 0.64 µg/mL, respectively. Based on the maximum concentration, the calculated infant daily exposure from breast milk was 97 µg/kg/d, and the infant weight-adjusted percentage of maternal dosage was 0.18%. There were no dermatologic or gastrointestinal side effects noted in the breastfed infant. Meropenem appears to be acceptable to use during breast-feeding.

Topics: Adult; Anti-Bacterial Agents; Breast Feeding; Escherichia coli Infections; Female; Humans; Infant, Newborn; Lactation; Meropenem; Milk, Human; Pregnancy; Thienamycins; Urinary Tract Infections

Among 213 Pseudomonas aeruginosa isolates collected from 10 South Korean hospitals, 57 isolates (26.8%) were carbapenem-resistant. All but three of the isolates had a relevant decrease of oprD expression. However, decreased oprD expression was also detected in five of ten carbapenem-susceptible isolates. Outer membrane protein analysis confirmed porin loss in carbapenem-resistant P. aeruginosa isolates. Based on the mutations of oprD gene sequences, carbapenem-resistant P. aeruginosa isolates could be classified into five oprD mutational groups. However, there was no difference of OprD expression or carbapenem minimum inhibitory concentrations among the five mutational groups. Among the 57 carbapenem-resistant P. aeruginosa isolates, 41 (71.9%) overexpressed efflux systems or ampC. MexAB-OprM and AmpC overexpression (56.1% and 47.4%, respectively) was prevalent and was significantly associated with carbapenem resistance. However, no synergistic effect of efflux systems and AmpC on carbapenem resistance was evident. In conclusion, combination of several mutation-driven mechanisms leading to OprD inactivation and overexpression of efflux systems was the main carbapenem resistance mechanism, but acquisition of a transferable resistance determinant such as metallo-β-lactamase could be problematic in clinical settings in South Korea.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Gene Silencing; Genes, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Mutation; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Urinary Tract Infections

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; India; Infant; Meropenem; Thienamycins; Travel; Treatment Outcome; Urinary Tract Infections

Topics: Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Bacterial Proteins; beta-Lactamases; Coinfection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; R Factors; Thienamycins; Urinary Tract Infections

A total of 950 gram-negative bacterial isolates from patients with bacteremia and urinary tract infections were collected from tertiary-care hospitals in Korea. In vitro antimicrobial susceptibility testing was performed using broth microdilution test according to Clinical and Laboratory Standards Institute protocol. In general, carbapenems such as doripenem, imipenem, and meropenem were very active against Enterobacteriaceae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Acinetobacter sp. isolates. Doripenem was more potent than imipenem against most Enterobacteriaceae species except Proteus spp. based on minimum inhibitory concentration (MIC)(50) and MIC(90). In addition, doripenem displayed similar activity to meropenem but was superior to imipenem against ceftazidime-resistant Enterobacteriaceae isolates. For P. aeruginosa and Acinetobacter spp. isolates, MIC(50)s of doripenem were 1 and 0.5 mg/L, respectively, which were the same with those of meropenem but two- to fourfold lower than those of imipenem (both 2 mg/L). On the basis of the in vitro data, we conclude that doripenem has equivalent or more activity than other carbapenems such as imipenem and meropenem against most gram-negative pathogens from Korea. Thus, doripenem may be a promising new antimicrobial agent for the treatment of infections caused by gram-negative pathogens in Korea.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Doripenem; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Korea; Meropenem; Microbial Sensitivity Tests; Republic of Korea; Thienamycins; Urinary Tract Infections

Emphysematous pyelonephritis (EPN) is a rare, life threatening, upper urinary tract infection with high mortality rate.. We report a type-2 diabetes mellitus patient presenting with persistent fever, vomiting and pyuria despite appropriate treatment, diagnosed as a case of EPN, recovered without any surgical intervention.. Suspicion of EPN should be entertained in diabetes mellitus patient with persistent pyuria and deteriorating condition despite adequate treatment with antibiotics.

Topics: Anti-Infective Agents; Diabetes Mellitus, Type 2; Diagnosis, Differential; Emphysema; Escherichia coli; Escherichia coli Infections; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Meropenem; Metronidazole; Middle Aged; Pyelonephritis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome; Urinary Tract Infections

Topics: Acetamides; Acidosis, Lactic; Anti-Infective Agents; Citrobacter freundii; Enterobacteriaceae Infections; Female; Humans; Immunocompromised Host; Kidney Transplantation; Linezolid; Meropenem; Middle Aged; Oxazolidinones; Thienamycins; Urinary Tract Infections

A 25-year-old female was admitted to our intensive care unit with septic shock and multiorgan failure caused by extended-spectrum beta-lactamase-producing Escherichia coli originating from the right renal pelvis. A 16-day course of treatment with meropenem reversed the septic condition, but the infection recurred thereafter. The patient recovered fully after therapy was changed to tigecycline.

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Meropenem; Minocycline; Recurrence; Shock, Septic; Thienamycins; Tigecycline; Urinary Tract Infections

The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90: < or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to > 128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).

Topics: Aminoglycosides; Ampicillin; Anti-Infective Agents; Aztreonam; Cefixime; Cefozopran; Cefpirome; Cefpodoxime; Ceftizoxime; Cephalosporins; Dibekacin; Drug Resistance, Bacterial; Enterococcus faecalis; Escherichia coli; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Proteus mirabilis; Pseudomonas aeruginosa; Quinolones; Serratia marcescens; Staphylococcus aureus; Thienamycins; Urinary Tract Infections; Vancomycin

A 76-year-old woman had recurrent urosepsis due to extended-spectrum beta -lactamase-positive Escherichia coli. Imipenem resistance was detected after long-term imipenem-meropenem therapy. The carbapenem-hydrolyzing enzyme gene was identified as blaKPC-3. To our knowledge, this is the first documented case in which carbapenem-resistant E. coli emerged during therapy with imipenem and meropenem, and the first identification of the carbapenem-hydrolyzing enzyme in E. coli isolates.

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins; Urinary Tract Infections

The incidence of candiduria is increasing in teaching hospitals. We examined the hypothesis that this trend was correlated with the amount of departmental antibiotic consumption. In the setting of a large teaching hospital in Israel, the correlation coefficient between departmental intravenous antibiotic consumption (expressed as daily defined dose (DDD)/1000 patient-days) and the incidence of candiduria per 1000 patient-days was 0.47 (P=0.03). For broad-spectrum antibiotics, the corresponding correlation coefficient was 0.66 (P=0.001). The strongest correlation with candiduria was shown for the use of meropenem (r=0.79, P<0.001) and ceftazidime (r=0.66, P=0.001). This is the first time that departmental habits of antibiotic use have been shown to be strongly correlated with the incidence of candiduria in hospitalized patients. These results add an important new dimension to the strategy of restricting broad-spectrum antibiotics.

Topics: Anti-Bacterial Agents; Candida; Candidiasis; Ceftazidime; Cross Infection; Drug Utilization; Hospital Bed Capacity, 500 and over; Hospital Departments; Hospitals, Teaching; Humans; Incidence; Infection Control; Infusions, Intravenous; Internal Medicine; Israel; Meropenem; Organizational Policy; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Surgery Department, Hospital; Thienamycins; Urinary Tract Infections

The antibacterial activity of S-4661, a new parenteral carbapenem antibiotic, was assessed against the major urological pathogens isolated from patients with complicated urinary tract infections. S-4661 was slightly less active than imipenem and panipenem, but more active than meropenem and ceftazidime against Gram-positive bacteria. Against Gram-negative bacteria, S-4661 was similar to meropenem, similar to or more effective than imipenem, and more active than panipenem and ceftazidime. Thus S-4661 possesses potent and well-balanced wide-spectrum antibacterial activity against various urological pathogens.

Topics: Anti-Bacterial Agents; Bacteria; Carbapenems; Ceftazidime; Doripenem; Humans; Imipenem; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; Thienamycins; Urinary Tract Infections

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.

Topics: Bacterial Infections; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Infant, Premature; Meningitis, Bacterial; Meropenem; Neutropenia; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Thienamycins; Urinary Tract Infections

We compared the antimicrobial activities of penems in human urine with those in Mueller-Hinton broth in order to clarify the usefulness of penems for urinary tract infections. Furthermore, we also investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activities of penems. Three penems, i.e., imipenem, panipenem and meropenem were employed. And two bacterial strains, i.e., Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18s, were tested. There was no significant difference in MBCs between human urine and Mueller-Hinton broth against E. coli. However, MBCs of penems in human urine was lower than those in Mueller-Hinton broth against P. aeruginosa. On the other hand, MBCs of penems against these two strains were low when urine pH was high or urine calcium concentration was low. No influence of urine magnesium concentration on MBCs of penems was seen. From these results, it was suggested that we should measure the antimicrobial activities of penems not only in Mueller-Hinton broth, but also in human urine, when we administer penems to patients with urinary tract infections. And we should foresee the clinical effects of penems against urinary tract infections paying attention to urine pH of the patients.

Topics: Cations, Divalent; Escherichia coli; Humans; Hydrogen-Ion Concentration; Imipenem; Meropenem; Pseudomonas aeruginosa; Thienamycins; Urinary Tract Infections; Urine

Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Escherichia coli Infections; Guinea Pigs; Immunosuppression Therapy; Lung Diseases; Male; Meropenem; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Pseudomonas Infections; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections