meropenem and Klebsiella-Infections

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

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

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

Klebsiella pneumoniae infection can induce multiple invasive abscesses, and the invasive infection is severe and life-threatening.. A 69-year-old previously healthy Chinese male presented with fever, chill, backache, and ocular pain.. The blood culture results indicated Klebsiella pneumoniae of the K1 serotype. Multiple invasive abscesses in liver, lung, eye, soft tissue, and central nervous system were identified by imaging examination. Subsequently, the patient experienced right ocular pain accompanied by visual disturbance. Tyndall sign was strongly positive, and lens opacity was observed by the ophthalmologist.. Full-dose and long-term treatment with meropenem was performed. Intraventricular injection of glass and anterior chamber puncture with antibiotics were performed twice. The patient also underwent an evacuation of the brain abscess.. The patient's headache and lumbar backache were relieved, his ophthalmodynia disappeared, and his vision recovered after nearly 3 months of treatment.. Imaging examination is very important for severe Klebsiella pneumoniae infection. The choice of antibiotics is complex, and the antimicrobial regimen should be adjusted according to the assessment of illness and the therapeutic effect. Surgical intervention must be considered for patients with multiple invasive abscesses.

Topics: Abscess; Aged; Anti-Bacterial Agents; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem

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

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

17-year-old man had been involved in a traffic accident. He underwent a bilateral craniotomy with artificial dura mater to remove bilateral acute subdural hematomas. Seven months later, a right cranioplasty was performed using frozen auto-bone, and he developed extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae meningitis and an epidural abscess. Since his general status was poor, we could not remove the foreign body (artificial dura mater). He was successfully treated with meropenem and chronic suppression with oral trimethoprim-sulfamethoxazole. By describing this case and the results of a review of the pertinent literature, we discuss the importance of ESBL-producing Klebsiella pneumoniae meningitis in posttraumatic/postoperative patients.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactamases; Craniotomy; Drug Therapy, Combination; Epidural Abscess; Hematoma, Subdural, Acute; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Meropenem; Postoperative Period; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Septic arthritis due to Klebsiella species is a rare but serious infection that may destroy a joint and cause serious immobility. This is a report of two immunocompromised adult patients presenting with acute septic arthritis due to extended spectrum beta lactamase producing Klebsiella pneumoniae. The infection was treated successfully with a course of meropenem and amikacin in combination with early arthroscopic washout of the joint. Little information has been published on the management of this infection. We are therefore presenting a systematic literature review summarizing risk factors, clinical presentation, laboratory diagnosis, treatment regimens and outcome of this condition.. On the basis of our study, we recommend an early diagnostic arthrocentesis of the joint for Gram stain microscopy, culture and antibiotic sensitivity testing to guide the appropriate use of antibiotics. In cases of hospital acquired infections where drug resistant Gram negative bacteria are suspected or prevalent, broad-spectrum antibiotics such as meropenem plus or minus amikacin may be given as the empirical treatment until the sensitivities are confirmed. In addition, adequate surgical joint lavage should be considered as the mainstay of treatment.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Arthritis, Infectious; beta-Lactamases; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Middle Aged; Risk Factors; Thienamycins

To review the laboratory diagnosis of extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase-producing bacteria and evaluate potential treatment options.. A PubMed search, restricted to English-language articles, was conducted (1966-May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles.. All studies that evaluated laboratory methods for the detection of ESBLs and AmpC beta-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated.. Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC beta-lactamases are limited, particularly for plasmid-mediated AmpC beta-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC beta-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms.. Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute-recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC beta-lactamases. No established guidelines exist for the detection of AmpC beta-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC beta-lactamase-producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins

Increasing prevalence of multidrug-resistant gram-negative organisms has led to a rise in clinically significant infections with these organisms and an increasing therapeutic dilemma. We present a case of a neurosurgical patient who developed ventriculoperitoneal shunt-associated ventriculitis due to ceftazidime-resistant Klebsiella pneumoniae susceptible to cefepime, imipenem, meropenem, and polymyxin B only. Successful management was accomplished by removal of the shunt and therapy with systemic meropenem and intraventricular polymyxin B. Rapid cerebrospinal fluid (CSF) sterilization occurred, with CSF bactericidal titers of 1:32 to 1:128. Polymyxin B should be considered as adjunctive therapy for life-threatening multidrug-resistant gram-negative infections. Prior literature on use of intrathecal polymyxin B in therapy for meningitis supports its potential efficacy.

Topics: Anti-Bacterial Agents; Ceftazidime; Cerebrospinal Fluid; Cross Infection; Drug Resistance, Microbial; Female; Humans; Injections, Intravenous; Injections, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Middle Aged; Polymyxin B; Thienamycins

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

Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.. To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.. Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.. Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

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

Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens.. Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1-2 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5 h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4× MIC (fCmin > 4× MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR).. Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean ± standard deviation (SD) value, 9.38 ± 4.47 L/h). Mean C min value was 7.90 ± 7.91 mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5 % of patients achieved effective C min > 4× MIC values after 3- and 5-h i.v. infusions of meropenem 2 g × 3/day, respectively. On the contrary, the same total daily doses reached the target C min > 4× MIC values in 100 % of patients when administered as continuous i.v. infusions.. Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Models, Biological; Sepsis; Thienamycins

Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.. The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.. The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Clinical Protocols; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Klebsiella Infections; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sample Size; Thienamycins

Recently, new broad spectrum carbapenem has been investigated on a world-wide scale for the treatment of moderate to severe infections. In the neonatal intensive care units the extensive use of third generation cephalosporins for therapy of neonatal sepsis may lead to rapid emergence of multiresistant gram-negative organisms. We report the use of meropenem in 35 infants with severe infections due to Acinetobacter baumanii and Klebsiella pneumoniae. All gram negative bacteria were resistant to ampicillin, amoxicillin, ticarcilin, cefazoline, cefotaxime, ceftazidime, ceftriaxone and aminoglycosides. Eighty two percent of the cases (29/35) were born prematurely. Assisted ventilation was needed in 85.7% (30/35). All infants deteriorated during their conventional treatment and were changed to meropenem monotherapy. Six percent (2/35) died. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 8.5%. No adverse effects such as diarrhea, vomiting, rash, glossitis, oral or diaper area moniliasis, thrombocytosis, thrombocytopenia, eosinophilia and seizures were observed. At the end of therapy, overall satisfactory clinical and bacterial response was obtained in 33/35 (94.3%) of the newborns treated with meropenem. Clinical and bacterial response rates for meropenem were 100% for sepsis and 87.5% for nosocomial pneumonia. This report suggests that meropenem may be a useful antimicrobial agent in neonatal infections caused by multiresistant gram negative bacilli. Further studies are needed to confirm these results: Meropenem, newborn, sepsis and nosocomial infection.

Topics: Acinetobacter Infections; Cross Infection; Drug Resistance, Multiple; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Male; Meropenem; Prospective Studies; Thienamycins

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Thienamycins

Carbapenem-resistant bacterial infections pose an urgent threat to public health worldwide. Horizontal transmission of the β-lacatamase Klebsiella pneumoniae carbapenemase (blaKPC) multidrug resistance gene is a major mechanism for global dissemination of carbapenem resistance. Here, we investigated the effects of baicalein, an active ingredient of a Chinese herbal medicine, on plasmid-mediated horizontal transmission of blaKPC from a meropenem-resistant K. pneumoniae strain (JZ2157) to a meropenem-sensitive Escherichia coli strain (E600). Baicalein showed no direct effects on the growth of JZ2157 or E600. Co-cultivation of JZ2157 and E600 caused the spread of meropenem resistance from JZ2157 to E600. Baicalein at 40 and 400 µg/mL significantly inhibited the spread of meropenem resistance. Co-cultivation also resulted in plasmid-mediated transmission of blaKPC from JZ2157 to E600, which was inhibited by baicalein. Therefore, baicalein may be used in clinical practice to prevent or contain outbreaks of carbapenem-resistant infections by inhibiting the horizontal transfer of resistance genes across bacteria species.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Escherichia coli; Genes, MDR; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Paraoxon; Plasmids

In this study, we aimed to clarify the evolutionary trajectory of a Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) population during β-lactam antibiotic therapy. Five KPC-Kp isolates were collected from a single patient. Whole-genome sequencing and a comparative genomics analysis were performed on the isolates and all

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Cefiderocol; Ceftazidime; Drug Combinations; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Moxalactam

Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L.. This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours.. Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016).. Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

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

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

Dissemination of hypervirulent and carbapenem-resistant Klebsiella pneumoniae (CRKP) has been reported worldwide, posing a serious threat to antimicrobial therapy and public health. Outer membrane vesicles (OMVs) act as vectors for the horizontal transfer of virulence and resistance genes. However, K. pneumoniae OMVs that transfer carbapenem resistance genes into hypervirulent K. pneumoniae (hvKP) have been insufficiently investigated. Therefore, this study investigates the transmission of the

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

Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations.. Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested.. Eleven patients were included: eight with infection [four with ventilator-associated pneumonia and four with bloodstream infections] and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance.. Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options.

Topics: Agar; Ceftazidime; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem

OXA-232 carbapenemase is becoming a threat in China due to its high prevalence, mortality, and limited treatment options. However, little information is available on the impact of OXA-232-producing Klebsiella pneumoniae in China. This study aims to characterize the clonal relationships, the genetic mechanisms of resistance, and the virulence of OXA-232-producing K. pneumoniae isolates in China. We collected 81 OXA-232-producing K. pneumoniae clinical isolates from 2017 to 2021. Antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular types, multilocus sequence types, virulence genes, antimicrobial resistance (AMR) determinants, plasmid replicon types, and single-nucleotide polymorphism (SNP) phylogeny were inferred from whole-genome sequences. OXA-232-producing K. pneumoniae strains were resistant to most antimicrobial agents. These isolates showed partial differences in susceptibility to carbapenems: all strains were resistant to ertapenem, while the resistance rates to imipenem and meropenem were 67.9% and 97.5%, respectively. Sequencing and capsular diversity analysis of the 81 K. pneumoniae isolates revealed 3 sequence types (ST15, ST231, and one novel ST [ST-V]), 2 K-locus types (KL112 and KL51), and 2 O-locus types (O2V1 and O2V2). The predominant plasmid replicon types associated with the OXA-232 and

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Plasmids

The incidence of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasing worldwide, and very limited number of effective antibiotics are available for therapy. In our study, the in vitro efficacy of meropenem/polymyxin B and meropenem/fosfomycin combinations against CRKP strains was investigated. The efficiency of meropenem/polymyxin B and meropenem/fosfomycin combinations was tested by checkerboard microdilution and checkerboard agar dilution methods, respectively, against 21 CRKP strains containing major carbapenem resistant genes (7 blaKPC, 7 blaOXA-48 gene, and 7 blaOXA-48+ blaNDM), and seven additional CRKP strains without carbapenemase genes.Among the 28 CRKP strains, the meropenem/polymyxin B combination was synergistic in ten (35.7%), partially synergistic in 12 (42.8%), and indifferent in six (21.4%) isolates. The meropenem/fosfomycin combination was found to be synergistic in three isolates (10.7%), partially synergistic in 20 (71.4%), and indifferent in five (17.8%). In 21 strains containing carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations exhibited synergistic/partial synergistic effects in 15 (71.4%) and 16 (76.2%) strains, respectively, compared to 100% synergistic/partial synergistic efficiency in both combinations in seven strains free of carbapenemase genes. No antagonistic effect was detected in either combination.Regardless of presence or absence of carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations both demonstrated high synergistic and partial synergistic activity against 78.4% and 82.1% of CRKP strains, respectively. Also, they have no antagonistic effects and can be used successfully to prevent therapeutic failure with monotherapy, according to our in vitro studies.

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

Topics: Animals; Anti-Bacterial Agents; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactamases; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

In 2021, Klebsiella pneumoniae sequence type 307 (ST307) strains causing pulmonary and bloodstream infections identified in a hospital in Rome, Italy, reached high levels of resistance to ceftazidime-avibactam (CZA). One of these strains reached high levels of resistance to both CZA and carbapenems and carried two copies of

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Carbapenems; Ceftazidime; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Plasmids

OXA-48 carbapenemases are frequently expressed by Klebsiella pneumoniae clinical isolates; they decrease the effectiveness of carbapenem therapy, particularly with meropenem. Among these isolates, meropenem-susceptible carbapenemase-producers may show decreased meropenem effectiveness. However, the probability of the emergence of resistance in susceptible carbapenemase-producing isolates and its dependence on specific K. pneumoniae meropenem MICs is not completely known. It is also not completely clear what resistance patterns will be exhibited by these bacteria exposed to meropenem, if they would follow the patterns of non-beta-lactamase-producing bacteria and other than beta-lactams antibiotics. These issues might be clarified if patterns of meropenem resistance related to the mutant selection window (MSW) hypothesis. To test the applicability of the MSW hypothesis to meropenem, OXA-48-carbapenemase-producing K. pneumoniae clinical isolates with MICs in a 64-fold range (from susceptible to resistant) were exposed to meropenem in a hollow-fiber infection model; epithelial lining fluid meropenem pharmacokinetics were simulated following administration of 2 grams every 8 hours in a 3-hour infusion. Strong bell-shaped relationships between the meropenem daily dose infused to the model as related to the specific isolate MIC and both the antimicrobial effect and the emergence of resistance were observed. The applicability of the MSW hypothesis to meropenem and carbapenemase producing K. pneumoniae was confirmed. Low meropenem efficacy indicates very careful prescribing of meropenem to treat K. pneumoniae infections when the causative isolate is confirmed as an OXA-48-carbapenemase producer.

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

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major threat to global public health. CRKP infections are challenging to treat owing to the limited number of antibiotic species, especially in preterm infants. Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic with activity against CRKP. At present, there have been no reports of using CAZ-AVI to treat osteoarthritis in premature infants.. We describe 2 preterm infants with CRKP osteoarthritis treated with CAZ-AVI in a tertiary children's hospital in China. Clinical characteristics, laboratory and microbiologic data, treatment and follow-up information were retrospectively collected and analyzed.. The 2 cases were both premature infants who contracted sepsis and CRKP osteoarthritis. Meropenem and polymyxin B were initially chosen for the first infant. CAZ-AVI was then used due to persistent infection. The second infant was commenced immediately on CAZ-AVI after receipt of antimicrobial susceptibility on the 4th day after admission. Both recovered with CAZ-AVI (50 mg/kg q8h) and surgical incision and drainage. Neither had a joint deformity or limb length discrepancy at 36 and 34 months, respectively.. This is the first report on the use of CAZ-AVI to treat CRKP osteoarthritis in premature infants. Successful treatment depends on prompt recognition of the pathogen and treatment with a combination of antibiotics with or without surgery. Further study is needed to determine the pharmacokinetics and pharmacodynamics of CAZ-AVI for treating preterm infants with serious CRKP osteoarthritis.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Child; Drug Combinations; Humans; Infant, Newborn; Infant, Premature; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Critical Illness; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated

In recent years, the rapid spread of carbapenem-resistant K. pneumoniae, their higher mortality rates, and limited treatment alternatives cause difficulties in the treatment of these infections. New treatment alternatives are needed to cope with resistant strains. In recent years, natural products such as Quercetin have started to be preferred in combination studies due to their antimicrobial effects and low side-effect profiles. The aim of this study was to investigate the in vitro efficacy of the combination of Quercetin and Meropenem on carbapenemase-producing (blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP), carbapenem-resistant K.pneumoniae isolates using the checkerboard method.. Thirty Carbapenem-resistant K.pneumoniae strains in the culture collection of our laboratory were included in our study. Carbapenemase genes were determined using the Xpert® Carba-R (Cepheid, USA). Synergism with meropenem was assessed by checkerboard analysis, followed by FIC index, and combination index calculation.. Twenty (66.6%) strains had OXA-48, 6 (20%) NDM, 1 (3.3%) KPC, 1 (3.3%) OXA-48+NDM genes, and 2 strains (6.6%) gene could not be detected. In the Quercetin and Meropenem combination study, synergy was found in 24 (80%) of the strains; an additive effect was found in 5 (16.6%) and an antagonist effect in 1 (3.3%). In 19 (63.3%) of the strains, meropenem MIC values were below the sensitive limit (MIC ≤ 2 μg/mL).. Although the combination of quercetin and meropenem has a high synergistic effect in carbapenem-resistant K. pneumoniae isolates, it seems that the carbapenemase species affects this situation. however, more work is needed on this subject.

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

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

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

In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitalization, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bacterial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infecting the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 resistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA siderophore gene, resulting in high levels of cefiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other infective agents. K. pneumoniae can stably colonize a patient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicating a substantial public health threat.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefiderocol; Ceftazidime; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

This study aimed to illustrate the status of carbapenem-resistant Enterobacterales (CRE) infections in a Chinese tertiary hospital and to investigate the role of outer membrane vesicles (OMVs) in antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP).. The data of CRE infections was collected from laboratory records, and the CRE isolates from two distinct periods (2015/07 to 2017/07 and 2020/04 to 2021/04) were enrolled to detect the carbapenemase genes by polymerase chain reaction (PCR). Multilocus sequence typing (MLST) was used to analyze the molecular characterization of CRKP. The conjugation assay was performed to verify the transmission of the antibiotic resistance plasmid. The OMVs of CRKP were isolated with a method combining an electrophoretic technique with a 300 kDa cut-off dialysis bag. The protein components in CRKP OMVs were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS), and the meropenem-hydrolyzing bioactivity of KPC in CRKP OMVs was determined with different treatments in vitro.. A total of 178 CRE isolates, including 100 isolates from 2015/07 to 2017/07 and 78 isolates from 2020/04 to 2021/04, were collected for the detection of carbapenemase genes. We found that the carbapenemase gene blaKPC was the most prevalent, followed by blaNDM. By MLST, we found that sequence type (ST) 11 CRKP (96.1%) was the leading type during 2015/07 to 2017/07 and that the ST15 CRKP increased to 46.2% in the late period of 2020/04 to 2021/04. The diameters of Klebsiella pneumoniae OMVs ranged from 100 to 200 nm, and by proteomics analysis the most proteins from OMVs belonged to the "enzyme" group. The KPC enzyme was found in the OMVs from CRKP, and the OMVs could protect inside KPC from proteinase K digestion. Moreover, the KPC enzymes within OMVs, which could be released after Triton X-100 treatment, could hydrolyze meropenem.. CRE has increasingly caused infections in hospitals, and blaKPC-positive CRKP infections have constituted a major proportion of infections in the past decade. The OMVs play a critical role in antibiotic resistance in CRKP.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Chromatography, Liquid; Drug Resistance, Microbial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Tandem Mass Spectrometry; Tertiary Care Centers

This study aimed to evaluate the antibiotic resistance patterns and prevalence of carbapenemase genes in Klebsiella pneumoniae isolates in different clinical samples from Tabriz city, northwestern Iran.. This cross-sectional study was conducted in the Department of Microbiology, Islamic Azad University, Ahar Branch, Iran, in 2020. K. pneumoniae isolates were collected from different clinical samples, including blood, wounds, sputum, and urine. The isolates were identified using a series of standard bacteriological tests. Antibiotic resistance was determined by the disc diffusion method. The presence of bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cross-Sectional Studies; Humans; Imipenem; Iran; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Topics: Adult; Amikacin; Anti-Bacterial Agents; Brain Abscess; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Meropenem; Microbial Sensitivity Tests; Pneumonia; Sulfamethoxazole

The emergence of multi-drug resistant pathogenic bacteria, especially Gram-negative bacteria, is a worldwide health problem. New antibiotics directed at previously unexplored targets are urgently needed to overcome resistance to existing antibiotic classes. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is an attractive target for a new antibacterial agent. Although a number of LpxC inhibitors have been identified, none have been approved as antibacterial agents. These LpxC inhibitors contain a hydroxamate moiety, which is a robust zinc ion chelator. The nonspecific inhibition of metalloenzymes through zinc ion chelation is one of possibilities leading to unwanted side effects. Herein, we report that TP0586532, a non-hydroxamate LpxC inhibitor, has a broad spectrum of antibacterial activity against carbapenem-resistant Enterobacteriaceae. The MIC

Topics: Amidohydrolases; Animals; Anti-Bacterial Agents; Chelating Agents; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Zinc

The objective was to study ceftazidime-avibactam resistant and susceptible Klebsiella pneumoniae isolated from a patient admitted to the Policlinico Umberto I of Rome for SARS-CoV2. Data on the evolution of patient's conditions, antimicrobial therapies, and microbiological data were collected. Whole-genome sequencing performed by Illumina and Nanopore sequencing methods were used to type the strains. During the hospitalization, a SARS-CoV2-infected patient was colonized by a KPC-producing K. pneumoniae strain and empirically treated with ceftazidime-avibactam (CZA) when presenting spiking fever symptoms. Successively, ST2502 CZA-resistant strain producing the KPC-31 variant gave a pulmonary infection to the patient. The infection was treated with high doses of meropenem. The KPC-31-producing strain disappeared but the patient remained colonized by a KPC-3-producing K. pneumoniae strain. An interplay between highly conserved KPC-31- and KPC-3-producing ST2502 strains occurred in the SARS-CoV2 patient during the hospitalization, selected by CZA and carbapenem treatments, respectively.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftazidime; COVID-19; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Boronic Acids; Ceftazidime; Drug Combinations; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Resistance levels of Gram-negative bacteria producing OXA-48 carbapenemase can vary greatly and some of them can even be categorized as susceptible to imipenem and meropenem according to EUCAST breakpoints. This study aimed to reveal resistance mechanisms leading to varying levels of resistance to carbapenems in Klebsiella pneumoniae with blaOXA-48 submitted to the German National Reference Centre for MDR Gram-negative bacteria.. Meropenem-susceptible clinical blaOXA-48-bearing K. pneumoniae isolates were put under gradually increasing selective pressure of meropenem. Clinical isolates and spontaneous meropenem-resistant mutants were whole-genome sequenced with Illumina and Oxford Nanopore Technology. Identified mutations apart from porin mutations were genetically constructed in the original clinical isolates using CRISPR/Cas. Clinical isolates and mutants were analysed for MICs, growth rates and expression of porins on mRNA and protein levels.. Mutations associated with meropenem resistance were predominantly found in ompK36, but in some cases ompK36 was unaffected. In two mutants, ISs within the rpoE (sigma factor E; σE) operon were detected, directly in or upstream of rseA. These IS1R elements were then inserted into the same position of the susceptible clinical isolates using CRISPR/Cas. CRISPR-rseA-rseB-rseC mutants showed higher resistance levels to carbapenems and cephalosporins, reduced growth rates and reduced expression of major porins OmpK36 and OmpK35 in quantitative RT-PCR and SDS-PAGE.. Enhanced synthesis of σE leads to increased resistance to cephalosporins and carbapenems in clinical K. pneumoniae isolates. This effect could be based upon remodelling of expression patterns of outer membrane proteins. The up-regulated σE stress response also leads to a significant reduction in growth rates.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Porins

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

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

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

Carbapenem-resistant Enterobacteriales has become a threat in Taiwan. This is the first local study focusing on the association between carbapenem-resistant Enterobacteriales and antimicrobial consumption. From January 2012 to December 2020, data were collected in a tertiary care hospital in Taipei, Taiwan. Antimicrobial consumption was estimated by the defined daily dose/1,000 patient-days. During the same period, the prevalence of carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected through routine surveillance data. The following retrospective analyses were conducted: 1) analysis of antimicrobial consumption over time, (2) analysis and forecast of CREC and CRKP prevalence over time, and 3) analysis of correlation between antimicrobial consumption and the prevalence of CREC and CRKP. The consumption of piperacillin/tazobactam (β = 0.615), fluoroquinolones (β = 0.856), meropenem (β = 0.819), and doripenem (β = 0.891) increased during the observation period (P < 0.001), and the consumption of aminoglycosides (β = -0.852) and imipenem/cilastatin (β = -0.851) decreased (P < 0.001). The prevalence of CRKP rose over time (β = 0.522, P = 0.001) and correlated positively with the consumption of fluoroquinolones, levofloxacin, penicillin/β-lactamase inhibitor, piperacillin/tazobactam, meropenem, and doripenem (P < 0.05). The prevalence of CRKP and CREC both correlated negatively with consumption of aminoglycosides (P < 0.01). The prevalence of CRKP in our hospital increased as the forecast predicted based on an autoregressive integrated moving average model. This study provides alarming messages for members participating in antimicrobial stewardship programs, including the increasing prevalence of CRKP, the increasing consumption of broad-spectrum antibiotics, and the positive correlation between them.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cross Infection; Doripenem; Escherichia coli; Fluoroquinolones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Taiwan; Tertiary Care Centers

An ertapenem-resistant Klebsiella pneumoniae clinical isolate (KP20) without carbapenemase and negative for the efflux pump inhibition test was resistant to ertapenem at a high level [minimum inhibitory concentration (MIC) = 64 mg/L] but susceptible to meropenem and imipenem. Second-generation sequencing was performed and a termination mutation was found in ramR. Complementation of ramR in KP20 reduced the ertapenem MIC by 128 times (from 64 mg/L to 0.5 mg/L). Overexpression of ramA and loss of OmpK35 were discovered in strain KP20 by quantitative reverse transcription PCR (RT-qPCR) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Furthermore, ramA deletion in strain KP20 resulted in a 128-fold decrease in the MIC of ertapenem (from 64 mg/L to 0.5 mg/L), and expression of OmpK35 was observed in KP20ΔramA by SDS-PAGE. Complementation of ramA in KP20ΔramA led to a 45.45-fold downregulation of ompK35. Complementation of ompK35 in KP20 could restore susceptibility to ertapenem (MIC reduced from 64 mg/L to 0.25 mg/L). Furthermore, results of the electrophoretic mobility shift assay showed that RamA could bind to the promoter of micF. These results showed that the termination mutation in ramR resulted in overexpression of ramA causing loss of OmpK35 expression through upregulation of micF, revealing the mechanism of ertapenem resistance only in K. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Down-Regulation; Ertapenem; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sodium Dodecyl Sulfate

Klebsiella variicola is a pathogen that is increasingly recognized as being associated with human infections, but the methods available to clinical microbiology laboratories for accurate identification are limited. In this study, we assessed the accuracy of identification of

Topics: Ceftriaxone; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Laboratories; Meropenem; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Ceftazidime; Cephalosporins; Drug Combinations; Escherichia coli; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Docking Simulation; Thymol

There is an urgent need for efficient tools for genetic manipulation to assess plasmid function in clinical drug-resistant bacterial strains. To address this need, we developed an all-in-one CRISPR interference (CRISPRi) system that easily inhibited the gene expression of a natural multidrug-resistant plasmid in an sequence type 23 (ST23) Klebsiella pneumoniae isolate. We established an integrative CRISPRi system plasmid, pdCas9gRNA, harboring a

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Clustered Regularly Interspaced Short Palindromic Repeats; Escherichia coli; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Plasmids

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

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

To characterize one OXA-232-producing. Minimum inhibitory concentrations (MICs) were measured. Early detection of CRKP strains carrying chromosomal

Topics: Amikacin; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Chromosomes; Ciprofloxacin; DNA Transposable Elements; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Plasmids; Sepsis; Virulence; Virulence Factors; Whole Genome Sequencing

Klebsiella spp. are gram-negative bacteria that are considered serious public health problems causing urinary tract infections, bloodstream infections, pneumonia infections, and soft tissue infections. This study was designed to investigate the prevalence of

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Female; Iraq; Klebsiella Infections; Klebsiella oxytoca; Male; Meropenem

The emergence and rapid increase of carbapenem-resistant Enterobacteriaceae among food-producing animals poses a serious threat to public health. The aim of this study was to investigate the presence and dissemination of bla

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Clone Cells; Drug Resistance, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Plasmids; Swine; Swine Diseases

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

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

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes high morbidity and mortality worldwide. The purpose of the study was to assess the synergistic activity of fosfomycin in combination with other antimicrobial agents against CRKP isolated from patients in Songklanagarind Hospital, Thailand.. A total of 35 K. pneumoniae isolates were obtained from patients in Songklanagarind Hospital. The MICs of imipenem and meropenem were determined in all isolates by broth microdilution. In all CRKP isolates, the presence of carbapenemase and extended-spectrum β-lactamase (ESBL) genes was investigated by PCR, while the production of these enzymes was determined by combined disk test. In the carbapenemase-genes-negative CRKP isolates, the porin loss and efflux pump were characterized by SDS-PAGE and broth microdilution, respectively. Finally, the synergistic effects of fosfomycin and other antimicrobial agents were evaluated by checkerboard analysis.. Twenty-one of 35 K. pneumoniae isolates were classified as CRKP. Most of CRKP isolates carried bla. These findings suggested that the fosfomycin and gentamicin combination might be useful as a possible treatment option for CRKP infection.

Topics: Anti-Bacterial Agents; beta-Lactamases; Fosfomycin; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thailand

Topics: Anti-Bacterial Agents; Cefoperazone; Cerebrospinal Fluid; Drug Combinations; Epididymis; Humans; Klebsiella Infections; Klebsiella pneumoniae; Magnetic Resonance Imaging; Male; Meropenem; Middle Aged; Perineum; Skull; Sulbactam; Testis; Ultrasonography; Vancomycin

This study investigated whether captopril can reverse drug resistance in metallo-β-lactamase (MBL)-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) and increase their sensitivity to antimicrobial agents. And also aimed to further characterize the affinity of captopril for imipenemase 4 (IMP-4) to explore the drug resistance treatment of MBL-producing bacteria. Five clinically isolated MBL-producing strains of CRKP were screened and the combined effects of captopril and meropenem were examined in vitro and in vivo to analyze whether captopril can reverse antimicrobial resistance in drug-resistant bacteria. Additionally, enzyme inhibition kinetics was analyzed to characterize the affinity of captopril for IMP-4. In MBL-producing Klebsiella pneumoniae, combined treatment with captopril significantly reduced the minimum inhibitory concentration (MIC) of carbapenems to 1 μg/mL at least, and captopril inhibited New-Delhi metallo-β-lactamase 1 (NDM-1) and IMP-4 in a concentration-dependent manner in vitro. Following the infection of Galleria mellonella by IMP-expressing bacteria, the survival rates were significantly higher in the combination treatment group than in the monotherapy groups. And the bacterial load in the combination treatment group was significantly lower than those in the monotherapy groups and IMP-4-producing bacteria were more sensitive to the combination treatment than NDM-1-producing bacteria. Additionally, enzyme inhibition kinetics firstly illustrated that the half-maximal inhibitory concentration of captopril for IMP-4 was 26.34 μM, and the dissociation constant was 37.14 μM. In brief, captopril potentiated meropenem activity and restored its efficacy against MBL-producing CRKP. Additionally, analysis of enzyme inhibition kinetics confirmed that captopril has good inhibitory effects on IMP-4 activity. Therefore, captopril or its derivatives may have clinical utility for overcoming antibiotic resistance.

Topics: Anti-Bacterial Agents; Antihypertensive Agents; beta-Lactamases; Captopril; Carbapenem-Resistant Enterobacteriaceae; Drug Therapy, Combination; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Infections caused by KPC-producing Klebsiella pneumoniae (Kp-KPC) are associated with high mortality rates due to the increased number of resistant isolates and the scarcity of therapeutic options. This scenario reinforces the urgent need for new chemotherapeutics. Herein, we investigated the effects of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Cu(phendione)

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Coordination Complexes; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Phenanthrolines

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

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

Polymicrobial. We conducted a single-center retrospective cohort study of patients with KP-BSI from 1 January 2013 to 31 December 2018 and collected the clinical data by reviewing electronic medical records.. Of the 818 patients with KP-BSI recruited, 13.9% (114/818) were polymicrobial KP-BSI. The severity of illness in polymicrobial and monomicrobial KP-BSI was similar, while the rate of resistance to carbapenems was obviously higher in polymicrobial KP-BSI (78.1% vs. 65.6%,. It was observed that polymicrobial KP-BSI accounted for a significant proportion among all KP-BSI in the current study. Hospitalization in burn ward and intensive care unit was an independent risk factor for the development of polymicrobial KP-BSI. The patients with polymicrobial KP-BSI had a higher rate of carbapenem-resistant

Topics: Adult; Aged; Bacteremia; Carbapenems; Ertapenem; Female; Hospitalization; Humans; Imipenem; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Odds Ratio; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Topics: Bacteremia; beta-Lactamases; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem

Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.. From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed.. Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients.. It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Topics: Adolescent; Adult; Bacterial Proteins; beta-Lactamases; Carbapenems; Child; Drug Resistance, Bacterial; Female; Humans; Infant; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Tigecycline; Tissue Donors; Young Adult

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

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

Topics: beta-Lactamases; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Tigecycline

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Boronic Acids; Carrier State; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genome, Bacterial; Heterocyclic Compounds, 1-Ring; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged

Hospital-acquired infections caused by K pneumoniae are difficult to eradicate since K pneumoniae carries resistance genes for many antimicrobials, including carbapenems. The study aimed to determine the prevalence of hospital-acquired infections caused by multiple drug-resistant K pneumoniae and identify carbapenem and fluoroquinolone resistance by phenotypic and genotypic methods amongst hospitalised patients.. Two hundred and fifty samples from patients with hospital-acquired infections were included. Identification and susceptibility testing for K pneumoniae isolates was performed by standard methods. The detection of carbapenemase resistance (bla. Out of 250 samples, 42 (16.8%) were multiple drug-resistant K pneumoniae, and the frequency of K Pneumoniae isolation was higher in urine samples, in the age group (<10 years), in ICU and in patients with longer hospital stay. Twenty-four (57%) of the isolates were resistant to Meropenem, 13 (31%) were resistant to Imipenem and 35 (83.3%) were resistant to Ciprofloxacin. bla. Multidrug-resistant K pneumoniae isolates harbouring bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Ciprofloxacin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Phenotype; Young Adult

Carbapenemase-producing strains of Klebsiella pneumoniae (KPC) are a great health concern, and therapy with ceftazidime-avibactam represents a choice for the treatment of infections involving these strains. We report a strain resistant to ceftazidime-avibactam due to a deletion of six nucleotides in the bla. Two strains, namely AMP920 and AMP2009, were isolated from the same patient a month apart. Antimicrobial susceptibility testing was performed both by broth microdilution and by Etest. Immunoenzymatic assay to detect carbapenemase was performed for both strains. The bla. The two isolates differed in antimicrobial susceptibility. AMP920 showed meropenem and imipenem resistance (MIC 32 and 32 mg/mL). A month later the carbapenem MIC decreased to 8 and 1 mg/mL respectively, while the ceftazidime-avibactam MIC increased from 1 to 16 mg/mL. Both isolates showed a positive immunoenzymatic test for the KPC enzyme, but only AMP920 showed a positive CarbaNP test hydrolysing imipenem. The Bla. We detected a new deletion in the bla

Topics: Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sequence Analysis, DNA; Sequence Deletion

Meropenem-vaborbactam resistance in

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Boronic Acids; Down-Regulation; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutation; Porins

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Boronic Acids; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Abdominal Pain; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Diagnosis, Differential; Drainage; Emphysema; Humans; Hypertension; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Male; Meropenem; Middle Aged

The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia.. Agar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection.. This study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia

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

Enterobacteria producing NDM carbapenemases represent a severe diagnostic and therapeutic challenge in healthcare settings. Infections caused by NDM-positive strains are usually associated with high mortality rates and very limited treatment options. A total number of 33 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were included in this study, comprising 30 recovered from clinical diagnostic samples and 3 cultured from screening rectal swabs taken at patient admission. Bacterial identification was performed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) and antibiotic susceptibility testing was performed by reference broth microdilution and a commercial automated method. Isolates were investigated for carbapenemase production using the β-CARBA test, the modified carbapenem inactivation method (mCIM) and, for the 30 clinical isolates, by MALDI-TOF/MS, using the MBT STAR

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Drug Resistance, Bacterial; Egypt; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tertiary Care Centers

Multi-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections. Two MDR K. pneumoniae strains were employed, producing either the NDM-1 or KPC-3 carbapenemase. Efficacy of combinations of AZT with meropenem were compared with monotherapies against infections in Galleria mellonella larvae by measuring larval mortality and bacterial burden. The effect of the same combinations in vitro was determined via checkerboard and time-kill assays. In vitro, both K. pneumoniae strains were resistant to meropenem but were susceptible to AZT. In G. mellonella, treatment with either AZT or meropenem alone offered minimal therapeutic benefit against infections with either strain. In contrast, combination therapy of AZT with meropenem presented significantly enhanced efficacy compared to monotherapies. This was correlated with prevention of bacterial proliferation within the larvae but not elimination. Checkerboard assays showed that the interaction between AZT and meropenem was not synergistic but indifferent. In summary, combination therapy of AZT with meropenem represents a potential treatment for carbapenemase-producing MDR K. pneumoniae and merits further investigation.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Zidovudine

Enterobacterales resistant to carbapenems, a class of last-resort antimicrobials, are ranked as an "urgent" and "critical" public health hazard by CDC and WHO. IMP-type carbapenemase-containing Enterobacterales are endemic in Japan, and blaIMP-6 is one of the notable carbapenemase genes responsible for the resistance. The gene is plasmid-encoded and confers resistance to meropenem, but not to imipenem. Therefore, IMP-6-producing Enterobacterales isolates are occasionally overlooked in clinical laboratories and are referred to as 'stealth-type'. Since previous reports in Japan were confined only to some geographical regions, their distribution across prefectures and the factors affecting the distribution remain unclear. Here, we revealed the dynamics of the geographical distribution of Enterobacterales with IMP-6 phenotype associated with antimicrobial use in Japan. We utilized comprehensive national surveillance data of all routine bacteriological test results from more than 1,400 hospitals in 2015 and 2016 to enumerate Escherichia coli and Klebsiella pneumoniae isolates with the antimicrobial susceptibility pattern (phenotype) characteristic of IMP-6 (imipenem susceptible, meropenem resistant), and to tabulate the frequency of isolates with the phenotype for each prefecture. Isolates were detected in approximately half of all prefectures, and combined analysis with the national data of antimicrobial usage revealed a statistically significant association between the frequency and usage of not carbapenems but third-generation cephalosporins (p = 0.006, logistic mixed-effect regression) and a weaker association between the frequency and usage of fluoroquinolones (p = 0.043). The usage of third-generation cephalosporins and fluoroquinolones may select the strains with the IMP-6 phenotype, and contribute to their occasional spread. We expect the findings will promote antimicrobial stewardship to reduce the spread of the notable carbapenemase gene.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Japan; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Phenotype

Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy.. A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy.. A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37).. Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.

Topics: Aged; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Case-Control Studies; Cefepime; Ciprofloxacin; Colombia; Drug Resistance, Multiple, Bacterial; Endemic Diseases; Female; Genotype; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Meropenem; Middle Aged; Phenotype; Prospective Studies; Risk Factors; Survival Analysis; Urinary Catheters

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

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

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

OXA-48-producing Klebsiellapneumoniae isolates often show growth of colonies within inhibition zones in carbapenem diffusion assays. The nature of these colonies was investigated in a series of clinical isolates of OXA-48-producing K. pneumoniae obtained in the context of a hospital outbreak, and they were found to be persistent colonies that reproduced again the same phenotype when they were collected and tested in diffusion assays again. The frequency of mutations conferring resistance to meropenem (8 μg/mL) was determined for the same isolates. The average mutation frequency was 5.47·10

Topics: Anti-Bacterial Agents; beta-Lactamases; Cohort Studies; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

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

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Hepatic Artery; Heterocyclic Compounds, 1-Ring; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Male; Meropenem; Microbial Sensitivity Tests; Salvage Therapy; Thrombosis; Young Adult

A woman infected by carbapenem-resistant Klebsiella pneumoniae is reported in this study.. Tigecycline and meropenem combination was used, and indeed, in vitro checkerboard synergy test confirmed the antagonism between the two antibiotics. Thus, meropenem was ceased and single high-dose tigecycline was successful against the infection. Subsequent experiments showed that the isolates of the KPC-2-producing K. pneumoniae ST11 clone caused the infection.. Therefore, tigecycline and meropenem combination should be used with caution.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; China; Drug Resistance, Bacterial; Female; Gene Expression Regulation, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tigecycline

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

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

Topics: Aged; Anti-Bacterial Agents; Ceftazidime; Cohort Studies; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Male; Melioidosis; Meropenem; Middle Aged; Mortality; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Proportional Hazards Models; Retrospective Studies; Severity of Illness Index; Streptococcal Infections

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

We investigated variations in the rate of persister cell formation against meropenem in 68 Klebsiella pneumoniae isolates from blood. The persister cell formation rates varied markedly but were not significantly different between the patient survival group and death group at 30 days. In addition, they were not associated with the patients' underlying diseases. However, the isolates of CC15 and CC23 showed higher survival rates against 10× MIC of meropenem than CC11. The survival rate of persister cells was less for amikacin and colistin than that for ciprofloxacin. When combinations of meropenem and other antibiotics were administered, persister formation rates decreased compared with those against only meropenem. However, no synergistic effect to remove persister cells was observed. Further investigation is needed to understand persister cell formation in K. pneumoniae with respect to the mechanism involved and clinical implications and that diverse strategies should be explored to remove persister cells.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Tolerance; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Phenotype

The progressive increase of infections produced by extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae (XDR-CPKP) represents an important threat to public health. Unfortunately, optimal therapeutic options are scarce. Retrospective studies have recommended combined therapy with more than one antibiotic and, more recently, a double-carbapenem regimen has been reported to be an effective alternative therapy. Here, we describe an episode of sepsis in an immunocompromised patient after allogeneic hematopoietic stem cell transplantation, caused by an XDR-CPKP. Several in vitro synergy tests revealed a synergistic effect combining ertapenem and meropenem, which were used as combination therapy achieving clinical and microbiological success.

Topics: Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; beta-Lactams; Drug Combinations; Ertapenem; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Sarcoma, Myeloid; Sepsis; Thienamycins; Transplantation, Homologous; Treatment Outcome

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Tertiary Care Centers; Thienamycins; Treatment Outcome

Efficacies of ceftazidime-avibactam (4:1 w/w) and ceftazidime were tested against ceftazidime-susceptible (bla

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Ceftazidime; Disease Models, Animal; Drug Combinations; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Rats; Thienamycins

In this study, we characterize a concurrent disseminated infection with a virulent hypermucoviscous (HMV) Klebsiella pneumoniae and an OXA-181-producing XDR K. pneumoniae from a patient with recent hospitalization in India. During exposure to meropenem therapy, the highly susceptible HMV K. pneumoniae became resistant to carbapenems, consistent with the acquisition of blaOXA-181.. Twelve K. pneumoniae isolates were recovered from the patient and the hospital room environment over a 3 month hospitalization. Phenotypic and molecular studies were completed to characterize the isolates. Oxford Nanopore and Illumina MiSeq WGS were performed to study phylogeny (MLST and SNPs), plasmids and virulence genes and demonstrate changes in the organism's resistome that occurred over time.. WGS revealed that the HMV K. pneumoniae belonged to ST23 and harboured an IncH1B virulence plasmid, while the XDR K. pneumoniae belonged to ST147 and possessed two MDR plasmids (IncR and IncFII), the blaOXA-181-bearing ColKP3 plasmid and chromosomal mutations conferring the XDR phenotype. Sequential isolates demonstrated plasmid diversification (fusion of the IncR and IncFII plasmids), mobilization of resistance elements (ompK35 inactivation by ISEcp1-blaCTX-M-15 mobilization, varying numbers of resistance genes on plasmid scaffolds) and chromosomal mutations (mutations in mgrB) leading to further antibiotic resistance that coincided with antibiotic pressure. Importantly, the HMV strain in this study was unable to preserve the carbapenem-resistant phenotype without the selective pressure of meropenem.. To the best of our knowledge, we are the first to report a carbapenem-resistant HMV K. pneumoniae strain in the USA. Ultimately, this case demonstrates the role of antibiotic pressure in the acquisition and loss of important genetic elements.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Hospitalization; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Travel; Treatment Outcome; United States; Virulence

New Delhi metallo-β-lactamase-1 (NDM-1) is the major contributor to the emergence of carbapenem resistance in Gram-negative pathogens (GNPs) and has caused many clinically available β-lactam antibiotics to become obsolete. A clinically approved inhibitor of metallo-β-lactamase (MBL) that could restore the activity of carbapenems against resistant GNPs has not yet been found, making NDM-1 a serious threat to human health. Here, we have rationally developed an inhibitor for the NDM-1 enzyme, which has the ability to penetrate the outer membrane of GNPs and inactivate the enzyme by depleting the metal ion (Zn

Topics: Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cell Membrane Permeability; Drug Synergism; Enzyme Activation; Female; Gene Expression Regulation, Bacterial; Gram-Negative Bacteria; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Molecular Structure; Vancomycin

The aim of this study was to assess the minimum inhibitory concentration (MIC) distribution for meropenem and other antimicrobials with Gram-negative activity against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) clinical isolates collected at a tertiary hospital in Italy between 2013-2016.. The antimicrobial susceptibility of KPC-Kp strains was tested by the broth microdilution method using customised 96-well plates and the results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations.. Among 169 consecutive KPC-Kp clinical isolates, 45 (26.6%) were susceptible to meropenem (MIC≤2mg/L). Among the 124 meropenem-resistant isolates, 73 (58.9%) had a meropenem MIC between 16-64mg/L. The overall resistance rate for the other antimicrobials tested was very high both for ciprofloxacin and levofloxacin (99.0%), was moderate for amikacin (37.4%) and was low for gentamicin (11.2%), colistin (8.2%) and tigecycline (7.7%). Aminoglycosides had a dichotomous behaviour in relation to meropenem MIC increase. The resistance rate for gentamicin remained <20% across all meropenem MICs; conversely, that for amikacin increased from <20% in the presence of meropenem MIC≤8mg/L up to ca. 80% in the presence of meropenem MIC≥64mg/L. Resistance rates for tigecycline and colistin remained <20% in the presence of meropenem MICs up to 64mg/L.. The overall susceptibility rates of antimicrobials with Gram-negative activity may vary greatly among KPC-Kp clinical isolates. A tight relationship between meropenem MIC increase and the resistance rate for amikacin was documented.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Ciprofloxacin; Drug Resistance, Bacterial; Humans; Italy; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Tertiary Care Centers

A multidrug-resistant

Topics: Aged, 80 and over; Amino Acid Substitution; Anti-Bacterial Agents; Base Sequence; beta-Lactam Resistance; beta-Lactamases; Ertapenem; Humans; Hydrolysis; Imipenem; Isoenzymes; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutagenesis, Insertional; Plasmids; Sequence Deletion

Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae.. A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage.. The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan.. Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage.. The infection was out of control and the patient died of spontaneous breath and heartbeat arrest.. Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Fatal Outcome; Fever; Headache; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Shock, Septic; Thienamycins; Vancomycin

Meropenem-vaborbactam is a new β-lactam/β-lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem-vaborbactam was United States Food and Drug Administration-approved for complicated urinary tract infections in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem-vaborbactam. In addition, the safety and efficacy of meropenem-vaborbactam in a pediatric patient have yet to be described in the literature. The authors conducted a retrospective single-patient chart review for a 4-year-old male patient with short bowel syndrome, colostomy and gastrojejunal tube, bronchopulmonary dysplasia, and a central line for chronic total parenteral nutrition and hydration management, complicated with multiple central line-associated bloodstream infections (BSIs). The patient was brought to our medical center with fever concerning for a BSI. On day 2, the patient was started on meropenem-vaborbactam at a dosage of 40 mg/kg every 6 hours infused over 3 hours for KPC-producing K. pneumoniae BSI. Meropenem serum concentrations obtained on day 5 of meropenem-vaborbactam therapy, immediately following the completion of the infusion and 1 hour after the infusion, were 51.3 and 13.6 μg/ml, respectively. Serum concentrations correlated to a volume of distribution of 0.59 L/kg and a clearance of 13.1 ml/min/kg. Repeat blood cultures remained negative, and meropenem-vaborbactam was continued for a total of 14 days. A meropenem-vaborbactam regimen of 40 mg/kg every 6 hours given over 3 hours was successful in providing a target attainment of 100% for meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval and was associated with successful bacteremia clearance in a pediatric patient.

Topics: Anti-Bacterial Agents; Boronic Acids; Child, Preschool; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Treatment Outcome

To determine the burden of AmpC beta-lactamase producing Klebsiella pneumoniae and its antimicrobial profile among paediatric patients.. This cross-sectional study was conducted at the Microbiology Department of The Children's Hospital and the Institute of Child Health in Lahore, Pakistan, from May 2014 to April 2015, in which isolates of Klebsiella pneumoniae were screened by using the cefoxitin disc. Confirmation was done by inhibitor-based method using 400 micro grams of boronic acid dispensed on the cefoxitin discs. The zone sizes of cefoxitin with and without the boronic acid were compared. The antimicrobial susceptibility testing was performed using Kirby Bauer disc diffusion method.. Positive cultures yielded 585 Klebsiella pneumoniae out of which 220(37.6%) strains were AmpC beta-lactamase-positive on the basis of cefoxitin screening and 126(21.53%) were positive on the basis of inhibitor-based confirmatory method. Most of the infected patients 73(57.9%) were neonates. All AmpC beta-lactamase-producing strains were resistant to cephalosporins. They also exhibited resistance to ciprofloxacin 109(86.5%), amikacin 98(77.8%), levofloxacin 8(77.8%), cefoperazone-sulbactam 81(64.3%), piperacillin-tazobactam 82(65.1%), meropenem, 56(44.4%) and imipenem 32(25.4%).. Prompt identification of AmpC beta-lactamases using inhibitor-based confirmatory test can help reduce the burden of these pathogens.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefoperazone; Cefoxitin; Cephalosporins; Child; Child, Preschool; Ciprofloxacin; Cross-Sectional Studies; Disk Diffusion Antimicrobial Tests; Drug Combinations; Drug Resistance, Bacterial; Female; Hospitals, Pediatric; Humans; Imipenem; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Pakistan; Piperacillin, Tazobactam Drug Combination; Sulbactam

The aim of this study was to analyze the metabolome of several Klebsiella pneumoniae strains characterized by different resistance patterns. A total of 59 bacterial strains (27 carbapenemase-negative and 32 carbapenemase-positive) were included and their metabolic features were assessed in basal conditions. Moreover, 8 isolates (4 wild-type and 4 KPC-producers) were randomly selected to evaluate the impact of sub-lethal concentrations of meropenem on bacterial metabolism. The metabolomic analysis was performed by 1H-NMR spectroscopy both on filtered supernatants and cell lysates. A total of 40 and 20 molecules were quantified in the intracellular and the extracellular metabolome, respectively. While in basal conditions only five metabolites showed significant differences between carbapenemase-positive and negative strains, the use of meropenem had a profound impact on the whole bacterial metabolism. In the intracellular compartment, a reduction of different overflow metabolites and organic acids (e.g. formate, acetate, isobutyrate) was noticed, whereas, in the extracellular metabolome, the levels of several organic acids (e.g. succinate, acetate, formate, lactate) and amino acids (aspartate, threonine, lysine, alanine) were modified by meropenem stimulation. Interestingly, carbapenemase-positive and negative strains reacted differently to meropenem in terms of number and type of perturbed metabolites. In wild-type strains, meropenem had great impact on the metabolic pathways related to methane metabolism and alanine, aspartate and glutamate metabolism, whereas in KPC-producers the effect was predominant on pyruvate metabolism. The knowledge about the bacterial metabolic profiles could help to set up innovative diagnostic methods and new antimicrobial strategies to fight the global crisis against carbapenemase-positive K. pneumoniae.

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

Ventriculoperitoneal (VP) shunt infections are seen in 3%-17% of patients with VP shunts. These infections may cause severe morbidity and mortality. Staphylococci are the most common cause of CSF shunt-associated infections, although gram-negative bacteria (especially multidrug-resistant [MDR] and extensive drug-resistant [XDR] bacteria) also play an important role. Due to increased antibiotic resistance, sometimes off-label usage of antibiotics is considered. Tigecycline is one of these antibiotics. It should not be used unless there are no other antibiotic treatment options available, especially in children. It belongs to the glycylcycline class of antibiotic agents and inhibits protein translation in bacteria by binding to the 30S ribosomal subunit. The authors describe the case of a patient who had an XDR Klebsiella pneumoniae-positive VP shunt infection. After removal of his VP shunt, an external ventricular drain was inserted, and the patient was treated with a combination of intravenous (1.2 mg/kg/day) and intraventricular (4 mg/day) tigecycline in addition to his meropenem (120 mg/kg/day) treatment. On the 7th day of the combined therapy, his CSF culture was sterile. Because tigecycline distribution into the tissues is not sufficient with intravenous administration, combining it with intraventricular infusion can provide new treatment methods. However, further studies are needed for its use as a treatment method in children.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Infant; Infusions, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Prosthesis-Related Infections; Tigecycline; Ventriculoperitoneal Shunt

Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Microbial Sensitivity Tests; Monobactams; Pyridones; Rats, Sprague-Dawley; Structure-Activity Relationship; Thiazoles

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

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

The horizontal transfer of a plasmid bearing the bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Enterobacter cloacae; Gene Transfer, Horizontal; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Plasmids; Respiratory Tract Infections; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactams; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multiple Organ Failure; Thienamycins

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

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

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Therapy, Combination; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Polymyxin B

Klebsiella pneumoniae, which exists in the intestinal and respiratory tracts of humans and animals, is an important conditional pathogen in many animals. The aim of the current study was to investigate the antimicrobial resistance profiles and genotypes of extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase-producing K. pneumoniae isolated from dogs.. A total of 285 isolates, collected from faecal and urine samples of diseased dogs in a Veterinary Teaching Hospital in Beijing, were characterised by antimicrobial susceptibility testing and screened for ESBL and AmpC β-lactamase phenotypes. The relevant genes were identified by polymerase chain reaction and sequencing.. All K. pneumoniae isolates were susceptible to meropenem, while the rates of resistance to the remaining 27 tested antimicrobials ranged from 24% to 97%. A total of 53% and 18% of K. pneumoniae isolates were positive for ESBL and AmpC β-lactamase production, respectively. ESBL/AmpC-producing strains were significantly resistant to more antimicrobial agents compared non-ESBL/AmpC-producing strains (P<0.05). CTX-M groups 1 and 9, and DHA-1 were the predominant genotypes of the ESBL/AmpC-producing K. pneumoniae isolates.. In conclusion, the high percentage of drug resistance among K. pneumoniae isolates suggests that routine detection of ESBL production by reliable laboratory methods is required in small animal clinical practice.

Topics: Animals; Autopsy; Bacterial Proteins; beta-Lactamases; Dog Diseases; Dogs; Drug Resistance, Bacterial; Feces; Genotyping Techniques; Hospitals, Animal; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sequence Analysis, DNA; Urine

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Carbapenems; Drug Resistance, Multiple, Bacterial; Ertapenem; Female; Fosfomycin; Humans; Intestines; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Postoperative Complications; Precision Medicine

Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.

Topics: Cell Membrane; Cell Membrane Permeability; Drug Synergism; Drug Therapy, Combination; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Oils, Volatile; Thienamycins

Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistant K. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Cell Line; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Humans; Immunity, Humoral; Immunologic Factors; Immunotherapy; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; O Antigens; Serogroup; Survival Rate; Thienamycins

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

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

Topics: beta-Lactamases; Cross Infection; Genotype; Hospitals; Humans; Hungary; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Thienamycins

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP.. We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively.. Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002).. Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Liver Cirrhosis; Male; Meropenem; Middle Aged; Peritonitis; Prospective Studies; Streptococcal Infections; Thienamycins

Shunt infections are seen in 3% to 20% of patients who have cerebrospinal fluid (CSF) shunts. Although the staphylococcal species are the most common cause of shunt-related infections, Gram-negative bacteria are increasingly reported with higher mortality rates. Tigecycline, a glycylcycline, is not approved for children. But in the era of nosocomial infections due to multidrug-resistant pathogens, it can be the life-saving option. We report an infant with ventriculoperitoneal shunt-related meningitis treated with a tigecycline combination regimen. A 5-month-old boy who had a ventriculoperitoneal shunt was admitted with meningitis. Extended spectrum β-lactamase-producing Klebsiella pneumoniae grew in the CSF. At the end of the fourth week of intravenous meropenem plus gentamicin therapy, carbapenem-resistant K pneumoniae grew in the CSF (mean inhibitory concentration value for meropenem >4 μg/mL, by E-test). The infected shunt was removed, and an external ventricular drainage catheter was inserted. With permission, intravenous tigecycline (1.2 mg/kg per dose twice a day) and intrathecal amikacin were added to the meropenem. Intrathecal amikacin could be given for only 7 days. On the sixth day of tigecycline treatment, the CSF was sterilized. Antibiotic therapy was given and consisted of a total of 60 days of meropenem and 20 days of tigecycline therapy. Because no available efficacy and safety data from randomized-controlled studies exist, tigecycline must be used only as salvage therapy, in combination with other drugs, for critically ill children who have no alternative treatment options.

Topics: Amikacin; Drug Therapy, Combination; Humans; Hydrocephalus; Infant; Infant, Premature, Diseases; Infusions, Intravenous; Injections, Spinal; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Minocycline; Off-Label Use; Salvage Therapy; Thienamycins; Tigecycline; Ventriculoperitoneal Shunt

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

Extended-spectrum β-lactamase (ESBL)-producing

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Critical Care; Doripenem; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Genotype; Humans; Imipenem; Klebsiella; Klebsiella Infections; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Thienamycins; United States

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

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

Antibiotic resistance has become a major problem in treating bacterial infections. The aim of this study was to elucidate the effects of meropenem on a bla. Analysis was performed by two-dimensional gel electrophoresis of whole-cell extracts of bacteria exposed to a sublethal concentration of meropenem compared with the untreated control. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF).. These overexpressed proteins may play an important role in bacterial resistance mechanisms against carbapenems, however their role in resistance needs to be further validated. High expression of lysine M domain/BON superfamily protein may indicate its possible involvement in modulating the bacterial response to antibiotic stress, but its actual role requires more investigation. These findings may also help in the development of newer therapeutic agents or diagnostic markers against carbapenem resistance.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Electrophoresis, Gel, Two-Dimensional; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Ertapenem; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sepsis; Thienamycins

OBJECTIVE An improved understanding of carbapenem-resistant Klebsiella pneumoniae (CRKP) in long-term acute care hospitals (LTACHs) is needed. The objective of this study was to assess risk factors for colonization or infection with CRKP in LTACH residents. METHODS A case-control study was performed at a university-affiliated LTACH from 2008 to 2013. Cases were defined as all patients with clinical cultures positive for CRKP and controls were those with clinical cultures positive for carbapenem-susceptible K. pneumoniae (CSKP). A multivariate model was developed to identify risk factors for CRKP infection or colonization. RESULTS A total of 222 patients were identified with K. pneumoniae clinical cultures during the study period; 99 (45%) were case patients and 123 (55%) were control patients. Our multivariate analysis identified factors associated with a significant risk for CRKP colonization or infection: solid organ or stem cell transplantation (OR, 5.05; 95% CI, 1.23-20.8; P=.03), mechanical ventilation (OR, 2.56; 95% CI, 1.24-5.28; P=.01), fecal incontinence (OR, 5.78; 95% CI, 1.52-22.0; P=.01), and exposure in the prior 30 days to meropenem (OR, 3.55; 95% CI, 1.04-12.1; P=.04), vancomycin (OR, 2.94; 95% CI, 1.18-7.32; P=.02), and metronidazole (OR, 4.22; 95% CI, 1.28-14.0; P=.02). CONCLUSIONS Rates of colonization and infection with CRKP were high in the LTACH setting, with nearly half of K. pneumoniae cultures demonstrating carbapenem resistance. Further studies are needed on interventions to limit the emergence of CRKP in LTACHs, including targeted surveillance screening of high-risk patients and effective antibiotic stewardship measures. Infect. Control Hosp. Epidemiol. 2015;37(1):55-60.

Topics: Aged; Anti-Bacterial Agents; Carbapenems; Carrier State; Case-Control Studies; Drug Resistance, Bacterial; Fecal Incontinence; Female; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Metronidazole; Middle Aged; Organ Transplantation; Respiration, Artificial; Risk Factors; Stem Cell Transplantation; Thienamycins; Time Factors; Vancomycin

The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in nursing home residents has rarely been reported in Taiwan.. A retrospective study was performed at medical wards of a district hospital at southern Taiwan between July 2009 and June 2011. Patients were included if they were older than 18 years, admitted via the emergency department, and their blood, sputum, or urine culture revealed the growth of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. From each patient only the first isolate from the infection site was included. Antimicrobial susceptibility was determined using the disc diffusion method.. Overall, 827 patients were included, with 354 (42.8%) coming from the community and 473 (57.2%) referred from a nursing home. Of the isolates acquired in nursing home, 45.5% (215/473) harbored ESBL. By contrast, 20.6% (73) of 354 isolates acquired in the community exhibited the ESBL production phenotype (p < 0.001). Of the isolates obtained from blood, urine, or sputum, 28.2% (37/131), 36.0% (208/578), or 36.4% (43/118) harbored ESBL, respectively, whereas 41% (211) of 515 E. coli isolates, 34.3% (72) of 210 K. pneumoniae, and 4.9% (5) of 102 P. mirabilis had ESBL. In general, the isolates from a nursing home or those with ESBL had lower antimicrobial susceptibility rates than those from the community or those without ESBL production. Only amikacin, piperacillin/tazobactam, ertapenem, and imipenem/meropenem were active against >90% Enterobacteriaceae isolates, irrespective of ESBL production.. ESBL production was common among clinical Enterobacteriaceae isolates, especially E. coli or those isolated from nursing home residents.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Blood; Drug Resistance, Multiple, Bacterial; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Nursing Homes; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proteus Infections; Proteus mirabilis; Retrospective Studies; Sputum; Taiwan; Thienamycins; Urine

VIM-producing Klebsiella pneumoniae isolates are usually associated with high MICs to carbapenems. Preclinical studies investigating the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of carbapenems against these isolates are lacking. The in vitro antibacterial activity of meropenem against one WT and three VIM-producing K. pneumoniae clinical isolates (median MICs 0.031, 8, 16 and 128 mg l- 1) was studied in a dialysis-diffusion PK-PD model and verified in a thigh infection neutropenic animal model by testing selected strains and exposures. The in vitro PK-PD target associated with bactericidal activity was estimated and the target attainment for different dosing regimens was calculated with Monte Carlo analysis. The in vitro model was correlated with the in vivo data, with log10CFU/ml reduction of < 1 for the VIM-producing (MIC 16 mg l- 1) and >2 for the WT (MIC 0.031 mg l- 1) isolates, with %f T >MIC 25 and 100%, respectively. The in vitro bactericidal activity for all isolates was associated with 40 % f T>MIC and attained in >90% of cases with the standard 1 g q8 0.5 h infusion dosing regimen only for isolates with MICs up to 1 mg l- 1. For isolates with MICs of 2-8 mg l- 1, prolonged infusion regimens (4 h infusion q8 or 2 h infusion q4) of standard (1 g) and higher (2 g) doses or continuous infusion regimens (3-6 g) are required. For isolates with a MIC of 16 mg l- 1 the unconventional dosing regimen of 2 g as 2 h infusion q4 or 12 g continuous infusion will be required. Prolonged and continuous infusion regimens of meropenem may increase efficacy against VIM-producing K. pneumoniae isolates.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Thienamycins

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

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

Dose optimization is required to increase carbapenem's efficacy against carbapenemase-producing isolates. Four clinical Klebsiella pneumoniae isolates were used: one susceptible to meropenem with minimum inhibitory concentration (MIC) 0.031 mg/L and 3 verona integron-borne metallo bete-lactamase-1-producing isolates with MICs 8, 16, and 128 mg/L. The human pharmacokinetics of short (0.5-h) and prolonged (3-h) infusion regimens of 1 g meropenem every 8 h were simulated in an in vitro pharmacokinetic-pharmacodynamic model. Time-kill curves were constructed for each isolate and dosing regimen, and the %T > MIC associated with maximal bactericidal activity was estimated. The percentage of pharmacodynamic target attainment for isolates with different MICs was calculated for 350 ICU, surgical, and internal medicine patients. The isolates with MIC ≤8 mg/L were killed with both dosing regimens. The %T > MIC corresponding to maximal bactericidal activity was ∼40%. The percentages of target attainment were >90%, 61%-83%, 23%-33%, and <3% with the short infusion regimen and >90%, 98%-99%, 55%-79%, and <5% with the prolonged infusion regimen for isolates with MIC ≤2, 4, 8, and ≥16 mg/L, respectively. The lowest target attainment rates were observed for the ICU patients and the highest for internal medicine patients. The prolonged infusion regimen was more effective than the short infusion regimen against isolates with MIC 4-8 mg/L.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Equipment Design; Female; Humans; Infusion Pumps; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Models, Biological; Thienamycins; Young Adult

Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cephalosporins; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppressive Agents; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Retrospective Studies; Survival Analysis; Thienamycins; Treatment Outcome

Topics: Anti-Bacterial Agents; Drug Monitoring; Extracorporeal Membrane Oxygenation; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Thienamycins

To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics.. Adescriptive and cross-sectional study.. Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012.. Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted.. Staphylococcus aureuswas the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients.. Staphylococcus aureuswas the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cross-Sectional Studies; Diabetic Foot; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pakistan; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

The aim of this study was to develop a rapid detection method of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains both MALDI-TOF MS and flow cytometry (FCM).. A total of 174 K. pneumoniae strains were included in this study. Molecular characterization of carbapenemase gene was performed by PCR. Bacterial identification was performed by MALDI-TOF-MS. Meropenem susceptibility was tested at the concentrations of breakpoints described by the Clinical and Laboratory Standards Institute (CLSI) guide by FCM.. Sixty-two CRKP were positive for at least one carbapenemase gene. A total of 174 K. pneumoniae isolates obtained from clinically relevant material were correctly identified by Bruker MALDI-TOF MS with log (score) >2.0. These results were 100% concordant with the Phoenix. We conclude that reliable results on bacterial identification and meropenem susceptibility test can be obtained within 2 hr combined by MALDI-TOF-MS and FCM.

Topics: Anti-Bacterial Agents; Female; Flow Cytometry; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; ROC Curve; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thienamycins

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

The ultrastructural alterations caused by polymyxin B and meropenem and by the association between polymyxin B and meropenem were investigated in two multiresistant isolates of Klebsiella pneumoniae (K3-A2 and K12-A2) carriers of blaKPC-2, coming from infection and colonization in patients in a public hospital in Recife, Brazil. The ultrastructural changes were detected by transmission electron microscopy and scanning. The susceptibility of the isolates to antimicrobials was tested by the disc diffusion method and microdilution in broth. The analysis by electron microscopy showed that the isolates presented morphological and ultrastructural cellular changes when subjected to a clinically relevant concentration of antimicrobials alone or in combination. When subjected to meropenem, they presented retraction of the cytoplasmic material, rupture of the cell wall and extravasation of the cytoplasmic content. When submitted to polymyxin B, the isolates showed condensation of the ribosomes, DNA clotting, cell wall thickening and the presence of membrane compartment. When subjected to polymyxin B and meropenem in combination, the isolates showed a higher intensity of the ultrastructural changes visualized. This is the first report of the ultrastructural changes caused by polymyxin B and meropenem in multiresistant isolates of K. pneumoniae carriers of the blaKPC-2 gene. It should be noted that even when the K. pneumoniae isolates were multiresistant carriers of the blaKPC-2 gene, they underwent important structural change owing to the action of polymyxin B and meropenem.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Polymyxin B; Thienamycins

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

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

The objective of this study is to investigate the profile of antimicrobial resistance of Gram-negative bacteria in blood cultures from 2004-2011. Pathogens from positive blood cultures were subcultured, and identified in the First Affiliated Hospital of Nanjing Medical University from January 2004 to December 2011. The antibiotic resistance pattern was analyzed by WHONET 5.4. A total of 1224 cases of Gram-negative bacterial isolates were documented, accounting for 38.6% of the total pathogens isolated from positive blood cultures in the 8-year period. The isolation rates of Klebsiella pneumoniae and Acinetobacter baumannii increased nearly three times over the same time span. Most Gram-negative bacteria isolates, except the isolates of Pseudomonas aeruginosa, showed a significantly increased resistance rate to cephalosporins (in particular third/fourth generation cephalosporins). Noteworthy, the antimicrobial resistance of K. pneumoniae, A. baumannii and P. aeruginosa isolates to carbapenem (imipenem and meropenem) was significantly increased and the resistant rate to carbapenem was >80.0% in A. baumannii in 2011. The results from PCR detection for carbapenemases were as follows: 82.8% (24/29) isolates of K. pneumoniae carried the kpc-2 gene; only three metallo-beta-lactamase-positive P. aeruginosa isolates were detected; and 93.1% (67/72) A. baumannii isolates were blaOXA-23 positive. The antimicrobial resistance rate of Gram-negative bacteria isolated from blood cultures significantly increased from 2004 to 2011, with significant resistance to the third/fourth generation cephalosporins and carbapenem.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cephalosporins; China; Drug Resistance, Bacterial; Gram-Negative Bacteria; Hospitals, University; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins

To describe the identification of two carbapenem-resistant, NDM-1 and IMP-4, carbapenemases coproducing Enterobacteriaceae isolates recovered from hospitalized patients in China. Both Klebsiella pneumoniae clinical isolates (Kpn922 and Kpn9599) were resistant to meropenem and imipenem and were subjected to additional antibiotic susceptibility testing. Polymerase chain reaction (PCR) and sequence analyses were used to characterize bacterial carbapenemase resistance genes, extended-spectrum β-lactamases, plasmid-mediated AmpC enzymes, quinolone resistance, and 16s RNA methylase. Genetic relatedness was determined using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmids were analyzed by S1-PFGE and Southern blot.. PCR analyses revealed that the Kpn922 isolate carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-1 genes, while Kpn9599 carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-12 genes. MLST determined that the two isolates were ST1043 and ST571 sequence types. Southern blot analyses revealed that metallo-β-lactamase genes were plasmid borne in both isolates. Plasmids ∼300 kb simultaneously carried blaNDM-1 and blaIMP-4.. Coexistence of blaNDM-1 and blaIMP-4 in these clinical isolates may herald the emergence of a new pattern of drug resistance. Surveillance of carbapenemases, particularly metallo-β-lactamases, in Enterobacteriaceae is urgently needed to control and prevent the spread of these resistance determinants in China.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Plasmids; Quinolones; Thienamycins

In this case report we describe a boy with extrahepatic biliary atresia who underwent a Kasai hepatoportoenterostomy at six weeks of age. Beginning several weeks post-op, he had recurrent cholangitis inadequately controlled by various antibiotic prophylaxis regimens. Imaging revealed the development of several bile lakes in the liver hilum. Due to the recurrent nature of his cholangitis, and some evidence of acutely impaired biliary drainage, he underwent a refashioning of his portoenterostomy with resultant improved drainage. However, shortly thereafter, the patient developed ongoing fever and anemia. Culture of the bile lake aspirate grew multiresistant Klebsiella and a 6 week course of parenteral meropenume controlled his fever and his anemia improved. Following treatment cessation his fever and anemia returned. A biliary drain was inserted into his larger bile lake and following another course of parenteral antibiotics he has remained free of clinically detected cholangitis despite ongoing contamination of drained bile fluid. The development of bile lakes after Kasai hepatoportoenterostomy is not an uncommon finding. This have been associated with worse prognosis including increased incidence of cholangitis. Often, conservative treatment with prophylactic antibiotics suffices, however, in rare cases, more aggressive intervention may be considered including percutaneous bile drainage or surgical management. The benefit of these management strategies must be balanced with the potential gain regarding quality of life and delaying transplant, on an individual basis.

Topics: Anti-Bacterial Agents; Bile; Biliary Atresia; Cholangitis; Drug Resistance, Multiple, Bacterial; Humans; Infant; Klebsiella Infections; Male; Meropenem; Portoenterostomy, Hepatic; Postoperative Complications; Thienamycins

This study aimed to forecast the incidence rate of carbapenem resistance and to assess the impact of an antimicrobial stewardship intervention using routine antimicrobial consumption surveillance data. Following an outbreak of OXA-48-producing Klebsiella pneumoniae (January 2008-April 2010) in a renal cohort in London, a forecasting ARIMA model was derived using meropenem consumption data [defined daily dose per 100 occupied bed-days (DDD/100OBD)] from 2005-2014 as a predictor of the incidence rate of OXA-48-producing organisms (number of new cases/year/100,000OBD). Interrupted times series assessed the impact of meropenem consumption restriction as part of the outbreak control. Meropenem consumption at lag -1 year (the preceding year), highly correlated with the incidence of OXA-48-producing organisms (r=0.71; P=0.005), was included as a predictor within the forecasting model. The number of cases/100,000OBD for 2014-2015 was estimated to be 4.96 (95% CI 2.53-7.39). Analysis of meropenem consumption pre- and post-intervention demonstrated an increase of 7.12 DDD/100OBD/year (95% CI 2.97-11.27; P<0.001) in the 4 years preceding the intervention, but a decrease thereafter. The change in slope was -9.11 DDD/100OBD/year (95% CI -13.82 to -4.39). Analysis of alternative antimicrobials showed a significant increase in amikacin consumption post-intervention from 0.54 to 3.41 DDD/100OBD/year (slope +0.72, 95% CI 0.29-1.15; P=0.01). Total antimicrobials significantly decreased from 176.21 to 126.24 DDD/100OBD/year (P=0.05). Surveillance of routinely collected antimicrobial consumption data may provide a key warning indicator to anticipate increased incidence of carbapenem-resistant organisms. Further validation using real-time data is needed.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Disease Outbreaks; Drug Utilization; Epidemiological Monitoring; Forecasting; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; London; Meropenem; Models, Statistical; Retrospective Studies; Thienamycins

The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ≤35, 0.46; 95% CI 0.23-0.92; and for those with scores >35, 0.14; 95% CI, 0.02-0.99).In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

Topics: Aged; Anti-Infective Agents; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Medication Therapy Management; Meropenem; Microbial Sensitivity Tests; Middle Aged; Outcome Assessment, Health Care; Pneumonia; Proportional Hazards Models; Severity of Illness Index; Taiwan; Thienamycins

Most post-neurosurgical meningitis research has been focused on large cohorts with numerous cases followed over several years. However, the characteristics of post-neurosurgical meningitis in an entire single year are still unclear, and knowledge of these characteristics might influence the selection of appropriate antibiotics and therapeutic strategies for the successful management of this disease. Our aim is to obtain a better understanding of post-neurosurgical meningitis over a single entire year.. Patients with positive meningitis cultures after neurosurgical operations in our hospital during the entire year of 2012 were included in the analysis. We report demographic characteristics, morbidity during different seasons, clinical and bacteriological profiles, sensitivity to antibiotics and causes of the post-neurosurgical meningitis infections in our cohort.. Of the 6407 patients who underwent neurosurgical procedures during the study period, 146 developed post-neurosurgical meningitis and the overall incidence of meningitis was 2.28%. The incidence of meningitis was significantly higher in patients who underwent surgery in the autumn and winter than spring or summer (p=0.000). The most common organisms causing meningitis were Gram-positive bacteria, followed by the Klebsiella and Baumannii species. Compound sulfamethoxazole (52.6%) and vancomycin (10.5%) were the most active antibiotics against Gram-positive bacteria strains, whereas meropenem (43.8%) and polymyxin (18.8%) were active against Gram-negative bacillus strains.. Post-neurosurgical meningitis usually occurs in the autumn and winter of the year in our hospital. Gram-positive organisms, which are sensitive to compound sulfamethoxazole and vancomycin, are the most common causative pathogens of post-neurosurgical meningitis in the northern mainland of China.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; China; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Neurosurgical Procedures; Polymyxins; Postoperative Complications; Pseudomonas Infections; Retrospective Studies; Seasons; Staphylococcal Infections; Sulfamethoxazole; Thienamycins; Vancomycin; Young Adult

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

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

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are the leading causes of hospital-associated infections, but community-acquired cases are increasingly being reported. This study determined the prevalence of ESBL-producing E. coli and K. pneumoniae carriers, their bla genes and risk factors of 452 patients admitted to the emergency room (ER) of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand between April and August 2011. Prevalence of ESBL-producing E. coli and K. pneumoniae from rectal swabs was 16.5% and 1.0%, respectively. Factors associated with ESBL-producing carriers were a previous history of hospital admission (p = 0.001) and visits to health care facilities (p = 0.002) during the previous 3 months. All ESBL-producing isolates were susceptible to imipenem, meropenem and ertapenem. The majority (78%) of ESBL-producing E. coli isolates showed very high resistance to cefotaxime and ceftriaxone (MIC50 and MIC90 > 256 µg/ml). ESBL-producing E. coli harbored chromosomal blaTEM (96%), blaCTX-M (70%) and blaSHV (1%), while 8%, 73% and 3%, respectively, were located on plasmid. The prevalence of these genes in ESBL-producing K. pneumoniae was 75%, 50% and 25%, respectively on chromosome; and 100%, 25% and 50%, respectively on plasmid. Nucleotide sequence analysis revealed that these bla genes were of the type blaTEM-1' blaTEM-116' blaCTX-M-15' blaCTX-M-161' blaSHV-12, blaSHV-28 and blaSHV-148. Detailed epidemiologic and clinical characteristics of ER patients with history of prior hospital visits should be carried out to identify the ESBL-producing organisms they have acquired in order to institute appropriate treatment for these patients as well as control measures against further dissemination of these life-threatening organisms.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cross Infection; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Plasmids; Thailand; Thienamycins; Young Adult

Several studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect the in vivo efficacy. Meropenem generics were compared with the innovator in vitro by microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient, in vitro susceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.

Topics: Animals; Anti-Bacterial Agents; Biotransformation; Brain; Cilastatin; Dipeptidases; Drug Stability; Drugs, Generic; GPI-Linked Proteins; Guinea Pigs; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Mice; Microbial Sensitivity Tests; Muscle, Skeletal; Protease Inhibitors; Pseudomonas aeruginosa; Pseudomonas Infections; Therapeutic Equivalency; Thienamycins; Thigh; Treatment Outcome

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

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

To investigate control of an outbreak due to orthopedic infections caused by Enterobacteriaceae producing IMP carbapenemases.. The sporadic orthopedic infections with Enterobacteriaceae producing carbapenemase (CPE) were retrospectively analyzed in a Chinese tertiary care hospital from November 2010 to September 2012.. The CPE were isolated from four distinct orthopedic patients, three patients infected with Enterobacter cloacae while the other with Klebsiella oxytoca. All strains were resistant to almost all the conventional antimicrobial. The strains produced IMP-4 type detected in the two early patients, while other strains could produce IMP-8 type. All of the four patients had ever undergoing invasive surgical procedure, and three of them were given fluoroquinolones for anti-infection treatment while the other patients was treated with meropenem. Ultimately, all patients were cured and discharged, without outbreak of nosocomial infection caused by CPE.. Our study shows that strict infection control plays an important role in limiting dissemination of Enterobacteriaceae producing IMP carbapenemase. In addition, reasonable supporting treatment and disinfection protection seems to be more effective for the infection of strains.

Topics: Adolescent; Anti-Bacterial Agents; Arthritis, Infectious; beta-Lactam Resistance; beta-Lactamases; China; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Fluoroquinolones; Fracture Fixation, Internal; Humans; Infection Control; Klebsiella Infections; Klebsiella oxytoca; Levofloxacin; Male; Meropenem; Middle Aged; Osteitis; Patient Isolation; Protective Clothing; Retrospective Studies; Surgical Wound Infection; Thienamycins; Universal Precautions; Wound Infection

Carbapenem resistance in Gram-negative bacteria is on the rise in the United States. A regional network was established to study microbiological and genetic determinants of clinical outcomes in hospitalized patients with carbapenem-resistant (CR) Klebsiella pneumoniae in a prospective, multicenter, observational study. To this end, predefined clinical characteristics and outcomes were recorded and K. pneumoniae isolates were analyzed for strain typing and resistance mechanism determination. In a 14-month period, 251 patients were included. While most of the patients were admitted from long-term care settings, 28% of them were admitted from home. Hospitalizations were prolonged and complicated. Nonsusceptibility to colistin and tigecycline occurred in isolates from 7 and 45% of the patients, respectively. Most of the CR K. pneumoniae isolates belonged to repetitive extragenic palindromic PCR (rep-PCR) types A and B (both sequence type 258) and carried either blaKPC-2 (48%) or blaKPC-3 (51%). One isolate tested positive for blaNDM-1, a sentinel discovery in this region. Important differences between strain types were noted; rep-PCR type B strains were associated with blaKPC-3 (odds ratio [OR], 294; 95% confidence interval [CI], 58 to 2,552; P < 0.001), gentamicin nonsusceptibility (OR, 24; 95% CI, 8.39 to 79.38; P < 0.001), amikacin susceptibility (OR, 11.0; 95% CI, 3.21 to 42.42; P < 0.001), tigecycline nonsusceptibility (OR, 5.34; 95% CI, 1.30 to 36.41; P = 0.018), a shorter length of stay (OR, 0.98; 95% CI, 0.95 to 1.00; P = 0.043), and admission from a skilled-nursing facility (OR, 3.09; 95% CI, 1.26 to 8.08; P = 0.013). Our analysis shows that (i) CR K. pneumoniae is seen primarily in the elderly long-term care population and that (ii) regional monitoring of CR K. pneumoniae reveals insights into molecular characteristics. This work highlights the crucial role of ongoing surveillance of carbapenem resistance determinants.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Female; Genome, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Polymerase Chain Reaction; Public Health Surveillance; Survival Analysis; Thienamycins; Treatment Outcome

The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Disease Models, Animal; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Meropenem; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Survival Analysis; Thienamycins

We characterized 53 OXA-48-producing Klebsiella pneumoniae (OXA-48-Kp) isolated between 2011 and 2013 in 21 French hospitals. All the isolates were genotyped using MLST and PFGE and the population structure of the species was determined by a nucleotide-based analysis of the entire K. pneumoniae MLST database. Most of the OXA-48-Kp isolates also produced CTX-M-15 and remained susceptible to imipenem and meropenem. The isolates were distributed into 20 STs, of which five were dominant (ST15, ST101, ST147, ST395 and ST405). All the OXA-48-Kp clustered in the major clade of K. pneumoniae KpI.

Topics: Anti-Bacterial Agents; beta-Lactamases; Electrophoresis, Gel, Pulsed-Field; France; Genotype; Hospitals; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Molecular Epidemiology; Multilocus Sequence Typing; Thienamycins

The use of three classical β-lactamase inhibitors (Clavulanic acid, tazobactam and sulbactam) in combination with β-lactam antibiotics is presently the mainstay of antibiotic therapy against Gram-negative bacterial infections. However these inhibitors are unable to inhibit carbapenemase KPC-2 effectively. They being β-lactam derivatives behave as substrates for this enzyme instead of inactivating it. We have initiated our study to check the in vitro inhibition activity of the two novel screened inhibitors (ZINC01807204 and ZINC02318494) in combination with carbapenems against KPC-2 expressing bacterial strain and their effect on purified enzyme KPC-2. The MIC values of meropenem and ertapenem showed maximum reduction (8 folds) in combination with screened compounds (ZINC01807204 and ZINC02318494). CLSM images also depicted their strong antibacterial activity in comparison to conventional β-lactamase inhibitors. Moreover no toxic effect has been shown on HeLa cell line. Though the IC50 value of ZINC01807204 was high (200 µM), it exhibited fairly good affinity for KPC-2 (Ki = 43.82 µM). With promising results this study identifies ZINC01807204 as a lead molecule for further optimization and development of more potent non β-lactam inhibitors against KPC-2.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Cell Line; Ertapenem; HeLa Cells; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Protein Binding; Thienamycins

Carbapenem-resistant Enterobacteriaceae (CRE) are a growing problem worldwide. Guidelines focus on carbapenemase-producing organisms, and little is known about whether strict adherence to infection control measures is effective for CRE without carbapenemase. During 2009, CRE increased markedly in a tertiary hospital, and enhanced infection control measures without active surveillance were adopted.. Beginning in April 2010, enhanced antimicrobial stewardship, strict contact precautions, and cohort isolation were adopted. After September 2010, hand hygiene performance was prospectively monitored by active surveillance, and results were monthly fed back to medical personnel. Available carbapenem-resistant Escherichia coli (ECO) and carbapenem-resistant Klebsiella pneumoniae (KPN) isolated during 2008-2010 were characterized. Imipenem and meropenem minimal inhibitory concentrations were confirmed by E-test (AB biodisk, Solna, Sweden). Phenotypic screening assays and polymerase chain reaction (PCR) amplification of known β-lactamase and carbapenemase genes were performed.. From 3,511 ECO and 2,279 KPN, 44 (0.76%) were CRE (3 ECO, 41 KPN). CRE incidence rates rose from 1.61 in 2008 to 5.49 in 2009; they rose further to 9.81 per 100,000 patient days in early 2010. After adoption of strict infection control measures, CRE frequency fell back in 2011 and remained at baseline afterward. Phenotypic screening and PCR showed AmpC β-lactamase and extended spectrum β-lactamases with or without loss of porins; carbapenemases were not detected.. Enhanced infection control measures, even without active surveillance, seem effective to prevent further spread of CRE in a low-prevalence setting with mainly carbapenemase-nonproducing CRE.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Containment of Biohazards; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals, Teaching; Humans; Imipenem; Incidence; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Phenotype; Prevalence; Prospective Studies; Republic of Korea; Retrospective Studies; Thienamycins

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

New Delhi metallo-β-lactamase-1 (NDM-1) has emerged as a major global threat to human health for its rapid rate of dissemination and ability to make pathogenic microbes resistant to almost all known β-lactam antibiotics. In addition, effective NDM-1 inhibitors have not been identified to date. In spite of the plethora of structural and kinetic data available, the accurate molecular characteristics of and details on the enzymatic reaction of NDM-1 hydrolyzing β-lactam antibiotics remain incompletely understood. In this study, a combined computational approach including molecular docking, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations was performed to characterize the catalytic mechanism of meropenem catalyzed by NDM-1. The quantum mechanics/molecular mechanics results indicate that the ionized D124 is beneficial to the cleavage of the C-N bond within the β-lactam ring. Meanwhile, it is energetically favorable to form an intermediate if no water molecule coordinates to Zn2. Moreover, according to the molecular dynamics results, the conserved residue K211 plays a pivotal role in substrate binding and catalysis, which is quite consistent with previous mutagenesis data. Our study provides detailed insights into the catalytic mechanism of NDM-1 hydrolyzing meropenem β-lactam antibiotics and offers clues for the discovery of new antibiotics against NDM-1 positive strains in clinical studies.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Discovery; Drug Resistance, Bacterial; Humans; Hydrolysis; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Molecular Docking Simulation; Molecular Dynamics Simulation; Thienamycins

Klebsiella pneumoniae strains co-producing klebsiella pneumoniae carbapenemase (KPC) and verona integron-encoded metallo-beta-lactamase (VIM) are frequently isolated in Greece and have also occurred in other European countries. Conventional combined disc tests exhibit low sensitivity against these emerging pathogens. We have evaluated modifications of the KPC/Metallo-β-Lactamase Confirmation kit (ROSCO) exhibiting high diagnostic value against KPC, VIM and KPC + VIM producers. The key changes were the inclusion of additional combined tablets containing meropenem plus two inhibitors (dipicolinic acid (1000 μg per tablet) for metallo-β-lactamases and a boronic acid derivative for KPCs) and the replacement of aminophenylboronic acid by phenylboronic acid (400 μg per tablet).

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cloxacillin; Europe; Greece; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Picolinic Acids; Reproducibility of Results; Thienamycins

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriuria; Brazil; Drug Resistance, Bacterial; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Linear Models; Meropenem; Microbial Sensitivity Tests; Rectum; Thienamycins

Klebsiella pneumoniae showing high resistance to all β-lactams except imipenem, designated as ISMRK (imipenem-susceptible meropenem-resistant Klebsiella) is emerging in Japan. The carbapenem resistance of ISMRK cannot be screened by the Vitek and the RAISUS rapid automated susceptibility test systems, which may lead to inappropriate antimicrobial therapy, resulting in compromised patient outcomes.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Diagnostic Errors; Humans; Imipenem; Japan; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

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

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

Topics: Aged; Drug Resistance, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Phenotype; Sepsis; Thienamycins

Resistance to carbapenems is a significant therapeutic threat. The increasing frequency of car bapenemase enzymes among Gram-negative bacilli makes their early detection and differentiation urgent. Carbapenemases belonging to Class A are most commonly produced by members of family Enterobacteriaceae and are inhibited to various degrees by clavulanic acid. The present study is aimed to determine the occurrence and phenotypic detection of Class A carbapenemases in Escherichia coli and Klebsiella pneumoniae blood isolates from septicemic patients.. A total of 75 isolates of K. pneumoniae and 25 E. coli were screened for resistance to carbapenems by using meropenem and imipenem discs and meropenem E-test. Positive strains were then subjected to a modified Hodge test combined with carbapenemase inhibition tests to phenotypically detect and differentiate Class A serine carbapenemases from other classes of carbapenem hydrolyzing enzymes.. The screening test showing the number of isolates resistant to meropenem and imipenem were 41 and 35 for K. pneumoniae and nine and four for E. coli, respectively. A total of 25 (33.3%) K. pneumoniae isolates and two (8.0%) E. coli isolates were classified as Class A carbapenemase producers. Multidrug resistance with coexistence of extended spectrum-beta-lactamases occurred in 44.4% isolates. However, all of the isolates were susceptible to colistin, polymyxin B, and tigecycline by disc diffusion test.. We conclude from the present study that Class A carbapenemases appear to be the predominant cause of resistance to carbapenems in Enterobacteriaceae at our center and, thus, phenotypic detection based on simple methods should be employed routinely in clinical microbiology laboratories.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Prevalence; Sepsis; Tertiary Care Centers; Thienamycins

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colombia; Cross Infection; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Stroke; Thienamycins

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

We identified 5 Klebsiella pneumoniae isolates showing high resistance to β-lactams except imipenem and designated them ISMRK (imipenem-susceptible but meropenem-resistant Klebsiella). They carried the bla(IMP-6) and bla(CTX-M-2) on a self-transmissible plasmid. ISMRK may be falsely categorized as susceptible to carbapenems if imipenem is used to screen carbapenem resistance.

Topics: Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Conjugation, Genetic; Female; Gene Transfer, Horizontal; Humans; Imipenem; Japan; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Plasmids; Thienamycins

A woman aged 56 years of age had a community-acquired left neck abscess and internal jugular vein thrombosis with septicemia due to extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. Even though she was treated with intravenous meropenem, the bacteremia persisted. She was complicated with multiple brain abscesses, seizure, and leucopenia. After a combination of intravenous fosfomycin and meropenem, her clinical condition became stable. Combination treatment was continued for 2 months and she recovered. In individual cases of Lemierre syndrome with brain abscess caused by ESBL-producing Enterobacteriaceae, fosfomycin combination therapy may be the alternative choice.

Topics: Anti-Bacterial Agents; beta-Lactamases; Brain; Brain Abscess; Community-Acquired Infections; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Lemierre Syndrome; Meropenem; Middle Aged; Sepsis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

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

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

Carbapenemase-producing Klebsiella pneumoniae has recently spread rapidly throughout China. In this study, we characterized a carbapenem-resistant K. pneumoniae isolate that produced both KPC-2 and IMP-4 type carbapenemases. A clinical isolate of K. pneumoniae, resistant to both meropenem and imipenem, was recovered from a urine sample. Antibiotic susceptibility was determined using the broth microdilution method and Etest (bioMérieux, France). Pulsed-field gel electrophoresis and multilocus sequence typing (MLST) were used for gene type analysis. bla (KPC) and the encoding genes of ESBLs and plasmid-mediated AmpC enzymes were polymerase chain reaction (PCR) amplified and sequenced. Plasmids were analyzed by transformation, enzyme restriction and Southern blot. PCR analysis revealed that the isolate was simultaneously carrying bla (KPC-2), bla (IMP-4), bla (TEM-1), and bla (OKP-B) genes. MLST assigned the isolate to a novel sequence type, ST476. bla (KPC-2)-harbouring plasmids of the isolate and comparative strains had similar EcoRI and HindIII restriction maps, while IMP-4-harbouring plasmids had variable HindIII restriction maps. Coexistence of bla (KPC-2) and bla (IMP-4) was probably due to bla (IMP-4)-harbouring plasmid transmission into KPC-2-producing K. pneumoniae (ST476). The concomitant presence of these genes is alarming and poses both therapeutic and infection control problems.

Topics: Anti-Bacterial Agents; beta-Lactamases; Blotting, Southern; China; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Imipenem; Infant; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA; Thienamycins; Urine

Three closely related Klebsiella pneumoniae strains isolated from the same patient harboured bla(CTX-M-15), bla(OXA-1), bla(SHV-11), qnrS1, aac(6')-Ib-cr, oqxAB, aac(3)-II and aph(3')-Ia genes. Two of the isolates were recovered after treatment with meropenem and showed resistance to carbapenems. Sequencing of ompK35 and ompK36 porin genes of the carbapenem-resistant strains revealed the presence of premature stop codons in both, and OmpK35 and OmpK36 porins were not detected by SDS-PAGE. One carbepenem-resistant strain showed a high amount of LamB protein and did not express OmpK26 porin whereas the other strain expressed OmpK26 but not LamB. The lack of major porins apparently causes changes in the expression of other, specific, porins.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Carbapenems; Drug Resistance, Multiple, Bacterial; Electrophoresis, Polyacrylamide Gel; Female; Genes, Bacterial; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutation; Porins; Thienamycins

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

A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P = 0.1) or sepsis-related mortality rate (P = 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P = 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P = 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P = 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤ 0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P = 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.

Topics: Adult; Bacteremia; beta-Lactams; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Thienamycins; Young Adult

To describe an outbreak of KPC-2-producing Klebsiella pneumoniae with inter-hospital spread and measures taken to control transmission.. Between January and March 2011, 13 K. pneumoniae isolates were collected from nine patients at hospital A and two patients at hospital B. Meropenem, imipenem and ertapenem MICs were determined by Etest, carbapenemase production was confirmed by the modified Hodge method and by a disc synergy test, and confirmed carbapenemase producers were tested for the presence of carbapenemase-encoding genes by PCR. PFGE, plasmid analysis, multilocus variable-number tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST) analysis were performed on all or a subset of isolates.. Meropenem, imipenem and ertapenem MICs were 4 to >32, 8-32 and >16 mg/L, respectively. PCR and sequencing confirmed the presence of bla(KPC-2). PFGE identified four distinguishable (≥88%) pulsed-field profiles (PFPs). Isolates distinguishable by PFGE had identical MLVA profiles, and MLST analysis indicated all isolates belonged to the ST258 clone. Stringent infection prevention and control measures were implemented. Over a period of almost 8 months no further carbapenemase-producing Enterobacteriaceae (CPE) were isolated. However, KPC-2-producing K. pneumoniae was detected in two further patients in hospital A in August (PFP indistinguishable from previous isolates) and October 2011 (PFP similar to but distinguishable from previous isolates).. Stringent infection prevention and control measures help contain CPE in the healthcare setting; however, in the case of hospital A, where CPE appears to be established in the population served, it may be virtually impossible to achieve eradication or avoid reintroduction into the hospital.

Topics: beta-Lactamases; beta-Lactams; Disease Outbreaks; Ertapenem; Genes, Bacterial; Hospitals; Humans; Imipenem; Ireland; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Polymerase Chain Reaction; Thienamycins

Carbapenem resistance due to metallo-β-lactamases (MBLs) in Enterobacteriaceae has gained much prominence in recent months. The emergence and subsequent spread of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes a potential threat in terms of the management of affected patients and institutional infection control efforts. We evaluated an in-house prepared meropenem impregnated MacConkey agar versus CHROMagar KPC.. The lowest limit of detection (LLD) was compared for nine clinical isolates of NDM-1 producing Enterobacteriaceae on the above mentioned agar media.. LLD was comparable for all the nine clinical isolates on both media. The cost of the antibiotic impregnated MacConkey agar was considerably lower (US$0.39) as compared to the commercial media, while its performance remained unaltered for a period of at least 8 weeks of storage.. The in-house medium proved to be a suitable and cheap alternative to the CHROMagar KPC.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Culture Media; Drug Stability; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins

Carbapenem-resistant Klebsiella pneumoniae has recently been reported as a new, multidrug-resistant nosocomial pathogen in several hospitals from various Italian regions. Through Micronet, a new Italian sentinel laboratory-based surveillance network, we studied the trend of non-susceptibility of K. pneumoniae to selected carbapenems (imipenem and/or meropenem) in 14 of the 15 hospitals participating in the network. Analysis of data from 1 January 2009 to 30 April 2012 revealed a statistically significant increasing trend (p<0.01) in the proportion of carbapenem non-susceptible K. pneumoniae isolates from clinical specimens (from 2.2 % in 2009 to 19.4% in 2012). The increase in the proportion of non-susceptibility was very large for isolates from the respiratory tract (from 5.3% in 2009 to 38.5% in 2012) and blood (from 5.4% in 2009 to 29.2% in 2012). The results demonstrate the urgent need in Italy for infection control, guidelines, antibiotic stewardship programmes and utilisation of surveillance systems, such as Micronet, which are capable of receiving data from hospitals in real time for many pathogens and types of clinical specimens.

Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Hospitals; Humans; Imipenem; Italy; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sentinel Surveillance; Thienamycins

Cutaneous infection develops because of environmental and local factors, host immunity, and organism adherence and virulence. The authors report a case of exuberant cutaneous ulcers on the buttocks of a diabetic patient. Microbiologic examination allowed the identification of Klebsiella pneumoniae and complete resolution was achieved with the appropriate antibiotic.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Buttocks; Diabetes Complications; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Skin Diseases, Bacterial; Skin Ulcer; Thienamycins

Detection of rectal colonization with carbapenem-resistant Klebsiella pneumoniae (CRKP) is the most important step in the infection control protocols in order to prevent infections caused by CRKP which has an increasing incidence all over the world. In this study, it was aimed to compare the detection rate of 2 mg/L ertapenem EMB agar medium with the other methods recommended by various international guidelines. These methods include direct plate method using ertapenem disc, enrichment method in tryptic soy broth containing 2 mg/L ertapenem and the investigation of the predominant betalactamases in the colonized patients. The lowest inoculum detected by different methods was determined by using simulative challenge test prepared for this purpose. The ability to detect CRKP from rectal swabs was evaluated by using the clinical specimens of 801 patients. For all bacteria isolated, carbapenem susceptibility was evaluated by using E-test method, the presence of beta-lactamases was determined by using modified Hodge test (MHT), and the carbapenemase genes were investigated by using multiplex polymerase chain reaction (PCR). The lowest inoculum detected by ertapenem-EMB agar was 50 CFU/mL whereas the lowest inocula were 1 x 105 and 1 x 103, respectively by tryptic soy broth with ertapenem and direct plate method. No resistance gene were identified by PCR in 13 (39.4%) of 33 isolates, whereas blaOXA-48 was detected in 19 (95%) and blaIMP in 1 (5%) of 20 positive isolates. All of the positive strains were resistant to imipenem and ertapenem, while 2 (10%) strains were found to be susceptible to doripenem and meropenem. While MHT was negative in all strains which were negative for resistance genes, all resistance gene positive strains except one blaOXA-48 strain that was also sensitive to doripenem and meropenem, were found to be positive with MHT. According to the results of PCR, the sensitivities of the three methods were found to be 80%. The specificities, positive and negative predictive values were found to be 15.4%, 59% and 33.3% for ertapenem-EMB agar, 23%, 61.5% and 42.9% for broth with ertapenem and 61.5%, 76% and 66.6% for direct plate method, respectively. Average labor time of the methods (isolation + identification + sensitivity + MHT) was determined as 48 hours for ertapenem-EMB agar, whereas it was 96 hours for the other methods. In conclusion, since ertapenem- EMB agar method is a sensitive and rapid method, it can be used safely for the preliminar

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Carbapenems; Culture Media; Doripenem; Drug Resistance, Bacterial; Ertapenem; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Multiplex Polymerase Chain Reaction; Rectum; Sensitivity and Specificity; Thienamycins; Time Factors

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

We evaluated the efficacy of NXL104, a novel β-lactamase inhibitor, in combination with ceftazidime (CAZ) in two murine infection models (septicemia and thigh infection). We chose two KPC-producing Klebsiella pneumoniae strains (VA-361 and VA-406) showing MICs of CAZ of ≥256 μg/ml. Septicemia was induced by the intraperitoneal injection of KPC-producing K. pneumoniae followed 30 min later by a single subcutaneous treatment with CAZ alone or CAZ-NXL104 in ratios of 2:1, 4:1, 8:1, and 16:1. In this model, the median effective doses for 50% (ED(50)) of the animals for CAZ alone versus VA-361 and VA-406 were 1,578 and 709 mg/kg of body weight, respectively. When combined with NXL104 at 2:1, 4:1, 8:1, and 16:1 ratios, the CAZ ED(50)s for VA-361 and VA-406 were reduced to 8.1 and 3.5 mg/kg, 15.1 and 3.8 mg/kg, 16.9 and 7.2 mg/kg, and 29.5 and 12.1 mg/kg, respectively. For thigh infection, neutropenia was induced by the intraperitoneal injection of cyclophosphamide at days -4 and -1 preinfection. Infection was established by the intramuscular injection of KPC-producing K. pneumoniae into the right thigh. Mice were treated 1.5 h postinfection with either CAZ alone or CAZ-NXL104 at constant ratios of 4:1. When thighs were removed at 24 h postinfection, a >2-log CFU reduction was observed for mice treated with CAZ-NXL104 at doses of ≥128:32 mg/kg. In contrast, CAZ doses of ≥1,024 mg/kg were unable to reduce the numbers of CFU. Despite resistance to CAZ and possessing a complex β-lactamase background, NXL104 combined with CAZ proved to be very effective in murine models of infection due to contemporary highly resistant KPC-producing K. pneumoniae isolates.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Sepsis

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla(NDM-1) carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Kenya; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

We describe the first report of simultaneous blood infection with KPC-2 producing Klebsiella pneumoniae and Escherichia coli in a Brazilian patient. We highlight the importance of implementing efficient infection control measures to limit the spread of these phenotypes in a hospital setting.

Topics: Aged, 80 and over; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Catheter-Related Infections; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Thienamycins

Doripenem is a carbapenem with potent broad-spectrum activity against Gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. As the incidence of extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacilli is increasing, it was of interest to examine the in vivo comparative efficacy of doripenem, imipenem, and meropenem against a Klebsiella pneumoniae isolate expressing the TEM-26 ESBL enzyme. In a murine lethal lower respiratory infection model, doripenem reduced the Klebsiella lung burden by 2 log(10) CFU/g lung tissue over the first 48 h of the infection. Treatment of mice with meropenem or imipenem yielded reductions of approximately 1.5 log(10) CFU/g during this time period. Seven days postinfection, Klebsiella titers in the lungs of treated mice decreased an additional 2 log(10) CFU/g relative to those in the lungs of untreated control animals. Lipopolysaccharide (LPS) endotoxin release assays indicated that 6 h postinfection, meropenem- and imipenem-treated animals had 10-fold more endotoxin in lung homogenates and sera than doripenem-treated mice. Following doripenem treatment, the maximum endotoxin release postinfection (6 h) was 53,000 endotoxin units (EU)/ml, which was 2.7- and 6-fold lower than imipenem or meropenem-treated animals, respectively. While the levels of several proinflammatory cytokines increased in both the lungs and sera following intranasal K. pneumoniae inoculation, doripenem treatment, but not meropenem or imipenem treatment, resulted in significantly increased interleukin 6 levels in lung homogenates relative to those in lung homogenates of untreated controls, which may contribute to enhanced neutrophil killing of bacteria in the lung. Histological examination of tissue sections indicated less overall inflammation and tissue damage in doripenem-treated mice, consistent with improved antibacterial efficacy, reduced LPS endotoxin release, and the observed cytokine induction profile.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; Carbapenems; Cytokines; Disease Models, Animal; Doripenem; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins; Treatment Outcome

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported all over the world. In this study, we aimed to investigate the risk factors for the acquisition of nosocomial CRKP infections.. We conducted a case-control study with data collected from thirty-nine patients with nosocomially acquired CRKP infection between July 2006 and July 2008. Controls were selected at a ratio of 1:2 from patients with nosocomial carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection and were matched with CRKP cases for site of infection and the date of hospital admission (± within 5 days). T test, chi-square test, and logistic regression were used for statistical analysis.. Bivariable analysis showed that the age of the patients (P=0.038), days of hospital stay prior to isolation of Klebsiella pneumoniae (K. pneumoniae) (P=0.043), altered consciousness (P=0.007), intensive care unit (ICU) admission within two weeks (P=0.003), tracheal intubation (P=0.027), mechanical ventilation (P=0.009), number of changes in antibiotics≥4 (P=0.001), exposure to carbapenems (P = 0.002), exposure to fourth-generation cephalosporins (P=0.027), and exposure to piperacillin-tazobactams/cefoperazone-sulbactams (P=0.043) and glycopeptides (P=0.042) were related to CRKP infection. The multivariable analysis showed that ICU admission (within two weeks) [odds ratio (OR):4.68, 95% confidence intervals (CI):1.15-19.09, P=0.031], exposure to carbapenems (OR: 12.69, 95% CI: 2.09-77.10, P=0.006) and exposure to glycopeptides (OR: 3.57, 95% CI: 1.11-11.42, P=0.032) were independent risk factors for nosocomial CRKP infections.. Several factors are related to CRKP infections. ICU admission (within two weeks) or prior exposure to carbapenems or glycopeptides are independent risk factors for the acquisition of nosocomial CRKP infections.

Topics: Age Factors; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Case-Control Studies; Chi-Square Distribution; Confidence Intervals; Cross Infection; Drug Resistance, Bacterial; Ertapenem; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Logistic Models; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Thienamycins

OmpK35 and OmpK36 are the major outer membrane porins of Klebsiella pneumoniae. In this study, a virulent clinical isolate was selected to study the role of these two porins in antimicrobial resistance and virulence. The single deletion of ompK36 (ΔompK36) resulted in MIC shifts of cefazolin, cephalothin, and cefoxitin from susceptible to resistant, while the single deletion of ompK35 (ΔompK35) had no significant effect. A double deletion of ompK35 and ompK36 (ΔompK35/36) further increased these MICs to high-level resistance and led to 8- and 16-fold increases in the MICs of meropenem and cefepime, respectively. In contrast to the routine testing medium, which is of high osmolarity, susceptibility tests using low-osmolarity medium showed that the ΔompK35 mutation resulted in a significant (≥ 4-fold) increase in the MICs of cefazolin and ceftazidime, whereas a ΔompK36 deletion conferred a significantly (4-fold) lower increase in the MIC of cefazolin. In the virulence assays, a significant (P < 0.05) defect in the growth rate was found only in the ΔompK35/36 mutant, indicating the effect on metabolic fitness. A significant (P < 0.05) increase in susceptibility to neutrophil phagocytosis was observed in both ΔompK36 and ΔompK35/36 mutants. In a mouse peritonitis model, the ΔompK35 mutant showed no change in virulence, and the ΔompK36 mutant exhibited significantly (P < 0.01) lower virulence, whereas the ΔompK35/36 mutant presented the highest 50% lethal dose of these strains. In conclusion, porin deficiency in K. pneumoniae could increase antimicrobial resistance but decrease virulence at the same time.

Topics: Animals; Bacterial Proteins; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Genetic Complementation Test; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Sequence Data; Phagocytosis; Porins; Sequence Analysis, DNA; Thienamycins; Virulence

Detection of bla(KPC)-harboring Klebsiella pneumoniae (KP) in the clinical laboratory remains a difficult task. Decreased ertapenem (ERT) susceptibility has been considered one of the most sensitive phenotypic indicators of K. pneumoniae carbapenemase (KPC) production, but has been found to be nonspecific. Susceptibility testing using imipenem or meropenem lacks the sensitivity for detection of KPCs, and there is limited experience using doripenem (DOR). Fifty-five individual ERT-nonsusceptible KP isolates and 19 isolates that were ERT-susceptible, extended spectrum β-lactamase-positive KP were collected from the clinical laboratory and tested for DOR susceptibility by Etest methodology. PCR screening for bla(KPC) was performed on all specimens. All but three isolates with ERT resistance were KPC positive by PCR. Compared to PCR, ERT detection of KPC had a sensitivity of 98% and a false-positive rate of 6%. Overall, there was a 97% agreement between ERT and DOR susceptibility results. However, there was one KPC-positive isolate that was discrepant (ERT susceptible, DOR nonsusceptible by Etest). Selected isolates of KP from both groups underwent pulsed-field gel electrophoresis analysis to determine the degree of genetic relatedness of KPC-positive and KPC-negative isolates. Pulsed-field gel electrophoresis of selected KPC-positive and KPC-negative KP identified a common pattern between both groups. The resistance to DOR and/or ERT is sensitive and a specific indicator for detection of bla(KPC) in KP.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; DNA, Bacterial; Doripenem; Electrophoresis, Gel, Pulsed-Field; Ertapenem; Genotype; Hospitals, Urban; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Phylogeny; Polymerase Chain Reaction; Sensitivity and Specificity; Thienamycins; United States

Infections caused by extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella spp. constitute severe problems. Carbapenems are commonly used to treat these infections. However, infections caused by carbapenem-resistant gram-negative bacteria show an increasing trend recently. The aim of this study was to investigate the susceptibilities of ESBL-producing E.coli and Klebsiella spp. to ertapenem and other carbapenems. A total of 239 E.coli, 28 K.pneumoniae and 11 K.oxytoca strains isolated from clinical specimens (208 urine, 16 blood, 26 wound, 17 sterile body fluids, four tracheal aspirates and seven others) of hospitalized patients and outpatients between January 2007-February 2008, were included to the study. The isolates were identified by conventional methods, and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method according to Clinical and Laboratory Standards Institute (CLSI) standards. ESBL production was tested by double disk diffusion method. When ESBL production was indeterminate, cefotaxime-clavulanic acid E test (BioMerieux, France) was used. According to the CLSI standards modified Hodge test was performed for carbapenem resistant isolates and minimal inhibitory concentration (MIC) values were detected for ertapenem (Etest®, BioMerieux, France), imipenem and meropenem (M.I.C. Evaluator Strips, Oxoid, UK). All of the isolates were found susceptible to amikacin (278/278; 100%), whereas the susceptibility rates for imipenem/meropenem and ertapenem were 99.3% (276/278) and 98.6% (274/278), respectively. When evaluated individually, ertapenem susceptibilities of E.coli, K.pneumoniae and K.oxytoca strains were 99.2%, 96.4% and 90.9%, respectively, while these rates were 100%, 96.4% and 90.9%, respectively, for imipenem/meropenem. Carbapenem resistance was detected in two E.coli, one K.oxytoca and one K.pneumoniae isolates. While two Klebsiella spp. İsolates were resistant to all of the tested carbapenems (MIC > 32 µg/ml), two E.coli isolates were resistant to ertapenem (MIC > 32 µg/ml) but susceptible to imipenem (MIC= 0.25 µg/ml) and meropenem (MIC= 0.5 µg/ml). Carbapenemase production was demonstrated by modified Hodge test in all of the carbapenem-resistant isolates. In conclusion, ESBL-producing gram-negative isolates should be routinely tested with a screening method for carbapenemase activity and confirmation tests should be performed in suspected cases.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

For 244 patients with bacteremia due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae treated by ertapenem (73, 29.9%) or either imipenem or meropenem (171, 70.1%), the therapeutic efficacy was evaluated. Ertapenem therapy was effective for patients with ESBL-producing E. coli or K. pneumoniae bacteremia in terms of mortality and microbiological responses, as compared with imipenem or meropenem.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

Polymyxin B (PB) plus meropenem (MER) or rifampin (RIF) was tested by Etest® method and time-kill assay (TKA) against 14 genetically unique clinical Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. PB + MER: Etest, 43% synergy; TKA, 64% synergy. Concordance between methods was 79%. For PB + RIF: Etest, 21% synergy; TKA, 100% synergy. Concordance between methods was 21%.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Polymyxin B; Rifampin; Thienamycins; Time Factors

Gram-negative bacterial resistance to antibiotics is of increasing concern. Carbapenem resistance among strains of Klebsiella pneumoniae is a relatively new phenomenon. Resistance attributable to production of carbapenemases is notoriously difficult to combat.. Case report and review of the pertinent English-language literature.. A patient, hospitalized for aortic dissection complicated by intra-abdominal catastrophe and acute kidney injury, developed bacteremia exhibiting meropenem non-susceptibility secondary to expression of bla(KPC-2). High-dose, continuous-infusion meropenem achieved serum drug concentrations above the minimum inhibitory concentration and eradicated the infection.. This is the first report of a meropenem-non-susceptible carbapenamase-positive Klebsiella pneumoniae blood stream infection treated successfully with high-dose, continuous-infusion meropenem. Application of this regimen in certain patients, such as those with mild-to-moderate renal insufficiency, may be a reasonable option for multi-drug-resistant nosocomial infections.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Serum; Thienamycins; Treatment Outcome

We recently experienced the case of an intramuscular chloroma with infection in a 7-year-old boy diagnosed with acute myeloid leukemia. Conventional magnetic resonance imaging (MRI) showed that the lesion mimicked an abscess, but diffusion-weighted imaging showed no diffusion restriction. These results suggested that the interior cystic portion was serous. On histopathological findings, a chloroma was diagnosed on the wall of a mass. Culture of the interior fluid revealed that Klebsiella pneumoniae was present. MRI differentiation is difficult even with diffusion-weighted images.

Topics: Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Child; Contrast Media; Cytarabine; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Gentamicins; Humans; Image Enhancement; Klebsiella Infections; Klebsiella pneumoniae; Leg; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Meropenem; Muscle Neoplasms; Necrosis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sarcoma, Myeloid; Teicoplanin; Thienamycins; Treatment Outcome

To devise a local strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).. Quasi-experimental, before-and-after, interrupted time-series study.. A 1,000-bed tertiary-care university teaching hospital.. Retrospectively, all relevant data were collected from the medical records of patients with CRKP infections from May 2006 through April 2007, the preintervention period. From May 1, 2007, through May 1, 2010, the postintervention period, the intervention was applied and prospectively followed. The 5 key elements of this strategy were an emergency department flagging system, the building of a cohort ward, the eradication of clusters, environmental and personnel hand cultures, and a carbapenem-restriction policy. The demographic and clinical parameters of patients colonized by and/or infected with CRKP were collected from medical records.. A total of 10,680 rectal cultures were performed for 8,376 patients; 433 (5.16%) and 370 (4.4%) were CRKP-colonized and CRKP-infected patients, respectively, and 789 (98%) of 803 patients were admitted to the CRKP cohort ward. The CRKP infection density was reduced from 5.26 to 0.18 per 10,000 patient-days (P ≤ .001), and no nosocomial CRKP infections were diagnosed. Twenty-three percent of environmental cultures were found to be positive. Meropenem use was reduced from 283 ± 70.92 to 118 ± 74.32 defined daily doses per 1,000 patient-days (P ≤ .001).. This intervention produced an enormous impact on patient location, surveillance cultures, and antibiotic policies and a massive investment in infection control resources.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Feces; Female; Humans; Infection Control; Israel; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Nursing Homes; Patient Isolation; Thienamycins; Young Adult

Respiratory infections caused by Klebsiella pneumoniae are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including beta-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia.

Topics: Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Culture Media; Defensins; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Phenotype; Plasmids; Polymyxin B; Polysaccharides; Repressor Proteins; RNA, Bacterial

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

Sporadic isolates of carbapenem-resistant KPC-2-producing Klebsiella pneumoniae were isolated in Tel Aviv Medical Center during 2005 and 2006, parallel to the emergence of the KPC-3-producing K. pneumoniae sequence type 258 (ST 258). We aimed to study the molecular epidemiology of these isolates and to characterize their bla(KPC)-carrying plasmids and their origin. Ten isolates (8 KPC-2 and 2 KPC-3 producing) were studied. All isolates were extremely drug resistant. They possessed the bla(KPC) gene and varied in their additional beta-lactamase contents. The KPC-2-producing strains belonged to three different sequence types: ST 340 (n = 2), ST 277 (n = 2), and a novel sequence type, ST 376 (n = 4). Among KPC-3-producing strains, a single isolate (ST 327) different from ST 258 was identified, but both strains carried the same plasmid (pKpQIL). The KPC-2-encoding plasmids varied in size (45 to 95 kb) and differed among each of the STs. Two of the Klebsiella bla(KPC-2)-carrying plasmids were identical to plasmids from Escherichia coli, suggesting a common origin of these plasmids. These data indicate that KPC evolution in K. pneumoniae is related to rare events of interspecies spread of bla(KPC-2)-carrying plasmids from E. coli followed by limited clonal spread, whereas KPC-3 carriage in this species is related almost strictly to clonal expansion of ST 258 carrying pKpQIL.

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Humans; Israel; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology; Phylogeny; Plasmids; Polymerase Chain Reaction

Carbapenemase-producing Klebsiella pneumoniae (KPC) bacteria are rapidly becoming one of the most detrimental drug-resistant Gram-negative pathogens. Doripenem is the newest FDA-approved carbapenem that has the greatest in vitro potency against a wide range of Gram-negative organisms, including multidrug-resistant organisms. Previous work in an animal model has shown efficacy against Pseudomonas aeruginosa with MICs above the current breakpoints of susceptibility. The purpose of this study is to evaluate the efficacy of 1-g and 2-g dose prolonged infusions of doripenem against KPC isolates in both an immunocompetent and neutropenic murine thigh model. Seven clinical KPC isolates (broth microdilution [BMD] MIC range, 4 to 32 μg/ml; Etest MIC range, 3 to >32 μg/ml) were used. After infection, groups of mice were administered doripenem doses previously shown to simulate the exposures observed in humans after the administration of 1 or 2 g every 8 h as a 4-h infusion. In immunocompromised mice, 1- and 2-g doses of doripenem achieved bacteriostasis against isolates with MICs up to and including 8 μg/ml and 16 μg/ml, respectively. In immunocompetent animals, statistically significant reductions in the number of CFU were observed with overall decreases of approximately 1 log (P < 0.05). While carbapenemase-producing Klebsiella pneumoniae continues to decrease our meager supply of active agents, the ability of doripenem to produce CFU reductions in the presence of white blood cells (WBCs) using humanized exposures suggests the potential utility of this agent in combination against this increasingly problematic pathogen.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Doripenem; Female; Humans; Immunocompetence; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Thigh

Topics: Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Klebsiella oxytoca; Meropenem; Netilmicin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proctitis; Thienamycins; Tomography, X-Ray Computed; Typhlitis; Vancomycin

We describe the levels of agreement between broth microdilution, Etest, Vitek 2, Sensititre, and MicroScan methods to accurately define the meropenem MIC and categorical interpretation of susceptibility against carbapenemase-producing Klebsiella pneumoniae (KPC). A total of 46 clinical K. pneumoniae isolates with KPC genotypes, all modified Hodge test and bla(KPC) positive, collected from two hospitals in NY were included. Results obtained by each method were compared with those from broth microdilution (the reference method), and agreement was assessed based on MICs and Clinical Laboratory Standards Institute (CLSI) interpretative criteria using 2010 susceptibility breakpoints. Based on broth microdilution, 0%, 2.2%, and 97.8% of the KPC isolates were classified as susceptible, intermediate, and resistant to meropenem, respectively. Results from MicroScan demonstrated the most agreement with those from broth microdilution, with 95.6% agreement based on the MIC and 2.2% classified as minor errors, and no major or very major errors. Etest demonstrated 82.6% agreement with broth microdilution MICs, a very major error rate of 2.2%, and a minor error rate of 2.2%. Vitek 2 MIC agreement was 30.4%, with a 23.9% very major error rate and a 39.1% minor error rate. Sensititre demonstrated MIC agreement for 26.1% of isolates, with a 3% very major error rate and a 26.1% minor error rate. Application of FDA breakpoints had little effect on minor error rates but increased very major error rates to 58.7% for Vitek 2 and Sensititre. Meropenem MIC results and categorical interpretations for carbapenemase-producing K. pneumoniae differ by methodology. Confirmation of testing results is encouraged when an accurate MIC is required for antibiotic dosing optimization.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sensitivity and Specificity; Thienamycins

Meropenem heteroresistance was investigated in six apparently meropenem-susceptible, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) clinical isolates, compared with that in carbapenemase-negative, meropenem-susceptible controls. In population analyses, the KPC-KP isolates grew at meropenem concentrations of 64 to 256 microg/ml. Heteroresistant colonies had significantly elevated expression of the bla(KPC) gene compared with the native populations but did not retain heteroresistance when subcultured in drug-free media. Time-kill assays indicated that meropenem alone was not bactericidal against KPC-KP but efficiently killed the control strains.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Disease Outbreaks; Greece; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Electrophoresis, Polyacrylamide Gel; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Porins; Thienamycins

Osteomyelitis in newborn infants is a rare infection. Lower extremity joints are commonly affected. Most of the cases have a haematogenous spread. Aerobes are the common group of organism involved, of which Staphylococcus aureus is the commonest. Klebsiella osteomyelitis has been reported as a cause of Osteomyelitis. However, to the best of our knowledge, this is the first case report of Klebsiella pneumoniae associated osteomyelitis in an infant from Pakistan.

Topics: Anti-Bacterial Agents; Follow-Up Studies; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Osteomyelitis; Radiography; Sepsis; Shoulder Joint; Thienamycins; Treatment Outcome

Carbapenem-resistant Klebsiella strains carrying Klebsiella pneumoniae carbapenemases (KPC) are endemic to New York City and are spreading across the United States and internationally. Recent studies have indicated that the KPC structural gene is located on a 10-kb plasmid-borne element designated Tn4401. Fourteen Klebsiella pneumoniae strains and one Klebsiella oxytoca strain isolated at a New York City hospital in 2005 carrying either bla(KPC-2) or bla(KPC-3) were examined for isoforms of Tn4401. Ten of the Klebsiella strains contained a 100-bp deletion in Tn4401, corresponding to the Tn4401a isoform. The presence of this deletion adjacent to the upstream promoter region of bla(KPC) in Tn4401a resulted in a different -35 promoter sequence of TGGAGA than that of CTGATT present in isoform Tn4401b. Complete sequencing of one plasmid carrying bla(KPC) from each of three nonclonal isolates indicated the presence of genes encoding other types of antibiotic resistance determinants. The 70.6-kb plasmid from K. pneumoniae strain S9 carrying bla(KPC-2) revealed two identical copies of Tn4401b inserted in an inverse fashion, but in this case, one of the elements disrupted a group II self-splicing intron. In K. pneumoniae strain S15, the Tn4401a element carrying bla(KPC-2) was found on both a large 120-kb plasmid and a smaller 24-kb plasmid. Pulsed-field gel electrophoresis results indicate that the isolates studied represent a heterogeneous group composed of unrelated as well as closely related Klebsiella strains. Our results suggest that endemic KPC-positive Klebsiella strains constitute a generally nonclonal population comprised of various alleles of bla(KPC) on several distinct plasmid genetic backgrounds. This study increases our understanding of the genetic composition of the evolving and expanding role of KPC-producing, healthcare-associated, gram-negative pathogens.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; DNA Transposable Elements; Drug Resistance, Bacterial; Hospitals, Urban; Humans; Isoenzymes; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Microbial Sensitivity Tests; New York City; Plasmids; Transposases

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Sequence Data; Poland

A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactamases; Carboxylic Ester Hydrolases; Cefotaxime; Cefuroxime; Cephalosporins; Cephalothin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; India; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillins; Sequence Analysis, DNA; Sequence Homology, Amino Acid

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae may appear susceptible to imipenem or meropenem by routine susceptibility testing. We report a series of patients with infections caused by K. pneumoniae isolates, which yielded imipenem-susceptible results but were subsequently KPC-positive by polymerase chain reaction. When these infections were treated with imipenem or meropenem, frequent clinical and microbiologic failures were observed.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Female; Genes, Bacterial; Humans; Imipenem; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Polymerase Chain Reaction; Thienamycins; Treatment Failure; Treatment Outcome; Young Adult

Infection with resistant gram-negative bacteria is a growing threat to hospitalised patients.. To determine factors associated with mortality among infants infected by extended-spectrum beta-lactamase-producing Klebsiella species (Klebs-ESBL) and to assess whether selective empirical use of meropenem (MERO) is associated with high mortality.. Medical records of neonates admitted from January 2002 to December 2003 who had positive blood and/or cerebrospinal fluid (CSF) culture with Klebs-ESBL were reviewed for clinical, management and outcome information. Univariate and multivariate logistic regression analyses were performed to determine factors associated with mortality among infants with culture-proven Klebs-ESBL.. A hundred patients had positive blood (n=97) and/or CSF cultures (n=9) owing to Klebs-ESBL. Overall mortality rate was 30%. The mortality rates among those who were empirically started on a combination of piperacillin-tazobactam and amikacin (Pip-Taz+Amik) (n=48), meropenem (MERO) (n=40) and in those not started on MERO or Pip-Taz+Amik) (n=12) were 25%, 32% and 42%, respectively. Non-survivors were younger (p=0.01), had cardio-respiratory compromise or required assisted ventilation at presentation (p<0.001), and were not started on antibiotics, MERO or Pip-Taz+Amik (p<0.001). On multivariate analysis, factors associated with mortality were vaginal delivery (OR -7.07, 95% CI 2.14-23.39), a need for assisted ventilation at onset of illness (OR -4.94, 95% CI 1.12-21.86) and not starting empirical MERO or Pip-Taz+Amik (OR -17.01, 95% CI 2.41-120.23).. While empirical use of carbapenems for nosocomial sepsis might be appropriate in areas where Klebs-ESBL is prevalent, their use can be restricted to those with cardio-respiratory compromise or severe sepsis without an increase in mortality.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cohort Studies; Drug Administration Schedule; Female; Humans; Infant, Newborn; Klebsiella; Klebsiella Infections; Male; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pregnancy; Regression Analysis; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins

We recovered a carbapenem-resistant Klebsiella pneumoniae isolate H224 under in vivo meropenem selection pressure. Insertional inactivation of a major porin gene, ompK36, by IS5 element might play a role in acquiring carbapenem resistance in this strain harboring plasmid-borne DHA-1 AmpC beta-lactamase.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; DNA, Bacterial; Female; Gene Deletion; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Porins; Selection, Genetic; Sequence Analysis, DNA; Thienamycins

Botulism is the acute, flaccid paralysis caused by a neurotoxin produced by Clostridium botulinum. In the infant, clinical symptoms are usually unspecific such as poor feeding, weak suck, feeble cry, drooling, followed by a symmetric, descending, flaccid paralysis beginning with the cranial nerve musculature. The initial symptoms of the disease are often similar to several diseases and therefore differential diagnosis is very difficult and rarely suspected by the physician. Since 2004 only 22 cases of infant botulism have been reported in Italy. Since most paediatricians are unfamiliar with the clinical manifestations of infant botulism, the diagnosis can be easily missed. Hence the disease may well be underestimated and underreported. We report a clinical case of botulism presenting initially with abdominal distention, thereby mimicking acute abdomen.

Topics: Abdomen, Acute; Anti-Bacterial Agents; Botulism; Clostridium botulinum; Diagnosis, Differential; Electroencephalography; Follow-Up Studies; Humans; Incidence; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Pneumonia, Bacterial; Thienamycins; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Female; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the beta-lactamase bla KPC-2 gene was located on a novel Tn3-based transposon, Tn4401. Tn4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the beta-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7. Tn4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn4401a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn4401b, which was found in the Colombian isolates. In all isolates tested, Tn4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn4401 is likely at the origin of carbapenem-hydrolyzing beta-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.

Topics: Base Sequence; beta-Lactamases; beta-Lactams; Cloning, Molecular; Colombia; DNA Transposable Elements; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA; United States

The presence of plasmid-mediated quinolone resistance genes [i.e., qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA] was evaluated among 42 bla(KPC)-containing Klebsiella pneumoniae isolates collected in the eastern United States. One isolate carried the bla(KPC-3) and qnrB19 genes on the same conjugative plasmid, whereas another carried the bla(KPC-3) and qnrA1 genes on separate plasmids.

Topics: Aged; Bacterial Proteins; Base Sequence; beta-Lactamases; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Plasmids; Quinolones; United States

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae have rapidly spread worldwide and pose a serious threat for health care-associated (HA) infection. We conducted molecular detection and characterization of ESBL-related bla genes, including bla(TEM), bla(SHV), bla(CTX-M), bla(VEB), bla(OXA), bla(PER), and bla(GES), among 362 isolates of ESBL-producing E. coli (n = 235) and ESBL-producing K. pneumoniae (n = 127) collected from patients who met the definition of HA infection at two major university hospitals in Thailand from December 2004 to May 2005. The prevalence of ESBL-producing E. coli and ESBL-producing K. pneumoniae, patient demographics and the susceptibilities of these bacteria to various antimicrobial agents were described. A total of 87.3% of isolates carried several bla genes. The prevalence of bla(CTX-M) was strikingly high: 99.6% for ESBL-producing E. coli (CTX-M-14, -15, -27, -40, and -55) and 99.2% for ESBL-producing K. pneumoniae (CTX-M-3, -14, -15, -27, and -55). ISEcp1 was found in the upstream region of bla(CTX-M) in most isolates. Up to 77.0% and 71.7% of ESBL-producing E. coli and ESBL-producing K. pneumoniae, respectively, carried bla(TEM); all of them encoded TEM-1. ESBL-producing K. pneumoniae carried bla(SHV) at 87.4% (SHV-1, -2a, -11, -12, -27, -71, and -75) but only at 3.8% for ESBL-producing E. coli (SHV-11 and -12). bla genes encoding VEB-1 and OXA-10 were found in both ESBL-producing E. coli (8.5% and 8.1%, respectively) and ESBL-producing K. pneumoniae (10.2% and 11.8%, respectively). None of the isolates were positive for bla(PER) and bla(GES). Pulsed-field gel electrophoresis analysis demonstrated that there was no major clonal relationship among these ESBL producers. This is the first study to report CTX-M-3, CTX-M-27, CTX-M-40, SHV-27, SHV-71, and SHV-75 in Thailand and to show that CTX-M ESBL is highly endemic in the country.

Topics: Adult; Bacterial Proteins; beta-Lactamases; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Endemic Diseases; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymerase Chain Reaction; Sequence Analysis, DNA; Thailand

The first outbreak of carbapenem-resistant Klebsiella pneumoniae isolates producing the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 is reported. The 39 isolates belonged to two different clones and were collected at the University Hospital of Istanbul, Turkey, from May 2006 to February 2007, and they coproduced various beta-lactamases (SHV-12, OXA-9, and TEM-1 for clone A and CTX-M-15, TEM-1, and OXA-1 for clone B).

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Genetic; Turkey

Topics: Adult; Anti-Bacterial Agents; Belgium; beta-Lactamases; beta-Lactams; Carbapenems; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Plasmids

We report two premature infants who developed multiple brain abscesses following Klebsiella pneumoniae infection. Both the cases were diagnosed by ultrasonogram (USG) and cranial tomography. Abscess had intraventricular communication in one case. One infant was managed conservatively while the other required surgical drainage.

Topics: Amikacin; Anti-Bacterial Agents; Brain Abscess; Humans; Infant, Newborn; Infant, Premature; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Thienamycins

VIM-type metallo-betalactamases (MBLs) exhibit hydrolytic activity against most betalactam antibiotics, including carbapenems. So far, VIM-type-producing Klebsiella pneumoniae isolates had not been reported in Latin America.. In July 2005, a carbapenem-resistant Klebsiella pneumoniae was isolated from a urine sample collected from a 7-year-old girl hospitalized at the Hospital de Niños "J. M. de los Ríos" in Caracas, Venezuela. This strain was identified using conventional biochemical tests. The susceptibility analysis was conducted by disk diffusion, and MICs for Imipenem and Meropenem were performed by agar dilution. For the phenotypic detection of MBL we used the Imipenem-EDTA/SMA double-disk diffusion method. The hydrolytic activity against carbapenems was determined by the Masuda microbiological method. Purified protein was subjected to isoelectric focusing (IEF). Detection of antimicrobial resistance genes was performed by PCR amplification with specific VIM primers.. The strain showed resistance to most betalactam antibiotics, quinolones and amynoglicosides, but remained susceptible to Aztreonam and Cefepime. The use of phenotypic and microbiological methods detected the presence of a metallobetalactamase. By IEF we visualized three bands at pI 5.4, 7.6 and 7.9, corresponding to reduced-spectrum betalactamases, and a band at pI 5.8 that corresponded to the metallobetalactamase. PCR screening of bla genes revealed the presence of blaVIM, with an amplicon of 261 bp.. This is the first report of a MBL-mediated carbapenem-resistant Klebsiella pneumoniae in Latin America, which constitutes a public health concern in our region since their transference to other microorganisms with multiple antibiotic resistance mechanisms will increase the antimicrobial resistance problem.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Child; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Quinolones; Thienamycins; Urine; Venezuela

Topics: Adult; Anti-Bacterial Agents; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Neutrophils; Phagocytosis; Thienamycins

The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-beta-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10(5) inoculum. Three isolates were examined at a high 10(7) inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (microg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs wereMIC>or=23%) and meropenem (fT>MIC>or=75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of>or=2 microg/ml (fT>MICMIC=30 to 65%). At a 10(7) inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC=20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of>or=2 microg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.

Topics: Animals; beta-Lactamases; beta-Lactams; Disease Models, Animal; Ertapenem; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Thienamycins

Carbapenem resistance due to KPC has rarely been observed outside the United States. We noticed a sharp increase in carbapenem-resistant Klebsiella pneumoniae strains possessing KPC in Tel Aviv Medical Center from 2004 to 2006. Sixty percent of the isolates belonged to a single clone susceptible only to gentamicin and colistin and carried the bla(KPC-3) gene, while almost all other clones carried the bla(KPC-2) gene. This rapid dissemination of KPC outside the United States is worrisome.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Hospitals; Humans; Israel; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology

In this study, we examined the prevalence of and mechanisms of decreased susceptibility to either imipenem or meropenem in Klebsiella pneumoniae isolates. A total of 230 clinical isolates of K. pneumoniae were collected from 13 clinical laboratories from a nationwide distribution. The MICs of imipenem and meropenem were determined by the agar dilution method. To characterize the isolates with decreased susceptibility to carbapenems (MICs of >2 microg/mL), we performed polymerase chain reaction amplification of a variety of beta-lactamase genes, isoelectric focusing, and outer membrane profile analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Three isolates (BD6, BD8, and KN16) exhibited decreased susceptibility to carbapenems with imipenem MICs of 1, 4, and 8 microg/mL and meropenem MICs of 4, 8, and 4, respectively. Isolate BD6 produced bla(TEM-1), bla(SHV-12), and bla(OXA-17); isolate BD8 produced bla(GES-3), bla(SHV-12), and bla(OXA-17); and isolate KN16 produced bla(TEM-11), bla(SHV-12), and bla(DHA-1). In all the 3 isolates, OmpK35 porin was not expressed, and in 1 isolate (KN16), OmpK36 was not expressed either. The prevalence of decreased susceptibility to carbapenems was low (1.3%), and none of them showed overt resistance to carbapenems. Decreased susceptibility to carbapenems can occur in K. pneumoniae when bla(GES-3), bla(TEM-11), bla(SHV-12), bla(OXA-17), and/or bla(DHA-1) are produced in combination with porin loss. In addition, to our knowledge, this is the 1st report of bla(OXA-17) in Enterobacteriaceae.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Electrophoresis, Polyacrylamide Gel; Humans; Imipenem; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Korea; Mass Spectrometry; Meropenem; Microbial Sensitivity Tests; Molecular Sequence Data; Polymerase Chain Reaction; Porins; Prevalence; Sequence Analysis, DNA; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals, Urban; Humans; India; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

The study aimed to characterize the genetic basis of flomoxef and collateral ertapenem resistance in a clinical isolate of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) after flomoxef exposure.. Four ESBL-KP isolates (Lkp11-14) were recovered sequentially from four episodes of bacteraemia in an elderly patient. Laboratory investigations included genotyping by PFGE, resistance gene analysis by PCR and sequencing, and outer membrane protein analysis by SDS-PAGE. Plasmid analysis by DNA-DNA hybridization, electroporation and conjugation was also performed.. Lkp14 was recovered after 21 days of flomoxef therapy. It demonstrated an indistinguishable PFGE pattern when compared with those produced by Lkp11-13. However, resistance to both flomoxef and ertapenem emerged in Lkp14. Molecular characterization revealed that, in addition to the pre-existing ESBL production (CTX-M-3 and SHV-5) and OmpK35 deficiency found in Lkp11-13, Lkp14 had acquired an extra plasmid-mediated AmpC beta-lactamase gene (blaDHA-1) and failed to express OmpK36, because of insertional inactivation by an insertion sequence IS5. Other resistance mechanisms, such as production of carbapenem-hydrolysing enzymes or expression of chromosomal efflux, were apparently not involved. Conjugational transfer of the plasmid-mediated blaDHA-1 gene into Lkp11 resulted in a significant increase in the MICs of cephamycins and beta-lactamase inhibitors, but not in those of carbapenems.. Lkp14 was apparently derived from the previously flomoxef-susceptible isolates, Lkp11-13. After flomoxef exposure, the in vivo acquisition of the plasmid-mediated blaDHA-1 gene has led to flomoxef resistance in Lkp14, and the concomitant depletion of OmpK36 expression has resulted in a collateral effect of ertapenem resistance and diminished susceptibilities to imipenem and meropenem.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cephalosporins; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Bacterial; Electroporation; Ertapenem; Female; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Porins; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Blood; Culture Media; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Prevalence; Thienamycins

Shewanella putrefaciens is a facultatively anaerobic, non-motile, Gram-negative, non-fermentative bacterium. It is found in various environments and has been isolated worldwide. S. putrefaciens is a rare cause of brain abscesses and meningitis. This is a case report of a cerebellar abscess and meningitis caused by Shewanella putrefaciens and Klebsiella pneumoniae in a river trap fisherman.

Topics: Adult; Brain Abscess; Cerebellar Diseases; Gram-Negative Bacterial Infections; Head; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Otitis Media; Radiography; Shewanella putrefaciens; Thienamycins

The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC beta-lactamase ACT-1-producing Klebsiella pneumoniae strain (K. pneumoniae strain 12) and a derivative porin-deficient mutant (K. pneumoniae strain 12dp). No differences between these activities were seen with K. pneumoniae 12. Only meropenem showed an activity slightly better than that of imipenem with K. pneumoniae 12dp.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Colony Count, Microbial; Imipenem; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Plasmids; Pneumonia, Bacterial; Porins; Rats; Rats, Wistar; Thienamycins; Treatment Outcome

A 15-year-old girl developed a persistent bacteraemia with Klebsiella pneumoniae accompanied by systemic symptoms including high fever and rigors after appendectomy. Extensive laboratory and imaging work-up, including tests for an intra-vascular source of infection, did not reveal the origin of the persistent bacteraemia. The Klebsiella pneumoniae isolates were susceptible to gentamicin and colistin and intermediately susceptible to meropenem. The septicaemia persisted despite the intravenous administration of meropenem 1 g and later 2 g every 8 h in combination with intravenous gentamicin and later colistin. The patient was cured only after the continuous intravenous administration of meropenem of 6 g/d.

Topics: Adolescent; Anti-Bacterial Agents; Appendectomy; Appendicitis; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Postoperative Complications; Sepsis; Thienamycins

Three episodes of bacteremia occurred in the course of prosthetic valve endocarditis caused by an extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The second isolate developed resistance to ciprofloxacin and the third isolate to piperacillin-tazobactam (PIP-TZ) following sequential therapy with each agent. The first isolate was resistant to PIP-TZ only at high inocula, the second isolate acquired increased transcription of the acrA gene, and the third isolate became resistant to PIP-TZ due to loss of beta-lactamase inhibition by TZ. We question if and how PIP-TZ susceptibility should be reported for ESBL-producing Enterobacteriaceae.

Topics: beta-Lactamases; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prosthesis-Related Infections; Thienamycins

Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected.

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporin Resistance; Cross Infection; Humans; Imipenem; Klebsiella; Klebsiella Infections; Meropenem; Thienamycins

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Colony Count, Microbial; Guinea Pigs; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Porins; Thienamycins; Treatment Outcome

Extended spectrum beta-lactamases (ESBLs) usually associated with multiple drug resistance, including beta-lactam and non-beta-lactam antibiotics. This resistance can cause Limitation in the choice of drugs appropriate for using in clinical practice, especially in life-threatening infections. In this study we aimed to investigate in vitro activity of meropenem, ciprofloxacine and amikacin against ESBL-producing and non-producing blood isolates of Escherichia coli and Klebsiella pneumoniae strains. Fifty-eight E. coli (21 ESBL-producing, 37 non-ESBL producing) and 99 K. pneumoniae (54 ESBL-producing, 45 non-ESBL producing) strains were included in the study. The presence of ESBL was investigated by double disk synergy test and E-test methods. Antibiotic susceptibility test was done by microdilution method according to NCCLS guideline. In vitro susceptibilities of ESBL producing E. coli and K. pneumoniae strains were found as 100% for meropenem, 33.3% and 25.9% for ciprofloxacine, 94.5% and 83.3% for amikacin. It was observed that; meropenem was equally active agent in both ESBL-producing and non-producing strains, and its activity was not affected by ESBL production. Whereas amikacin activity was minimally affected and ciprofloxacine activity was markedly decreased by ESBL production. In conclusion, meropenem seems to be better choice of antibiotic should be used for ESBL positive life-threatening infections, because of remaining highest activity.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

Topics: Brain Abscess; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Meningitis, Bacterial; Meropenem; Sepsis; Thienamycins; Treatment Outcome

An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Cohort Studies; Cross Infection; Disease Outbreaks; DNA Fingerprinting; DNA, Bacterial; Feces; Female; Genes, Bacterial; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Molecular Epidemiology; Polymerase Chain Reaction; Random Amplified Polymorphic DNA Technique; Sequence Analysis, DNA; Thienamycins

A 1994 survey of 35 intensive care units (ICUs) in Western and Southern Europe found extended-spectrum beta-lactamases (ESBLs) in 220/966 (23%) klebsiellae. A follow-up survey from May 1997 to October 1998 collected klebsiellae from 24 ICUs, including 23 that participated in 1994. Twenty-one ICUs sent 433 eligible isolates, of which 110 (25%) had ESBLs. The prevalence of ESBLs had not changed significantly from 1994 but the proportion of ESBL-producers resistant to piperacillin/tazobactam had risen from 31% to 63% (P < 0.001), and most of this resistance was high level (MICs >/= 128 + 4 mg/L). The proportion of Klebsiella oxytoca isolates hyperproducing K1 beta-lactamase rose from 8% in 1994 to 21% in 1997-1998 (P < 0. 001). Most klebsiellae (99%) were very susceptible to meropenem (mode MIC 0.03 mg/L) but three had decreased susceptibility (MICs 2-4 mg/L). These could not hydrolyse carbapenems. Aminoglycoside resistance was not significantly changed in prevalence from 1994; ciprofloxacin resistance occurred in 31% of ESBL-producers in both years, but had increased among non-producers (2% in 1994 versus 7% in 1997-1998, P < 0.001).

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Europe; Humans; Intensive Care Units; Klebsiella; Klebsiella Infections; Meropenem; Microbial Sensitivity Tests; Thienamycins; Time Factors

We have evaluated the ability of imipenem and meropenem to select, in vitro, resistant mutants of two clinical isolates of Klebsiella pneumoniae producing both SHV and TEM beta-lactamases. Only meropenem selected mutants of both isolates for which the MICs of meropenem, but not imipenem, were markedly higher than those for the parent strains; the MICs of several other beta-lactam antibiotics, including beta-lactam/beta-lactamase inhibitor combinations, for these mutants were also higher than those for the parent strains. In contrast, the MICs for the imipenem-selected mutants were the same as, or similar to, those for the parent strains. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis revealed that an outer membrane protein in both parent strains was absent in the meropenem-selected mutants, but not in the imipenem-selected mutants. This protein is likely to be a porin, the absence of which is presumably associated with impaired beta-lactam permeability and, therefore, the reduced susceptibilities to these antibiotics exhibited by the mutant strains. We believe that this is the first report of the in-vitro selection of porin-deficient mutants of K. pneumoniae following exposure to meropenem.

Topics: beta-Lactamases; Drug Resistance, Microbial; Electrophoresis, Polyacrylamide Gel; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutation; Polymerase Chain Reaction; Porins; Thienamycins