In Vitro Activity of Ceftolozane Alone and in Combination with Tazobactam against Extended-Spectrum-β-Lactamase-Harboring Enterobacteriaceae
| Autor: | Johan W. Mouton, Maria J. Melchers, Anita C. van Mil |
|---|---|
| Přispěvatelé: | Medical Microbiology & Infectious Diseases |
| Rok vydání: | 2015 |
| Předmět: |
Tazobactam
medicine.drug_class Cephalosporin Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Penicillanic Acid Microbial Sensitivity Tests Biology medicine.disease_cause beta-Lactamases Microbiology Enterobacteriaceae medicine polycyclic compounds Humans Pharmacology (medical) Escherichia coli GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Pharmacology Enterobacteriaceae Infections biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease bacterial infections and mycoses Citrobacter freundii Anti-Bacterial Agents Cephalosporins Infectious Diseases lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Susceptibility bacteria Ceftolozane Drug Therapy Combination Klebsiella pneumonia Enterobacter cloacae medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy, 59, 4521-5 Antimicrobial Agents & Chemotherapy, 59(8), 4521-4525. American Society for Microbiology Antimicrobial Agents and Chemotherapy, 59, 8, pp. 4521-5 |
| ISSN: | 0066-4804 |
| Popis: | Ceftolozane, formally CXA-101, is a new antipseudomonal cephalosporin that is also active in vitro against Enterobacteriaceae but is vulnerable to extended-spectrum β-lactamases (ESBLs). The addition of tazobactam is intended to broaden coverage to most ESBL-producing Escherichia coli and Klebsiella pneumonia as well as other Enterobacteriaceae . The in vitro activities of ceftolozane-tazobactam combinations against 67 clinically and molecularly characterized ESBL-producing isolates were examined by checkerboard MIC testing to evaluate their potential clinical feasibility and to assess the optimal tazobactam concentrations to be used in MIC determinations of ceftolozane. Isolates included those from E. coli ( n = 32), K. pneumoniae ( n = 19), Enterobacter cloacae ( n = 15), and Citrobacter freundii ( n = 1). Checkerboard experiments were performed to study interactions over the range of 0.008 to 64 mg/liter ceftolozane and 0.063 to 32 mg/liter tazobactam using 2-fold-dilution series. The MIC 50 and MIC 90 of ceftolozane alone for all isolates were 16 and ≥64 mg/liter, respectively. Increasing concentrations of tazobactam resulted in decreasing MICs of ceftolozane. The 50th and 90th percentile concentrations of tazobactam required to reduce the MIC of ceftolozane to 8 mg/liter for all organisms in this ESBL collection were 0.5 and 4 mg/liter, respectively. For E. coli , K. pneumoniae , and E. cloacae , these values were 0.5 and 2, 1 and 16, and 0.5 and 4 mg/liter, respectively. When combined with a fixed amount of 4 mg/liter tazobactam (current CLSI concentration used for susceptibility testing), 90% of the isolates would have an MIC of ≤4 mg/liter. The combination ceftolozane-tazobactam is a promising alternative option for treating infections due to ESBL-harboring isolates. |
| Databáze: | OpenAIRE |
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