Polymyxin B in combination with meropenem against carbapenemase-producing Klebsiella pneumoniae: pharmacodynamics and morphological changes
| Autor: | Saloni Patel, Cely S. Abboud, Keith S. Kaye, Neang S. Ly, Jian Li, Gauri G. Rao, John K. Diep, Jason M. Pogue, Rajnikant Sharma |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Combination therapy medicine.drug_class Klebsiella pneumoniae Polymyxin 030106 microbiology Antibiotics Microbial Sensitivity Tests Biology Meropenem beta-Lactam Resistance Article Microbiology 03 medical and health sciences medicine polycyclic compounds Humans Pharmacology (medical) Polymyxin B Microbial Viability Drug Synergism General Medicine biochemical phenomena metabolism and nutrition biology.organism_classification Antimicrobial bacterial infections and mycoses Anti-Bacterial Agents Klebsiella Infections Infectious Diseases Carbapenems Pharmacodynamics Microscopy Electron Scanning Thienamycins medicine.drug |
| Zdroj: | International journal of antimicrobial agents. 49(2) |
| ISSN: | 1872-7913 |
| Popis: | Combination therapy provides a useful therapeutic approach to overcome resistance until new antibiotics become available. In this study, the pharmacodynamics, including the morphological effects, of polymyxin B (PMB) and meropenem alone and in combination against KPC - producing Klebsiella pneumoniae clinical isolates was examined. Ten clinical isolates were obtained from patients undergoing treatment for mediastinitis. KPCs were identified and MICs were measured using microbroth dilution. Time–kill studies were conducted over 24 h with PMB (0.5–16 mg/L) and meropenem (20–120 mg/L) alone or in combination against an initial inoculum of ca. 10 6 CFU/mL. Scanning electron microscopy (SEM) was employed to analyse changes in bacterial morphology after treatment, and the log change method was used to quantify the pharmacodynamic effect. All isolates harboured the bla KPC-2 gene and were resistant to meropenem (MICs ≥8 mg/L). Clinically relevant PMB concentrations (0.5, 1.0 and 2.0 mg/L) in combination with meropenem were synergistic against all isolates except BRKP28 (polymyxin- and meropenem-resistant, both MICs >128 mg/L). All PMB and meropenem concentrations in combination were bactericidal against polymyxin-susceptible isolates with meropenem MICs ≤16 mg/L. SEM revealed extensive morphological changes following treatment with PMB in combination with meropenem compared with the changes observed with each individual agent. Additionally, morphological changes decreased with increasing resistance profiles of the isolate, i.e. increasing meropenem MIC. These antimicrobial effects may not only be a summation of the effects due to each antibiotic but also a result of differential action that likely inhibits protective mechanisms in bacteria. |
| Databáze: | OpenAIRE |
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