| Autor: |
Rajnikant Sharma, Estefany Garcia, John K. Diep, Vince H. Lee, Faisal Minhaj, Brian Jermain, Evelyn J. Ellis-Grosse, Cely S. Abboud, Gauri G. Rao |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
International journal of antimicrobial agents. 59(4) |
| ISSN: |
1872-7913 |
| Popis: |
Determining the role of the immune response in preventing antimicrobial resistance and optimising antibiotic regimens against carbapenemase-producing Klebsiella pneumoniae is a research gap that exists and needs to be further explored. The objective of this study was to determine the pharmacodynamic and immunomodulatory effects of fosfomycin alone and in combination with polymyxin B against KPC-2-producing K. pneumoniae clinical isolates. Six K. pneumoniae isolates were selected (polymyxin B MIC, 0.5-64 mg/L; fosfomycin MIC, 16-128 mg/L) to evaluate the pharmacodynamics of monotherapy and combination therapies in static time-kill studies. A mechanism-based model was used to characterise the joint activity of polymyxin B and fosfomycin. A549 human airway epithelial cells were infected with four isolates to evaluate the immunomodulatory effects of treatment. Our mechanism-based model indicated greater bacterial killing efficacy of fosfomycin with polymyxin B compared with monotherapy. In combination, polymyxin B was assumed to exert an outer membrane effect that resulted in an increase in the ability of fosfomycin to reach its target site. The mechanism-based model described the data well across all six strains, with R |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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