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Enhanced activity of cefepime-tazobactam (WCK 4282) against KPC-producing Enterobacteriaceae when tested in media supplemented with human serum or sodium chloride.
Diagnostic Microbiology and Infectious Disease 2017 December
The aim of this study was to evaluate the in vitro activity of cefepime-tazobactam cation-adjusted Mueller-Hinton broth (CA-MHB) supplemented with 0.85% sodium chloride (NaCl) or 50% human serum in comparison to standard CA-MHB when testing KPC-producing isolates. A total of 209 contemporary Enterobacteriaceae clinical isolates carrying blaKPC were tested, and cefepime-tazobactam (tazobactam at fixed 8mg/L) activity was enhanced 2-fold when tested in CA-MHB supplemented with 0.85% NaCl or 50% human serum (MIC50/90 , 8/32mg/L for both media) compared to standard CA-MHB (MIC50/90 , 16/64mg/L). Cefepime-tazobactam at a concentration of ≤16mg/L, which is the pharmacokinetics/pharmacodynamics tentative susceptibility breakpoint based on a high dosing regimen of cefepime-tazobactam (2g-2g q8h 90-minute infusion), inhibited 79.4-80.4% of Enterobacteriaceae isolates carrying blaKPC in MHB supplemented with 0.85% NaCl or 50% human serum. A similar decrease in MIC values was observed when cefepime alone was tested against a subset of the isolates (n=54) in CA-MHB supplemented with 50% human serum or 0.85% NaCl; however, imipenem activity against these 54 organisms was similar or 2-fold higher in CA-MHB supplemented with 0.85% of NaCl (MIC50/90 , 8/16mg/L) or with 50% human serum (MIC50 and MIC90 , 16mg/L) compared standard CA-MHB (MIC50/90 , 8/16mg/L). In summary, cefepime-tazobactam MIC values against Enterobacteriaceae isolates carrying blaKPC were consistently lower in media supplemented with human serum or NaCl, which better mimics physiological conditions. These results suggest that this carbapenem-sparing candidate agent has potential to be used to treat infections caused by KPC-producing Enterobacteriaceae.
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