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• W2100910040 abstract "Abstract Objectives Temocillin is a 6α-methoxy derivative of ticarcillin that is resilient to ESBLs. Prospective data about its in vivo activity remain scarce. Our aims were: (i) to evaluate the activity of temocillin in a urinary tract infection (UTI) model due to ESBL-producing Escherichia coli and compare it with that of imipenem; and (ii) to define in vivo susceptibility breakpoints. Methods Mice were infected with a susceptible E. coli CFT073-RR or its transconjugant (CFT073-RR Tc) harbouring a blaCTX-M-15-carrying plasmid, using an ascending UTI model. Therapeutic regimens were chosen in order to reproduce percentage of time of free drug concentrations above MIC (fT&gt;MIC) obtained in humans with standard regimens of temocillin (200 mg/kg every 2 h for 2 g every 12 h) or imipenem (100 mg/kg every 2 h for 1 g every 8 h). Additional regimens of temocillin (200 mg/kg every 4 and 6 h) with reduced fT&gt;MIC were studied. Results MICs of temocillin and imipenem were 4/8 and 0.5/0.5 mg/L, for CFT073-RR and CFT073-RR Tc, respectively. In vivo, when given every 2 h (fT&gt;MIC = 82% and 70%), temocillin was bactericidal and as effective as imipenem in kidneys against both strains without selecting resistant mutants. Temocillin remained active even when given every 4 h, generating an fT&gt;MIC of 41% and 35%, which corresponded to a breakpoint of 16 mg/L in humans with the standard regimen. Conclusions Our observations support the consideration of a standard regimen of temocillin as an alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains with an MIC of 16 mg/L or less." @default.
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• W2100910040 date "2015-01-05" @default.
• W2100910040 modified "2023-09-30" @default.
• W2100910040 title "Activity of temocillin in a murine model of urinary tract infection due to <i>Escherichia coli</i> producing or not producing the ESBL CTX-M-15" @default.
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• W2100910040 doi "https://doi.org/10.1093/jac/dku542" @default.
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