Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum β-lactamases, AmpC β-lactamases and reduced susceptibility to carbapenems using an in vitro model

simulate the fCmax (free peak serum concentration) and t1/2 (serum half-life) obtained after standard dosing of 100 mg intravenously every 24 h ( fCmax ,0 .15 mg/L;t1/2, 42 h). Samples were collected over 48 h. Results: For isolates with a tigecycline fAUC24/MIC of 2.0 (tigecycline MIC50.5 mg/L), tigecycline demonstrated bacteriostatic activity with < 1l og10 reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC24/MIC was 4.0 (tigecycline MIC50.25 mg/L), tigecycline demonstrated bacteriostatic activity with 1.5 log10 reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC24/MIC was 8.0 (tigecycline MIC50.12 mg/L), tigecycline demonstrated bacteriostatic activity with 2.0 log10 reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Conclusions: Tigecycline demonstrated 1–2 log10 killing against E. coli harbouring ESBLs, AmpC b-lactamases and CRS when simulating clinically achievable serum concentrations, and represents a potential therapy for infections caused by these isolates.