In vitro assessment of chloramphenicol and florfenicol as second-line antimicrobial agents in dogs

Abstract

The aim of this study was to evaluate the potential of chloramphenicol and florfenicol as second-line antimicrobial agents for treatment of infections caused by methicillin-resistant Staphyococcus pseudintermedius (MRSP) and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in dogs, through a systematic in vitro assessment of the pharmacodynamic properties of the two drugs. Minimum inhibitory concentrations (MIC) and phenicol resistance genes were determined for 169 S. pseudintermedius and 167 E. coli isolates. Minimum bactericidal concentrations (MBC), time-killing kinetics, and postantibiotic effect (PAE) of both agents against wild-type isolates of each species were assessed. For S. pseudintermedius, the chloramphenicol MIC90 was 32 μg/mL. No florfenicol resistance was detected in this species (MIC90 = 4 μg/mL). The MIC90 of both agents against E. coli was 8 μg/mL. Resistance genes found were catpC221 in S. pseudintermedius and catA1 and/or floR in E. coli. The phenicols displayed a time-dependent, mainly, bacteriostatic effect on both species. Prolonged PAEs were observed for S. pseudintermedius, and no PAEs were detected for E. coli. More research into determination of PK/PD targets of efficacy is needed to further assess the clinical use of chloramphenicol and florfenicol as second-line agents in dogs, optimize dosage regimens, and set up species-specific clinical break points.