Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus

Synergistic effects between the same class of antibiotics are rarely reported. In the current study, two amphenicols, namely florfenicol and thiamphenicol, exhibited both in vitro and in vivo synergism against clinical isolates of Staphylococcus aureus from chickens, cattle and pigs. Checkerboard assays on 21 S. aureus isolates showed that in 80 per cent of methicillin-susceptible S. aureus (MSSA) and 82 per cent of methicillin-resistant S. aureus (MRSA) isolates tested, the minimal inhibitory concentration (MIC) of florfenicol could be reduced by 75 per cent (1/4 MIC) or more (up to 1/16 MIC) when combined with 1/2 MIC of thiamphenicol to exhibit antimicrobial activity comparable to the respective drugs at original strength (1×MIC). A synergistic effect (fractional inhibitory concentration index ≤0.5 or ≥2-log10 decrease in colony-forming unit/ml in time-kill study) was evident against 30 per cent of MSSA and 45 per cent of MRSA strains tested. A study in mice revealed that the florfenicol/thiamphenicol combination at reduced dosages provided sufficient protection against S. aureus challenge. The possible mechanism warrants further study but likely includes the facilitated uptake of thiamphenicol via florfenicol action, and this facilitation was not limited to amphenicol class. The present study may offer new strategy for combination therapy and provide potential alternatives for effective treatment against S. aureus infections.