title: Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus.
abstract: 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 ofStaphylococcus aureusfrom chickens, cattle and pigs. Checkerboard assays on 21S. aureusisolates showed that in 80 per cent of methicillin-susceptibleS. aureus(MSSA) and 82 per cent of methicillin-resistantS. 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-log10decrease 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 againstS. aureuschallenge. 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 againstS. aureusinfections.
authors: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors: C-F
authors: CF
authors: Wei
authors: Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan.
authors: S-K
authors: SK
authors: Chang
authors: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors: J-H
authors: JH
authors: Shien
authors: Department of Veterinary Medicine, National Chiayi University, Chiayi 600, Taiwan.
authors: H-C
authors: HC
authors: Kuo
authors: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors: W-Y
authors: WY
authors: Chen
authors: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei 114, Taiwan.
authors: C-C
authors: CC
authors: Chou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D002645:Chickens; D004357:Drug Synergism; D005260:Female; D051379:Mice; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000662:veterinary; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D013552:Swine; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C035534:florfenicol; D013839:Thiamphenicol
keywords: Antibiotic combination; Florfenicol; Staphylococcus aureus; Synergism; Thiamphenicol