Treatment of experimental staphylococcal infections: effect of rifampin alone and in combination on development of rifampin resistance.
Rifampin is a potentially useful anti-staphylococcal agent, but resistance develops frequently when the drug is used alone. The efficacy of rifampin, trimethoprim, and a penicillin alone or in combination was examined in mice with acute or subacute infections. Mice were infected intraperitoneally with penicillin-susceptible Staphylococcus aureus. Survival after penicillin therapy was only 9.1% in contrast to survival after rifampin therapy which was 68% (P less than 0.001). No rifampin-resistant S. aureus were isolated from peritoneal fluid or heart blood samples from dead animals in these short-term experiments. Rifampin was ineffective (survival, 4.8%) for infections instituted with rifampin-resistant strains. Long-term experiments were conducted after intravenous injection of 4 x 10(8) S. aureus. Forty percent of the animals survived after methicillin therapy; 77% survived after rifampin therapy (P less than 0.001). However, 40% of those animals that died after rifampin therapy died with rifampin-resistant organisms. No animal dying in groups treated with a combination of rifampin and trimethoprim (85% survival) or rifampin and methicillin (79% survival) died with rifampin-resistant organisms. Thus, rifampin combined with a penicillin or trimethoprim was effective in preventing the development of rifampin-resistant strains.
D000208:Acute Disease; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D008712:Methicillin / Q000008:administration & dosage; D051379:Mice; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage* / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014295:Trimethoprim / Q000008:administration & dosage
D010406:Penicillins; D014295:Trimethoprim; D008712:Methicillin; D012293:Rifampin