Activities of the combination of quinupristin-dalfopristin with rifampin in vitro and in experimental endocarditis due to Staphylococcus aureus strains with various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics.

Abstract

We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 microg/ml) and to Q-D (MICs, 0.5 to 1 microg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 microg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 microg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 microg/ml, respectively). In vitro time-kill curve studies showed an additive effect [corrected] between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.

• Authors: V Zarrouk, B Bozdogan, R Leclercq, L Garry, C Feger, C Carbon, B Fantin
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 4 Pg. 1244-8 (Apr 2001) ISSN: 0066-4804 [Print] United States
• PMID: 11257041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Lincosamides
• Macrolides
• Virginiamycin
• quinupristin-dalfopristin
• Rifampin

Topics

• Animals
• Anti-Bacterial Agents (blood, pharmacology, therapeutic use)
• Drug Resistance, Microbial
• Drug Synergism
• Drug Therapy, Combination (blood, pharmacology, therapeutic use)
• Endocarditis, Bacterial (blood, drug therapy)
• Female
• Kinetics
• Lincosamides
• Macrolides
• Microbial Sensitivity Tests
• Mutation
• Phenotype
• Rabbits
• Rifampin (blood, pharmacology, therapeutic use)
• Staphylococcal Infections (blood, drug therapy)
• Staphylococcus aureus (drug effects, genetics)
• Virginiamycin (blood, pharmacology, therapeutic use)