Combination of quinupristin-dalfopristin and gentamicin against methicillin-resistant Staphylococcus aureus: experimental rabbit endocarditis study

Antimicrob Agents Chemother. 2002 Jul;46(7):2174-8. doi: 10.1128/AAC.46.7.2174-2178.2002.

Abstract

The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested against two strains of gentamicin- and dalfopristin-susceptible methicillin-resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides, lincosamides, and streptogramin B type antibiotics (MLS(B)), and the other was constitutively resistant to these antibiotics by virtue of the ermA gene. The checkerboard method and time-kill curves showed that the combination of Q-D and gentamicin was indifferent. A rabbit endocarditis model simulated the pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5 mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For the MLS(B)-susceptible strain, a 4-day regimen reduced mean bacterial titers (MBT) in vegetations from 8.5 +/- 0.8 log CFU/g (control group) to 4.1 +/- 2.6 (gentamicin), 3.0 +/- 0.9 (Q-D), and 2.6 +/- 0.5 log CFU/g (Q-D plus gentamicin). For the strain constitutively resistant to MLS(B), a 4-day regimen reduced MBT in vegetations from 8.7 +/- 0.9 log CFU/g (control group) to 5.0 +/- 2.2 (gentamicin), 5.2 +/- 2.2 (Q-D), and 5.1 +/- 2.4 log CFU/g (Q-D plus gentamicin). The differences between control and treatment groups were significant for both strains (P < 0.0001), although there was no significant difference between treatment groups. No resistant variant was isolated from vegetations, and no significant difference in MBT in vegetations of treatment groups after 1-day regimens was observed. This experimental study found no additive benefit in combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible MRSA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Therapy, Combination / therapeutic use*
  • Endocarditis, Bacterial / drug therapy*
  • Gentamicins / administration & dosage*
  • Gentamicins / blood
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Rabbits
  • Staphylococcal Infections / drug therapy*
  • Virginiamycin / administration & dosage*
  • Virginiamycin / blood

Substances

  • Gentamicins
  • Virginiamycin
  • quinupristin-dalfopristin