Combination of quinupristin-dalfopristin and gentamicin against methicillin-resistant Staphylococcus aureus: experimental rabbit endocarditis study.
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.
Batard
Eric
E
Laboratoire d'Antibiologie, Faculté de Médecine, Université de Nantes, Nantes, France.
Jacqueline
Cedric
C
Boutoille
David
D
Hamel
Antoine
A
Drugeon
Henri B
HB
Asseray
Nathalie
N
Leclercq
Roland
R
Caillon
Jocelyne
J
Potel
Gilles
G
Bugnon
Denis
D
D000818:Animals; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014769:Virginiamycin / Q000008:administration & dosage* / Q000097:blood
D005839:Gentamicins; D014769:Virginiamycin; C062940:quinupristin-dalfopristin