Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus.
In order to determine the microbiological and pharmacokinetic parameters that best predicted the in vivo antistaphylococcal activity of the streptogramin RP 59500 (quinupristin-dalfopristin), we evaluated the activity in rabbit aortic endocarditis of three regimens of quinupristin-dalfopristin against five strains of Staphylococcus aureus with various streptogramin B-type antibiotic resistance phenotypes and susceptible to streptogramin A-type antibiotics. Quinupristin-dalfopristin was as active as vancomycin against three strains that were susceptible to its streptogramin B component quinupristin, including one strain that was inducibly resistant to erythromycin, but had a significantly decreased activity against two strains that were resistant to quinupristin, for all quinupristin-dalfopristin regimens tested (P < 0.05). The area under the concentration-time curve for quinupristin-dalfopristin in plasma divided by the MIC of quinupristin was the only parameter retained by multilinear regression that predicted the in vivo activity of quinupristin-dalfopristin (P = 0.0001), emphasizing the importance of determining the susceptibility to quinupristin in order to predict the in vivo activity of quinupristin-dalfopristin against S. aureus.
Fantin
B
B
Institut National de la Santé et de la Recherche Médicale, Unité 13, Paris, France.
Leclercq
R
R
Merlé
Y
Y
Saint-Julien
L
L
Veyrat
C
C
Duval
J
J
Carbon
C
C
D000818:Animals; D004352:Drug Resistance, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology; D014769:Virginiamycin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D014640:Vancomycin