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Antimicrobial Agents and Chemotherapy, April 2001, p. 1244-1248, Vol. 45, No. 4
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.4.1244-1248.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Virginie Zarrouk,1 Bülent Bozdogan,2 Roland Leclercq,2 Louis Garry,1 Celine Feger,3 Claude Carbon,1 and Bruno Fantin1,*

Institut National de la Santé et de la Recherche Médicale, EMI 9933, Hôpital Bichat-Claude Bernard, Paris,1 Service de Microbiologie, Hôpital de la Côte de Nacre, Caen,2 and Anti-Infective Clinical Research, Aventis,3 France

Received 17 July 2000/Returned for modification 29 September 2000/Accepted 25 January 2001

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 µg/ml) and to Q-D (MICs, 0.5 to 1 µg/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 µg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 µg/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 µg/ml, respectively). In vitro time-kill curve studies showed no difference 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.

* Corresponding author. Mailing address: Service de Médecine Interne, Hôpital Beaujon, 100 avenue du Général Leclerc, 92110 Clichy, France. Phone: 33 1 40 87 52 27. Fax: 33 1 40 87 54 95. E-mail: bruno.fantin{at}bjn-ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, April 2001, p. 1244-1248, Vol. 45, No. 4
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.4.1244-1248.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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