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Antimicrobial Agents and Chemotherapy, July 2002, p. 2174-2178, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2174-2178.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Combination of Quinupristin-Dalfopristin and Gentamicin against Methicillin-Resistant Staphylococcus aureus: Experimental Rabbit Endocarditis Study

Eric Batard,¹ Cedric Jacqueline,¹ David Boutoille,¹ Antoine Hamel,¹ Henri B. Drugeon,¹ Nathalie Asseray,¹ Roland Leclercq,² Jocelyne Caillon,¹ Gilles Potel,^1* and Denis Bugnon¹

Laboratoire d'Antibiologie, Faculté de Médecine, Université de Nantes, Nantes,¹ Laboratoire de Bactériologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France²

Received 28 September 2001/ Returned for modification 29 January 2002/ Accepted 10 April 2002

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.

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* Corresponding author. Mailing address: Laboratoire d'antibiologie, Faculté de médecine, 1 rue Gaston-Veil, 44035 Nantes Cedex 01, France. Phone and fax: 33 240 412 854. E-mail: gpotel{at}sante.univ-nantes.fr.

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Antimicrobial Agents and Chemotherapy, July 2002, p. 2174-2178, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2174-2178.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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