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Antimicrobial Agents and Chemotherapy, May 2000, p. 1168-1173, Vol. 44, No. 5
Institut National de la Santé et de la
Recherche Médicale, EMI 9933,1 and
Service de Médecine Interne,5
Hôpital Bichat Claude-Bernard, Paris, Service de
Médecine Interne, Hôpital Beaujon,
Clichy,2 Service de
Bactériologie-Virologie-Hygiène, Hôpital Henri
Mondor, Créteil,3 and Service
de Microbiologie, Hôpital de la Côte de Nacre,
Caen,4 France
Received 23 August 1999/Returned for modification 21 December
1999/Accepted 7 February 2000
We evaluated the activity of quinupristin-dalfopristin (Q-D)
against three clinical strains of Staphylococcus aureus
susceptible to Q (MIC, 8 µg/ml) and Q-D (MICs, 0.5 to 1 µg/ml) but
displaying various levels of susceptibility to D. D was
active against S. aureus HM 1054 (MIC, 4 µg/ml) and had
reduced activity against S. aureus RP 13 and S. aureus N 95 (MICs, 32 and 64 µg/ml, respectively). In vitro,
Q-D at a concentration two times the MIC (2×MIC) produced reductions
of 4.3, 3.9, and 5.8 log10 CFU/ml after 24 h of
incubation for HM 1054, RP 13, and N 95, respectively. Comparable
killing was obtained at 8×MIC. Q-D-resistant mutants were selected in vitro at a frequency of 2 × 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Influence of Resistance to Streptogramin A Type
Antibiotics on the Activity of Quinupristin-Dalfopristin In
Vitro and in Experimental Endocarditis Due to
Staphylococcus aureus
8 to 2 × 107 for the three strains on agar containing 2×MIC of
Q-D; no resistant bacteria were detected at 4×MIC. Rabbits with aortic
endocarditis were treated for 4 days with Q-D at 30 mg/kg of body
weight intramuscularly (i.m.) three times a day (t.i.d.) or vancomycin
at 50 mg/kg i.m. t.i.d. In vivo, Q-D and vancomycin were similarly
active and bactericidal against the three tested strains compared to
the results for control animals (P < 0.01). Among animals
infected with RP 13 and treated with Q-D, one rabbit retained
Q-D-resistant mutants that were resistant to Q and to high levels of D
(MICs, 64, >256, and 8 µg/ml for Q, D, and Q-D, respectively). We
conclude that the bactericidal activity of Q-D against strains with
reduced susceptibility to D and susceptible to Q-D is retained and is
comparable to that of vancomycin. Acquisition of resistance to both Q
and D is necessary to select resistance to Q-D.
*
Corresponding author. Mailing address: Service de
Médecine Interne, Hôpital Beaujon, 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, May 2000, p. 1168-1173, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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