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Antimicrobial Agents and Chemotherapy, November 2001, p. 3076-3083, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3076-3083.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Efficacies of Moxifloxacin, Ciprofloxacin, and Vancomycin against Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus Expressing Various Degrees of Ciprofloxacin Resistance

J. M. Entenza, Y. A. Que, J. Vouillamoz, M. P. Glauser, and P. Moreillon*

Division of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

Received 10 July 2000/Returned for modification 1 February 2001/Accepted 28 July 2001

The new 8-methoxyquinolone moxifloxacin was tested against two ciprofloxacin-susceptible Staphylococcus aureus strains (strains P8 and COL) and two ciprofloxacin-resistant derivatives of strain P8 carrying a single grlA mutation (strain P8-4) and double grlA and gyrA mutations (strain P8-128). All strains were resistant to methicillin. The MICs of ciprofloxacin and moxifloxacin were 0.5 and 0.125 mg/liter, respectively, for P8; 0.25 and 0.125 mg/liter, respectively, for COL; 8 and 0.25 mg/liter, respectively, for P8-4; and >= 128 and 2 mg/liter, respectively, for P8-128. In vitro, the rate of spontaneous resistance of P8 and COL was 10-7 on agar plates containing ciprofloxacin at two times the MIC, whereas it was <= 10-10 on agar plates containing moxifloxacin at two times the MIC. Rats with experimental aortic endocarditis were treated with doses of drugs that simulate the kinetics in humans: moxifloxacin, 400 mg orally once a day; ciprofloxacin, 750 mg orally twice a day; or vancomycin, 1 g intravenously twice a day. Treatment was started either 12 or 24 h after infection and lasted for 3 days. Moxifloxacin treatment resulted in culture-negative vegetations in a total of 20 of 21 (95%) rats infected with P8, 10 of 11 (91%) rats infected with COL, and 19 of 24 (79%) rats infected with P8-4 (P < 0.05 compared to the results for the controls). In contrast, ciprofloxacin treatment sterilized zero of nine (0%) vegetations infected with first-level resistant mutant P8-4. Vancomycin sterilized only 8 of 15 (53%), 6 of 11 (54%), and 12 of 23 (52%) of the vegetations, respectively. No moxifloxacin-resistant derivative emerged among these organisms. However, moxifloxacin treatment of highly ciprofloxacin-resistant mutant P8-128 failed and selected for variants for which the MIC increased two times in 2 of 10 animals. Thus, while oral moxifloxacin might deserve consideration as treatment for staphylococcal infections in humans, caution related to its use against strains for which MICs are borderline is warranted.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland. Phone: 41-21-314.10.25. Fax: 41-21-314.10.36. E-mail: Philippe.Moreillon{at}chuv.hospvd.ch.

Antimicrobial Agents and Chemotherapy, November 2001, p. 3076-3083, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3076-3083.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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