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Antimicrobial Agents and Chemotherapy, May 2002, p. 1503-1509, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1503-1509.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Comparison of Levofloxacin, Alatrofloxacin, and Vancomycin for Prophylaxis and Treatment of Experimental Foreign-Body-Associated Infection by Methicillin-Resistant Staphylococcus aureus

Pierre Vaudaux,* Patrice Francois, Carmelo Bisognano, Jacques Schrenzel, and Daniel P. Lew

Division of Infectious Diseases, Geneva University Hospital, CH-1211 Geneva 14, Switzerland

Received 18 July 2001/ Returned for modification 11 November 2001/ Accepted 26 January 2002

The prophylactic and therapeutic activities of two fluoroquinolones, levofloxacin and alatrofloxacin (the L-Ala-L-Ala prodrug of trovafloxacin), were compared to those of vancomycin in two different experimental models of foreign-body-associated infections caused by methicillin-resistant but quinolone-susceptible Staphylococcus aureus (MRSA) isolates. In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected with 103 CFU of MRSA, which was a 100% infectious dose in control animals. A single dose of 50 mg of levofloxacin per kg of body weight, administered intraperitoneally 3 h before bacterial challenge, was more efficient than vancomycin for the prevention of infections in tissue cages with MRSA inocula of 104 and 105 CFU. In a rat model used to evaluate therapy of chronic tissue cage infection caused by MRSA, the efficacies of 7-day high-dose regimens of levofloxacin (100 mg/kg once a day [q.d.] or 50 mg/kg twice a day [b.i.d.]) or alatrofloxacin (50 mg/kg q.d.) were compared to the efficacy of vancomycin (50 mg/kg b.i.d.). Active levels of levofloxacin, trovafloxacin, and vancomycin were continuously present in tissue cage fluid, with the levels exceeding the minimal bactericidal concentrations for MRSA during therapy. The q.d. and b.i.d. regimens of levofloxacin had equivalent activities and were significantly (P < 0.05) more active than alatrofloxacin or vancomycin in decreasing the viable counts of MRSA in tissue cage fluids. No quinolone-resistant mutants emerged during therapy with either fluoroquinolone. The mechanisms explaining the inferior activity of alatrofloxacin compared to the activity of levofloxacin against chronic foreign-body-associated infections by MRSA are unknown.

* Corresponding author. Mailing address: Division of Infectious Diseases, University Hospital, CH-1211 Geneva 14, Switzerland. Phone: (4122) 37 29 826. Fax: (4122) 37 29 830. E-mail: Pierre.vaudaux{at}hcuge.ch.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1503-1509, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1503-1509.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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