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 10 3 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 10 4 and 10 5 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. Antimicrobial therapy of prosthetic device infections, in particular, those due to Staphylococcus aureus, is notoriously difficult, and microbial eradication frequently requires the removal of infected materials. Several clinical and experimental studies have reported on the therapeutic values of the fluoroquinolones ciprofloxacin, ofloxacin, or pefloxacin, alone or in combination with rifampin, against serious S. aureus infections (8-10, 24, 44, 46). In particular, some very interesting results were recently reported from studies with either ciprofloxacin (44, 46) or ofloxacin (8) in combination with rifampin for the treatment of orthopedic prosthetic device-associated S. aureus infections (without prosthesis removal). Newer molecules of the quinolone family such as levofloxacin, trovafloxacin, gatifloxacin, or moxifloxacin not only demonstrate enhanced in vitro activities and broader spectra of activity against most important gram-positive bacterial pathogens, but they are also endowed with optimized pharmacokinetic and pharmacodynamic properties (for a review, see reference 22).Unfortunately, strains of methicillin-resistant S. aureus (MRSA) (32,33,39) are generally resistant to ciprofloxacin and all newer fluoroquinolones, which severely limits the therapeutic armamentarium (42) for the treatment of foreignbody-associated infections. Thus, the glycopeptides vancomycin and teicoplanin, alone or in combination with rifampin (2, 17, 31), may remain the only therapies available for the treatment of severe MRSA infections. Furthermore, combination therapy does not always prevent the emergence of rifampinresistant mutants (1,11,12,39).The aim of our experimental study was to evaluate the efficacy of levofloxacin or alatrofloxacin in either a prophylactic (40, 45) or a therapeutic (29) model of foreign-body-associated infections caused by a quinolone-susceptible strain of MRSA. Levofloxacin is the L isomer of ofloxacin and is available both in an oral dosage form and as an intravenous preparation, while alatrofloxacin is the L-Ala-L-Ala prodrug of trovafloxacin used for parenteral administr...