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.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.