COMPARATIVE EFFICACIES OF CIPROFLOXACIN AND PEFLOXACIN ALONE OR IN COMBINATION WITH FOSFOMYCIN IN EXPERIMENTAL ENDOCARDITIS INDUCED BY MULTIDRUG-SUSCEPTIBLE AND MULTIDRUG-RESISTANT PSEUDOMONAS-AERUGINOSA

The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combin ation with fosfomycin was evaluated in experimental aortic valve endoc arditis induced in 133 rabbits by a multidrug-susceptible or multidrug -resistant strain of Pseudomonas aeruginosa, Therapy was initiated ear ly (12 h after infection), when bacterial counts in aortic valve veget ations were relatively low, or late (48 h after infection), when veget ations contained a larger inoculum, Antibiotics were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of cip rofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/k g) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the mu ltidrug-susceptible strain, all regimens except pefloxacin alone signi ficantly reduced the number of CFU per gram of vegetation versus contr ols, whether treatment was performed early or late: For the multidrug- resistant strain, none of the regimens showed differences from untreat ed controls, except ciprofloxacin-fosfomycin, which significantly redu ced bacterial counts in vegetations compared with controls when therap y was begun early (4.1 +/- 1.1 log(10) CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by mu ltidrug-susceptible P. aeruginosa.