Use of animal models in evaluation of the quinolones.

Abstract

Discriminative animal models of infection are important in helping to define the role of new antibacterial drugs in the treatment of human diseases. Several animal models have been used to compare the efficacies of quinolones with those of standard therapies against selected bacterial pathogens. In animal models of endocarditis, pefloxacin, enoxacin, and ciprofloxacin have been shown to be equivalent to standard therapies against methicillin-sensitive Staphylococcus aureus and as effective as vancomycin against methicillin-resistant strains. Difloxacillin has been shown to be equivalent to vancomycin in a model of osteomyelitis due to S. aureus. Ciprofloxacin is as effective as the combination of ceftazidime and tobramycin in a model of pseudomonal meningitis, although the levels of ciprofloxacin (6 mg/L) in serum required to produce a bactericidal effect in the cerebrospinal fluid are higher than those usually obtained in humans. Ciprofloxacin and other quinolones are also effective therapy for pseudomonal infections in neutropenic animals with pneumonia, peritonitis, osteomyelitis, and endocarditis. Data obtained from these animal studies suggest that the quinolones may have an important role in the treatment of endocarditis, meningitis, osteomyelitis, and other serious infections in humans caused by S. aureus and Pseudomonas aeruginosa.