CI-990

Certain new fluoroquinolones have high activity against enterococci. Against Enterococcus faecalis (n = 18), MICs at which 90% of the isolates were inhibited were as follows (in micrograms per milliliter): clinafloxacin, 0.125; CI-990, 0.5; and PD 138312, 0.25 (compared with 1 microgram/ml for ciprofloxacin and 2 micrograms/ml for ofloxacin). Strains producing beta-lactamase or that were vancomycin resistant or resistant to high-level gentamicin were not quinolone cross-resistant. The drugs were bactericidal and were unaffected by 50% human serum. Oral efficacies (in milligrams per kilogram of body weight for 50% protective doses) in lethal mouse infections with quinolone-susceptible strains were 4.3 to 24 for clinafloxacin, 7.2 to 39 for CI-990, 7.2 to 76 for PD 138312, and 41 to > 100 for ciprofloxacin; when the drugs were given subcutaneously, the order was similar and values ranged from 1.1 to 12.5. Clinafloxacin, CI-990, and PD 138312 may have therapeutic potential in systemic enterococcal infections in humans.

The effect of oral therapy with 6 quinolones, lomefloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, and CI-990 in the prevention of post-irradiation bacteraemia and mortality was tested in mice. Two models were used, the C3H/HeN mouse strain for endogenously acquired infection and the B6D2F1 mouse strain for studies of exogenously acquired Pseudomonas aeruginosa infection. Each therapy or water-fed control group included 40 mice, 20 for monitoring survival and 20 for obtaining liver cultures. In C3H/HeN mice, mortality in the groups that received each of the quinolones except CI-960 was significantly lower (P < 0.05) than in the water-treated mice. Survival was 54/60 (90%) with lomefloxacin 51/60 (85%) with ofloxacin, 50/60 (83%) with CI-990, 45/60 (75%) with sparfloxacin, 37/60 (62%) with temafloxacin, 9/60 (15%) for the control group, and 6/60 (10%) for CI-960. Enterobacteriaceae were isolated from 38 of 53 (72%) and Streptococcus spp. from 13 of 53 (25%) of the livers of control mice. The number of Enterobacteriaceae was lower in quinolone-treated mice. However, isolation of streptococci was similar to controls, except in those treated with sparfloxacin and CI-990. In B6D2F1 mice, mortality and isolation of P. aeruginosa in each of the quinolone group was significantly lower than for controls (P < 0.001). These data illustrate the efficacy of the quinolones in the therapy of exogenous infection, and the inability of those effective against anaerobic bacteria to prevent endogenous infection.