Clinafloxacin and trovafloxacin are two new fluoroquinolones for which few comparative data are available. When MICs of ciprofloxacin against Gram-positive and Gram-negative nosocomial species were compared, clinafloxacin was the most potent although trovafloxacin was also more active than ciprofloxacin against Staphylococcus aureus and enterococci. All three drugs were bactericidal. Clinafloxacin displayed the lowest frequency of resistance, approximating 10(-11). Development of resistance studies over 13-14 passages in the presence of drug revealed a 32-fold increase in MIC of clinafloxacin against S. aureus compared with 512- and 1024-fold for trovafloxacin and ciprofloxacin respectively, although the three drugs were comparable against Enterococcus faecalis and the Gram-negative bacilli.
PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for .90% of strains were 0.125 to 0.25 ,ug/ml for staphylococci, Streptococcus pyogenes, and S. pneumoniae; 0.5 ,ug/ml for S. agalactiae and Enterococcus faecalis; 0.125 jug/ml for members of the family Enterobacteriaceae and Acinetobacter spp.; 0.5 ,Lg/mI for Pseudomonas aeruginosa; and <0.03 ,ug/ml for Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Neisseria gonorrhoeae. In these in vitro comparisons with ciprofloxacin, PD 131628 is more active against gram-positive organisms, approximately equivalent against gram-negative organisms, and, like most other quinolones, relatively inactive against gram-negative anaerobes. In most instances, the in vitro potency of PD 131628 exceeded those of widely used compounds:
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 g/ml for ciprofloxacin and 2 g/ml for ofloxacin). Strains producing -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.Enterococci have gained increasing recognition as primary human pathogens. Resistance to penicillins, aminoglycosides, and glycopeptides (6,13,14,(20)(21)(22) and to quinolones such as ciprofloxacin (18) Frequencies of single-step spontaneous mutations were determined in duplicate by spreading ϳ10 11 CFU onto MuellerHinton agar (Difco Laboratories) containing drugs; colonies were counted after 24 to 72 h of incubation. Multistep resistance selection measured increases in MICs over daily transfers in 5-ml volumes (0.1-ml inoculum harvested from a tube
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