In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci.
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.
Infectious Diseases Section/Therapeutics Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105-2495, USA.
M A
MA
Cohen
S L
SL
Yoder
M D
MD
Huband
G E
GE
Roland
C L
CL
Courtney
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects; D005260:Female; D024841:Fluoroquinolones; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C092809:PD 131112; D015363:Quinolones; C085884:PD 138312; C057477:clinafloxacin