Correlation of in vitro activities of the fluoroquinolones to their in vivo efficacies.
The new fluoroquinolones have activity against Gram-positive and Gram-negative bacteria. In order to differentiate between the compounds, the authors have compared their in vitro activities and correlated these results with their in vivo efficacies. Norfloxacin (N), pefloxacin (P), enoxacin (E), ofloxacin (O), difloxacin (D), ciprofloxacin (C), fleroxacin (F), A-61827 (A), temafloxacin (T) and lomefloxacin (L) were used in these studies. In vitro, C was the most active compound against Gram-negative aerobic bacteria and A was the most active compound against Gram-positive cocci and anaerobic bacteria. In mouse protection tests, C, D, A, O, T and F had similar activities against Escherichia coli and Pseudomonas aeruginosa. D, T and A were the most active quinolones against Staphylococcus aureus and Streptococcus pyogenes and Strep. pneumoniae in mouse protection tests. D was the most active agent against intracellular infection with Salmonella typhimurium, followed by O, T, A and F. The other compounds were ineffective in this test. All the quinolones were effective in treating E. coli pyelonephritis in mice. The doses required to treat P. aeruginosa pyelonephritis in mice were four times greater than those required to treat E. coli. Resistant P. aeruginosa mutants could be isolated from the kidneys after quinolone treatment. Systemic infections with E. coli, Staph. aureus and P. aeruginosa in neutropenic mice required high doses of the fluoroquinolones and F, T and A were ineffective at doses of 100 mg/kg against P. aeruginosa in this model. Differences in in vitro potencies were not reflected in in vivo efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)
Fernandes
P B
PB
Anti-infective Research, Abbott Laboratories, Abbott Park, IL 60064.
Swanson
R N
RN
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D015365:Enoxacin / Q000494:pharmacology; D016576:Fleroxacin; D024841:Fluoroquinolones; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D015366:Pefloxacin / Q000494:pharmacology; D015363:Quinolones
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; C054745:temafloxacin; D015366:Pefloxacin; D015365:Enoxacin; D002939:Ciprofloxacin; C047225:difloxacin; D015242:Ofloxacin; C055185:tosufloxacin; C053091:lomefloxacin; D009643:Norfloxacin; D016576:Fleroxacin