Urinary concentrations and bactericidal activities of newer fluoroquinolones in healthy volunteers.
Eleven healthy male subjects participated in a crossover study to compare the urine concentrations and bactericidal activities of newer fluoroquinolones against common uropathogens. Each volunteer received a single oral dose of gatifloxacin (400 mg), levofloxacin (250 mg), moxifloxacin (400 mg) and trovafloxacin (200 mg), and a urine sample was obtained at 2, 6, 12 and 24 h after the dose. Urine concentrations were highest with gatifloxacin and levofloxacin and lowest with trovafloxacin. Each drug concentration was studied against a levofloxacin susceptible and moderately-susceptible strain of Escherichia coli (minimal inhibitory concentration, MICs: 0.125 and 4 mg/l), K. pneumoniae (MICs: 0.125 and 4 mg/l), Pseudomonas aeruginosa (MICs: 0.5 and 4 mg/l) and Enterococcus faecalis (MICs: 0.25 and 4 mg/l). The duration of urine bactericidal activity (UBA) was based upon the median bactericidal titre at each time period. Both gatifloxacin and levofloxacin exhibited prolonged (> or = 6 h) UBA against all of the study isolates. Moxifloxacin exhibited prolonged UBA against both isolates of E. coli, K. pneumoniae and E. faecalis but not against either strain of P. aeruginosa. Prolonged UBA was not observed for trovafloxacin against the moderately-susceptible strains with the exception of E. faecalis. Furthermore, UBA was not observed for trovafloxacin against the susceptible strain of P. aeruginosa. Although these newer fluoroquinolones exhibited similar in vitro activity against these uropathogens, only those compounds with the highest urinary concentrations (gatifloxacin and levofloxacin) produced prolonged UBA against both strains of P. aeruginosa. The findings from this study suggest that both microbiological activity and urinary concentrations are important parameters to consider when choosing a fluoroquinolone for empirical treatment of urinary tract infections (UTIs).
Stein
Gary E
GE
B323 Life Science Building, Michigan State University, East Lansing, MI 48824, USA. steing@msu.edu
Schooley
Sharon
S
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine*; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000652:urine; D004755:Enterobacteriaceae / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine*; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000077266:Moxifloxacin; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000652:urine; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology / Q000652:urine; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000652:urine
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D009287:Naphthyridines; D011804:Quinolines; D064704:Levofloxacin; C080163:trovafloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin