URINARY PHARMACODYNAMICS OF LOW-DOSE CIPROFLOXACIN AND OFLOXACIN

The incidence of resistant uropathogens to the fluoroquinolones is inc reasing, but their effectiveness in the urine against these strains is unknown. In this investigation, we studied the urinary pharmacodynami cs of ciprofloxacin (100 mg) and ofloxacin (200 mg) against urinary is olates that were moderately resistant to ciprofloxacin (Escherichia co li, MIC = 4; Klebsiella pneumoniae, MIC = 4; Staphylococcus saprophyti cus, MIC = 8) and ofloxacin. Seven healthy female volunteers received three doses (one dose every 12 h) of ciprofloxacin and ofloxacin in a randomized, crossover design with a 1-week washout period between regi mens. Urine bactericidal activity was determined after the first and t hird nose of each drug. Both ciprofloxacin and ofloxacin exhibited pro longed (greater than or equal to 6 h) urine bactericidal activity agai nst the E. coli and K. pneumoniae isolates after the first dose. No ba ctericidal activity was demonstrated for ciprofloxacin against the S. saprophyticus strain. In contrast, ofloxacin exhibited urine bacterici dal activity for 8 it against this isolate. Similar findings were obse rved after the third dose, with the exception that ciprofloxacin exhib ited a short period (4 h) of bactericidal activity against the S. sapr ophyticus strain. In summary, low-dose regimens of ciprofloxacin and o floxacin exhibited prolonged bactericidal activity against moderately resistant strains of common bacterial uropathogens. Only ofloxacin dem onstrated bactericidal activity in the urine during the first dosing i nterval against a moderately resistant isolate of S. saprophyticus. (C ) 1998 Elsevier Science Inc.