Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers

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Abstract
Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N -demethyl-fleroxacin, and N -oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis . Against Staphylococcus saprophyticus , UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.