Bactericidal activity of ciprofloxacin, norfloxacin and ofloxacin in serum and urine after oral administration to healthy volunteers

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 forEnterococcus 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.

Section: Discussionmentioning

confidence: 99%

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

Naber

Theuretzbacher

Kinzig

et al. 1998

“…Calculation of AUBCs from serial measurement of SBTs has been proposed to be a rational method to compare antibacterial drugs (1,16). A number of investigators have determined SBTs after administration of ofloxacin or ciprofloxacin (5, 9, 18, 24), and three investigations have directly compared the SBTs of ciprofloxacin and ofloxacin after single-dose intravenous or oral administration (12,25,28). The overall results of the present study are consistent with previous investigations in finding SBTs and AUBCs for E. coli and E. cloacae to be very high for both drugs, lower for S. aureus and P. aeruginosa, and poorest for S. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and serum bactericidal titers of ciprofloxacin and ofloxacin following multiple oral doses in healthy volunteers

Israel

Gillum

Turik

et al. 1993

Fourteen adult males participated in a randomized three-way crossover study to compare the pharmacokinetics and serum bactericidal titers (SBTs) of 500 mg of ciprofloxacin (regimen A), 750 mg of ciprofloxacin (regimen B), and 400 mg of ofloxacin (regimen C) administered every 12 h for seven doses. Mean steady-state peak concentrations in serum for regimens A, B, and C were 3.0, 4.4, and 6.5 ,g/ml, respectively (P < 0.01, all comparisons) and mean half-lives were 4.5, 4.3, and 6.5 h, respectively (P < 0.05, C versus A and B). Mean steady-state areas under the concentration-time curve were 14.1, 21.1, and 48.1 ,g/h/ml for regimens A, B, and C, respectively (P < 0.05, all comparisons). SBTs were determined at different times postdose for three isolates each of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coi, Enterobacter cloacae, and Pseudomonas aeruginosa. Mean steady-state peak SBTs for regimens A, B, and C, respectively, were as follows: S. pneumoniae, <1:2, 1:8, 1:8; S. aureus, 1:16, 1:16, 1:16; E. coli, 1:2 128, 1:2 128, 1:64; E. cloacae, 1:2 128, 1:2 128, 1:64; P. aeruginosa, 1:8, 1:8, 1:2. These differences in SBTs within each genus were statistically significant. The majority of predicted SBTs were within one dilution of measured SBTs. Areas under the serum bactericidal time curves forE. coli, E. cloacae, and P. aeruginosa were significantly higher for ciprofloxacin; areas under the serum bactericidal time curves for S. pneumoniae and S. aureus were significantly greater for ofloxacin. Ofloxacin achieved higher concentrations in serum than ciprofloxacin, but differences in in vitro activity were a more important determinant of SBTs.Ciprofloxacin and ofloxacin are fluoroquinolone antibiotics which are well absorbed by the oral route and are active against a broad range of pathogenic bacteria (7). Since these quinolones differ in both pharmacokinetics and in vitro activity, measurement of serum bactericidal titers (SBTs) integrates both characteristics and allows for direct comparison of their pharmacodynamic properties (1,4,16). The purpose of this study was to compare the pharmacokinetics and SBTs of ciprofloxacin and ofloxacin in healthy volunteers after multiple-dose oral administration.(A portion of this manuscript appeared as an abstract in the program of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif., October 1992 [6a].)

“…In a number of other studies, various dosages were examined noncomparatively. Van Several studies (3,14,19,25,37) investigated the SBA following oral administration of ciprofloxacin at various doses (mainly 500 and 750 mg). The same trend of good-to-excellent activity against members of the family Enterobacteriaceae, mediocre activity against P. aeruginosa, and poor performance against S. aureus and other gram-positive organisms was observed.…”

mentioning

confidence: 99%

Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously

Dan

Poch

Quassem

et al. 1994