Urinary excretion and bactericidal activity of intravenous ciprofloxacin compared with oral ciprofloxacin

Twelve healthy volunteers participated in a randomized crossover study to compare urinary concentrations, serum parameters, and urinary bactericidal activity of ciprofloxacin after single intravenous (i.v.) doses of 200 mg and 400 mg and an oral (p.o.) dose of 500 mg. The median serum concentrations at 1 h after administration were 1 microg/ml, 4.3 microg/ml, and 2.2 microg/ml, respectively. Between the first collection period (0-2 h) and the last collection period (38-48 h), the median urinary concentrations decreased from 394 microg/ml, 675 microg/ml, and 585 microg/ml, respectively, to 0.3 microg/ml, 0.6 microg/ml, and 1 microg/ml, respectively. The urinary concentrations after the 400 mg i.v. and the 500 mg p.o. doses were not statistically different but were significantly higher than those after the 200 mg i.v. dose. The urinary bactericidal titers (UBTs), defined as the highest urinary dilution bactericidal for the organism tested, were determined against Escherichia coli (ATCC 25922) and eight uropathogens up to 48 h after administration of ciprofloxacin. The UBTs after the 400 mg i.v. and the 500 mg p.o. doses were similar and were significantly higher (P < 0.05) than those following the 200 mg i.v. dose. After 400 mg i.v. and 500 mg p.o., median UBTs of > or = 1:4 were present up to 48 h for all strains for which the MIC was < or = 0.5 microg/ml, except for one nalidixic-acid resistant Escherichia coli strain for which the MIC was 0.25 microg/ml. Species for which the MIC is > or = 1 microg/ml showed median UBTs of > or = 1:4 for 8-16 h. Median UBTs of > or = 1:4 were present up to 8 and 12 h for both Pseudomonas strains tested. A once-daily dosage of 400 mg i.v. or 500 mg p.o. might be sufficient for treatment of urinary tract infections caused by highly susceptible pathogens. A twice-daily dosing scheme seems to be preferable for complicated infections caused by pathogens with intermediate susceptibilty (MIC > or = 1 microg/ml) or for empiric therapy.