Urinary Tract Infections
Many of the newer fluoroquinolones achieve high concentrations in human urine (see preceding section). Although the antimicrobial activities of these agents are diminished in the presence of urine, urinary drug concentrations for most agents substantially exceed the minimum inhibitory concentrations (MICs) for both gram-negative and gram-positive urinary tract pathogens, including members of the Enterobacteriaceae, P. aeruginosa, enterococci, and Staphylococcus saprophyticus.
Of the newer fluoroquinolones, norfloxacin and ciprofloxacin have been studied most extensively. Studies with norfloxacin and ciprofloxacin have been reviewed recently. In the two largest randomized studies of uncomplicated urinary tract infections comparing therapy with norfloxacin (400 mg given orally twice daily for 3 to 7 days) and that with trimethoprim-sulfamethoxazole (TMP-SMX), eradication of bacteriuria was significantly higher after treatment with norfloxacin in a double-blind randomized study or comparable in the two groups. Similar results were seen in a large number of other comparative studies of smaller size. For treatment of uncomplicated urinary tract infections in women, ciprofloxacin (250 mg twice daily) was compared with trimethoprim-sulfamethoxazole in a double-blind randomized trial. After 10 days of treatment, 29 of 31 (93%) patients treated with ciprofloxacin had sterile urine at 4 weeks follow-up compared with 26 of 34 (76%) patients treated with trimethoprim-sulfamethoxazole. In three other smaller comparative studies of uncomplicated infections, treatment with ciprofloxacin (250 mg twice daily) was comparable to that with cinoxacin (500 mg twice daily), cephalexin (1 g three times daily), or, when used in a lower dose (100 mg twice daily), trimethoprim alone (200 mg twice daily). Ofloxacin (200 or 300 mg twice daily for 7 days) has also been shown to be comparable to trimethoprim-sulfamethoxazole for treatment of uncomplicated urinary tract infections. Treatment of uncomplicated urinary tract infections with a single dose of ciprofloxacin (250 mg) or fleroxacin (400 or 600 mg) was effective in 88 to 100% of small numbers of patients. A low single dose (100 mg) of ofloxacin was somewhat less effective (73% eradication).
Development of bacterial resistance as a cause of failure of therapy of urinary tract infections, a problem with nalidixic acid in some studies, has been encountered infrequently with the newer quinolones (see next section). Failures with single-dose ciprofloxacin therapy were dominated by Staphylococcus saprophyticus in one small study, possibly because this organism is killed by quinolones more slowly than are enteric gram-negative bacilli.
Complicated urinary tract infections occurring in patients with structural or functional abnormalities of the urinary tract, including intermittent urinary catheterization, renal stones, neurogenic bladders, and azotemia, are more often caused by resistant and difficult to treat organisms such as P. aeruginosa. In four studies comparing norfloxacin with trimethoprim-sulfamethoxazole, amoxicillin, or several parenteral regimens, bacteriologic cures were equivalent or significantly more frequent with the norfloxacin regimen. Results of norfloxacin therapy of 78 infections caused by P. aeruginosa tabulated from eight noncomparative studies indicated an overall eradication rate of 83%. In a prospective randomized double-blind trial in which patients were required to receive an agent active by disk testing against their infecting organism, significantly more (18 of 22, 82%) patients given ciprofloxacin (250 mg twice daily) had sterile urine 5 to 9 days after completion of therapy than patients given trimethoprim-sulfamethoxazole (12 of 23, 52%) (P = 0.). By 4 to 6 weeks after completion of therapy, however, there were no differences between the groups. In another comparative, but not randomized study, comparable rates of eradication were seen with ciprofloxacin (100 mg; 31 of 33, 94%), ciprofloxacin (250 mg; 23 of 26, 88%), and trimethoprim-sulfamethoxazole (160 to 800 mg; 14 of 16, 87%). A single study has compared intravenous preparations of ciprofloxacin (100 mg twice daily) and mezlocillin (2 g twice daily) for complicated urinary tract infections with similar favorable results. In a large number of open studies of ciprofloxacin therapy of complicated urinary tract infections including 623 patients, the overall eradication rate was 84%. For P. aeruginosa infections, the eradication rate was 70% (111 of 158) for ciprofloxacin in 11 studies. In a direct comparison of ciprofloxacin (250 mg) and ofloxacin (100 mg), both given twice daily for 7 days, identical rates of eradication were found (19 of 30 patients, 63%). Ten- to 14-day courses of twice-daily ofloxacin (200 mg) and enoxacin (400 mg) were also each comparable to trimethoprim-sulfamethoxazole in randomized studies. In open studies, complicated urinary tract infections have been eradicated as well in 65 to 92% of cases with either enoxacin or pefloxacin. Bacterial resistance to fluoroquinolones has been seen more commonly in some studies of complicated urinary tract infections compared with studies of uncomplicated urinary tract infections, in particular in those infections caused by P. aeruginosa (see ).
