Approximately 250,000 cases of acute pyelonephritis occur annually in the United States, accounting for as many as 100,000 hospitalizations. Optimal antimicrobial therapy and treatment duration are not well defined. However, some studies suggest that women with uncomplicated lower urinary tract infections can be treated adequately with antimicrobials for less than seven to 14 days, the current standard duration of therapy for women with acute uncomplicated pyelonephritis. Talan and colleagues compared the effectiveness of a seven-day course of ciprofloxacin with a traditional 14-day course of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of uncomplicated pyelonephritis in otherwise healthy women.
This randomized, double-blind comparative trial included premenopausal women, at least 18 years of age, who had been diagnosed with acute uncomplicated pyelonephritis. Eligible patients had flank pain and/or costovertebral angle tenderness, an oral temperature of at least 38.0°C (100.4°F) and pyuria. Patients with diabetes mellitus, an immunocompromised condition, severe sepsis, low creatinine clearance or urologic abnormality, and those who required hospitalization were excluded from the study. All patients underwent a history and physical examination; one urine specimen and two pretherapy blood cultures were obtained for culture and sensitivity testing. The treating physician decided whether the initial antimicrobial dose should be given orally or intravenously. Patients were then randomized to receive 500-mg tablets of ciprofloxacin or 160/800-mg tablets of TMP-SMX. Patients receiving an initial intravenous dose were given 400 mg of ciprofloxacin (in the ciprofloxacin group) or 1 g of ceftriaxone (in the TMP-SMX group) over 60 minutes. All patients received one capsule twice daily for 14 days: ciprofloxacin-treated patients received placebo twice daily for the last seven days. Follow-up urine cultures were obtained at days 3 to 5 during therapy, and days 4 to 11 and 22 to 48 post-therapy.
The main outcomes were bacteriologic and clinical cure (less than 104 colony-forming units per mL for a clean-catch specimen or less than 103 units per mL for a catheterized specimen). Continued clinical cure was defined as absence of all signs and symptoms of illness through the follow-up period. Of the 378 patients enrolled and randomized, 255 were evaluated for efficacy analyses (128 in the ciprofloxacin group and 127 in the TMP/SMX group). The breakdown of patients evaluable for bacterial and clinical outcomes is shown in the accompanying figure. Bacterial cure continued through day 4 to day 11 post-therapy for 112 of 113 patients (99 percent) who received oral ciprofloxacin for seven days (with or without an initial intravenous dose) and for 90 of 101 patients (89 percent) who received oral TMP/SMX for 14 days (with or without an initial intravenous dose). Bacteriologic cure continued during days 22 through 48 post-therapy in 94 of 111 patients (85 percent) who received ciprofloxacin and 80 of 108 patients (74 percent) who received TMP/SMX. Among women who received ciprofloxacin, bacteriologic cure rates were similar regardless of whether the initial dose was given intravenously. In women who received TMP/SMX, an initial intravenous dose of ceftriaxone was associated with a greater bacterial cure rate at days 4 through 11, but not days 22 through 48 post-therapy, compared with that seen in women who received only oral TMP/SMX. Clinical cure rates in the ciprofloxacin group and the TMP/SMX group were similarly skewed in favor of ciprofloxacin. Initial intravenous antimicrobial therapy did not significantly change these results. One quarter (24 percent) of the women in the ciprofloxacin group had adverse effects, compared with 33 percent of those in the TMP/SMX group.
The authors conclude that women with acute uncomplicated pyelonephritis can be successfully and safely treated in the outpatient setting and that a seven-day course of ciprofloxacin was statistically superior to a 14-day course of TMP/SMX. Although ciprofloxacin is more expensive, women in the ciprofloxacin group had fewer side effects and the drug was given for a shorter period, leading to potentially improved compliance. Outpatient treatment is not recommended in women with severe sepsis or complicated pyelonephritis, or in men.