Sylvia Luther, MD

BACKGROUND: The current recommendation for management of uncomplicated pyelonephritis is a 14-day course of ciprofloxacin.¹ Studies have shown this to be 90% effective.² Few studies have evaluated shorter courses of therapy for pyelonephritis. The purpose of this study was to compare the effectiveness of 7 days of ciprofloxacin with 14 days of trimethoprim-sulfamethoxazole (TMP-SMZ) for treatment of acute uncomplicated pyelonephritis in an outpatient setting.

POPULATION STUDIED: The study participants were premenopausal women aged 18 years or older with a clinical diagnosis of pyelonephritis, defined as flank pain or costovertebral angle tenderness, fever, and pyuria. Patients were excluded if they had abnormal renal function (creatinine >2.7), severe sepsis, urologic abnormalities, persistent vomiting, or if they were immunocompromised, had diabetes, were admitted to the hospital, or were pregnant or lactating.

STUDY DESIGN AND VALIDITY: A total of 378 patients were randomized to receive either 7 days of ciprofloxacin 500 mg twice daily or 14 days of TMP-SMZ 800/160 mg twice daily. In both groups, managing physicians had the option to treat patients with an initial dose of intravenous antibiotic, if clinically indicated (400 mg of ciprofloxacin in the ciprofloxacin group or 1 gram of ceftriaxone in the TMP-SMZ group). Blood cultures and a urine culture were obtained by either clean catch or catheterization before therapy was initiated. Urine cultures were repeated on days 3 to 5 of treatment. Patients were evaluated at 4 to 11 days and 22 to 48 days following treatment to assess for clinical cure and to repeat urine cultures.

OUTCOMES MEASURED: Primary study outcomes were bacteriologic and clinical cures at a visit 4 to 11 days post-therapy, as determined by urine culture and signs and symptoms, respectively. Secondary outcomes included bacteriologic and clinical responses at the visit 22 to 48 days post-therapy, adverse drug events, and a health resource analysis.

RESULTS: At 4 to 11 days post-therapy, the efficacy analysis showed that patients treated with ciprofloxacin had a better bacteriologic cure rate than the patients treated with TMP-SMZ (99% vs 89%, P=.004; number needed to treat [NNT]=10) and a better clinical cure rate (96% vs 83%, P=.002; NNT=7.6). Escherichia coli represented 90% of cultured organisms, of which 18% were resistant to TMP-SMZ, and <1% were resistant to ciprofloxacin. When the analysis was done using only organisms sensitive to TMP-SMZ, the efficacy rates were similar. An initial IV dose was associated with a greater cure rate in the TMP-SMZ group, but not in the ciprofloxacin group. In the intention-to-treat analysis, clinical cure rates for ciprofloxacin were better than TMP-SMZ at 22 to 48 days post-therapy (82% vs 72%; 95% confidence interval [CI], 0.01-0.19; NNT=10). Benefits were also seen when comparing ciprofloxacin with TMP-SMZ for bacteriologic cure (84% vs 74%; 95% CI, 0.01-0.19; NNT=10). Adverse events occurred in 24% of the ciprofloxacin and 33% of the TMP-SMZ group; 6% of patients taking ciprofloxacin and 11% taking TMP-SMZ discontinued the drug. The cost per cure was $615 for ciprofloxacin compared with $770 for TMP-SMZ; however, this study did not have enough power to detect a statistically significant difference.

BACKGROUND: The current recommendation for management of uncomplicated pyelonephritis is a 14-day course of ciprofloxacin.¹ Studies have shown this to be 90% effective.² Few studies have evaluated shorter courses of therapy for pyelonephritis. The purpose of this study was to compare the effectiveness of 7 days of ciprofloxacin with 14 days of trimethoprim-sulfamethoxazole (TMP-SMZ) for treatment of acute uncomplicated pyelonephritis in an outpatient setting.

POPULATION STUDIED: The study participants were premenopausal women aged 18 years or older with a clinical diagnosis of pyelonephritis, defined as flank pain or costovertebral angle tenderness, fever, and pyuria. Patients were excluded if they had abnormal renal function (creatinine >2.7), severe sepsis, urologic abnormalities, persistent vomiting, or if they were immunocompromised, had diabetes, were admitted to the hospital, or were pregnant or lactating.

STUDY DESIGN AND VALIDITY: A total of 378 patients were randomized to receive either 7 days of ciprofloxacin 500 mg twice daily or 14 days of TMP-SMZ 800/160 mg twice daily. In both groups, managing physicians had the option to treat patients with an initial dose of intravenous antibiotic, if clinically indicated (400 mg of ciprofloxacin in the ciprofloxacin group or 1 gram of ceftriaxone in the TMP-SMZ group). Blood cultures and a urine culture were obtained by either clean catch or catheterization before therapy was initiated. Urine cultures were repeated on days 3 to 5 of treatment. Patients were evaluated at 4 to 11 days and 22 to 48 days following treatment to assess for clinical cure and to repeat urine cultures.

OUTCOMES MEASURED: Primary study outcomes were bacteriologic and clinical cures at a visit 4 to 11 days post-therapy, as determined by urine culture and signs and symptoms, respectively. Secondary outcomes included bacteriologic and clinical responses at the visit 22 to 48 days post-therapy, adverse drug events, and a health resource analysis.

RESULTS: At 4 to 11 days post-therapy, the efficacy analysis showed that patients treated with ciprofloxacin had a better bacteriologic cure rate than the patients treated with TMP-SMZ (99% vs 89%, P=.004; number needed to treat [NNT]=10) and a better clinical cure rate (96% vs 83%, P=.002; NNT=7.6). Escherichia coli represented 90% of cultured organisms, of which 18% were resistant to TMP-SMZ, and <1% were resistant to ciprofloxacin. When the analysis was done using only organisms sensitive to TMP-SMZ, the efficacy rates were similar. An initial IV dose was associated with a greater cure rate in the TMP-SMZ group, but not in the ciprofloxacin group. In the intention-to-treat analysis, clinical cure rates for ciprofloxacin were better than TMP-SMZ at 22 to 48 days post-therapy (82% vs 72%; 95% confidence interval [CI], 0.01-0.19; NNT=10). Benefits were also seen when comparing ciprofloxacin with TMP-SMZ for bacteriologic cure (84% vs 74%; 95% CI, 0.01-0.19; NNT=10). Adverse events occurred in 24% of the ciprofloxacin and 33% of the TMP-SMZ group; 6% of patients taking ciprofloxacin and 11% taking TMP-SMZ discontinued the drug. The cost per cure was $615 for ciprofloxacin compared with $770 for TMP-SMZ; however, this study did not have enough power to detect a statistically significant difference.

BACKGROUND: The current recommendation for management of uncomplicated pyelonephritis is a 14-day course of ciprofloxacin.¹ Studies have shown this to be 90% effective.² Few studies have evaluated shorter courses of therapy for pyelonephritis. The purpose of this study was to compare the effectiveness of 7 days of ciprofloxacin with 14 days of trimethoprim-sulfamethoxazole (TMP-SMZ) for treatment of acute uncomplicated pyelonephritis in an outpatient setting.

POPULATION STUDIED: The study participants were premenopausal women aged 18 years or older with a clinical diagnosis of pyelonephritis, defined as flank pain or costovertebral angle tenderness, fever, and pyuria. Patients were excluded if they had abnormal renal function (creatinine >2.7), severe sepsis, urologic abnormalities, persistent vomiting, or if they were immunocompromised, had diabetes, were admitted to the hospital, or were pregnant or lactating.

STUDY DESIGN AND VALIDITY: A total of 378 patients were randomized to receive either 7 days of ciprofloxacin 500 mg twice daily or 14 days of TMP-SMZ 800/160 mg twice daily. In both groups, managing physicians had the option to treat patients with an initial dose of intravenous antibiotic, if clinically indicated (400 mg of ciprofloxacin in the ciprofloxacin group or 1 gram of ceftriaxone in the TMP-SMZ group). Blood cultures and a urine culture were obtained by either clean catch or catheterization before therapy was initiated. Urine cultures were repeated on days 3 to 5 of treatment. Patients were evaluated at 4 to 11 days and 22 to 48 days following treatment to assess for clinical cure and to repeat urine cultures.

OUTCOMES MEASURED: Primary study outcomes were bacteriologic and clinical cures at a visit 4 to 11 days post-therapy, as determined by urine culture and signs and symptoms, respectively. Secondary outcomes included bacteriologic and clinical responses at the visit 22 to 48 days post-therapy, adverse drug events, and a health resource analysis.

RESULTS: At 4 to 11 days post-therapy, the efficacy analysis showed that patients treated with ciprofloxacin had a better bacteriologic cure rate than the patients treated with TMP-SMZ (99% vs 89%, P=.004; number needed to treat [NNT]=10) and a better clinical cure rate (96% vs 83%, P=.002; NNT=7.6). Escherichia coli represented 90% of cultured organisms, of which 18% were resistant to TMP-SMZ, and <1% were resistant to ciprofloxacin. When the analysis was done using only organisms sensitive to TMP-SMZ, the efficacy rates were similar. An initial IV dose was associated with a greater cure rate in the TMP-SMZ group, but not in the ciprofloxacin group. In the intention-to-treat analysis, clinical cure rates for ciprofloxacin were better than TMP-SMZ at 22 to 48 days post-therapy (82% vs 72%; 95% confidence interval [CI], 0.01-0.19; NNT=10). Benefits were also seen when comparing ciprofloxacin with TMP-SMZ for bacteriologic cure (84% vs 74%; 95% CI, 0.01-0.19; NNT=10). Adverse events occurred in 24% of the ciprofloxacin and 33% of the TMP-SMZ group; 6% of patients taking ciprofloxacin and 11% taking TMP-SMZ discontinued the drug. The cost per cure was $615 for ciprofloxacin compared with $770 for TMP-SMZ; however, this study did not have enough power to detect a statistically significant difference.