Dan Rosenbaum, MD

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

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.