1. A double-blinded, randomized controlled trial found that there were no significant differences between afebrile men treated for 7 days versus 14 days of ciprofloxacin or trimethoprim/sulfamethoxazole for urinary tract infection.
2. More than 90% of patients in both groups achieved the primary outcome of symptom resolution by day 14 of the trial; secondary outcomes evaluated included urinary tract infection recurrence and adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Urinary tract infections (UTI) are one of the most common indications for antibiotic therapy. Currently, the optimal duration of therapy for UTI management in select populations is unknown. This double-blinded randomized controlled trial (RCT) sought to evaluate the noninferiority of a 7-day antibiotic course with either ciprofloxacin or trimethoprim/sulfamethoxazole compared to a 14-day antibiotic course for afebrile men with a urinary tract infection. The trial was conducted at two Veterans Affairs medical centres in the United States. Patients presenting with urinary complaints were recruited at outpatient clinic visits. 272 adult, male patients being treated on an outpatient basis for an afebrile urinary tract infection were enrolled and randomized. Both groups received antibiotic therapy for days 1-7. The control group received antibiotics on days 8-14 as well, while the intervention group received one week of placebo pills. The treatment ended on day 14, at which time all participants were evaluated for symptomatology, any co-interventions, adherence and adverse events. After 14 days of the trial, 93.1% of patients in the 7-day treatment group and 90.2% in the 14-day treatment group had demonstrated symptom resolution. The rates of recurrence were 9.9% in the 7-day group and 12.9% in the 14-day group. Finally, 20.6% of the 7-day patients and 24.3% of the 14-day patients experienced adverse events from this trial. Drekonja et al’s trial provides convincing evidence for recommending a shorter duration of antibiotic therapy for male patients with an afebrile UTI. Given the high prevalence of UTIs, the results of this trial could imply significant cost savings for the healthcare payer and reduce the risk of antibiotic resistance through minimized exposure. A primary limitation of this study is the recruitment method, which did not confirm through microbiology that all enrolled patients truly had a UTI at baseline. This is an example of non-differential misclassification bias. Secondly, the reported findings are limited in their application to patients prescribed either ciprofloxacin or trimethoprim/sulfamethoxazole. Although these are commonly-used agents, these results might not be generalizable to the variety of other agents used to treat UTIs. Finally, the small sample size of the trial compared to the projected enrollment (290 patients) limits the conclusions we can draw for its results.
In-Depth (randomized controlled trial): Randomization was performed using a random-number generator stratified for confounding factors (presence of a urinary catheter, study cite, prescribed antibiotic). Blocked randomization using a 1:1 ratio between treatment groups was used. The median age of patients was 69 years; demographic factors and comorbidities were equally balanced between groups. Of 272 patients randomized, 254 were included in the as-treated analysis, meaning these patients took at least 26 of the 28 doses of medication or placebo that was prescribed. A noninferiority margin of 10% was selected based on expert opinion. Consequently, target enrollment was 290 participants using a single-sided alpha value of 0.025 to detect a difference with 85% power. The most commonly-isolated infectious organism in both groups was Escherichia coli (43% in the 14-day group, 39% in the 7-day group). A 1-sided 97.5% confidence interval was used to establish noninferiority for the primary and secondary outcomes. The absolute difference between groups for symptom resolution was 2.9 percentage points with a 1-sided 97.5% confidence interval of -5.2 to infinity. Several post hoc analyses were conducted to understand the differential effect that the antibiotic drug of choice, pre-treatment bacteriuria count, and study site may have had on the outcome. Using a linear regression model it was reported that none of the three variables had a significant impact on the results. The p-values for interaction were reported as follows: 0.37 for antibiotic choice, 0.53 for pre-treatment bacteriuria and 0.88 for study site.
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