Proponents of the “shorter is better” philosophy for antibiotic treatment of many common bacterial infections can add another study to their list: In results published this week in JAMA, researchers reported that, in men who had presumed symptomatic urinary tract infections (UTIs) with no fever, 7 days of antibiotics was noninferior to 14 days for resolving symptoms.
The findings are from a randomized clinical trial conducted among men at two Veterans Affairs (VA) hospitals in Minneapolis and Houston who were treated with ciprofloxacin or trimethoprim/sulfamethoxazole. No significant differences in recurrence of symptoms or adverse events occurred.
“The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI,” the study authors wrote.
UTI treatment duration in men ‘all over the map’
Lead study author Dimitri Drekonja, MD, MS, chief of the infectious diseases section of the Minneapolis VA Health Care System and an associate professor of medicine at the University of Minnesota, said the idea for the trial came following studies of VA data showing that treatment duration for UTIs in men was “all over the map.”
“There were big peaks of 7 and 14 days, and it didn’t seem like there was any hint of benefit, and if anything, there was some hint of harm,” Drekonja said.
Part of the reason for that variation is because there are no formal guidelines for antibiotic treatment for UTIs in men. The Infectious Diseases Society of America recommends 3 to 5 days of antibiotics for uncomplicated UTIs in women, but, because of limited data, has not developed guidance for men.
To determine whether 7 days of antibiotics is noninferior to 14 days, Drekonja and colleagues from the University of Minnesota Medical School, Minneapolis VA, Michael E. DeBakey VA Medical Center in Houston, and Baylor College of Medicine randomized 272 male VA patients with presumed symptomatic UTI and no fever to receive either 7 or 14 days of ciprofloxacin or trimethoprim/sulfamethoxazole. The patients in the double-blinded trial who received 7 days of antibiotics were given a placebo for days 8 through 14.
The trial was conducted from April 2014 through December 2019, with 76% of participants enrolled at the Minneapolis VA and 24% at the Houston site (average age, 69 years). The primary outcome was resolution of symptoms by 14 days after completion of antibiotic treatment. The noninferiority margin was 10%.
The primary analysis looked at outcomes in the as-treated population (those who took at least 26 of 28 doses and missed no more than two consecutive doses), and a secondary analysis included all patients as randomized, regardless of treatment adherence.
In the primary as-treated analysis, symptom resolution occurred in 93.1% of participants in the 7-day group (122 of 131) and 90.2% of the 14-day group (111 of 123), for a difference of 2.9 percentage points, which met the noninferiority criterion. In the as-randomized analysis, symptom resolution occurred in 91.9% in the 7-day group (125 of 136) versus 90.4% of the 14-day group (123 of 136), for a difference of 1.5 percentage points.
Recurrence of UTI symptoms within 28 days of stopping medication occurred in 9.9% of the 7-day group versus 12.9% of the 14-day group in the as-treated analysis, with comparable results in the as-randomized population. Across the as-randomized patients, adverse events occurred in 20.6% people in the 7-day group and 24.3% of the 14-day group.
Results should help guide treatment
Drekonja said the findings have prompted the Minneapolis VA to change its recommended treatment for UTIs in afebrile men to 7 days. While he acknowledges that there are will always be circumstances where 7 days is not enough, he believes it should be the first option in UTI cases where no fever is present.
He also noted that cutting off a week of antibiotics for an infection as common as a UTI makes it more convenient for patients, and, more importantly, could reduce the selective pressure that drives antibiotic resistance. “With this infection, and for many others, it does seem like you can get by with fewer antibiotics, which makes your patients happy, and the microbial environment happy,” he said.
Writing in an accompanying editorial, Daniel Morgan, MD, MS, of the University of Maryland School of Medicine and the VA Maryland Health Care System, said that while the study was small and had other limitations, it’s the most rigorous to date in evaluating antibiotic duration in male UTIs, and should help guide treatment decisions.
“Shorter courses of antibiotic treatment are inherently easier for patients and are preferred when clinical outcomes are noninferior compared with longer duration of treatment,” Morgan wrote. “This study should inform guidelines and should give clinicians confidence to treat thoughtfully for the shortest effective treatment duration.”
More evidence for shorter antibiotic courses
The results add to a growing body of evidence that, for many common infections, shorter treatments are just as effective, and potentially less harmful, than longer treatments, according to Neil Clancy, MD, an infectious disease expert at the University of Pittsburgh and chief of the infectious diseases section at the VA Pittsburgh Health Care System.
“The study offers yet more evidence for the short course narrative of treating diverse types of infections, by diverse types of pathogens,” said Clancy, who was not involved in the study. “Many of the broadly accepted treatment durations for infections are excessive, as shown by an expanding body of studies. Short course therapy and risk stratification of patients will be important areas of antimicrobial stewardship investigation and intervention in future.”
Reflecting this shift in thinking, in April, the American College of Physicians released new guidelines recommending a short course of antibiotics for UTIs and three other common bacterial infections (community acquired pneumonia, acute bronchitis with chronic obstructive pulmonary disease, and cellulitis).
“We all have, in medicine, a tendency to believe that if a little bit is good, more must be better,” Drekonja said. “But we’re building a pretty robust evidence base that with antibiotics, that is rarely the case.”