By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: Symptom resolution after seven days of antibiotic therapy in afebrile males with presumed urinary tract infection was not inferior to 14 days of therapy.

SOURCE: Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 days of antibiotic therapy on resolution of symptoms among afebrile men with urinary tract infection: A randomized clinical trial. JAMA 2021;326:324-331.

Drekonja and colleagues performed a pragmatic clinical trial in afebrile male veterans with new onset of symptoms suggestive of urinary tract infection (UTI). Patients had been started on treatment with either ciprofloxacin (57%) or trimethoprim-sulfamethoxazole (TS, 43%) and were randomized before the eighth day after antibiotic initiation to continue their originally prescribed antimicrobial or to receive a placebo from days 7-14. One-half the 262 randomized patients were enrolled by mail.

In this population who received their care through Veterans Administration Medical Centers in Houston or Minneapolis, the median age was 69 years. Overall, a pretreatment urinalysis was obtained from 253 (95.0%) patients, and a pretreatment urine culture was obtained from 239 (87.9%). Of the 239, the culture detected > 100,000 colony forming units (CFU)/mL in 145 patients (60.7%), < 100,000 CFU/mL in 39 patients (16.3%), and no growth was detected in 55 patients (23.0%). Thus, almost 40% did not meet the usual criterion for significant bacteriuria, and approximately one-fifth had totally negative pretreatment cultures.

Resolution of symptoms by 14 days after completion of active antibiotic therapy, the primary outcome, occurred in 122/131(93.1%) and 111/123 (90.2%) of the seven- and 14-day treatment groups, respectively. UTI recurrence occurred in 9.9% and 12.9%, respectively. The incidence of adverse events also did not significantly differ between the two groups.

In a post hoc analysis with stratification by the results of urine culture, there were no significant differences in symptom resolution whether the culture yielded > 100,000 CFU/mL, was positive but with < 100,000 CFU/mL, or was culture negative. Symptom resolution occurred in > 90% in each cohort, and in the group without detectable bacteriuria, this occurred in 28/30 (93.3%) of the seven-day group and 25/25 of the 14-day group.

COMMENTARY

This study, which took place in 2014-2019, was modestly underpowered because enrollment was discontinued when funding ran out. Furthermore, the fact that one-fifth had negative pretreatment urine cultures also affects interpretation of the results. Despite these facts and others, there was not a hint of benefit of extending treatment from seven to 14 days.

Perhaps most intriguing is the fact that symptoms resolved with antibiotic therapy as frequently in those without detectable bacteriuria as in those with high or intermediate levels of bacteriuria. Of course, there was no control group who did not receive antibiotics — something which could have shed light in the interpretation of the results.

It can be concluded from these results that seven days of antibiotic therapy is associated with a high frequency of resolution of urinary tract symptoms in afebrile males and that extending therapy for another seven days does not provide additional benefit. It also can be concluded that the etiology of new-onset urinary symptoms in patients without bacteriuria is unknown, and the fact that they resolved raises question about at least some patients with true bacteriuria. We must face the fact that our understanding of UTI in males is severely lacking.