In a Swiss comparative trial, diclofenac was inferior to norfloxacin for treatment of urinary tract infection (UTI). The randomized, double-blind, noninferiority clinical trial of 253 women with uncomplicated infection was initiated to determine if use of a nonsteroidal anti-inflammatory drug (NSAID) could reduce use of antibiotics and thus risk of antibiotic resistance—a key tenet of antimicrobial stewardship—in ambulatory care settings.
Estimates indicate that half of women will experience at least one UTI in their lifetimes and up to one-third will experience recurrent UTIs. Ten percent to 20% of all antibiotic prescriptions written in ambulatory care settings are for UTIs.
An NSAID was chosen for this study based on the hypothesis that UTI symptoms may be associated with local increases in prostaglandins and other pro-inflammatory factors and because a small pilot trial had found that ibuprofen was non-inferior to the antibiotic ciprofloxacin in 80 women with uncomplicated UTI. Subsequently, two larger randomized trials were conducted in 2012 to further investigate the potential of NSAIDs—this one in Switzerland and another in Germany.
In the current prospective trial, women aged 18 to 70 years who presented to 17 general practices in Switzerland between February 2012 and December 2014 were randomly assigned to receive diclofenac 75 mg or norfloxacin 400 mg for 3 days. Urine dipstick testing was used to confirm UTI. Women in both groups had a mean age of 36.8 years and had been experiencing symptoms for a mean duration of 3.4 days. Urgency, frequency, and dysuria were the most commonly reported symptoms.
Fifty-four percent of the women (N = 72) who received diclofenac had a resolution of their UTI symptoms by Day 3 of treatment compared with 80% of the subjects (N = 96) assigned to norfloxacin. Women treated with the NSAID were 27% less likely to experience symptom resolution by Day 3 of treatment (95% confidence interval 15% to 38%, P = 0.98 for non-inferiority and P < 0.001 for superiority in favor of the antibiotic). In addition, they were 12% less likely to have symptom resolution by Day 7 and had higher mean symptom scores, needed more doctor visits, and were less satisfied with their treatment than women who were randomized to receive the antibiotic. Eighty-two women in the diclofenac group also used a rescue antibiotic, typically fosfomycin, and most of them decided to do so within the first 3 days of treatment.
The study subjects were followed for up to 30 days. Adverse events were more common in the NSAID group than the antibiotic group, including pyelonephritis in six participants the diclofenac group versus zero in the norfloxacin group.
In the concurrent German trial published in the British Journal of Medicine, two-thirds of women with uncomplicated UTI had symptom resolution by Day 3 of treatment with ibuprofen 400 mg TID for 3 days and received significantly fewer courses of antibiotics. Yet that study also found that more women treated with the NSAID developed pyelonephritis than those treated with fosfomycin 3 g dosed once and that the NSAID group had a significantly higher total burden of symptoms. The German authors cautioned that the “results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI.”
The Swiss authors concluded that norfloxacin is clinically superior to symptomatic treatment with diclofenac, and while the latter drug does reduce antibiotic use in women with uncomplicated UTI, it is also associated with an increased risk of pyelonephritis.