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Diclofenac reduces the use of antibiotics in women with uncomplicated lower urinary tract infection (UTI) but remains less effective than norfloxacin for symptom relief of UTI, according to a recent study. In addition, diclofenac appears to be associated with an elevated risk of pyelonephritis.

“Symptomatic treatment is inferior to antibiotic treatment for women with uncomplicated lower UTI in an ambulatory setting, as it increases median symptom duration by 2 days and is likely to be associated with an increased risk of clinically diagnosed pyelonephritis,” researchers said.

A total of 253 women with uncomplicated lower UTI were randomized to either symptomatic treatment with the nonsteroidal anti-inflammatory drug (NSAID) diclofenac (n=133) or antibiotic treatment with norfloxacin (n=120). Resolution of symptoms at day 3 was the primary outcome, while the secondary outcome was the use of any antibiotic up to day 30. This was an intention-to-treat analysis.

More women assigned to norfloxacin than to diclofenac (80 vs 54 percent) had symptom resolution at day 3 (risk difference, 27 percent; 95 percent CI, 15 to 38 percent; p=0.98 for noninferiority; p<0.001 for superiority). The median time until resolution of symptoms in the norfloxacin and diclofenac groups was 2 and 4 days, respectively. [BMJ 2017;359:j4784]

“Those treated with diclofenac were 27 percent less likely to have symptom resolution at day 3 after randomization and 12 percent less likely to have symptom resolution at day 7 after randomization, with higher mean symptom scores, more frequent reconsultations, a higher incidence of clinically diagnosed pyelonephritis and lower patient satisfaction than those in the norfloxacin group,” researchers said.

Antibiotics was used by 82 (62 percent) women in the diclofenac group and 118 (98 percent) in the norfloxacin group up to day 30 (risk difference, 37 percent; 28 to 46 percent; p<0.001 for superiority). A clinical diagnosis of pyelonephritis was reported in six (5 percent) women in the diclofenac group but none in the norfloxacin group (p=0.03).

In a meta-analysis of five trials, antibiotics was found to be clinically superior to placebo in women with uncomplicated lower UTI. [J Infect 2009;359:91-102]

“Our trial, in conjunction with the recently published trial by Gágyor et al, suggests that antibiotics are also clinically superior to symptomatic treatment with NSAIDs,” researchers said. “This contrasts with the findings of a small pilot trial by Bleidorn et al, where clinical outcomes of treatment with ibuprofen were similar to those of antibiotic treatment with ciprofloxacin.” [BMC Med 2010;359:30; BMJ 2015;359:h6544]

The present study and that of Gágyor and colleagues were adequately powered, but both trials failed to detect noninferiority of NSAIDs vs antibiotics for symptom control. The two studies also suggest that symptomatic treatment with NSAIDs correlates with an increased risk of pyelonephritis, which translates into a number needed to harm of 23 compared with antibiotic treatment in the present trial.

“The observed clinically relevant reduction in antibiotic use, which would likely contribute directly to decreasing resistance rates in the affected population, suggests that alternative approaches of combining symptomatic treatment with deferred, selective antibiotic use should be developed and tested in future trials,” researchers said.

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