Research Article: Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women—A double-blind, randomized non-inferiority trial

Date Published: May 15, 2018

Publisher: Public Library of Science

Author(s): Ingvild Vik, Marianne Bollestad, Nils Grude, Anders Bærheim, Eivind Damsgaard, Thomas Neumark, Lars Bjerrum, Gloria Cordoba, Inge Christoffer Olsen, Morten Lindbæk, Sanjay Basu

Abstract: BackgroundAlthough uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%.Methods and findingsThis was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18–60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks’ follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable.ConclusionsIbuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs.Trial registrationClinicalTrials.gov NCT01849926EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14

Partial Text: More than half of all women will experience an uncomplicated urinary tract infection (UTI) during life [1], and 20% will have recurring infections [2]. The condition is mostly self-limiting and rarely progresses to an upper UTI [3,4]. Despite this, most women who see a doctor are prescribed antibiotic treatment, as it is known to give quick symptom relief and shorten the course of the condition. Some general practitioners (GPs) in Scandinavia use a urinary dipstick result to confirm a UTI, but if the clinical suspicion of the diagnosis is there, a negative dipstick result is not considered a good method to rule out infection. In Norway the guidelines state that the diagnosis of uncomplicated UTI can be given based on symptoms alone [5]. A Norwegian study showed that prescribing for uncomplicated UTI that was delegated to a nurse who followed a diagnostic algorithm provided the same outcome as a doctor’s consultation [6].

More than half of the women treated with ibuprofen achieved symptom resolution without any additional treatment. Initial treatment with ibuprofen could reduce unnecessary use of antibiotics in this group. However, until we can identify those women in need of antibiotic treatment to prevent complications, we cannot recommend ibuprofen alone to women with uncomplicated UTIs.

Source:

http://doi.org/10.1371/journal.pmed.1002569

 

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