Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial

Abstract

Study question: Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications?

Methods: Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3 × 400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain.

Study answer and limitations: The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. 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.

What this paper adds: Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms.

Funding, competing interests, data sharing: German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of identification is low.Trial registration No ClinicalTrialGov Identifier NCT01488955.

Conflict of interest statement

Competing interests: All authors have completed the uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the German Federal Ministry of Education and Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. The University of Göttingen was responsible for the initiation, quality control and financial management the clinical study but did not participate in the collection, clinical project management, analysis, and interpretation of data.

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Figures

Fig 1  Flow of participants through trial of ibuprofen versus fosfomycin for women with urinary tract infection

Fig 2  Total number of antibiotic prescriptions by randomisation group on days 0-28 (range 0-2, intention to treat population)

Fig 3  Symptom sum score for dysuria, frequency/urgency, and low abdominal pain on days 0-7by randomisation group (range 0-12, intention to treat population)

Fig 4  Distribution of area under curve (AUC) of symptom sum scores for dysuria, frequency/urgency, and low abdominal pain on days 0-7 by random group (intention to treat population)

Fig 5  Sum scores for assessment of activity impairment related to urinary tract infection (5 items, range 0-20, intention to treat population)

Fig 6  Symptom sum score for women with negative results on urine culture (subgroup analysis, n=111, intention to treat population) on days 0-7

Fig 7  Symptom sum score for women with positive results on urine culture (subgroup analysis, n=360, intention to treat population) on days 0-7

Fig 8  Symptom sum score for women in fosfomycin group with positive versus negative results on urine culture (subgroup analysis, n=234, intention to treat population) on days 0-7

Fig 9  Symptom scores of women with pyelonephritis according to treatment with ibuprofen or fosfomycin on days 0-7