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

BMJ 2015; 351 doi: (Published 23 December 2015) Cite this as: BMJ 2015;351:h6544

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

Author's reply

Uncomplicated urinary tract infections (UTI) in general practice are known as often self-limiting conditions as shown in placebo controlled trials (1, 2) and reported by women (3). In this pragmatic trial we did not compare two drugs but rather two different treatment strategies: symptomatic treatment first and antibiotics only if symptoms persist or worsen versus antibiotic treatment first. Relief of symptoms and cure of infection are different aspects of treatment indeed but the main aspect for women is symptom relief (4). For this purpose, symptomatic treatment may be effective in many cases, in particular since increasing resistance rates request prescribing antibiotics only to those who really need them. With this rationale, the Ethic Committees did not see ethical problems with the trial.

Furthermore, it is known that many otherwise healthy women have bacteria in their urine. To focus on bacterial cure as a treatment target is not recommended any more (5, 6), nor to treat otherwise healthy non-pregnant women with asymptomatic bacteriuria.

Use of ibuprofen when there is evidence of UTI: In the pilot trial HWI-01 urine cultures were tested initially and again at day 7 (7). Negative cultures were seen more often in the ciprofloxacin group (23/33, 71.9%) than in the ibuprofen group (16/36, 48.5%) while the symptom relief was achieved in almost all participants. Women who received antibiotic treatment during the follow-up period consulted their GPs up to day 9. Within the follow-up period of four weeks none of the women with asymptomatic bacteriuria consulted their GP again. In the study reported in the BMJ (ICUTI) second urine cultures were not done but the re-consultations were distributed similarly during the follow-up period. We assume that women with bacteriuria did not differ from those with a negative urine culture.

Pyelonephritis is a rare but potentially severe acute condition which can also occur as complication of uncomplicated UTI (8, 9). We agree that the risk of pyelonephritis after non- antibiotic UTI treatment should be monitored carefully, but pyelonephritis is too rare an occurrence to act as primary outcome. The ICUTI trial was not powered to compare the numbers but meta-analyses of current and future European UTI trials are planned.

Symptomatic treatment might be recommended to women who want to avoid antibiotics when this treatment is as safe as antibiotic treatment. Another approach could be to identify women with a high risk to develop pyelonephritis when they initially present. Therefore, we are now conducting a systematic review of UTI- trials to identify factors associated with worsening UTI outcomes including pyelonephritis.

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7) Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?--results of a randomized controlled pilot trial. BMC Med. 2010;8:30.
8) Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014 Mar;28:1-13.
9) Czaja CA, Scholes D, Hooton TM, Stamm WE.Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007;45:273-80.

Competing interests: No competing interests

08 January 2016
Ildiko Gagyor
Academic General Practitioner
Jutta Bleidorn, Michael Kochen, Eva Hummers-Pradier, Karl Wegscheider, Guido Schmiemann
Dept. of General Practice, University Medical Center Göttingen
Humboldtallee 38, 37073 Göttingen