Urinary tract infection symptoms resolved by three days for 80% of women given antibiotics compared with 54% given anti-inflammatories. Anti-inflammatories reduced antibiotic use, but 5% of women developed more severe infection of the kidneys.
Urinary infections are the second most common reason for prescribing antibiotics in general practice, after respiratory infection. As such, this use may be contributing to increasing antibiotic resistance.
This Swiss trial provided an important head-to-head comparison of antibiotic treatment with the anti-inflammatory diclofenac in 253 women.
The findings don’t indicate that a switch to prescribing anti-inflammatories for women with clear symptoms of urinary infection would be a suitable move to tackle antibiotic resistance.
Symptoms are prolonged to about four days compared with two with antibiotics. This comes at the cost of increased risk of potentially serious complications.
Delayed antibiotic prescribing could be used alongside a non-steroidal anti-inflammatory drug (NSAID) first strategy.
Why was this study needed?
Urinary infections are very common in women, affecting at least one in five in their lifetime.
It’s estimated over 90% of otherwise healthy women presenting to their GP with symptoms of painful and frequent urination will have bacteria in their urine. Therefore it’s standard practice to prescribe a short, three-day course of antibiotics on the basis of symptoms alone. Urine dipstick is sometimes helpful if a woman has only mild or a single symptom, in which case the presence of white blood cells or nitrite indicates a high likelihood of infection.
Around 10-20% of all antibiotic prescriptions in general practice are for urinary infections. Reducing antibiotic prescription for uncomplicated infections in women might help reduce growing antibiotic resistance.
As urinary symptoms may be caused by inflammation, NSAIDs might be a way to reduce antibiotic use.
What did this study do?
This randomised controlled trial was conducted in 17 general practices in Switzerland. It included 253 adult women (aged 18 to 70 years) with symptoms and urine dipstick positive for white blood cells and/or nitrites. Pregnant women and those with possible kidney infection were excluded, as were women with various other medical conditions.
Women were given the antibiotic norfloxacin (400mg daily) or the NSAID diclofenac (75mg daily) for three days. Both drugs had the same appearance and dosing frequency, so neither women nor doctors knew which treatment was given. A “rescue” antibiotic (fosfomycin) was available to all women if symptoms persisted after three days.
The initial plan was to recruit 400 women, but recruitment was slow and terminated early. However, the researchers calculated they had sufficient women to reliably detect a difference in outcomes.
What did it find?
- Antibiotics were better than NSAIDs for resolving symptoms by three days. Symptoms resolved for 80% of women in the norfloxacin group (96/120) compared with 54% in the diclofenac group (72/133).
- The time to symptom resolution was doubled when NSAIDs were used: average (median) four days compared with two days for antibiotics.
- Unsurprisingly prescribing NSAIDs reduced antibiotic use. Ninety-eight per cent of women in the norfloxacin group had taken antibiotics by 30 days compared with 62% of the diclofenac group. Forty-one per cent of the diclofenac group felt the need to take the rescue antibiotic fosfomycin by day three compared with 8% of the norfloxacin group.
- NSAIDs increased the risk of complications related to infection. There were six cases of kidney infection (pyelonephritis) in the diclofenac group (5%) compared with none in the norfloxacin group.
What does current guidance say on this issue?
The NICE quality standard on urinary tract infections in adults, states that urine culture is required for those who don’t respond to initial antibiotics.
NICE recommendations are drawn from the 2012 SIGN guideline. SIGN advises prescribing antibiotics (trimethoprim or nitrofurantoin for three days) to healthy women aged <65 who have three or more symptoms. They advise using a urine dipstick to diagnose infection in women with mild symptoms.
What are the implications?
There is need to reduce antibiotic use to tackle growing antibiotic resistance. But this study doesn't indicate that prescribing anti-inflammatories for urinary tract infection is the answer.
Women who have several symptoms are almost certain to have a bacterial infection. Giving anti-inflammatories may reduce antibiotic use, but symptom resolution is less likely, and there is a higher risk that infection will ascend to the kidneys.
As the authors note, they chose an antibiotic with known effectiveness in their region. In countries and settings with higher levels of antibiotic resistance, the difference between antibiotics and NSAIDs may be less marked.
Citation and Funding
Kronenberg A, Butikofer L, Odutayo A, et al. Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: randomised, double blind trial. BMJ. 2017;359:j4784.
This study was funded by the by the Swiss National Foundation, Swiss Academy of Medical Sciences, SwissLife foundation, and Else Kroener-Fresenius foundation.
Gágyor I, Bleidorn J, Kochen MM, et al. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ. 2015;351:h6544.
NICE. Urinary tract infections in adults. QS90. London: National Institute for Health and Care Excellence; 2015.
SIGN. Management of suspected urinary tract infections in adults. SIGN 88. Edinburgh: Scottish Intercollegiate Guidelines Network; 2012.
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