Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank

Sanyaolu, Leigh, Ahmed, Haroon ORCID: https://orcid.org/0000-0002-0634-8548, Best, Victoria, Farewell, Daniel ORCID: https://orcid.org/0000-0002-8871-1653, Schoenbuchner, Simon, Wood, Fiona ORCID: https://orcid.org/0000-0001-7397-4074, Edwards, Adrian ORCID: https://orcid.org/0000-0002-6228-4446, Akbari, Ashley, Hayward, Gail and Cannings-John, Rebecca ORCID: https://orcid.org/0000-0001-5235-6517 2026. Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank. The Lancet Obstetrics, Gynaecology, & Women's Health 10.1016/s3050-5038(25)00178-5

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Abstract

Background: Prophylactic antibiotics are recommended for the prevention of recurrent urinary tract infections (rUTIs) but can cause antibiotic resistance, a growing global concern. Estimates of the absolute risk of resistance with prophylactic antibiotic use are limited. We aimed to estimate the effect of prophylactic antibiotic use on antibiotic resistance in women with rUTIs. Methods: We did a retrospective cohort study within the target trial framework using electronic health records of Welsh residents held by the Secure Anonymised Information Linkage (known as SAIL) Databank. We emulated a pragmatic trial of women aged 18 years or older with rUTIs, comparing the initiation of prophylactic antibiotics versus non-initiation. The primary outcome was hospital admission with an antibiotic-resistant infection by 52 weeks. Secondary outcomes were hospital admission with an antibiotic-resistant urine infection and uropathogen antibiotic resistance to one or more or two or more antibiotics. Using the survival probabilities, we calculated the risk, risk ratio, risk difference, and number needed to harm of each outcome for each treatment strategy by 52 weeks. Findings: We identified 48 297 women in the SAIL Databank who were eligible for inclusion between Jan 1, 2015, and Dec 31, 2020, of whom 839 initiated prophylactic antibiotics. 616 women were admitted to hospital with an antibiotic-resistant infection by 52 weeks (thus, meeting the primary outcome). Prophylactic antibiotics did not increase the risk of hospital admission with an antibiotic-resistant infection by 52 weeks, with a risk of 1·4% (95% CI 1·3–1·5) in the non-antibiotic group and a risk of 1·9% (1·0–3·1) in the antibiotic prophylaxis group (risk ratio 1·41; 95% CI 0·74–2·24). Furthermore, the risk of admission with an antibiotic-resistant urine infection did not increase with prophylactic antibiotics (1·56, 0·76–2·49). However, prophylactic antibiotics increased the risk of uropathogen resistance to at least one antibiotic on urine culture (risk ratio 1·29, 95% CI 1·14–1·44) and resistance to two or more antibiotics on urine culture (1·57, 1·37–1·79). Interpretation: In our target trial emulation, prophylactic antibiotic use did not increase the risk of hospital admission with an antibiotic-resistant infection or urine infection, but it did increase the risk of uropathogen antibiotic resistance and multidrug antibiotic resistance on urine culture. This study provides new data for the absolute risk and number needed to harm for individual-level antibiotic resistance that could be used to support shared decision-making discussions on rUTI prevention.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine Research Institutes & Centres > Centre for Trials Research (CNTRR)
Publisher:	Elsevier BV
ISSN:	3050-5038
Date of First Compliant Deposit:	23 February 2026
Date of Acceptance:	28 November 2025
Last Modified:	24 Feb 2026 09:43
URI:	https://orca.cardiff.ac.uk/id/eprint/185114

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