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

Leigh Sanyaolu, Haroon Ahmed, Victoria Best, Daniel Farewell, Simon Schoenbuchner, Fiona Wood, Adrian Edwards, Ashley Akbari Orcid Logo, Gail Hayward, Rebecca Cannings-John

The Lancet Obstetrics, Gynaecology, & Women's Health, Volume: 2, Issue: 3, Pages: e209 - e217

Swansea University Authors: Victoria Best, Ashley Akbari Orcid Logo

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DOI (Published version): 10.1016/s3050-5038(25)00178-5

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 eff...

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Published in: The Lancet Obstetrics, Gynaecology, & Women's Health
ISSN: 3050-5038
Published: Elsevier BV 2026
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URI: https://cronfa.swan.ac.uk/Record/cronfa71402
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2026-04-27T10:48:43.7372706</datestamp><bib-version>v2</bib-version><id>71402</id><entry>2026-02-12</entry><title>Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank</title><swanseaauthors><author><sid>0c82f7076d0fc5c916ecbcc472a6a9ae</sid><ORCID/><firstname>Victoria</firstname><surname>Best</surname><name>Victoria Best</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>aa1b025ec0243f708bb5eb0a93d6fb52</sid><ORCID>0000-0003-0814-0801</ORCID><firstname>Ashley</firstname><surname>Akbari</surname><name>Ashley Akbari</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2026-02-12</date><deptcode>MEDS</deptcode><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&#x2008;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&#xB7;4% (95% CI 1&#xB7;3&#x2013;1&#xB7;5) in the non-antibiotic group and a risk of 1&#xB7;9% (1&#xB7;0&#x2013;3&#xB7;1) in the antibiotic prophylaxis group (risk ratio 1&#xB7;41; 95% CI 0&#xB7;74&#x2013;2&#xB7;24). Furthermore, the risk of admission with an antibiotic-resistant urine infection did not increase with prophylactic antibiotics (1&#xB7;56, 0&#xB7;76&#x2013;2&#xB7;49). However, prophylactic antibiotics increased the risk of uropathogen resistance to at least one antibiotic on urine culture (risk ratio 1&#xB7;29, 95% CI 1&#xB7;14&#x2013;1&#xB7;44) and resistance to two or more antibiotics on urine culture (1&#xB7;57, 1&#xB7;37&#x2013;1&#xB7;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.</abstract><type>Journal Article</type><journal>The Lancet Obstetrics, Gynaecology, &amp; Women's Health</journal><volume>2</volume><journalNumber>3</journalNumber><paginationStart>e209</paginationStart><paginationEnd>e217</paginationEnd><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>3050-5038</issnPrint><issnElectronic/><keywords/><publishedDay>1</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2026</publishedYear><publishedDate>2026-03-01</publishedDate><doi>10.1016/s3050-5038(25)00178-5</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>This study was funded by Health and Care Research Wales through a Health and Care Research Wales and National Institute for Health and Care Research Doctoral Fellowship (NIHR-FS-2021-LS to LS).</funders><projectreference/><lastEdited>2026-04-27T10:48:43.7372706</lastEdited><Created>2026-02-12T00:25:46.2899235</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Health Data Science</level></path><authors><author><firstname>Leigh</firstname><surname>Sanyaolu</surname><order>1</order></author><author><firstname>Haroon</firstname><surname>Ahmed</surname><order>2</order></author><author><firstname>Victoria</firstname><surname>Best</surname><orcid/><order>3</order></author><author><firstname>Daniel</firstname><surname>Farewell</surname><order>4</order></author><author><firstname>Simon</firstname><surname>Schoenbuchner</surname><order>5</order></author><author><firstname>Fiona</firstname><surname>Wood</surname><order>6</order></author><author><firstname>Adrian</firstname><surname>Edwards</surname><order>7</order></author><author><firstname>Ashley</firstname><surname>Akbari</surname><orcid>0000-0003-0814-0801</orcid><order>8</order></author><author><firstname>Gail</firstname><surname>Hayward</surname><order>9</order></author><author><firstname>Rebecca</firstname><surname>Cannings-John</surname><order>10</order></author></authors><documents><document><filename>71402__36598__c926982c32174dcd9daf084b78bedfb7.pdf</filename><originalFilename>71402.VOR.pdf</originalFilename><uploaded>2026-04-27T10:46:12.5136660</uploaded><type>Output</type><contentLength>602612</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; 2026 The Author(s). 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spelling 2026-04-27T10:48:43.7372706 v2 71402 2026-02-12 Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank 0c82f7076d0fc5c916ecbcc472a6a9ae Victoria Best Victoria Best true false aa1b025ec0243f708bb5eb0a93d6fb52 0000-0003-0814-0801 Ashley Akbari Ashley Akbari true false 2026-02-12 MEDS 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. Journal Article The Lancet Obstetrics, Gynaecology, & Women's Health 2 3 e209 e217 Elsevier BV 3050-5038 1 3 2026 2026-03-01 10.1016/s3050-5038(25)00178-5 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee This study was funded by Health and Care Research Wales through a Health and Care Research Wales and National Institute for Health and Care Research Doctoral Fellowship (NIHR-FS-2021-LS to LS). 2026-04-27T10:48:43.7372706 2026-02-12T00:25:46.2899235 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Health Data Science Leigh Sanyaolu 1 Haroon Ahmed 2 Victoria Best 3 Daniel Farewell 4 Simon Schoenbuchner 5 Fiona Wood 6 Adrian Edwards 7 Ashley Akbari 0000-0003-0814-0801 8 Gail Hayward 9 Rebecca Cannings-John 10 71402__36598__c926982c32174dcd9daf084b78bedfb7.pdf 71402.VOR.pdf 2026-04-27T10:46:12.5136660 Output 602612 application/pdf Version of Record true © 2026 The Author(s). This is an Open Access article under the CC BY 4.0 license. true eng http://creativecommons.org/licenses/by/4.0/
title Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
spellingShingle Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
Victoria Best
Ashley Akbari
title_short Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
title_full Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
title_fullStr Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
title_full_unstemmed Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
title_sort Prophylactic antibiotics to prevent recurrent urinary tract infections and risk of antibiotic resistance: target trial emulation with the SAIL Databank
author_id_str_mv 0c82f7076d0fc5c916ecbcc472a6a9ae
aa1b025ec0243f708bb5eb0a93d6fb52
author_id_fullname_str_mv 0c82f7076d0fc5c916ecbcc472a6a9ae_***_Victoria Best
aa1b025ec0243f708bb5eb0a93d6fb52_***_Ashley Akbari
author Victoria Best
Ashley Akbari
author2 Leigh Sanyaolu
Haroon Ahmed
Victoria Best
Daniel Farewell
Simon Schoenbuchner
Fiona Wood
Adrian Edwards
Ashley Akbari
Gail Hayward
Rebecca Cannings-John
format Journal article
container_title The Lancet Obstetrics, Gynaecology, & Women's Health
container_volume 2
container_issue 3
container_start_page e209
publishDate 2026
institution Swansea University
issn 3050-5038
doi_str_mv 10.1016/s3050-5038(25)00178-5
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Health Data Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Health Data Science
document_store_str 1
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description 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.
published_date 2026-03-01T05:38:07Z
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