Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England

Abstract

Background

Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.

Methods and findings

We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007–2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations.

A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97–1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09–1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI.

Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.

Conclusions

In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients’ risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.

Abstract

In a study of electronic health record data, Laura Shallcross, Patrick Rockenschaub and colleagues investigate the associations between initiation of antibiotic treatment for UTI and blood stream infection and mortality among older adults in England.

Author summary

Why was this study done?

• Urinary tract infections (UTI) are common in older adults and, alongside respiratory infections, account for the majority of antibiotics prescribed in primary care

• Antibiotics are often prescribed inappropriately for UTI in the elderly, but the need to reduce prescribing must be balanced against the risk of increasing rare but severe outcomes, such as bloodstream infection, if antibiotic treatment is delayed

• A recent study in patients aged >65 years found that those who did not receive immediate antibiotic treatment for UTI were more likely to develop bloodstream infection

What did the researchers do and find?

• We reanalyzed the relationship between the timing of antibiotic prescribing for UTI and subsequent risk of bloodstream infection (BSI) using the same dataset

• We did not find evidence to suggest that not immediately prescribing antibiotics for UTI increased a patient’s risk of bloodstream infection, but we did find some evidence of increased mortality.

• Women were less likely to develop BSI compared with men (adjusted odds ratio [aOR] 0.49, 95% confidence interval [CI] 0.43–0.55, p-value < 0.001). Increasing age (aOR 1.22, 95% CI 1.18–1.27 per 5 years, p-value < 0.001) and social deprivation (Q5 versus Q1: aOR 1.45; 95% CI 1.19–1.76, p-value < 0.001) were also independently associated with BSI.

• Systematic differences between patients who were/were not treated immediately with antibiotics (residual confounding) remains a potential explanation for our findings in relation to mortality.

What do these findings mean?

• This population-based study highlights uncertainty around whether delaying antibiotics in older adults with suspected UTI increases their risk of adverse outcomes.

• The reasons for the systematic differences identified between patients who were and were not treated immediately with antibiotics warrants further study.

• Adverse consequences of antibiotic treatment in this population and the public health need to tackle antibiotic resistance highlight the need for novel diagnostic and/or risk prediction strategies to guide antibiotic prescribing decisions for suspected UTI.

Contributors

Laura Shallcross:

ORCID: http://orcid.org/0000-0003-1713-2555

Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing

Patrick Rockenschaub:

ORCID: http://orcid.org/0000-0002-6499-7933

Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Ruth Blackburn:

ORCID: http://orcid.org/0000-0002-3491-7381

Role: ValidationRole: Writing – review & editing

Irwin Nazareth: Role: Writing – review & editing

Nick Freemantle:

ORCID: http://orcid.org/0000-0001-5807-5740

Role: MethodologyRole: Writing – review & editing

Andrew Hayward:

ORCID: http://orcid.org/0000-0002-3549-6232

Role: Funding acquisitionRole: Writing – review & editing

Michael Moore: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS Med

Journal ID (iso-abbrev): PLoS Med

Journal ID (publisher-id): plos

Journal ID (pmc): plosmed

Title: PLoS Medicine

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Print): 1549-1277

ISSN (Electronic): 1549-1676

Publication date (Electronic): 21 September 2020

Publication date Collection: September 2020

Volume: 17

Issue: 9

Affiliations

[1 ] Institute of Health Informatics, University College London, London, United Kingdom

[2 ] Department of Primary Care and Population Health, University College London, London, United Kingdom

[3 ] Institute of Clinical Trials and Methodology, University College London, London, United Kingdom

[4 ] Institute of Epidemiology & Healthcare, University College London, London, United Kingdom

University of Southampton, UNITED KINGDOM

Author notes

The authors have declared that no competing interests exist.

* E-mail: l.shallcross@ 123456ucl.ac.uk

Article

Publisher ID: PMEDICINE-D-20-00884

DOI: 10.1371/journal.pmed.1003336

PMC ID: 7505443

PubMed ID: 32956399

Copyright statement: © 2020 Shallcross et al

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Page count

Figures: 2, Tables: 3, Pages: 18

Product

Funding

Funded by: funder-id http://dx.doi.org/10.13039/501100000269, Economic and Social Research Council;

Award ID: ES/P008321/1

Funded by: funder-id http://dx.doi.org/10.13039/501100000659, Research Trainees Coordinating Centre;

Award ID: CS-2016-007

Award Recipient :

ORCID: http://orcid.org/0000-0003-1713-2555

Laura Shallcross

This work was supported by the Economic and Social Research Council (ES/P008321/1) and by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. LS was funded by a National Institute for Health Research (NIHR) Clinician Scientist award (CS-2016-007) for this research project. RB was supported by a UKRI Innovation Fellowship funded by the Medical Research Council (Grant No: MR/S003797/1), AH was funded by an NIHR Senior Investigator award for this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Categories

Subject: Research Article

Subject: Medicine and Health Sciences

Subject: Pharmacology

Subject: Drugs

Subject: Antimicrobials

Subject: Antibiotics

Subject: Biology and Life Sciences

Subject: Microbiology

Subject: Microbial Control

Subject: Antimicrobials

Subject: Antibiotics

Subject: Medicine and Health Sciences

Subject: Urology

Subject: Genitourinary Infections

Subject: Urinary Tract Infections

Subject: Medicine and Health Sciences

Subject: Epidemiology

Subject: Medical Risk Factors

Subject: Medicine and Health Sciences

Subject: Health Care

Subject: Primary Care

Subject: Medicine and Health Sciences

Subject: Clinical Medicine

Subject: Signs and Symptoms

Subject: Sepsis

Subject: Medicine and Health Sciences

Subject: Health Care

Subject: Health Care Facilities

Subject: Hospitals

Subject: Medicine and Health Sciences

Subject: Hematology

Subject: Bloodstream Infections

Subject: Biology and Life Sciences

Subject: Microbiology

Subject: Microbial Control

Subject: Antimicrobial Resistance

Subject: Antibiotic Resistance

Subject: Medicine and Health Sciences

Subject: Pharmacology

Subject: Antimicrobial Resistance

Subject: Antibiotic Resistance

Custom metadata

Data Availability Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS) data cannot be directly shared by the researchers but are available directly from CPRD and NHS Digital subject to standard conditions. All statistical code is available from https://github.com/prockenschaub/CPRD_UTI_sepsis_elderly.