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Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study

BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k341 (Published 09 February 2018) Cite this as: BMJ 2018;360:k341
  1. Elizabeth Crellin, research assistant1,
  2. Kathryn E Mansfield, research fellow1,
  3. Clémence Leyrat, research fellow2,
  4. Dorothea Nitsch, professor1,
  5. Ian J Douglas, associate professor1,
  6. Adrian Root, research fellow1,
  7. Elizabeth Williamson, associate professor2,
  8. Liam Smeeth, professor1,
  9. Laurie A Tomlinson, associate professor1
  1. 1Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
  2. 2Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to: K Mansfield kathryn.mansfield{at}lshtm.ac.uk
  • Accepted 16 January 2018

Abstract

Objective To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population.

Design Cohort study.

Setting UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database.

Participants Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015.

Main outcome measures The outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics.

Results Among a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury.

Conclusion Trimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.

Footnotes

  • Contributors: LAT had the original idea for the study. All authors were involved in the study design. EC and KEM contributed equally to this paper. EC undertook the data management and primary analysis, and wrote early drafts of the manuscript. KM supervised each stage of data management and preliminary analyses, and wrote the first complete manuscript draft. CL undertook the inverse probability of treatment weighting analysis. All authors contributed to further drafts and approved the final manuscript. All authors had full access to the data in the study. EC and KEM are the guarantors.

  • Funding: LAT and KEM were funded by a Wellcome Trust intermediate clinical fellowship (101143/Z/13/Z). LS and EC were supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (098504/Z/12/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the London School of Hygiene and Tropical Medicine Research Ethics Committee (reference 12014) and by the Clinical Practice Research Datalink independent scientific advisory committee (ISAC protocol number: 16_087R).

  • Data sharing: No additional data are available.

  • Transparency: The manuscripts guarantors (EC and KEM) affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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