Trimethoprim and sudden death in patients over 65 years with urinary tract infection

Date of Approval
Application Number
16_087
Technical Summary

We aim to investigate the association between trimethoprim and sudden death. We will identify a cohort of all patients over 65 during the period April 1997 to September 2015.
To test whether trimethoprim is associated with sudden death, we will use logistic regression, adjusting for potential confounders, to estimate the odds ratio of sudden death following antibiotic prescription for trimethoprim compared to amoxicillin, nitrofurantoin, ciprofloxacin, or cefalexin. To limit confounding by antibiotic indication we will restrict the analysis to patients with antibiotic prescription for urinary tract infection. We will also examine whether diabetes mellitus, and ACEI/ARB or potassium-sparing diuretic therapy, modify the effect of trimethoprim on sudden death.
We will investigate acute kidney injury and hyperkalaemia (proposed as causal mechanisms for sudden death in this context) as secondary outcomes. We will examine the robustness of our results through sensitivity analyses. In a further analysis we will use propensity scores to ensure exposure groups are comparable.

Health Outcomes to be Measured

Death within 14 days of antibiotic exposure Hospitalisation for acute kidney injury (AKI) Hyperkalaemia

Collaborators

Laurie Tomlinson - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Elizabeth Crellin - Corresponding Applicant - The Health Foundation
Adrian Root - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Clémence Leyrat - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Elizabeth Williamson - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kathryn Mansfield - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Pascal Frey - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Pascal Frey - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Timo Smieszek - Collaborator - NOAA - National Oceanic and Atmospheric Administration
Timo Smieszek - Collaborator - NOAA - National Oceanic and Atmospheric Administration

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation