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

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.

SUBMITTER: Crellin E

PROVIDER: S-EPMC5806507 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Crellin Elizabeth E Mansfield Kathryn E KE Leyrat Clémence C Nitsch Dorothea D Douglas Ian J IJ Root Adrian A Williamson Elizabeth E Smeeth Liam L Tomlinson Laurie A LA

BMJ (Clinical research ed.) 20180209

<h4>Objective</h4>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.<h4>Design</h4>Cohort study.<h4>Setting</h4>UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database.<h4>Participants</h4>Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, ...[more]

PMID: 29438980

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Project description:BACKGROUND:Few studies have investigated the risk of adverse outcomes in older people with renal impairment presenting to primary care with a urinary tract infection (UTI). The aim of this study was to determine the risk of adverse outcomes in patients aged ?65 years presenting to primary care with a UTI, by estimated glomerular filtration rate (eGFR) and empirical prescription of nitrofurantoin versus trimethoprim. METHODS AND FINDINGS:This was a retrospective cohort study using linked health record data from 795,484 patients from 393 general practices in England, who were aged ?65 years between 2010 and 2016. Patients were entered into the cohort if they presented with a UTI and had a creatinine measurement in the 24 months prior to presentation. We calculated an eGFR to estimate risk of adverse outcomes by renal function, and propensity-score matched patients with eGFRs <60 mL/minute/1.73 m2 to estimate risk of adverse outcomes between those prescribed trimethoprim and nitrofurantoin. Outcomes were 14-day risk of reconsultation for urinary symptoms and same-day antibiotic prescription (proxy for treatment nonresponse), hospitalisation for UTI, sepsis, or acute kidney injury (AKI), and 28-day risk of death. Of 123,607 eligible patients with a UTI, we calculated an eGFR for 116,945 (95%). Median age was 76 (IQR, 70-83) years and 32,428 (28%) were male. Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR of <60 mL/minute/1.73 m2 had greater odds of hospitalisation for UTI (adjusted odds ratios [ORs] ranged from 1.14 [95% confidence interval (CI) 1.01-1.28, p = 0.028], for eGFRs of 45-59, to 1.68 [95% CI 1.01-2.82, p < 0.001] for eGFRs <15) and AKI (adjusted ORs ranged from 1.57 [95% CI 1.29-1.91, p < 0.001], for eGFRs of 45-59, to 4.53 [95% CI 2.52-8.17, p < 0.001] for eGFRs <15). Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR <45 had significantly greater odds of hospitalisation for sepsis, and those with an eGFR <30 had significantly greater odds of death. Compared to trimethoprim, nitrofurantoin prescribing was associated with lower odds of hospitalisation for AKI (ORs ranged from 0.62 [95% CI 0.40-0.94, p = 0.025], for eGFRs of 45-59, to 0.45 [95% CI 0.25-0.81, p = 0.008] for eGFRs <30). Nitrofurantoin was not associated with greater odds of any adverse outcome. Our study lacked data on urine microbiology and antibiotic-related adverse events. Despite our design, residual confounding may still have affected some of our findings. CONCLUSIONS:Older patients with renal impairment presenting to primary care with a UTI had an increased risk of UTI-related hospitalisation and death, suggesting a need for interventions that reduce the risk of these adverse outcomes. Nitrofurantoin prescribing was not associated with an increased risk of adverse outcomes in patients with an eGFR <60 mL/minute/1.73 m2 and could be used more widely in this population.

Project description:ObjectivesTo investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose.DesignCohort study of people aged 65 and over diagnosed as having depression.Setting570 general practices in the United Kingdom supplying data to the QResearch primary care database.Participants60,746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008.Main outcome measuresHazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs.Results54,038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1,398,359 antidepressant prescriptions were issued: 764,659 (54.7%) for selective serotonin reuptake inhibitors, 442,192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189,305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants.ConclusionsSelective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.

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

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

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