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

Crellin, Elizabeth; Mansfield, Kathryn E.; Leyrat, Clémence; Nitsch, Dorothea; Douglas, Ian; Root, Adrian; Williamson, Elizabeth; Smeeth, Liam; Tomlinson, Laurie

doi:10.1136/bmj.k341

Cited by 55 publications

(58 citation statements)

References 26 publications

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“…It may also be due to the possibility that nitrofurantoin efficacy was reduced in those with lower eGFRs but was offset by the high rates of trimethoprim resistance and thus resulted in apparent similar rates of reconsultation and re-prescription. Our finding that nitrofurantoin was associated with a reduced risk of death in those with moderate renal impairment is consistent with previously reported estimates in studies that compared nitrofurantoin with amoxicillin in the general population [ 18 , 19 ]. We also found a previously unreported lower risk of AKI associated with nitrofurantoin use across all three eGFR groups of our cohort.…”

Section: Discussionsupporting

confidence: 92%

“…Trimethoprim (with or without sulfamethoxazole) prescribing is associated with an increased risk of hyperkalaemia, AKI, and death, compared to amoxicillin [ 16 – 19 ]. Amoxicillin accounts for only about 5% of prescribing for UTI in the UK [ 9 ] and thus is a less helpful comparator for clinical decision-making.…”

Section: Discussionmentioning

confidence: 99%

“…However, outcomes following empirical nitrofurantoin prescribing in older adults with a UTI and an eGFR <60 mL/minute/1.73 m 2 are yet to be fully evaluated. There are also concerns about trimethoprim use in older adults with renal impairment, with increasing evidence of an association with hyperkalaemia and sudden death, especially when prescribed to patients already taking angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, or potassium-sparing diuretics [ 15 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Risk of adverse outcomes following urinary tract infection in older people with renal impairment: Retrospective cohort study using linked health record data

et al. 2018

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BackgroundFew 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 findingsThis 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.ConclusionsOlder 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Risk of adverse outcomes following urinary tract infection in older people with renal impairment: Retrospective cohort study using linked health record data

et al. 2018

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“…In particular the development of AKI following the use of sulphonamides, nitrofurantoin and trimethoprim has been well described (9)(10)(11). A recent large British cohort study showed an increase of 72% and 48% in the odds of AKI following treatment with trimethoprim and ciprofloxacin respectively for UTI in older patients in the community (12). A large Canadian case control study also reported a two-fold increase of hospital acquired AKI during fluoroquinolone administration (17).…”

Section: Introductionmentioning

confidence: 99%

Risk of acute kidney injury following community prescription of antibiotics: self-controlled case series

Rennie

Souza

Donnan

et al. 2018

Nephrology Dialysis Transplantation

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“…Antimicrobials, ranked in order of increasing MOR, included trimethoprim, co‐trimoxazole, norfloxacin, erythromycin, ciprofloxacin, roxithromycin, nitrofurantoin, and flucloxacillin. The finding that trimethoprim (MOR = 1.68; 95%CI = [1.54‐1.80]) poses the highest risk of AKI among the antimicrobial class is supported by evidence from another population‐level cohort study conducted in older adults using the UK primary care database, Clinical Practice Research Datalink . This UK study found that trimethoprim (adjusted OR 1.72, 95% CI [1.31‐2.24]) and ciprofloxacin (adjusted OR 1.48, 95% CI [1.03‐2.13]) increased the odds of AKI compared with amoxicillin.…”

Section: Discussionmentioning

confidence: 99%

Identifying drug combinations associated with acute kidney injury using association rules method

Nishtala

Chyou

2020

Pharmacoepidemiology and Drug

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Background: Older adults are at an increased risk of acute kidney injury (AKI) because of aging, multiple comorbidities, and polypharmacy.Objectives: The aim of this case-crossover study was to apply association rule (AR) analysis to ascertain drug combinations contributing to the risk of AKI in adults aged 65 years and older. Methods:We sourced a nationwide representative sample of New Zealanders aged ≥65 years from the pharmaceutical collections and hospital discharge information.Prescription records (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) of drugs of interest were sourced from New Zealand pharmaceutical collections (Pharms). We classified medication exposure, as a binary variable, at individual drug level belonging to medication classes including antimicrobials, antihistamines, diuretics, opioids, nonsteroidal antiinflammatory medications. Several studies have associated the drugs of interest from these medication classes with AKI in older adults. We extracted the first-time coded diagnosis of AKI from the National Minimal Data Set. A unique patient identifier linked the prescription data set to the event data set, to set up a case-crossover cohort, indexed at the first AKI event. ARs were then applied to identify frequent drug combinations in the case and the control periods (l-day observation with a 35-day washout period), and the association of AKI with each frequent drug combination was tested by computing a matched odds ratio (MOR) and its 95% confidence interval (CI). Results:We identified 55 747 individuals (mean age 82.14) from 2005 to 2014 with incident AKI and exposed to at least one of the drugs of interest. ARs identified several medication classes including antimicrobials, nonsteroidal anti-inflammatory drugs, and opioids are associated with AKI. The frequently used medicines associated with AKI are trimethoprim (MOR = 1.68; 95% CI = [1.54-1.80]), ondansetron (MOR = 1.43; 95% CI = [1.25-1.64]), codeine phosphate plus metoclopramide (MOR = 1.37; 95% CI = [1.11-1.63]), and norfloxacin (MOR = 1.24; 95% CI [1.05-1.42]). Conclusions:We applied ARs, a novel methodology, to big data to ascertain drug combinations associated with AKI. ARs uncovered previously implicated medication classes that increase the risk of AKI in older adults. The finding that ondansetron increases the risk of AKI requires further investigation. acute kidney injury, association rules, case-crossover design, older people, pharmacoepidemiology, pharmacovigilance

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

Cited by 55 publications

References 26 publications

Risk of adverse outcomes following urinary tract infection in older people with renal impairment: Retrospective cohort study using linked health record data

Risk of adverse outcomes following urinary tract infection in older people with renal impairment: Retrospective cohort study using linked health record data

Risk of acute kidney injury following community prescription of antibiotics: self-controlled case series

Identifying drug combinations associated with acute kidney injury using association rules method

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