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

Abstract

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.

Risk of antimicrobial-associated organ injury among the older adults: a systematic review and meta-analysis

“…Of the remaining 7562 studies, 7237 studies were excluded following title and abstract screening. A further 296 studies were excluded after the full-text screening, leaving 29 studies for inclusion into the the systematic review [ 11 – 39 ]. The full selection process is summarised in Fig.…”

“…Out of the 29 studies included for qualitative analysis, eight were prospective cohort studies [ 12 , 22 , 29 – 31 , 33 , 34 , 36 ] and the rest were all retrospective cohort studies. Most of the studies were hospital-based except four that were based on primary care data [ 11 , 13 , 16 , 37 ] and three that were based on population data [ 18 , 24 , 36 ]. Six of the studies were carried out in the United Kingdom [ 11 , 13 , 15 , 16 , 37 , 38 ], five from the United States of America [ 12 , 14 , 19 , 20 , 36 ], four from China [ 21 , 23 , 28 , 39 ], three from Japan [ 22 , 25 , 32 ], two each from Australia [ 29 , 35 ], Canada [ 18 , 24 ] and India [ 31 , 34 ], and one each from France [ 17 ], Iran [ 33 ], Israel [ 30 ], Singapore [ 27 ], and South Korea [ 26 ].…”

“…Most of the studies were hospital-based except four that were based on primary care data [ 11 , 13 , 16 , 37 ] and three that were based on population data [ 18 , 24 , 36 ]. Six of the studies were carried out in the United Kingdom [ 11 , 13 , 15 , 16 , 37 , 38 ], five from the United States of America [ 12 , 14 , 19 , 20 , 36 ], four from China [ 21 , 23 , 28 , 39 ], three from Japan [ 22 , 25 , 32 ], two each from Australia [ 29 , 35 ], Canada [ 18 , 24 ] and India [ 31 , 34 ], and one each from France [ 17 ], Iran [ 33 ], Israel [ 30 ], Singapore [ 27 ], and South Korea [ 26 ]. Out of the twenty-nine studies included for qualitative analysis, one reported on tendon rupture [ 36 ], three reported on drug-induced liver injury (DILI) [ 13 , 26 , 33 ], and the rest reported on acute kidney injury (AKI).…”

Antimicrobial-associated Organ Injury among the Older Adults: A Systematic Review and Meta-Analysis

“…Regardless of the heterogeneity, the random-effects model, using the DerSimonian and Laird method (10), was used to meta-analyse the studies. The meta-analyses were performed using the OpenMetaAnalyst software (11).…”

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

“…Co-trimoxazole is associated with some severe adverse effects, including neurologic changes, decreased oxygen-carrying capacity and other hematologic effects, toxic epidermal necrolysis and other drug hypersensitivity reactions, reproductive abnormalities and hypoglycemia [191]. Hyperkalemia and acute kidney injury are seen more commonly in the elderly and in pre-existing renal impairment (creatinine clearance <60 mL/min) [192,193].…”