Antibiotic-Associated Acute Kidney Injury Among Older Adults: A Case-Crossover Study.

BACKGROUND AND OBJECTIVES: Drug-related acute kidney injury is quite common in older adults. The associated drugs, including antibiotics, are often co-prescribed. The objective of this study was to ascertain antibiotic-associated acute kidney injury (AKI) in older adults aged 65 years or above in New Zealand using a case-crossover study design. METHODS: The International Statistical Classification of Diseases and Related Health Problems, tenth revision, Australian modification code N17.x was used to identify all individuals aged 65 years and above with a diagnosis of incident AKI on admission between 1 January 2005 and 31 December 2020, from the New Zealand National Minimum Data Set. A case-crossover cohort for antibiotic exposures, with a 3 day case period and two 30 day washout periods, summed up to a 66 day study period, was created. Using conditional logistic regression, the changed odds of AKI due to exposure to an antibiotic was calculated as matched odds ratios and their 95% confidence intervals. RESULTS: A total of 2399 incident cases of AKI were identified between 2005 and 2020 among older adults. The adjusted odds of consuming sulfamethoxazole/trimethoprim antibiotic during the case period was 3.57 times (95% CI 2.86-4.46) higher than the reference period among the incident AKI cases. Fluoroquinolone utilization was also associated with incident AKI (adjusted OR = 2.56; 95% CI 1.90-3.46). CONCLUSION: The potential of sulfamethoxazole/trimethoprim and fluoroquinolones to be associated with AKI raises the significant need for vigilant prescribing of these antibiotics in older adults.

Antibacterial-associated acute kidney injury among older adults: A post-marketing surveillance study using the FDA adverse events reporting system.

PURPOSE: Antibacterials induce a differential risk of acute kidney injury (AKI) in older adults. This study investigated the reporting risk of AKI associated with antibacterials using the individual case safety reports (ICSRs) submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A case/non-case method was used to assess AKI risk associated with antibacterials between 1 January 2000 and 30 September 2021. Cases were ICSRs for antibacterials with AKI as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' disorders. The analyses were completed on a de-duplicated data set containing only the recent version of the ICSR. Signals were defined by a lower 95% confidence interval (CI) of reporting odds ratio (ROR) ≥ 2, proportional reporting ratio (PRR) ≥ 2, information component (IC) > 0, Empirical Bayes Geometric Mean (EBGM) > 1 and reports ≥4. Sensitivity analyses were conducted a priori to assess the robustness of signals. RESULTS: A total of 3 680 621 reports on ADEs were retrieved from FAERS over the study period, of which 92 194 were antibacterial reports. Gentamicin, sulfamethoxazole, trimethoprim and vancomycin consistently gave strong signals of disproportionality on all four disproportionality measures and across the different sensitivity analyses: gentamicin (ROR = 2.95[2.51-3.46]), sulfamethoxazole (ROR = 2.97[2.68-3.29]), trimethoprim (ROR = 2.81[2.29-3.46]) and vancomycin (ROR = 3.35[3.08-3.64]). CONCLUSION: Signals for gentamicin, sulfamethoxazole, trimethoprim and vancomycin were confirmed by using antibacterials as a comparator, adjusting for drug-related competition bias and event-related competition bias.

Antimicrobial-associated organ injury among the elderly: a systematic review and meta-analysis protocol.

INTRODUCTION: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects this cohort of older adults and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for risk of organ injury following antimicrobial exposure among older adults. This protocol will outline how we will conduct a systematic review and meta-analyses to examine the relationship between antimicrobial exposure and organ injury in older adults. METHODS AND ANALYSIS: We will search for PsycINFO, PubMed and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles will be screened for inclusion into or exclusion from the study by two reviewers. Title and abstract screening will be done first, followed by full-text screening. The Newcastle-Ottawa scale will be used to assess the risk of bias for cohort and case control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies. ETHICS AND DISSEMINATION: During the conduct of the review, ethical principles will be observed to ensure integrity. Any potential conflicts of interests will be declared, all contributors acknowledged and no plagiarised material will be included in the review.The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal in geriatrics. The findings will also be presented at international conferences in geriatrics or pharmacoepidemiology. The results will be communicated to patient and public engagement networks supported by the NHS Research and Development. PROSPERO REGISTRATION NUMBER: This protocol is registered in the PROSPERO database (registration number CRD42020152621).

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

BACKGROUND: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for organ injury risk among older adults following antimicrobial exposure. This systematic review and meta-analysis examined the relationship between antimicrobial exposure and organ injury in older adults. METHODOLOGY: We searched for original research articles in PubMed, Embase.com , Web of Science core collection, Web of Science BIOSIS citation index, Scopus, Cochrane Central Register of Controlled Trials, ProQuest, and PsycINFO databases, using key words in titles and abstracts, and using MeSH terms. We searched for all available articles up to 31 May 2021. After removing duplicates, articles were screened for inclusion into or exclusion from the study by two reviewers. The Newcastle-Ottawa scale was used to assess the risk of bias for cohort and case-control studies. We explored the heterogeneity of the included studies using the Q test and I2 test and the publication bias using the funnel plot and Egger's test. The meta-analyses were performed using the OpenMetaAnalyst software. RESULTS: The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1% (95% CI: 12.8-17.3), 19.1% (95% CI: 15.4-22.7), and 0.3% (95% CI: 0.3-0.3), respectively. Only 3 studies reported antimicrobial associated drug-induced liver injury. Studies reporting on the association of organ injury and antimicrobial exposure by age or duration of treatment were too few to meta-analyse. The funnel plot and Egger's tests did not indicate evidence of publication bias. CONCLUSION: Older adults have a significantly higher risk of sustaining acute kidney injury when compared to the general adult population. Older adults prescribed aminoglycosides have a similar risk of acute kidney injury to the general adult population.