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

Chinzowu, Tichawona; Roy, Sandipan; Nishtala, Prasad S.

doi:10.1186/s12877-021-02512-3

Cited by 7 publications

(5 citation statements)

References 67 publications

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“…Among 1853 patients across eight studies, 15.8% developed acute kidney injury after treatment with aminoglycosides. The absolute risk was 15.1% (95% confidence interval [CI] 12.8–17.3%) and was significantly higher than the average risk among younger patients (10.5%, 95% CI 10.1–10.8%) [ 174 ].…”

Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

“…Neurotoxicities such as delirium and psychosis are rare, but although the association is still not clear, neurotoxic events may occur more easily in older patients [ 172 ]. A recent systematic review by Chinzowu et al highlighted an overall risk of acute kidney injury among older patients of 0.3% (95% CI 0.3–0.3%) [ 174 ].…”

Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

“…A recent meta-analysis by Hirai et al highlighted that among 634 patients across eight studies treated with teicoplanin, the overall incidence was 11.0% (95% CI 8.0–13.0), with a higher risk in patients aged > 65 years [ 178 ]. Chinzowu et al analyzed the risk of acute kidney injury among older adults in treatment with glycopeptides across eight studies (total of 23,431 participants), finding an overall absolute risk of 19.1% (95% CI 15.4–22.7%) [ 174 ]. The nephrotoxicity occurs as acute tubular necrosis but the mechanism of ADR is unknown [ 171 , 173 ].…”

Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

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Safety and Tolerability of Antimicrobial Agents in the Older Patient

et al. 2023

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Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug–drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

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Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

Section: Adverse Events From Antimicrobial Agents Among Older Patientsmentioning

confidence: 99%

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Safety and Tolerability of Antimicrobial Agents in the Older Patient

et al. 2023

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“…Elderly patients are at increased risk of nephrotoxicity, and probably of ototoxicity [ 124 ]. Based on eight studies, a meta-analysis from 2021 found the overall absolute risks of AKI following aminoglycoside exposure (with 68.6%–100% of patients receiving gentamicin) to be 15.1% among patients aged >65 years, significantly higher than the average 10.5% risk of AKI among patients >18 years ( p < 0.00001) [ 128 ]. In the aforementioned retrospective study including patients >75 years, nephrotoxicity was associated with treatment length ≥3 days and concomitant use of nephrotoxic drugs [ 127 ].…”

Section: Pharmacokinetics In Elderly Patientsmentioning

confidence: 99%

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

et al. 2022

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Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of shortterm empirical combination therapy. Gentamicin dosing schemes still need refinement, especially for subpopulations where pharmacokinetics can differ from pharmacokinetics in the general adult population: obese patients, critically ill patients, paediatric patients, neonates, elderly patients and patients on dialysis. This review summarizes the clinical pharmacokinetics of gentamicin in these patient populations and the consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria, highlighting new insights from the last 10 years. In this period, several new population pharmacokinetic studies have focused on these subpopulations, providing insights into the typical values of the most relevant pharmacokinetic parameters, the variability of these parameters and possible explanations for this variability, although unexplained variability often remains high. Both dosing schemes and pharmacokinetic/pharmacodynamic (PK/PD) targets varied widely between these studies. A gentamicin starting dose of 7 mg/kg based on total body weight (or on adjusted body weight in obese patients) appears to be the optimal strategy for increasing the probability of target attainment (PTA) after the first administration for the most commonly used PK/PD targets in adults and children older than 1 month, including critically ill patients. However, evidence that increasing the PTA results in higher efficacy is lacking; no studies were identified that show a correlation between estimated or predicted PK/PD target attainment and clinical success. Although it is unclear if performing therapeutic drug monitoring (TDM) for optimization of the PTA is of clinical value, it is recommended in patients with highly variable pharmacokinetics, including patients from all subpopulations that are critically ill (such as elderly, children and neonates) and patients on intermittent haemodialysis. In addition, TDM for optimization of the dosing interval, targeting a trough concentration of at least < 2 mg/L but preferably < 0.5-1 mg/L, has proven to reduce nephrotoxicity and is therefore recommended in all patients receiving more than one dose of gentamicin. The usefulness of the daily area under the plasma concentration-time curve for predicting nephrotoxicity should be further investigated. Additionally, more research is needed on the optimal PK/PD targets for efficacy in the clinical situations in which gentamicin is currently used, that is, as monotherapy for urinary tract infections or as part of short-term combination therapy.

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“…In one systematic review and meta‐analysis, it was found that older adults (65 years and above) had a 15.1% (95% CI = 12.8%–17.3%) risk of developing AKI when exposed to aminoglycosides and 19.1% (95% CI = 15.4%–22.7%) when exposed to glycopeptides. 6 In a recent study, Dylis et al 7 described the association between high Charlson's comorbidity index score with antibacterial prescriptions not adhering to guidelines, resulting in untoward ADEs among the older adults with multiple comorbidities. Due to the large body of evidence associating older age with increased risk of ADEs, the attention to accurate identification of antibacterial associated ADEs among older adults is becoming vital for the quality use of medicines.…”

Section: Introductionmentioning

confidence: 99%

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

Chinzowu¹,

Chyou

Nishtala

2022

Pharmacoepidemiology and Drug

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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.

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

Cited by 7 publications

References 67 publications

Safety and Tolerability of Antimicrobial Agents in the Older Patient

Safety and Tolerability of Antimicrobial Agents in the Older Patient

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review

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

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