Neurotoxicity with antimicrobials in the elderly: a review

Purpose: Mild adverse drug reactions typically associated with antimicrobials are familiar to most clinicians. However, rare phenomena, such as neurotoxicity, are often unpredictable and potentially unexpected. The toxic effects of antimicrobials on the central nervous system are often underreported and the mechanism(s) may be mixed or obscure. Geriatric patients are at increased risk for adverse drug reactions given physiologic alterations affecting pharmacokinetic processes. A dearth of information exists regarding neurotoxic presentations precipitated by antimicrobial use in the geriatric population. The purpose of this review is to present the available literature on neurotoxic effects of antimicrobials in geriatric patients, with an emphasis on manifestations of psychosis or delirium, or both.

Methods: A comprehensive literature search of the PubMed, Medline via Ovid, and Embase databases was conducted from 1966 to 2014. It included systematic reviews, randomized controlled trials, observational studies, case series, and case reports that involved neurologic effects, specifically delirium and psychosis associated with antimicrobial use.

Findings: Various antimicrobial classes are implicated with neurotoxicity. The classes with the most reported cases include fluoroquinolones, macrolides, sulfonamides, nitrofurans, and β-lactams. A higher risk of developing various symptoms of neurotoxicity was found in the elderly with use of piperacillin and tazobactam, cephalosporins, carbapenems, aminoglycosides, trimethoprim and sulfamethoxazole, nitrofurantoin, linezolid, and possibly the fluoroquinolones. Potential mechanisms of neurotoxicity differ between the agents. The etiology of neurotoxicity with some agents is not fully elucidated. Incidence may increase with reported risk factors, renal dysfunction, or drug interactions.

Implications: Awareness of antimicrobials causing or contributing to neurotoxic events may enhance clinical decisions in diagnosis and management when such incidents occur.