Abstract
BackgroundPrior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for.MethodsOur study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation.ResultsOf 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2–6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28–3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10–4.10, P = 0.024).ConclusionsFirst-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.
Highlights
Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures
The associations between antimicrobials and delirium have been limited by cross-sectional approaches and examination of only certain antibiotic classes, such as cephalosporins [2, 3, 5, 10,11,12,13], fluoroquinolones [14, 15], and macrolides [2, 4], without accounting for confounders related to baseline comorbidities, sepsis, severity of illness, exposure to analgesics, sedatives, and other antimicrobial possibilities [2]
We found that first, second, and third-generation cephalosporins doubled the odds of delirium after adjusting for baseline co-morbidities, the course of critical care, and other competing antimicrobials and psychotropic medications risks
Summary
Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for. The purpose of this study is to determine whether there is an independent association between antimicrobial class exposure in critically ill patients and the daily risk of delirium, measured by using a valid and reliable tool repeatedly over time. Accounting for daily ICU risks, we hypothesized that different classes of antimicrobials would have differential associations with the daily risk of delirium
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