Antimicrobial Exposure and the Risk of Delirium in Critically Ill Patients

Jessica J. Grahl; Joanna L. Stollings; Shayan Rakhit; Anna K. Person; Li Wang; Jennifer L. Thompson; Pratik P. Pandharipande; E. Wesley Ely; Mayur B. Patel


Crit Care. 2018;22(337) 

In This Article


Critically ill patients are commonly initiated on antimicrobial therapy for infection with one or more agents on the basis of physiologic, microbiologic, and pharmacologic factors.[1] Antimicrobial exposure may represent a risk for antibiotic-associated encephalopathy[2–5] or the other synonymous and broadly used term for encephalopathy (that is, delirium).[2,3,6,7] Delirium in hospitalized patients is a strong independent predictor of mortality, increased hospital length of stay, long-term cognitive impairment, cost of care, and subsequent hospitalizations.[2,8,9]

The associations between antimicrobials and delirium have been limited by cross-sectional approaches and examination of only certain antibiotic classes, such as cephalosporins (for example, cefepime),[2,3,5,10–13] 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 (for example, simultaneous exposure or no exposure).[2] Importantly, there are many risk factors for delirium per intensive care unit (ICU) patient, including ongoing infection, severity of illness, older age, and baseline cognitive impairment.[16–19] Furthermore, no study of antimicrobials and acute brain dysfunction has used a reliable or validated tool for the outcome of delirium.

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.