Natalie Haddad
The Univeristy of Chicago Medicine
Chicago, Illinois
Disclosure information not submitted.
Diana Schreier, PharmD, MBA
Pharmacist
Mayo Clinic, United States
Disclosure information not submitted.
Jennifer Ginestra, MD
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Disclosure information not submitted.
Ognjen Gajic, MD
Professor
Mayo Clinic
Rochester, Minnesota, United States
Disclosure information not submitted.
.jpg "Sara Hocker, MD photo")
Sara Hocker, MD
Division Chair, Hospital and Neurocritical Care
Mayo Clinic
Rochester, Minnesota
Disclosure information not submitted.
Calvin Ice, PharmD, BCPS, BCCCP
Pharmacist
Spectrum Health Butterworth Hospital, United States
Disclosure information not submitted.
Alejandro Rabinstein, MD
Neurointensivist
Mayo Clinic, United States
Disclosure information not submitted.
Erin Barreto, MSc, PharmD, FCCM
Associate Professor of Pharmacy and Medicine
Mayo Clinic
Rochester, Minnesota
Disclosure information not submitted.
Title: Incidence and Predictive Factors Associated with Beta-Lactam Neurotoxicity in the Critically Ill
Introduction: Beta-lactam neurotoxicity is an uncommon and difficult to diagnose adverse effect that can lead to serious harm in critically ill patients. Beta-lactam neurotoxicity can include changes in mental status, confusion, myoclonus, and seizures. Early recognition of high-risk patients is essential to limit the development and progression of neurotoxicity. Our objectives were to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults.
Methods: This single-center retrospective cohort study included critically ill patients treated with ≥ 48 hours of cefepime, piperacillin/tazobactam, or meropenem. Two cohorts were created, a derivation cohort with data from 2008-2013, and a validation cohort with data from 2018-2020. Patients with alternative explanations for altered mental status, those on deep sedation or concomitant paralytics, or those receiving alternative beta-lactams prior to the study drug were excluded.
Results: The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable model included weight, Charlson Score, age, and estimated creatinine clearance (eCrCl) as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a BMI > 30 kg/m2. The risk prediction model was found to have good discrimination (C-statistic of 0.71) and calibration in the derivation cohort. Discrimination was fair in the validation cohort (C-statistic 0.62). Use of the candidate variables in a neurotoxicity risk score suggested that a score > 35 would identify a patient at high risk for neurotoxicity with 75% sensitivity and 54% specificity.
Conclusions: In this single center cohort of critically ill patients, beta-lactam neurotoxicity was less frequent than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice to avoid drug-related harm.