Neurological burden and outcomes of excessive β-lactam serum concentrations of critically ill septic patients: a prospective cohort study

Abstract Background Therapeutic drug monitoring (TDM) contributes to optimizing exposure to β-lactam antibiotics. However, how excessive exposure to β-lactams can increase the burden of care of critically ill patients is unclear. Patients and methods In a prospective cohort study, we examined whether excessive β-lactam serum concentrations contribute to neurological deterioration and the associated complications of adult septic patients without recent history of neurological disease treated with β-lactams in a medical ICU. Excessive β-lactam concentrations were defined as serum concentrations that exceeded the upper limit of the therapeutic range recommended by the French Societies of Pharmacology and Therapeutics (SFPT) and Anesthesia and Intensive Care Medicine (SFAR). Neurological deterioration was defined as an increase in the neurological Sequential Organ Failure Assessment score (nSOFA) of ≥1 between the day of starting treatment at admission and the day of TDM performed 2 days after treatment initiation. Results We included 119 patients [median age: 65 years; males: 78 (65.5%)] admitted for acute respiratory distress [59 (49.6%)] or septic shock [25 (21%)]. In adjusted logistic regression analysis, an excessive β-lactam serum concentration was associated with neurological deterioration [OR (95% CI): 10.38 (3.23–33.35), P < 0.0001]. Furthermore, in adjusted linear regression analysis, an excessive β-lactam serum concentration was associated with longer time to discharge alive (β=0.346, P = 0.0007) and, among mechanically ventilated patients discharged alive, with longer time to extubation following the withdrawal of sedation (β=0.248, P = 0.0030). Conclusions These results suggest that excessive exposure to β-lactams could complicate the management of septic patients in the ICU and confirm the clinical relevance of the upper concentration limits recommended for dose reduction.