933

Introduction: Although β-lactams have a relatively safe therapeutic index, several cases of neurotoxicity have been reported. We assessed the correlation between β-lactams concentrations and the incidence of electroencephalographic (EEG) abnormalities in septic patients. Methods: We reviewed the data of all septic patients treated in our ICU from January 2012 and July 2013 with meropenem (MEM), piperacillin-tazobactam (PTAZ), aztreonam (AZT) or ceftazidim/cefepime (CEF) and in whom at least one therapeutic drug monitoring (TDM) and one EEG were performed the same day. Trough drug concentrations (Cmin) were measured using high-performance liquid chromatography. Cmin was normalized to the clinical breakpoint of Pseudomonas aeruginosa for each antibiotic (Cmin/MIC) following the EUCAST recommendations. EEG abnormalities included seizure activity, periodic EEG discharges (PEDs) or frontal intermittent rhythmic delta activity (FIRDA). Results: We obtained 181 TDMs (65 MEM, 84 PTAZ, 26 CEF, 6 AZT) in 136 patients. We found 24 (13%) seizure activities, 14 (7%) PEDs and 5 (3%) FIRDA. The proportion of patients with EEG abnormality was significantly correlated with increased Cmin/MIC ratio (p=0.002). This finding remained after exclusion of patients admitted for primary brain injury (p=0.03). EEG abnormalities were correlated with high Cmin/MIC for PTAZ (p=0.01) but not for MEM (p=0.49); CEF and AZT were not evaluated because of the limited number of patients. Conclusions: This is the first study reporting a relationship between high β-lactams concentrations and an increased incidence of EEG alterations in septic patients.