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Beumier M. 1, Casu G. S. 1, Hites M. 2, Wolff F. 3, Cotton F. 3, Vincent J.-L. 1, Jacobs F. 2, Taccone F. S. 1
1 Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium;
2 Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium;
3 Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
BACKGROUND: Although β-lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between β-lactam concentrations and neurological alterations in septic ICU patients.
METHODS: Retrospective study on all ICU patients who were treated with meropenem (MEM), piperacillin-tazobactam (TZP) or ceftazidime/cefepime (CEF) and in whom at least one β-lactam trough concentration (Cmin) was determined. Drug levels were measured using high-performance liquid chromatography; Cmin was normalized to the clinical breakpoint of Pseudomonas aeruginosa (as determined by EUCAST) for each drug (Cmin/MIC). Changes in neurological status were evaluated using changes in the neurological sequential organ failure assessment score (ΔnSOFA) using the formula: ΔnSOFA = nSOFA(day of TDM) - nSOFA(ICU admission). Worsening neurological status (NWS) was defined as a ΔnSOFA ≥1 for an nSOFA on admission of 0-2.
RESULTS: We collected 262 Cmin in 199 patients (130 MEM, 85 TZP, 47 CEF). Median APACHE II score and GCS on admission were 17 and 15, respectively. Overall ICU mortality was 27 %. There were no differences in the occurrence of NWS between antibiotics (39% for MEM, 32% for TZP and 35% for CEF). The occurrence of NWS increased with increasing Cmin/MIC ranges (P=0.008); this correlation was found for TZP (P=0.05) and MEM (P=0.01), but not for CEF. Cmin/MIC was an independent predictive factor for NWS (OR 1.12 [1.04-1.20]).
CONCLUSION: We found a correlation between high β-lactam trough concentrations and increased occurrence of neurological deterioration in septic ICU patients. Although our data cannot determine causality, monitoring of β-lactam levels should be considered when deterioration of neurological status occurs during critical illness.