Linezolid use in postoperative central nervous system infections: a pharmacokinetic simulation-based approach for critically ill patients - 04/03/26
, Marion Giry b, Paul Lozé c, Mathieu Lozouet d, Jean Glenisson c, Zoubir Djerada e, Kévin Alexandre f, Thomas Clavier g, Thomas Duflot hHighlights |
• | Linezolid emerges as a promising treatment for postoperative CNS infections. |
• | Despite more favorable PK than vancomycin, dosing uncertainties remain in ICU. |
• | This study used PK/PD modeling and Monte Carlo simulations to optimize dosing. |
• | Standard regimen fails to achieve optimal exposure in ICU patients. |
• | Our results support intensified (600 mg q8h) or continuous dosing strategies. |
Abstract |
Background |
Postoperative central nervous system (CNS) infections pose a significant challenge in neurosurgery. While linezolid may offer advantages over vancomycin, its optimal dosing for critically ill patients remains unclear. This study aims to optimize linezolid treatment in ICU patients with postoperative CNS infections using pharmacokinetic/pharmacodynamic modeling and simulation.
Methods |
ICU population PK models were analyzed using Monte Carlo simulations (n = 1,000) to evaluate six LZD regimens: 600 mg q12 h, 600 mg q8h, 600 mg q6h, and equivalent total daily doses by continuous infusion. Probability of target attainment (PTA) was calculated for time above MIC (%T>MIC) ≥85% and AUC/MIC > 100 in plasma and cerebrospinal fluid. MIC distributions of common pathogens were incorporated to estimate the cumulative fraction of response (CFR) for each regimen.
Results |
Standard 600 mg q12 h dosing failed to achieve >90% PTA at MIC = 1 mg/L in all models. Intensified regimens (600 mg q8h, q6h, or continuous infusion) improved target attainment. A 2400 mg/day continuous infusion was required to consistently cover pathogens with MIC = 2 mg/L, albeit with a non-negligible toxicity risk. As approximately 90% of clinical isolates show linezolid MICs of 1–2 mg/L, CFR analysis suggested that ∼50% of ICU patients may be underdosed with the standard regimen.
Conclusions |
Standard linezolid dosing appears inadequate for postoperative CNS infections in ICU patients. Optimized regimens are necessary to reliably target pathogens with MIC ≥ 1 mg/L. Due to linezolid’s narrow therapeutic window and toxicity risk at higher doses, individualized dosing and therapeutic drug monitoring may be recommended in neurocritical care settings.
Le texte complet de cet article est disponible en PDF.Keywords : Central nervous system infections, Critical care, Linezolid, Neurosurgery, Pharmacokinetics
Abbreviations : %T>MIC, AUC, BBB, CFR, CI, CL, C min , CNS, CSF, EUCAST, EVD, HPLC, IQR, IIV, LC-MS/MS, LZD, MIC, PBPK, PC, PCT, PD, PK, PKpop, PTA, Q, Q CSF , Q CSF,in , Q CSF,out , V 1 , V 2 , V CSF , VRE
Plan
Vol 45 - N° 3
Article 101768- mai 2026 Retour au numéro
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