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Linezolid use in post-neurosurgical central nervous system infections : a systematic review
Position du problème et objectif(s) de l’étude
Post-neurosurgical central nervous system (CNS) infections lead to prolonged hospital stays and poor functional and neurological outcomes. These infections are frequently associated with intraventricular catheters, and mainly caused by Gram-positive bacteria. Although vancomycin is the first-line treatment recommended by the Infectious Diseases Society of America (IDSA) guidelines1, its use is limited by nephrotoxicity and the worldwide emergence of glycopeptide-resistant strains. Pharmacokinetics of neurocritical care patients may complicates the use of vancomycin, with impaired cerebrospinal fluid (CSF) penetration. Linezolid, with better pharmacokinetic profile and potent activity against most Gram positive strains involved in CNS infections, may therefore be an alternative therapeutic option. The aim of this systematic review is to describe the use of linezolid and to evaluate and critically analyze the current evidence regarding its efficacy and safety in the treatment of post-neurosurgical CNS bacterial infections.
Matériel et méthodes
This systematic review was registered in PROSPERO (reference CRD42024496278) and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 611 records from five databases (PubMed, Web of Science, CINAHL Complete, Dimensions, and the Cochrane Library) until December, 11th 2023. After screening, 36 studies were included. We collected epidemiological, microbiological and pharmacological data. Outcomes related to all-cause mortality, safety issues, microbiological eradication and infection recurrence rates were also collected. A risk of bias and quality assessment procedure (MINORS scale)2 was conducted for each included study.
Résultats & Discussion
Out of the 36 studies reviewed, 27 were case reports. According to the mean MINORS scores, the clinical evidence supporting linezolid use is limited by the poor (7/9 non case-report analyzed studies) or moderate (2/9) methodological quality among included studies. Linezolid was mainly prescribed as a second-line treatment in case of treatment failure (46.3%), or culture of glycopeptide-resistant strains (20.6%). Methicillin-resistant Staphylococci (67%) and Vancomycin-Resistant Enterococci (VRE) (8.2%) were frequently isolated in CSF samples. It was administered in 600mg q12h standard doses, often via oral route (41.4%). Combination therapy was used in almost half of all cases (45.5%). Linezolid use led to high but variable microbiological eradication rates (65%), even in ICU patients. Death were reported in 10.6% of total cases. Furthermore, drug-related adverse effects were not uncommon, affecting 10% to 27.3% of treated patients. Hematological toxicity (14.1%) with anemia and thrombopenia was the most prevalent linezolid side effects.
Conclusion
Linezolid appears to be a promising alternative to glycopeptides in the treatment of CNS infections, with favorable patient outcomes reported even in salvage therapy settings. However, available literature is limited to case reports and retrospective studies with significant methodological limitations. More rigorous research, including prospective studies, is needed to confirm the potential role of Linezolid in managing these challenging infections.
Auteurs
Charles BAULIER (1), Noémie LE DENTU (1) , Mathieu LOZOUET (2), Yves KAM (1), Gaetan KERDELHUÉ (3), Marion GIRY (4), Kevin ALEXANDRE (5), Thomas CLAVIER (6) - (1)Rouen University Hospital, Department Of Anesthesiology, Intensive Care And Perioperative Medicine, Rouen, France, (2)Rouen University Hospital, Department Of Neurosurgery, Rouen, France, (3)Univ Rouen Normandie, Aims, Chu Rouen, Département De Santé Numérique, Rouen, France, (4)Univ Rouen Normandie, Université De Caen Normandie, Inserm, Normandie Univ, Dynamicure Umr 1311, Chu Rouen, Medical Intensive Care Unit,, Rouen, France, (5)Univ Rouen Normandie, Université De Caen Normandie, Inserm, Normandie Univ, Dynamicure Umr 1311, Chu Rouen, Department Of Infectious Diseases, Rouen, France, (6)Umr 1096 Inserm– Envi, Ufr Santé, University Of Rouen, Chu Rouen, Department Of Anesthesiology And Critical Care, Rouen, Rouen, France