Comparative efficacy of linezolid and vancomycin for endotracheal tube MRSA biofilms from ICU patients

Purpose: To compare the efficacy of systemic treatment with linezolid (LNZ) versus vancomycin (VAN) on methicillin-resistant Staphylococcus aureus (MRSA) burden and eradication in endotracheal tube (ETT) biofilm and ETT cuff from orotracheally intubated patients with MRSA respiratory infection. Methods: Prospective observational clinical study was carried out at four European tertiary hospitals. Plasma and endotracheal aspirate (ETA) levels of LNZ and VAN were determined 72 h after treatment initiation through high-performance liquid chromatography or bioassay. LNZ or VAN concentration in the ETT biofilm and MRSA burden and eradication was determined upon extubation. The minimum inhibitory concentration (MIC) for LNZ and VAN was assessed by E-test strips (Biomerieux®). Scanning electron microscopy images were obtained, and ETT biofilm thickness was compared between groups. Results: Twenty-five patients, 15 treated with LNZ and 10 with VAN, were included in the study. LNZ presented a significantly higher concentration (μg/mL) than VAN in ETT biofilm (72.8 [1.3-127.1] vs 0.4 [0.4-1.3], p < 0.001), although both drugs achieved therapeutic plasma levels 72 h after treatment initiation. Systemic treatment with LNZ achieved lower ETT cuff MRSA burdens than systemic treatment with VAN. Indeed, LNZ increased the MRSA eradication rate in ETT cuff compared with VAN (LNZ 75%, VAN 20%, p = 0.031). Conclusions: In ICU patients with MRSA respiratory infection intubated for long periods, systemic treatment with LNZ obtains a greater beneficial effect than VAN in limiting MRSA burden in ETT cuff.