The ZEPHyR study: A randomized comparison of linezolid and vancomycin for MRSA pneumonia

• Published in: Médecine et maladies infectieuses 2013-12, Vol.43 (11-12), p.451-455
• Main Author: Chavanet, P.
• Format: Article
• Language: English
• Subjects: Acetamides - adverse effects; Acetamides - therapeutic use; Adult; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cross Infection - drug therapy; Cross Infection - microbiology; Double-Blind Method; General aspects; Human infectious diseases. Experimental studies and models; Humans; Infectious diseases; Kidney Diseases - chemically induced; Linezolid; Linézolide; Medical sciences; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - isolation & purification; MRSA; Nosocomial pneumonia; Oxazolidinones - adverse effects; Oxazolidinones - therapeutic use; Pharmacology. Drug treatments; Pneumology; Pneumonia, Staphylococcal - drug therapy; Pneumonia, Staphylococcal - microbiology; Pneumonie nosocomiale; Prospective Studies; Randomized study; Respiratory system : syndromes and miscellaneous diseases; SARM; Staphylococcus aureus; Survival Analysis; Treatment Outcome; Vancomycin; Vancomycin - adverse effects; Vancomycin - therapeutic use; Vancomycine; Étude randomisée
• ISSN: 0399-077X; 1769-6690
• DOI: 10.1016/j.medmal.2013.09.011

Methicillin-resistant Staphylococcus aureus (MRSA) accounts for 10–40% of hospital-acquired pneumonia, and even more in intensive care units. The current guidelines for the treatment of MRSA nosocomial pneumonia include vancomycin and linezolid. The authors of 2 prospective randomized trials comparing vancomycin and linezolid in nosocomial pneumonia had concluded to the non-inferiority of linezolid. A slight superiority of linezolid was observed in the MRSA pneumonia subgroup, in terms of clinical success and survival, but no definite conclusion could be drawn. A prospective randomized study was made to compare a fixed linezolid dose to dose-optimized vancomycin for the treatment of bacteriologically proven MRSA nosocomial pneumonia (ZEPHyR Study). Among the 165 patients treated by linezolid (57.6%) in the PP population, 95 were clinically cured at the end of the study, compared to 81 of the 174 patients treated by vancomycin (46.6%) (IC 95% of the difference 0.5%–21.6%, P=0.042). Nephrotoxicity in the mITT population reached 8.4% in the linezolid group compared to 18.2% in the vancomycin group. LNZ was superior to vancomycin for the treatment of MRSA nosocomial pneumonia. Staphylococcus aureus résistant à la méticilline (SARM) est impliqué dans 10 à 40 % des pneumonies acquises en milieu hospitalier et dans une proportion plus importante encore des pneumonies dans les unités de soins intensifs. Les recommandations actuelles pour le traitement des pneumonies nosocomiales à SARM reposent sur la vancomycine ou le linézolide (LNZ). Deux études randomisées prospectives antérieures comparant la vancomycine au LNZ dans les pneumonies nosocomiales ont conclu à la non-infériorité de LNZ mais avec une tendance à la supériorité dans le sous-groupe des pneumonies à SARM. Étude randomisée prospective comparant LNZ et vancomycine optimisée chez des patients adultes atteints de pneumonie nosocomiale à SARM (étude ZEPHyR). Parmi les 165 patients traités par LNZ (57,6 %), 95 sont cliniquement guéris versus 81 des 174 patients traités par vancomycine (46,6 %) (ITT, IC 95 % 0,5 %–21,6 %, p=0,042). L’incidence de la néphrotoxicité est de 8,4 % dans le groupe LNZ vs 18,2 % dans le groupe vancomycine. Le traitement par LNZ des pneumonies nosocomiales à SAMR a une meilleure efficacité que le traitement par vancomycine.