A Phase 3 Randomized Double-Blind Comparison of Ceftobiprole Medocaril Versus Ceftazidime Plus Linezolid for the Treatment of Hospital-Acquired Pneumonia

• Published in: Clinical infectious diseases 2014-07, Vol.59 (1), p.51-61
• Main Authors: Awad, Samir S., Rodriguez, Alejandro H., Chuang, Yin-Ching, Marjanek, Zsuszanna, Pareigis, Alex J., Reis, Gilmar, Scheeren, Thomas W. L., Sánchez, Alejandro S., Zhou, Xin, Saulay, Mikaël, Engelhardt, Marc
• Format: Article
• Language: English
• Subjects: Acetamides - therapeutic use; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; and Commentaries; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; ARTICLES AND COMMENTARIES; Bacteria; Bacterial infections; Bacterial pneumonia; Biological and medical sciences; Ceftazidime - therapeutic use; Cephalosporins - therapeutic use; Clinical outcomes; Cross Infection - drug therapy; Double-Blind Method; Drug Therapy - methods; Enterobacteriaceae; Female; General aspects; Health outcomes; Human infectious diseases. Experimental studies and models; Humans; Infectious diseases; Klebsiella pneumoniae; Linezolid; Male; Medical sciences; Methicillin resistant staphylococcus aureus; Middle Aged; Oxazolidinones - therapeutic use; Pathogens; Pharmacology. Drug treatments; Pneumology; Pneumonia; Pneumonia, Bacterial - drug therapy; Pseudomonas aeruginosa; Respiratory system : syndromes and miscellaneous diseases; Staphylococcus aureus; Treatment Outcome; Ventilator associated pneumonia; Young Adult
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciu219

Background. Ceftobiprole, the active moiety of ceftobiprole medocaril, is a novel broad-spectrum cephalosporin, with bactericidal activity against a wide range of gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant strains) and penicillin- and ceftriaxone-resistant pneumococci, and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. Methods. This was a double-blind, randomized, multicenter study of 781 patients with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated pneumonia (VAP). Treatment was intravenous ceftobiprole 500 mg every 8 hours, or ceftazidime 2 g every 8 hours plus linezolid 600 mg every 12 hours; primary outcome was clinical cure at the test-of-cure visit. Results. Overall cure rates for ceftobiprole vs ceftazidime/linezolid were 49.9% vs 52.8% (intent-to-treat [ITT], 95% confidence interval [CI] for the difference, -10.0 to 4.1) and 69.3% vs 71.3% (clinically evaluable [CE], 95% CI, -10.0 to 6.1). Cure rates in HAP (excluding VAP) patients were 59.6% vs 58.8% (ITT, 95% CI, -7.3 to 8.8), and 77.8% vs 76.2% (CE, 95% CI, -6.9 to 10.0). Cure rates in VAP patients were 23.1% vs 36.8% (ITT, 95% CI, -26.0 to -1.5) and 37.7% vs 55.9% (CE, 95% CI, -36.4 to 0). Microbiological eradication rates in HAP (excluding VAP) patients were, respectively, 62.9% vs 67.5% (microbiologically evaluable [ME], 95% CI, -16.7 to 7.6), and in VAP patients 30.4% vs 50.0% (ME, 95% CI, -38.8 to -0.4). Treatment-related adverse events were comparable for ceftobiprole (24.9%) and ceftazidime/linezolid (25.4%). Conclusions. Ceftobiprole is a safe and effective bactericidal antibiotic for the empiric treatment of HAP (excluding VAP). Further investigations are needed before recommending the use of ceftobiprole in VAP patients. Clinical Trials Registration. NCT00210964, NCT00229008.