A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia.
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.
Section of Surgical Critical Care, Baylor College of Medicine, Houston, Texas.
Samir S
SS
Awad
Joan XXIII University Hospital, Tarragona, Spain.
Alejandro H
AH
Rodriguez
Chi-Mei Medical Center, Tainan City - Yung Kang District, Taiwan.
Yin-Ching
YC
Chuang
Javorsky Ödön City Hospital, Argenti Döme, Hungary.
Zsuszanna
Z
Marjanek
Medical Arts Associates Ltd, Moline, Illinois.
Alex J
AJ
Pareigis
Santa Casa de Belo Horizonte, Brazil.
Gilmar
G
Reis
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, The Netherlands Department of Anesthesia and Intensive Care, University Hospital Rostock, Germany.
Thomas W L
TW
Scheeren
Policlínico Modelo de Cipolletti, Rio Negro, Argentina.
Alejandro S
AS
Sánchez
First People's Hospital, Shanghai, China.
Xin
X
Zhou
Aptiv Solutions, Allschwil.
Mikaël
M
Saulay
Basilea Pharmaceutica International Ltd, Basel, Switzerland.
Marc
M
Engelhardt
D000081:Acetamides / Q000627:therapeutic use*; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy*; D004311:Double-Blind Method; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D000081:Acetamides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D023303:Oxazolidinones; D002442:Ceftazidime; D000069349:Linezolid; C505439:ceftobiprole medocaril
ceftazidime; ceftobiprole; hospital-acquired pneumonia; linezolid; ventilator-associated pneumonia