Format

Send to

Choose Destination
Clin Infect Dis. 2014 Jul 1;59(1):51-61. doi: 10.1093/cid/ciu219. Epub 2014 Apr 9.

A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia.

Author information

1
Section of Surgical Critical Care, Baylor College of Medicine, Houston, Texas.
2
Joan XXIII University Hospital, Tarragona, Spain.
3
Chi-Mei Medical Center, Tainan City - Yung Kang District, Taiwan.
4
Javorsky Ödön City Hospital, Argenti Döme, Hungary.
5
Medical Arts Associates Ltd, Moline, Illinois.
6
Santa Casa de Belo Horizonte, Brazil.
7
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, The Netherlands Department of Anesthesia and Intensive Care, University Hospital Rostock, Germany.
8
Policlínico Modelo de Cipolletti, Rio Negro, Argentina.
9
First People's Hospital, Shanghai, China.
10
Aptiv Solutions, Allschwil.
11
Basilea Pharmaceutica International Ltd, Basel, Switzerland.

Abstract

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.

KEYWORDS:

ceftazidime; ceftobiprole; hospital-acquired pneumonia; linezolid; ventilator-associated pneumonia

PMID:
24723282
PMCID:
PMC4305133
DOI:
10.1093/cid/ciu219
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center