1. A Phase 3 Randomized Double-Blind Comparison of Ceftobiprole Medocaril Versus Ceftazidime Plus Linezolid for the Treatment of Hospital-Acquired Pneumonia
- Author
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Xin Zhou, Yin-Ching Chuang, Alejandro S. Sánchez, Thomas Scheeren, Marc Engelhardt, Gilmar Reis, Alejandro Rodríguez, Zsuszanna Marjanek, Samir S. Awad, Mikael Saulay, Alex J. Pareigis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), and Vascular Ageing Programme (VAP)
- Subjects
Male ,METHICILLIN-RESISTANT ,Cephalosporin ,Ceftazidime ,STREPTOCOCCUS-PNEUMONIAE ,BROAD-SPECTRUM ,Hospital-acquired pneumonia ,chemistry.chemical_compound ,Acetamides ,NOSOCOMIAL PNEUMONIA ,ceftazidime ,Articles and Commentaries ,Aged, 80 and over ,Cross Infection ,Ventilator-associated pneumonia ,RESISTANT STAPHYLOCOCCUS-AUREUS ,Middle Aged ,Anti-Bacterial Agents ,PENICILLIN-BINDING PROTEINS ,Treatment Outcome ,Infectious Diseases ,ESCHERICHIA-COLI ,Administration, Intravenous ,Female ,ceftobiprole ,CLINICAL-TRIALS ,medicine.drug ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Ceftobiprole ,linezolid ,Young Adult ,stomatognathic system ,Double-Blind Method ,Drug Therapy ,Internal medicine ,Pneumonia, Bacterial ,medicine ,hospital-acquired pneumonia ,Humans ,Oxazolidinones ,Aged ,VENTILATOR-ASSOCIATED PNEUMONIA ,business.industry ,IN-VITRO ,medicine.disease ,Confidence interval ,Cephalosporins ,Surgery ,Penicillin ,chemistry ,Linezolid ,business - 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. {"type":"clinical-trial","attrs":{"text":"NCT00210964","term_id":"NCT00210964"}}NCT00210964, {"type":"clinical-trial","attrs":{"text":"NCT00229008","term_id":"NCT00229008"}}NCT00229008.
- Published
- 2014