Efficacy and Safety of Linezolid Compared with Vancomycin in a Randomized, Double-Blind Study of Febrile Neutropenic Patients with Cancer

• Published in: Clinical infectious diseases Vol. 42; no. 5; pp. 597 - 607
• Main Authors: Jaksic, Branimir, Martinelli, Giovanni, Oteyza, Jaime Perez, Hartman, Charlotte S., Leonard, Linda B., Tack, Kenneth J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-03-2006; University of Chicago Press; Oxford University Press
• Subjects: Acetamides - adverse effects; Acetamides - therapeutic use; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Articles and Commentaries; Biological and medical sciences; Bone marrow; Double-Blind Method; Drug therapy; Female; Fever; Fever - complications; Fever - drug therapy; Gram-Positive Bacterial Infections - complications; Gram-Positive Bacterial Infections - drug therapy; Health outcomes; Hematologic and hematopoietic diseases; Hospitals; Humans; Infections; Infectious diseases; Linezolid; Male; Medical sciences; Middle Aged; Mortality; Neoplasms - complications; Neutropenia; Neutropenia - complications; Neutrophils; Other diseases. Hematologic involvement in other diseases; Oxazolidinones - adverse effects; Oxazolidinones - therapeutic use; Pathogens; Pharmacology. Drug treatments; Platelets; Staphylococcus aureus; Studies; Vancomycin - adverse effects; Vancomycin - therapeutic use; Human; Linezolid; Leukopenia; Peptides; Hemopathy; Malignant tumor; Vancomycin; Fever; Infection; Antibiotic; Glycopeptide; Polypeptide; Oxazolidinone derivative; Double blind study; Antibacterial agent; Oxazole derivatives; Comparative study; Neutropenia
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/500139

Background. Gram-positive pathogens can cause serious infections in neutropenic patients with cancer, and vancomycin therapy is often initiated empirically. Linezolid may offer an option for these patients. Methods. To compare the safety and efficacy of linezolid and vancomycin in febrile, neutropenic patients with cancer, we conducted a double-blind, multicenter equivalence study. Eligible patients with proven or suspected infection due to a gram-positive pathogen were randomized to receive linezolid or vancomycin. Results. Clinical success rates 7 days after completion of therapy (primary end point) were equivalent between groups in the intent-to-treat (ITT) analysis (linezolid, 219 [87.3%] of 251 patients; vancomycin, 202 [85.2%] of 237 patients; 95% CI, -4.1 to 8.1; P = .52), modified ITT analysis, clinically evaluable analysis, and microbiologically evaluable analysis, as well as between subsets analyzed by malignancy and infection type. Mean time to defervescence was shorter for linezolid than vancomycin in the modified ITT (6.6 vs. 8.5 days; P = .04) and microbiologically evaluable subsets (5.9 vs. 9.1 days; P = .01), although post hoc analyses revealed delayed recovery of absolute neutrophil counts for linezolid in these subsets (P < .05). There were no between-group differences in microbiologic success rates in the modified ITT subset (41 [57.7%] of 71 patients vs. 29 [50.0%] of 58 patients; P = .38) and microbiologically evaluable subsets, as well as in mortality rates in the ITT subset (17 [5.6%] of 304 patients vs. 23 [7.6%] of 301 patients; P = .31) and all subsets. Distribution of adverse events, including reported hematologic events, was similar between groups, except that linezolid was associated with fewer drug-related adverse events (52 [17.2%] of 303 patients vs. 72 [24.0%] of 300 patients; P = .04) and fewer cases of drug-related renal failure (1 [0.3%] of 303 patients vs. 7 [2.3%] of patients; P = .04). Conclusions. Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.