Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer.
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.
Jaksic
Branimir
B
Department of Medicine, Merkur University Hospital, Zagreb, Croatia. branimir.jaksic@zg.htnet.hr
Martinelli
Giovanni
G
Perez-Oteyza
Jaime
J
Hartman
Charlotte S
CS
Leonard
Linda B
LB
Tack
Kenneth J
KJ
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000150:complications / Q000188:drug therapy; D016908:Gram-Positive Bacterial Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000150:complications*; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid