Background. Pediatric infections caused by resistant Gram-positive infections are an increasing concern with limited treatment options. Linezolid, a new oxazolidinone, is active against staphylococci, streptococci and enterococci.
Objective. To assess clinical efficacy and safety of linezolid vs.
vancomycin in antibiotic-resistant Gram-positive infections in children.
Design. Hospitalized children (birth to 12 years of age) with nosocomial pneumonia, complicated skin/skin structure infections, catheter-related bacteremia, bacteremia of unknown source or other infections caused by Gram-positive bacteria were randomized 2:1 to receive linezolid intravenously followed by oral linezolid or vancomycin and then by an appropriate oral agent. Treatment duration was 10 to 28 days.
Results. There were 321 patients enrolled (linezolid 219, vancomycin 102). Clinical cure rates were 79% vs. 74% (P = 0.36) and 89% vs. 85% (P = 0.31) for linezolid and vancomycin in intent-to-treat and clinically evaluable patients, respectively. Cure rates were similar by age and infection diagnosis. Pathogen eradication rates in microbiologically evaluable patients were high for linezolid and vancomycin, respectively, for methicillin-susceptible S. aureus (95% vs. 94%; P = 0.82), methicillin-resistant S. aureus (88% vs. 90%; P = 0.89) and methicillin-resistant coagulase-negative staphylococci (85% vs. 83%, P = 0.87). In clinically evaluable patients, linezolid-treated patients required significantly fewer days of intravenous therapy compared with vancomycin-treated patients (8.0 ± 4.8; 10.9 ± 5.8 days, respectively; P < 0.001). In addition significantly fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19% vs. 34%, respectively; P = 0.003). Hematologic events were uncommon and similar between treatment groups.
Conclusions. Linezolid was well-tolerated and as effective as vancomycin in treating serious Gram-positive infections in children.
From Baylor College of Medicine and Texas Children’s Hospital, Houston, TX (SLK); UCLA School of Medicine/UCLA Medical Center, Los Angeles, CA (JGD); Children’s Memorial Hospital, Chicago, IL (RY); Hospital Civil de Guadalajara, Guadalajara, Mexico (MRM); Hospital San Juan de Dios, Santiago, Chile (EW); Children’s Medical Center, Richmond, VA (SA); and Pharmacia Corp., Kalamazoo, MI (BEP, SNS, JBB).
Accepted for publication April 9, 2003.
Address for reprints: Sheldon L. Kaplan, M.D., Texas Children’s Hospital, 6621 Fannin Street, MC 3-2371, Feigin Center, No. 1150, Houston, TX 77030. Fax 832-825-4347; E-mail Skaplan@bcm.tmc.edu.