Safety and tolerability of linezolid in children.
BACKGROUND
Linezolid, an oxazolidinone, is effective in the treatment of adults and children with community-acquired and nosocomial pneumonia and uncomplicated and complicated skin and skin structure infections (SSSIs), including infections caused by Gram-positive resistant pathogens. Because of the increasing use of linezolid, it is important to review the common adverse events (AEs) associated with its use in children with the use of data from clinical trials.


OBJECTIVE
The safety and tolerability of linezolid in pediatric patients with Gram-positive infections were determined in four pediatric clinical studies. Study I included pediatric patients with community-acquired pneumonia; Study II included otitis media; Study III included SSSIs; and Study IV included complicated SSSIs, nosocomial pneumonia and bacteremia.


METHODS
Studies I and II had no comparator arm. Study III was randomized and compared linezolid with cefadroxil. Study IV also was randomized and compared linezolid with vancomycin. Patients <12 years of age received linezolid 10 mg/kg; patients age 12 years and older received 600 mg (intravenous/oral). Dosing frequency (two to three times daily) varied depending on age and clinical diagnosis. The primary safety endpoints were AEs, drug-related AEs, serious AEs and selected laboratory tests.


RESULTS
In the 4 studies 958 patients were included in the intent-to-treat analysis. In the linezolid vs. cefadroxil study (Study III), the most common AEs in patients treated with linezolid were diarrhea (7.8%), headache (6.5%) and upper respiratory tract infection (3.7%). In the linezolid vs. vancomycin study (Study IV), the most common AEs in the linezolid group were fever (14.1%), diarrhea (10.8%) and vomiting (9.4%). The most common drug-related AEs for linezolid in all 4 studies were diarrhea, vomiting, loose stools and nausea. None of these common AEs or drug-related AEs occurred more frequently in patients treated with linezolid than in those in the comparator group.


CONCLUSIONS
Linezolid was safe and well-tolerated in pediatric patients with community-acquired pneumonia, otitis media, SSSIs and infections caused by Gram-positive resistant pathogens.
Saiman
Lisa
L
Columbia University, New York, NY, USA.
Goldfarb
Johhanna
J
Kaplan
Sheldon A
SA
Wible
Kenneth
K
Edge-Padbury
Barbara
B
Naberhuis-Stehouwer
Sharon
S
Bruss
Jon B
JB
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000284:Administration, Oral; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy; D002434:Cefadroxil / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections; D003428:Cross Infection; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D015337:Multicenter Studies as Topic; D010033:Otitis Media / Q000188:drug therapy; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D011014:Pneumonia / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000139:chemically induced; D017192:Skin Diseases, Bacterial / Q000188:drug therapy
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D002434:Cefadroxil; D000069349:Linezolid