Worldwide assessment of linezolid's clinical safety and tolerability: comparator-controlled phase III studies.
Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (> or = 2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.
Rubinstein
Ethan
E
The Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel-Hashomer, Israel. erubins@yahoo.com
Isturiz
Raul
R
Standiford
Harold C
HC
Smith
Leon G
LG
Oliphant
Thomas H
TH
Cammarata
Sue
S
Hafkin
Barry
B
Le
Vu
V
Remington
Jack
J
D000081:Acetamides / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy; D003428:Cross Infection / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D023303:Oxazolidinones / Q000009:adverse effects* / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D011500:Protein Synthesis Inhibitors; D000069349:Linezolid