Linezolid, the first approved oxazolidinone, has activity against gram-positive bacteria, including strains resistant to other antibiotics. We report the adverse event (AE) profile during linezolid use in nosocomial pneumonia for the subset of patients with ventilator-associated pneumonia (VAP).
AE data were pooled for the subset of patients with VAP from 2 identical, randomized, double blind, IV studies comparing linezolid (LZD) and vancomycin (VAN) in patients with gram positive nosocomial pneumonia. The investigator recorded and rated AEs as serious or non-serious, with judgment on severity by standard definitions, and assessed the relationship of AEs to study medication.
544 VAP patients were treated (282 LZD, 262 VAN). There were no significant differences between groups in the number of patients with at least one AE (82% vs 84%, respectively), drug-related AEs (14% vs 12%), discontinuation due to drug-related AEs (1.4% vs 1.5%), serious AEs (37% vs 38%), or deaths (16% vs 20%). AEs ≥5%, regardless of causality, in LZD vs VAN groups, respectively, were diarrhea (13.1% vs 11.1%), fever (5.7% vs 6.1%), pneumonia (6.0% vs 7.3%), respiratory failure (8.2% vs 5.0%), sepsis (7.4% vs 9.5%), urinary tract infection (8.2% vs 7.3%), and vomiting (5.3% vs 5.3%). Additional AEs ≥5% were pressure sore (5.3%), nausea (5.0%) and hypertension (5.0%) in the LZD group, and rash (7.3%) and hypotension (5.0%) in the VAN group. The only AE in ≥2% of patients that was considered drug-related was diarrhea (4.3% LZD vs 2.3% VAN, p=.20). The most common serious AEs (≥3%) were related to patients’ underlying disease: respiratory and multi-organ failure for LZD and sepsis, pneumonia and respiratory failure for VAN.CONCLUSIONS: IV LZD is generally well tolerated in patients with ventilator-associated pneumonia. The nature and frequency of AEs were comparable in the LZD and VAN groups and were influenced by the severity of patients’ underlying disease.
Linezolid is a reasonable therapeutic option, with no increased risk of adverse events, in the treatment of patients with VAP.
G.J. Hooper, Pharmacia employee, Industry.