Linezolid: restricted indication
- Medicines and Healthcare products Regulatory Agency
- 1 August 2007
- Therapeutic area:
- Infectious disease
Linezolid is not active against infections caused by Gram-negative pathogens, and treatment should be started only after specialist microbiological advice.
Article date: August 2007
Linezolid (Zyvox▼) is an oxazolidinone antimicrobial, which selectively inhibits bacterial ribosomal translation; it also acts as a reversible monoamine oxidase inhibitor. Linezolid is indicated for treatment of nosocomial pneumonia, community acquired pneumonia, and complicated skin and soft tissue infections. Clinical efficacy has been shown for the Gram-positive aerobes Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes.
A study of intravascular catheter-related infections has shown increased mortality in patients who were treated with linezolid (78 of 363 [21·5%]) compared with those who were treated with vancomycin, dicloxacillin, or oxacillin (58 of 363 [16·0%]). The greatest imbalance occurred during treatment and within 7 days after discontinuation of study drug (43 of 363 [12%] deaths in the linezolid arm vs 22 of 363 [6%] in comparator arm). Mortality did not differ between groups of patients with pure Gram-positive infection (odds ratio 0·96 [95% CI 0·58–1·59]), but was significantly higher in the linezolid arm for patients with any other pathogen or no pathogen at baseline (2·48 [1·38–4·46], p=0·0162). More patients in the linezolid arm than in the comparator arm acquired Gram-negative infections during the study and died from Gram-negative and polymicrobial infections.
Prescribing advice for linezolid was updated in March, 2007: linezolid is now indicated for treatment of complicated skin and soft tissue infections only when microbiological testing has established that infection is caused by susceptible Gram-positive bacteria. Patients with complicated skin and soft tissue infections who have known or possible co-infection with Gram-negative organisms should receive linezolid only if no alternative treatment options are available. In these circumstances, treatment against Gram-negative organisms must be initiated concomitantly.
Specific Gram-negative treatment must be initiated concomitantly if a Gram-negative pathogen is documented or suspected in patients with nosocomial or community acquired pneumonia.
Linezolid should be initiated only in a hospital environment and after consultation with a relevant specialist such as a microbiologist.
For further information see Letter sent to healthcare professionals in March 2007Letter sent to healthcare professionals in March 2007
Article citation: Drug Safety Update August 2007; Vol 1, issue 1: 6-7.
Published: 1 August 2007
Therapeutic area: Infectious disease