Linezolid: An oxazolidinone antimicrobial agent

Background: Linezolid is the first oxazolidinone anti-infective agent marke ted in the United States. It is indicated for the treatment of nosocomial p neumonia, complicated skin and skin-structure infections caused by methicil lin-sensitive or methicillin-resistant Staphylococcus aureus and other susc eptible organisms, and vancomycin-resistant Enterococcus faecium infections . It also is indicated for the treatment of uncomplicated skin and skin-str ucture infections caused by methicillin-sensitive S aureus or Streptococcus pyogenes, and community-acquired pneumonia caused by penicillin-sensitive Streptococcus pneumoniae. Objective: This article reviews the pharmacologic properties and clinical u sefulness of linezolid. Methods: Using the terms linezolid, PNU-100766, and oxazolidinone, we perfo rmed a literature search of the following databases: MEDLINE (R) (1966 to S eptember 2000), HealthSTAR (R) (1993 to September 2000), Iowa Drug Informat ion Service (1966 to September 2000), International Pharmaceutical Abstract s (1970 to September 2000), PharmaProjects (January 2000 version), and meet ing abstracts of the Infectious Diseases Society of America and the Intersc ience Conference on Antimicrobial Agents and Chemotherapy (1996 to 2000). Results: Linezolid has a unique structure and mechanism of action. which ta rgets protein synthesis at an exceedingly early stage. Consequently, cross- resistance with other commercially available antimicrobial agents is unlike ly. It is primarily effective against gram-positive bacteria. To date, resi stance to linezolid has been reported in patients infected with enterococci . The pharmacokinetic parameters of linezolid in adults are not altered by hepatic or renal function, age. or sex to an extent requiring dose adjustme nt. Linezolid is metabolized via morpholine ring oxidation, which is indepe ndent of the cytochrome P450 (CYP450) enzyme system: as a result, linezolid is unlikely to interact with medications that stimulate or inhibit CYP450 enzymes. Compassionate-use trials and other clinical studies involving main ly adult hospitalized patients with gram-positive infections have shown tha t linezolid administered intravenously or orally is effective in a variety of nosocomial and community-acquired infections, including those caused by resistant gram-positive organisms. Reported adverse effects include thrombo cytopenia, diarrhea, headache, nausea, vomiting, insomnia, constipation, ra sh, and dizziness. Preliminary pharmacoeconomic data indicate that a signif icantly higher percentage of patients receiving linezolid therapy versus co mparator could be discharged from the hospital by day 7 (P = 0.005). Conclusions: Linezolid appears to be effective while maintaining an accepta ble tolerability profile. Due to the risk of bacterial resistance, linezoli d should be reserved for the treatment of documented serious vancomycin-res istant enterococcal infections.