Linezolid - A review of its use in the management of serious Gram-positiveinfections

Linezolid is the first of a new class of antibacterial drugs, the oxazolidi nones. It has inhibitory activity against a broad range of Gram-positive ba cteria, including methicillin-resistant Staphylococcus aureus (MRSA), glyco peptide-intermediate S. aureus (GISA), vancomycin-resistant enterococci (VR E) and penicillin-resistant Streptococcus pneumoniae. The drug also shows a ctivity against certain anaerobes. including Clostridium perfringens, C. di fficile, Peptostreptococcus spp. and Bacteroides fragilis. In controlled phase LII studies, linezolid was as effective as vancomycin i n the treatment of patients with infections caused by methicillin-resistant staphylococci and also demonstrated efficacy against infections caused by VRE, Further phase III studies have demonstrated that linezolid is an effec tive treatment for patients with nosocomial pneumonia, for hospitalised pat ients with community-acquired pneumonia, and for patients with compclicated skin or soft tissue infections (SSTIs), In these studies, linezolid was as effective as established treatments, including third-generation cephalospo rins in patients with pneumonia. and oxacillin in patients with complicated SSTIs. Oral linezolid 400 or 600mg twice daily was as effective as clarith romycin 250mg twice daily or cefpodoxime proxetil 200mg twice daily in the treatment of patients with uncomplicated SSTIs or community-acquired pneumo nia. Linezolid is a generally well tolerated drug, The most frequently reported adverse events in linezolid recipients were diarrhoea, headache, nausea and vomiting. Thrombocytopenia was also documented in a small proportion (abou t 2%) of patients treated with the drug. Conclusions: Linezolid has good activity against Gram-positive bacteria, pa rticularly multidrug resistant strains of S. aureus (including GISA), Enter ococcus faecium and E. faecalis (including VRE). In controlled clinical tri als, linezolid was as effective as vancomycin in eradicating infections cau sed by methicillin-resistant Staphylococcus spp. and has demonstrated effic acy against infections caused by VRE. As the level of resistance to vancomy cin increases among S. anl eus and enterococci, linezolid is poised to play an important role in the management of serious Gram-positive infections.