Zyvox (linezolid)

Commentary

Linezolid is the first drug of oxazolidinone class. It has both intravenous and oral formulations. Linezolid is rapidly and completely absorbed after oral administation with a mean absolute bioavailability of approximately 100%. It is active against penicillin-resistant Streptococcus pneumoniae (PRSP), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and E. faecalis (VRE). Its FAD-approved indications include hospital-acquired pneumonia (due to MRSA), community-acquired pneumonia, infections due to VRE, and complicated/uncomplicated skin and skin structure infection including diabetic foot ulcers (without osteomyelitis).

 

Clinical Trials

Nosocomial Pneumonia

Rubinstein E, Cammarata S, Oliphant T, Wunderink R; Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis. 2001 Feb 1;32(3):402-12

Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.

Wunderink RG, Cammarata SK, Oliphant TH, Kollef MH; Linezolid Nosocomial Pneumonia Study Group. Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia. Clin Ther. 2003 Mar;25(3):980-92.

Linezolid is as well tolerated and as effective as vancomycin, each in combination with aztreonam.

Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003 Nov;124(5):1789-97.

Initial therapy with linezolid was associated with significantly better survival and clinical cure rates than was vancomycin in patients with nosocomial pneumonia due to MRSA.

Kollef MH, Rello J, Cammarata SK, Croos-Dabrera RV, Wunderink RG. Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med. 2004 Mar;30(3):388-94.

Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.

Complicated Skin and Skin Structure Infections (CSSSIs)

Stevens DL, Smith LG, Bruss JB, McConnell-Martin MA, Duvall SE, Todd WM, Hafkin B. Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2000 Dec;44(12):3408-13.

Linezolid is not inferior to intravenous oxacillin or oral dicloxacillin for the treatment of CSSSIs.

Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C; Linezolid CSSTI Study Group. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother. 2005 Jun;49(6):2260-6.

Linezolid therapy is equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.

Itani KM, Weigelt J, Li JZ, Duttagupta S. Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents. 2005 Dec;26(6):442-8.

Linezolid treatment was associated with significantly shorter length of stay, decreased i.v. antibiotic treatment duration and higher discharge rates compared with vancomycin.

McKinnon PS, Sorensen SV, Liu LZ, Itani KM. Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections. Ann Pharmacother. 2006 Jun;40(6):1017-23.

Linezolid therapy was associated with improved clinical outcomes and significantly lower treatment costs than was vancomycin, especially patients with documented MRSA CSSSIs.

McCollum M, Sorensen SV, Liu LZ. A comparison of costs and hospital length of stay associated with intravenous/oral linezolid or intravenous vancomycin treatment of complicated skin and soft-tissue infections caused by suspected or confirmed methicillin-resistant Staphylococcus aureus in elderly US patients. Clin Ther. 2007 Mar;29(3):469-77.

Compared with vancomycine, linezolid treatment for elderly patients with cSSTI caused by suspected or confirmed MRSA was associated with reductions in the costs of care, length of stay, and duration of intravenous treatment without affecting the clinical outcomes.

Review Articles

Maclayton DO, Hall RG 2nd.

Pharmacologic treatment options for nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus. Ann Pharmacother. 2007 Feb;41(2):235-44.

Cornia PB, Davidson HL, Lipsky BA.

The evaluation and treatment of complicated skin and skin structure infections. Expert Opin Pharmacother. 2008 Apr;9(5):717-30.

Grau S, Rubio-Terrés C.

Pharmacoeconomics of linezolid. Expert Opin Pharmacother. 2008 Apr;9(6):987-1000.

Velissariou IM.

Use of linezolid in children: an overview of recent advances. Expert Rev Anti Infect Ther. 2006 Dec;4(6):947-52. Review.

Adverse Drug Reactions and Warnings

FDA Information

Manufacturer/Distributor Product Information