DRUG PROFILE

Linezolid

A review : The first oxazolidinone antibiotic

Resistance of Gram-positive bacterial pathogens, such as Staphylococcus aureus and Entercoccus faecium, to existing antibiotics continues to increase, and new antibiotics with activity against these pathogens are in demand. Linezolid is the first agent of new class of antibiotics called the oxazolidinones. Linezolid possesses excellent microbial activity against a wide variety of Gram-positive pathogens including those resistant to methicillin and vancomycin. Linezolid is available for intravenous and oral administration and possesses excellent bioavailabilility. It exhibits good penetration in to pulmonary, as well as skin and related structure tissues, and does not require dosage adjustment in hepatic or renal dysfunction. Linezolid is generally well tolerated with the predominant adverse effect manifesting as a duration dependent, reversible thrombocytopenia. Linezolid possesses monoamine oxidase inhibitor activity and caution is warranted with co-administration of adrenergic or seritonergic medications. Clinical trials conducted with linezolid in skin and structure infections, lower respiratory tract infections and vancomycin-resistant enterococcal infections demonstrate that linezolid is an effective therapy. Recent data suggest that linezolid may be superior to vancomycin for the treatment of infections caused by methicillin-resistant S. aureus. Linezolid is an excellent and promising new antibiotic. for the treatment of resistant Gram-positive pathogens.

Expert Rev. Anti-Infective Ther.2(1),51-59(2004)

Summary and future directions

Linezolid is the first of new class of drugs, the oxazolidinones, that have remarkable in vitro activity against strains of:

• S. aureus

• S. epidermidis

• Penicillin –resistant S. pneumoniae

• Streptococci, groups A, B and G

• Vacomycin-resistant Enterococcal species

• Gram-positive anaerobic rods and cocci

Linezolid has excellent bioavailability, a long plasma half-life allowing 12 h dosing either intravenously or orally. Tissue penetration, particularly of the lung, is very high and inhibitory drug levels persist for most of the dosing interval. The drug is well tolerated, with diarrhea being the most common minor side effect. Neutropenia and thrombocytopenia have been observed in patients receiving linezolid for greater than two weeks. These adverse events have resolved with discontinuation of drug and no bleeding complications have been reported. The incidence of neutropenia and thrombocytopenia has not been greater for linezolid compared with vancomycin in a number of clinical trials for MRSA infections where the mean duration of treatment is less than 14 days.

Linezolid has been approved for the treatment of complicated and uncomplicated soft tissue infections, for nosocomial pneumonia caused by resistant Gram- positive bacteria including MRSA and penicillin-resistant pneumococcus. Since FDA aooroval, it is apparent from additional studies that linezolid is superior to vancomycin for nosocomial MRSA infections. It should be emphasized that linezolid has been as efficacious for bacteremia secondary to a variety of staphaylococcal infections as vancomycin but should not be used as a first –line agent to treat staphylococcal ecndocarditis since it is a bacteriostatic and not a bactericidal antimicrobial agent . Since vancomycin is not an ideal agent for endocarditis either, we are in desperate need for novel new bactericidal agents for the treatment of MRSA and VRE endocarditis. Potential new indications for linezolid that deserve study are treatment of penicillin –resistant pneumococcal meningitis, osteomyelitis, ventilator-associated pneumonia and toxic shock syndrome.

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