An evidence-based review of linezolid for the treatment of methicillin-resistant Staphylococcus aureus (MRSA): place in therapy

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), including community-associated and hospital-associated strains, is a major cause of human morbidity and mortality. Treatment options have become limited due to the emergence of MRSA strains with decreased sensitivity to vancomycin, which has long been the first-line therapy for serious infections. This has prompted the search for novel antibiotics that are efficacious against MRSA. Linezolid, an oxazolidinone class of antibiotic, was approved by the Food and Drug Administration in 2000 for treatment of MRSA infections. Since then, there have been a multitude of clinical trials and research studies evaluating the effectiveness of linezolid against serious infections, including pneumonia (both community- and hospital-acquired), skin and soft-tissue infections such as diabetic foot ulcers, endocarditis, osteomyelitis, prosthetic devices, and others. The primary aim of this review is to provide an up-to-date evaluation of the clinical evidence for using linezolid to treat MRSA infections, with a focus on recently published studies, including those on nosocomial pneumonia. Other objectives are to analyze the cost-effectiveness of linezolid compared to other agents, and to review the pharmokinetics and pharmacodynamics of linezolid, emphasizing the most current concepts.

Keywords: MRSA; clinical trials; linezolid; pneumonia; skin infections.

Figure 1

Chemical structure of linezolid. Its molecular weight is 337.35 and its empirical formula is C₁₆H₂₀FN₃O_4. Note: The activity of the drug is enhanced by the morpholino group in the first ring (from the left) and the fluoride atom in the second ring.

Figure 2

Propensity-adjusted logistic regression model comparing linezolid to vancomycin in patients with ventilator-associated pneumonia from MRSA. Note: Data from Peyrani et al.