The clinical applications of pharmacodynamics and pharmacokinetics of linezolid [Las aplicaciones clínicas de la farmacodinámica y farmacocinética de linezolid]

Abstract

Background. Antimicrobial resistance among Gram-positive organisms is rising. Resistant Staphylococcus aureus, coagulase-negative Staphylococcus, Enterococcus, and Streptococcus pneumoniae, are now common pathogens of a variety of nosocomial and community infections. The treatment of Grampositive infections is complicated due to the frequent resistance of S. aureus to methicillin, S. pneumoniae to penicillin and the vancomycin resistance of Enterococcus. Purpose. To review the pharmacokinetic and pharmacodynamic properties of linezolid. Data sources. Medline search for studies examining the pharmacokinetics and pharmacodynamics of linezolid. Study selection. Fifty studies reviewed. Data synthesis. Linezolid is a new antibiotic that belongs to the Oxazolidinone class of antimicrobial agents. Linezolid inhibits the initiation of protein synthesis in a variety of bacteria. Linezolid is active against methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae and vancomycin-resistant Enterococcus faecium among other Gram-positive pathogens. After the administration of 600 mg of linezolid the half-life at the elimination phase is 5.5 h, the mean maximum concentration of the drug in plasma at steady state ranges from 15 to 21 μg/mL. The oral bioavailability is 100% after oral administration with a time to maximum concentration after an oral dose of 1.0 to 1.5 h. Linezolid has good tissue penetration including skin and lung. The usual linezolid dosage in adults is 600 mg every 12 h, and in children a dosage of 10 mg/kg every 8 h will be probably approved. A value of > 39% for the percentage of time during which the linezolid concentration exceeds the MIC of susceptible bacteria correlates with therapeutic success. The rapidly and extensively absorption after and oral dose facilitates the early discharge of patients with severe infections. Conclusions. Linezolid pharmacokinetics, pharmacodynamics and pharmacoeconomic properties support the use for the treatment of resistant Gram-positive infections.