Continuous administration of linezolid in pneumonia: what is the level of proof?

Excerpt

Linezolid, the first available oxazolidinone derivative, has been shown to be an interesting alternative to glycopeptides against resistant gram-positive strains [1]. It distributes well into the lung, with mean percentage penetration in epithelial lining fluid of approximately 100 %, indicating that serum concentrations adequately predict antibiotic concentrations at the target site for extracellular respiratory tract pathogens [1]. Linezolid is a time-dependent antimicrobial agent with a reduced post-antibiotic effect. The best pharmacokinetic/pharmacodynamic (PK/PD) parameters to define its activity are time with serum concentrations higher than the minimum inhibitory concentration (T > MIC) and area under the serum concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio [1]. Linezolid is mainly a bacteriostatic antimicrobial agent with T > MIC of at least 40 % being predictive of its efficacy. This objective can be easily achieved for pathogens with MICs of 2–4 mg/l by administration of standard dosing (600 mg intravenously twice a day) in healthy volunteers, suggesting that continuous infusion, the best antimicrobial administration modality for most time-dependent antibiotics as it prolongs effective serum concentrations, may not be essential [1]. …