title: Should the currently recommended twice-daily dosing still be considered the most appropriate regimen for treating MRSA ventilator-associated pneumonia with vancomycin?
abstract: Methicillin-resistant (methicillin-resistant) Staphylococcus aureus causes unacceptably high mortality from ventilator-associated pneumonia, even when appropriate early therapy with vancomycin is administered at a dosage of 15 mg/kg every 12 hours. However, because of the poor penetration of vancomycin in epithelial lining fluid, it is unlikely that this dosing schedule always achieves optimal vancomycin exposure in the lung. Conversely, there is probably enough evidence to suggest that continuous infusion enhances vancomycin efficacy with the standard 30 mg/kg daily dosage, thus avoiding the need to use higher daily dosages that could increase the risk of nephrotoxicity. It is worth noting that in the case of fully susceptible pathogens with a minimum inhibitory concentration (MIC) of < or =1 mg/L, the strategy of targeting a steady-state vancomycin concentration of 15 mg/L during continuous infusion may simultaneously enable an area under the plasma concentration-time curve (AUC)/MIC ratio of > or =360, so that both pharmacodynamic efficacy targets may be optimized.
authors.affiliation: Department of Experimental and Clinical Pathology and Medicine, Institute of Clinical Pharmacology and Toxicology, Medical School, University of Udine, Piazzale Maria della Misericordia 3, Udine, Italy. pea.federico@aoud.sanita.fvg.it
authors.forename: Federico
authors.initials: F
authors.lastname: Pea
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000401:mortality; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin