Vancomycin: We Can't Get There From Here

• Published in: Clinical infectious diseases Vol. 52; no. 8; pp. 969 - 974
• Main Authors: Patel, Nimish, Pai, Manjunath P., Rodvold, Keith A., Lomaestro, Ben, Drusano, George L., Lodise, Thomas P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.04.2011
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; ARTICLES AND COMMENTARIES; Biological and medical sciences; Dosage; Dose response relationship; Effectiveness studies; Humans; Infections; Infectious diseases; Kidneys; Medical sciences; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Monte Carlo methods; Nephrotoxicity; Pharmacology; Pharmacology. Drug treatments; Population estimates; Ratios; Regression analysis; Serum - chemistry; Simulation; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus infections; Toxicity; Vancomycin - administration & dosage; Vancomycin - adverse effects; Vancomycin - pharmacokinetics; Vancomycin - pharmacology; Infection; Antibiotic; Peptides; Glycopeptide; Polypeptide; Vancomycin; Antibacterial agent
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cir078

Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. Methods. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. Results. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%. At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. Conclusions. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin.