This questions was recently addressed by Michael J. Postelnick, Senior Infectious Diseas Pharmacist of Northwestern Memorial Hospital in Chicago, Illinois in an Ask-the-Experts post on the Medscape website. Postelnick gives a good explanation of how various pharmacokinetic and pharmacodynamic principles are related to antibiotic choice for infectious pathogens. According to Postelnick “research into antimicrobial pharmacokinetics and pharmacodynamics has established surrogate relationships between the 2 that correlate with outcomes such [as] bacterial eradication or clinical cure. These relationships include the ratio of Cmax to the MIC, time above the MIC (defined as the amount of time during the dosing interval that the antimicrobial concentration in the blood or at the site of infection remains above the MIC of the organism), and the ratio of the AUC to the MIC. For concentration-dependent antimicrobial agents such as fluoroquinolones and aminoglycosides, Cmax/MIC or AUC/MIC most closely correlates with clinical and microbiological outcomes. For time-dependent antimicrobial agents such as beta-lactams, the percentage of time during the dosing interval that the drug concentration remains above the MIC of the organism is the measure that most closely predicts outcomes.” In other words, selection of an antibiotic requires more than the MIC. Knowledge of the organism in addition to pharmacokinetic and pharmacodynamic principles of the drug is necessary to make an informed choice.
An article on the possible link between vancomycin trough concentrations and nephrotoxicity appears in a recent issue of Clinical Infectious Diseases (2009;49:507-14) . The article describes a retrospective study of 166 patients treated at Albany Medical Center Hospital in Albany, New York between January 2005 and December 2006. The study found that patients in the ICU, those with a weight of >/= 101 kg, and those with prolonged exposure to elevated vancomycin troughs (> 20mg/L) were associated with a greater risk for developing nephrotoxicity. The authors conclude that the vancomycin trough value was the parameter that best described this risk of toxicity. Based on this information, it appears that successful treatment of serious methicillin-resistant S.aureus infections with higher minimum inhibitory concentrations (MIC) may place patients at a greater risk for developing nephrotoxicity. The findings in the article are significant as recent guidelines recommend higher vancomycin trough concentrations for complicated S.aureus infections.
Although interesting and possibly informative, the information contained in the study is based on a small observational study in a single facility. The findings cannot necessarily be extrapolated to any significant degree to other patient populations and further studies are necessary to confirm the results on a larger scale. For now it appears that aggressive vancomycin therapy in addition to cautious monitoring of renal function and patient status is prudent when trough levels are approaching 20mg/L.