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IS THERE A RELATIONSHIP BETWEEN ELEVATED VANCOMYCIN TROUGH CONCENTRATIONS (VT) AND INCREASED EFFICACY OR TOXICITY? Bruce H Ackerman, PharmD, Kristen Phillips, Robert E Guilday, MD, Mary L Patton, MD, Linwood R Haith Jr, MD, Crozer-Chester Medical Center
Introduction: Recently observed increased isolation of Methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) ≥ 2mg/L has caused some to advocate increasing the VT to 10 5 mg/L or even higher for increased efficacy. Normally, only a VT is obtained however for 68 patients 116 vancomycin peak (VP) and VT were obtained. We evaluated serum concentration time data for toxicity and efficacy. Methods: Using these VP and VT data, serum concentrations at 0.25, 1, 1.5, 2, 4, 6, hours and midway through the dosing interval were estimated using 2 compartment pharmacokinetic data published by Rotschafer et al in 1982. These estimates and the VP and VT concentration were computer fitted with less than a 5% change in each VP and VT and an r-value in excess of 0.988. Patient data were stratified by increments of 50ml/min creatinine clearance from < 50 to 250 ml/min and by VTs of <5, 5-10, and >10 mg/L. Results: Resulting pharmacokinetic parameters were compared with the 1982 data. Time to negative sputum cultures, duration of therapy, time to normal white blood cell count, temperature and surface area burned did not differ among the stratified VTs ( F < 1; p >> 0.05). Chi square analysis noted no risk of nephrotoxicity with rising VT (X2 = 5.555; p = 0.06). Pharmacodynamic parameters such as the percent time over MIC (MIC = 1.75) interquartile range (IQR) 89.82 to 93.34 predicted nearly 100% clinical response while the area under the serum concentration time curve divided by the MIC of 1.75 showed an IQR of 235.8 to 412.5 predicting no more than 25% clinical response in these 68 patients. Using time to normal temperature, white blood cell count, heart rate, vancomycin therapy outcome was assessed and showed no difference using Analysis of Variance (F <2 for all parameters; p >>0.05). Conclusion: These data indicate that there is no clear prediction of vancomycin success or nephrotoxicity following analysis of the obtained vancomycin peak and trough concentrations and subsequent exhaustive pharmacodynamic analysis.
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