We are pleased to capture the attention of our colleagues and appreciate the opportunity to provide further discussions related to our prospective observational study examining the efficacy and safety of high-dose vancomycin therapy for the treatment of MRSA.1 Johnson requested definitions of “target” and “corrected” troughs used and an explanation of the outcome analysis performed in our study. Target trough was defined as achievement of an unbound vancomycin concentration at 4 to 5 times the MIC of the infected strain.1(p2139) Thus, for a strain with an MIC of 2 μg/mL and taking into account the 50% protein-binding property of vancomycin, attaining a target trough of 16 to 20 μg/mL is necessary to achieve 4 to 5 times the MIC of the infected strain, respectively (eg, bound + unbound drug concentration of 16 μg/mL = 2 μg/mL × 2 × 4). To determine the overall drug exposure during the course of therapy, we calculated a “corrected” trough for each patient, defined as the sum of each measured trough concentration multiplied by the number of days at that level, then divided by the number of total days of treatment.1(p2139) The “corrected” trough value was used to subgroup patients based on the achievement of the target trough in the efficacy analysis and the attainment of high vs low trough level in the safety analysis. Faulhaber et al raised concerns regarding the calculation of arithmetic rather than geometric mean of the trough levels attained. Both geometric and arithmetic means of the corrected vancomycin trough were calculated to be similar and did not result in different distribution of patient subgroups. Treatment response was evaluated at 2 time points, at 72 hours following initiation of therapy and end of treatment—“corrected” trough values based on the days of drug exposure were used accordingly, with the results shown in Figures 1 and 2, respectively.1(p2140) We observed a 20% lower response rate for those who did not achieve the target trough initially (52/68 [76%] vs 15/27 [56%]; P = .05); thus, aggressive empirical vancomycin dosing to achieve a trough greater than 15 μg/mL is recommended until the culture and sensitivity results are known.
Wong-Beringer A, Hidayat LK, Hsu DI. Treatment of MRSA Infections With Older Molecules: A Reasonable Option for Investigation—Reply. Arch Intern Med. 2007;167(11):1208-1209. doi:10.1001/archinte.167.11.1208