Guidelines for treatment of MRSA infections recommend VAN trough (TR) of 15-20 mg/L to achieve a 24-hour ratio of area-under-the-curve (AUC24) over minimum inhibitory concentration (MIC) ≥ 400, the primary pharmacodynamic (PD) parameter that predicts VAN efficacy. However, achieving this target TR in children is difficult in clinical settings and may not be necessary to achieve AUC24/MIC ≥ 400. Additionally, higher doses and TR >15 mg/L have been associated with increased risk for VAN nephrotoxicity. Use of CIV may lead to lower VAN exposure and subsequent toxicity while achieving the desired AUC24/MIC ratio. To our knowledge there are no reports exploring differences in VAN exposure, AUC24/MIC ratio and toxicity between CIV and IIV VAN in children.
We conducted a retrospective, cohort study between January 1, 2011 – December 30, 2016. Children ages 3 months – 18 years with an MRSA infection were included. Only the highest VAN level and total daily dose (TDD) within the first 72 hours of treatment were included for analysis. Patients with CrCl < 30 mL/min/1.73m2 were excluded. Primary outcome was differences in TDD, AUC24 and AUC24/MIC. Secondary outcomes evaluated adverse events.
Twenty-two patients were evaluated, 11 received IIV and 11 received CIV VAN. Median age, weight, gender, baseline serum creatinine, VAN clearance and volume of distribution were similar in both groups. Fewer patients in the IIV group received concomitant nephrotoxic drugs compared to CIV group (5/11 (45%) vs. 10/11 (91%), p=0.03). Patients in the IIV group received more VAN (median 85 mg/kg/day vs. 67 mg/kg/day, p=0.08) and had higher AUC24 (723 mg*h/L, (IQR 669-752) vs. 572 mg*h/L, (IQR 459-633), p=0.02) compared to CIV. Patients in IIV group had lower median TR (16 mg/L vs. 25 mg/L) that required longer time to attain (50.9 h, (IQR 42-70) vs 21.5 h (IQR 17-34), p=0.04) than serum levels in CIV. Both groups had a median VAN MIC 1 mg/L with a trend towards higher AUC24/MIC observed in IIV group (752 vs. 621, p=0.07). More patients in IIV group experienced VAN related adverse events (renal toxicity, infusion reactions, phlebitis) compared to CIV (7/11 (64%) vs. 1/11 (9%), p=0.01).
In pediatric patients, CIV VAN achieved the recommended PD target in shorter time, and with fewer adverse events compared to IIV.
A. Arrieta, None
M. T. Tran, None
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