Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients

ABSTRACT

BACKGROUND: Usual treatment regimens with vancomycin often fail to provide adequate serum levels in patients with severe infections. METHODS: Retrospective analysis of vancomycin trough serum measurements. The following parameters were calculated by Bayesian analysis: vancomycin clearance, distribution volume, and peak estimated concentrations. The area under the concentration curve (AUC) (total daily dose/24 h clearance of vancomycin) was used to determine the effectiveness of treatment through the ratio of AUC/minimum inhibitory concentration (MIC) above 400, using MIC = 1 µg/mL, based on isolates of Staphylococci in cultures. RESULTS: Sixty-one vancomycin trough measurements were analyzed in 31 patients. AUC/MIC > 400 was obtained in 34 out of 61 dosages (55.7%), but the mean vancomycin dose required to achieve these levels was 81 mg/kg/day. In cases where the usual doses were administered (40-60 mg/kg/day), AUC/MIC > 400 was obtained in nine out of 18 dosages (50%), in 13 patients. Trough serum concentrations above 15 mg/L presented a positive predictive value of 100% and a negative predictive value of 71% for AUC/MIC > 400. CONCLUSION: Higher than usual vancomycin doses may be required to treat staphylococcal infections in children with oncologic/hematologic diseases. Since the best known predictor of efficacy is the AUC/MIC ratio, serum trough concentrations must be analyzed in conjunction with MICs of prevalent Staphylococci and pharmacokinetic tools such as Bayesian analysis.