Practical approaches to improve vancomycin-related patient outcomes in pediatrics- an alternative strategy when AUC/MIC is not feasible

BACKGROUND: Anecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients. METHODS: After ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated. RESULTS: A total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2–6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8–55) days] in SD-group compared to HD-group [median 16 (range 8–37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)]. CONCLUSION: Initial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.