Population pharmacokinetics and resistance patterns of vancomycin and amikacin in pediatric oncology patients

Febrile episodes in pediatric oncology patients, particularly those with neutropenia, pose major clinical challenges and require prompt empiric antimicrobial therapy. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics of vancomycin and amikacin in pediatric oncology patients. A retrospective review was conducted in 105 pediatric oncology patients admitted between January 2020 and January 2024. Data collected included demographic characteristics, vital signs, laboratory findings, neutropenic status, malignancy type, microbial cultures, resistance profiles, and total serum concentrations of vancomycin and amikacin obtained during routine therapeutic drug monitoring (TDM). Blood cultures were positive in ∼39% of cases, with Staphylococcus epidermidis (∼24%) and methicillin-resistant Staphylococcus aureus (∼16%) being the predominant isolates. Vancomycin peak and trough concentrations were 18.37 ± 7.42 μg/mL and 8.63 ± 3.81 μg/mL, respectively. Amikacin peak and trough concentrations were 26.27 ± 12.11 μg/mL and 1.09 ± 0.67 μg/mL, respectively. Population PK analyses identified body weight and bilirubin level as key covariates for vancomycin (CL = 0.169 L/h/kg; V = 1.519 L/kg), and body weight and tumor type for amikacin (CL = 0.182 L/h/kg; V = 0.505 L/kg). Solid tumors were associated with a lower amikacin volume of distribution (∼0.32 L/kg). The calculated area under the curve (AUC) of vancomycin exposure over one dosing interval was estimated as AUC_0-6 = 62.76 ± 22.25 μg·h/mL; assuming steady-state every 6 hours dosing, the corresponding daily exposure was AUC_0-24 = 251.04 ± 89.00 μg·h/mL. Using a reference minimum inhibitory concentration (MIC) of 1 μg/mL, the mean vancomycin AUC_0-24/MIC remained well beneath the therapeutic target of ≥400. Similarly, the calculated Cpeak/MIC of amikacin was 6.57 ± 3.03, which was below the optimal PK/pharmacodynamics target (ie, 8-10), with only ∼30% accomplished therapeutic goals, highlighting the need for personalized dosing and TDM in this cohort. Analytical target attainment projections derived from the final population PK models confirmed that standard dosing regimens achieved suboptimal probability of target attainment for both drugs, and indicated that dose escalation to at least 20 mg/kg every 6 hours for vancomycin and 22.5 mg/kg every 24 hours for amikacin would be required to meaningfully improve exposure adequacy across this population. These outcomes emphasize the need for individualized dosing strategies and TDM in pediatric oncology patients receiving antimicrobial therapy. SIGNIFICANCE STATEMENT: Vancomycin and amikacin display pharmacokinetic variability in pediatric oncology patients, with body weight identified as determinant for both drugs, bilirubin level for vancomycin, and tumor type for amikacin. standard dosing was associated with lower-than-target exposure in a proportion of patients. Analytical target attainment projections from population PK models quantified this exposure gap and identified dose requirements to improve target attainment across this population. Findings support therapeutic drug monitoring and evaluation of individualized dosing approaches in this population.