Pharmacokinetic variability of vancomycin in patients undergoing hematopoietic stem cell transplantation: a retrospective cohort study in Peru.
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BACKGROUND: Vancomycin exhibits high pharmacokinetic variability, particularly in hematopoietic stem cell transplantation (HSCT) patients, where augmented renal clearance (ARC) may compromise therapeutic exposure. This variability necessitates individualized dosing strategies to ensure optimal treatment efficacy. OBJECTIVE: To evaluate the pharmacokinetic variability of vancomycin in pediatric and adult patients undergoing HSCT and to assess the association of ARC with serum drug concentrations. DESIGN: A retrospective cohort study. METHODS: We analyzed medical records of post-HSCT patients with febrile neutropenia who received intravenous vancomycin at a tertiary hospital in Lima, Peru. Vancomycin plasma concentrations were assessed at baseline and after dose adjustments. Pharmacokinetic parameters were estimated using Bayesian modeling via PrecisePK software. Regression models were used to evaluate associations between creatinine clearance and vancomycin area under the curve (AUC). RESULTS: A total of 40 post-HSCT patients were included, 50% of whom were female. The median age was 17.0 years (interquartile range (IQR): 12.0-39.5), with 25% belonging to the pediatric group. The most frequent disease was B-cell acute lymphoblastic leukemia (47.5%). A significant change was observed in the vancomycin area under the curve (AUC0-24/MIC) before and after dose adjustment (343 mg h/L vs 523 mg h/L; p < 0.001). The median relative dose adjustment percentage of vancomycin was 45% (IQR: 20-73.3). In the multivariate linear regression model, an increase in creatinine clearance was associated with a lower vancomycin AUC (β = -0.67; 95% CI: -1.14 to -0.19). This relationship was maintained after bootstrap resampling with 3000 repetitions (β = -0.67; 95% CI: -1.11 to -0.23). Sepsis was associated with the development of ARC (aRR: 1.378; 95% CI: 1.164-1.631), and as age increased, the risk of ARC decreased (aRR: 0.991; 95% CI: 0.99-0.996). CONCLUSION: Most post-HSCT patients had subtherapeutic vancomycin levels at the beginning of treatment, which were optimized through individualized adjustments. The pharmacokinetic variability associated with ARC in young patients and those with sepsis supports the use of AUC-based therapeutic drug monitoring over trough concentration monitoring. These findings also highlight the importance of early renal function monitoring in patients treated with HSCT.