Resident Boston Children's Hospital Boston Children's Hospital Boston, Massachusetts, United States
Background: Vancomycin is often used in empiric regimens for persistent febrile neutropenia in hematopoietic stem-cell transplant (HSCT) recipients. Extended durations of vancomycin when blood cultures are negative may predispose to acute kidney injury (AKI), for which HSCT recipients are already at risk.
Objective: An antimicrobial stewardship program (ASP) intervention to decrease prolonged (>72 hour) vancomycin courses was implemented in April 2017 for HSCT patients with febrile neutropenia and negative blood cultures at Boston Children’s Hospital. We evaluated the change in vancomycin days of therapy (DOT) after the intervention and whether the intervention was associated with a decrease in vancomycin-associated AKI.
Design/Methods: Vancomycin-associated AKI was defined as occurring during or within 72 hours after receipt of vancomycin within 3 months after transplant. AKI was defined as a 50% increase in serum creatinine within 7 days or a 0.3-mg/dL increase within 48 hours above baseline. An interrupted time series design with segmented Poisson regression was used to compare vancomycin DOT per 1000 inpatient days post-intervention (27 months) versus pre-intervention (27 months), accounting for repeated measures. A mediation analysis was used to evaluate the percent of intervention effect on AKI that was mediated by DOT.
Results: 439 vancomycin exposures (233 pre- and 206 post-intervention) across 300 unique transplants and 259 unique subjects were included. Median age at admission was 6.7 years (range: 0.3, 26). Median vancomycin DOT declined from 7 days pre-intervention to 3 days post, and the proportion of patients receiving prolonged (>72h) courses of vancomycin decreased significantly after the intervention (67.4% vs 50.0%, p=0.02). All other subject-level, transplant-level, and exposure-level characteristics did not differ between pre- and post-intervention groups (univariate repeated measures analysis, p>0.10). The baseline rate of vancomycin DOT was 270 per 1000 inpatient days (95% CI [199,342]) and decreased significantly post-intervention by 121/1000 inpatient days (p=0.02). Results from mediation analysis showed a 32.7% (95% CI [10.6,47.8], p<0.001) reduction in excess risk of AKI after the intervention, and that 45% of the excess risk was mediated by DOT (p=0.006). Conclusion(s): An ASP intervention successfully decreased patient exposure to vancomycin after HSCT which resulted in a decrease in risk of AKI. Reducing unnecessary antibiotic exposure for patients post-HSCT can improve clinical outcomes.
Authors/Institutions: Horace R. Hambrick, Boston Children's Hospital, Boston, Massachusetts, United States; Kimberly Greco, Boston Children's Hospital, Boston, Massachusetts, United States; Leslie Lehmann, Dana-Farber Cancer Institute, Boston, Massachusetts, United States; Edie Weller, Boston Children's Hospital, Boston, Massachusetts, United States; Lakshmi Ganapathi, Boston Children's Hospital, Boston, Massachusetts, United States; Thomas J. Sandora, Boston Children's Hospital, Boston, Massachusetts, United States
