Continuous Infusion Vancomycin Dosing and Area Under the Curve Target Attainment in a Freestanding Children’s Hospital

Abstract Corresponding author: Amanda Junker, PharmD, No conflict, Indiana University Health Academic Health Center, Indianapolis, IN, USA, 1701 N. Senate Ave | Office B222 | Indianapolis, IN, [email protected] Alternate Corresponding Author: Michelle L. Kussin, PharmD, BCOP, No conflict, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA, Indiana University School of Medicine Ryan White Center for Pediatric Infectious Diseases & Global Health, 705 Riley Hospital Drive l Office 5862A l Indianapolis, IN 46202, 317.944.6674 (office), [email protected] No conflicts of interest. BACKGROUND Intravenous vancomycin continuous infusion (IVCI) is an increasingly utilized vancomycin dosing strategy in adult populations due to potential advantages in time to target attainment, ease of drug sampling/calculations, reduced total daily dose and reduced nephrotoxicity. However, there is little literature available on the use, dosing, and monitoring of continuous infusion vancomycin in pediatric patients. Riley Hospital for Children at Indiana University Health current practice guidelines recommend initiating IVCI in patients requiring >25 mg/kg/dose intermittent infusion vancomycin, history of vancomycin infusion reaction, and when transitioning to outpatient antibiotic therapy. The objective of this study is to describe the use of IVCI in a free-standing pediatric hospital, including safety, dosing and whether patients are achieving therapeutic AUC24. METHODS This is a single-center, retrospective chart review of patients at Riley Hospital for Children who received continuous infusion vancomycin during an inpatient admission from January 2018 through September 2023. Data collected included vancomycin dose (continuous and intermittent infusions), vancomycin concentrations during IVCI course, number of dose changes, indication, pathogen targeted, outpatient parenteral antimicrobial therapy (OPAT) duration and concentrations, baseline serum creatinine (SCr), highest SCr during course, and allergy information. Endpoints of the study included average dose of IVCI to meet therapeutic targets, percent difference between final intermittent dosing versus IVCI dose in mg/kg/day, and incidence of acute kidney injury while receiving IVCI. RESULTS This retrospective cohort included 66 patients. The median age was 5.1 years (IQR 2.8, 10.9), 59% were male, 75.8% were Caucasian, the median percentile for weight was 62% (IQR 28, 85), and the median baseline serum creatinine was 0.21 mg/dL (IQR 0.2, 0.37). Osteomyelitis/septic arthritis (15/66, 22.7%) and central line associated bloodstream infections (13/66, 19.7%) were the most common indications for vancomycin in the cohort. In addition, 12 patients (18.2%) had an indication due to central nervous system infection (meningitis: 10/66, 15.2%; intracranial abscess: 2/66, 3%). The most common pathogens were methicillin resistant Staphylococcus aureus (35/66, 53%) and coagulase negative Staphylococci (16/66, 24.2%). Reasons for transitioning from intermittent to continuous infusion included facilitation of outpatient antimicrobial therapy (31/66, 47%), inability to meet therapeutic targets at IIV doses greater than 25 mg/kg/dose (14/66, 21.2%), and reduce line access (11/66, 16.7%). The average duration on inpatient courses of IVCI was 5.8 (IQR 2.9, 11) days and OPAT courses was 21.8 ± 3.6 days. The mean AUC24 at the end of the IVCI was 514 ± 13 mg*hr/L and on average patients required 1 dose change during the course. For the primary endpoint, the study found that the median dose required to achieve an AUC24 of 400-600 mg*hr/L for each age group was: <1 month 27.1 mg/kg/day; 1 to 5 months 35.8 mg/kg/day; 6 to 23 months 62.3 mg/kg/day; 2 to 5 years 61.7 mg/kg/day; 6 to 11 years 51.2 mg/kg/day; 12 to 29 years 37.1 mg/kg/day. Patients that met therapeutic target on IIV (n=15) had a median reduction in dose by 18.6% ± 18.1 to achieve therapeutic AUC24 on IVCI. The average time to meet therapeutic target on IVCI was 1.5 days for the cohort. Acute kidney injury was found in 11 (13.8%) patients. CONCLUSIONS The majority of patients in our cohort reached therapeutic AUC24 within 2 days of initiation of IVCI. Lower doses of vancomycin were required to obtain AUC within goal when administered via continuous infusion as compared to intermittent infusion, with an average reduction in total daily dose of approximately 20%. There were no concerning safety signals with use of continuous infusion vancomycin in this study.