A best-practice CCABSI prevention bundle that included ethanol lock prophylaxis in both the hospital and home was successfully implemented, well tolerated, and demonstrated a significant and sustained reduction in preventable harm in the form of CCABSIs in children with intestinal failure.

BACKGROUND At our institution, empirical vancomycin is overused in children with suspected bacterial community-acquired infections (CAIs) admitted to the PICU because of high community rates of methicillin-resistant Staphylococcus aureus (MRSA). Our goal was to reduce unnecessary vancomycin use for CAIs in the PICU. METHODS Empirical PICU vancomycin indications for suspected CAIs were developed by using epidemiological risk factors for MRSA. We aimed to reduce empirical PICU vancomycin use in CAIs by 30%. After retrospectively testing, the indications were implemented and monthly PICU empirical vancomycin use during baseline (May 2017–April 2018) and postintervention (May 2018–July 2019) periods. Education was provided to PICU providers, vancomycin indications were posted, and the antibiotic order set was revised. Statistical process control methods tracked improvement over time. Proven S aureus infections for which vancomycin was not empirically prescribed and linezolid or clindamycin use were balancing measures. RESULTS We identified 1620 PICU patients with suspected bacterial CAIs. Empirical vancomycin decreased from a baseline of 73% to 45%, a 38% relative reduction. No patient not prescribed empirical vancomycin later required the addition of vancomycin or other MRSA-targeted antibiotics. There was no change in nephrotoxicity or in the balancing measures. CONCLUSIONS Development of clear and concise recommendations, combined with clinician education and decision support via an order set, was an effective and safe strategy to reduce PICU vancomycin use. Retrospective validation of the recommendations with local data were key to obtaining PICU clinician buy in.

OBJECTIVE There is minimal published literature regarding the use of continuous-infusion vancomycin (CIV) in children. The objective of this study was to describe the use, dosing requirements, and outcomes of CIV at a free-standing children's hospital. METHODS This is a retrospective review of patients who received CIV while admitted to Nationwide Children's Hospital between July 1, 2010, and June 30, 2020. The total daily dose (TDD) of vancomycin required to attain a target serum vancomycin concentration (SVC) was compared between CIV and intermittent-infusion vancomycin (IIV) administration regimens. Safety outcomes and treatment failure were also explored. RESULTS Fourteen patients (77% male) with a median age of 7 years (IQR = 1, 10 years) were included. Most patients (71%) were started on CIV in anticipation of outpatient parenteral antimicrobial therapy. The median TDD required to achieve a target SVC was higher with IIV compared with CIV (82.4 mg/kg/day vs 50.5 mg/kg/day; p = 0.02). Despite higher TDD with IIV, median SVC with IIV was similar to SVC with CIV (16.6 mg/L vs 17.6 mg/L; p = 2.00). There were no safety concerns or therapeutic failures identified with CIV. CONCLUSIONS Continuous-infusion vancomycin was a well-tolerated and effective alternative to IIV for the patients included in this study. The TDD of vancomycin required to achieve a target SVC was lower in patients receiving CIV compared with those receiving IIV.

BackgroundReactivation of cytomegalovirus (CMV) in CMV‐seropositive patients after haploidentical T‐cell receptor αβ+/CD19+ depleted hematopoietic cell transplant (HCT) is common. Due to delayed CMV‐specific immune reconstitution, patients may require prolonged antiviral therapy, including secondary prophylaxis (SP). We present our clinical experience with the off‐label use of letermovir for SP in a severely immunocompromised 2‐year‐old toddler with refractory pre‐B‐cell ALL and bilateral retinitis caused by resistant CMV (A594V UL97 mutation) following a haploidentical TCRαβ+/CD19+ depleted HCT.MethodsThe patient underwent measurement of two separate sets of letermovir serum concentrations, drawn at pre‐dose, 1 and 4 h (and 8 h during the second therapeutic drug monitoring) post‐dose. Pharmacokinetic parameters, including AUC0–24 were calculated, and dose adjustment was performed based on the drug level.ResultsWhile receiving oral letermovir 240 mg once daily without cyclosporine, the observed AUC0–24 was high (75 815 ng h/mL) with a Cmin of 209 ng/mL. The dose was reduced by 25% to 180 mg once daily. Despite the dose reduction, both AUC0–24 and Cmin values further increased to 119 095 ng h/L and 959 ng/mL, respectively. The patient continued oral letermovir 180 mg once daily for about 3 months, with adequate viral suppression (CMV viral load in plasma <150 IU/mL) and no recurrent CMV end‐organ disease or adverse events.ConclusionsGiven limited options for anti‐CMV therapy in young children with resistant CMV, letermovir could be considered as an alternative antiviral for SP. Further studies are warranted to evaluate the pharmacokinetics of letermovir in pediatric allogeneic HCT recipients.