Katie B. Olney

Introduction The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC 0–24 ) over minimum concentration ( C min ) monitoring. Real‐world data supporting the feasibility of two‐concentration kinetics with first‐order equations for the estimation of vancomycin AUC 0–24 in pediatric patients are lacking. Objectives To describe the interplay of vancomycin dose, AUC 0–24 , and C min using first‐order equations within four pediatric age groups. Methods This is a single‐center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1–12 years), and adolescents (13–17 years). First‐order equations were utilized to estimate pharmacokinetic parameters and AUC 0–24 . Results Overall, 219 patients (median age of 6 years [IQR 1–12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median C min and AUC 0–24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC 0–24 values outside of the therapeutic range (400–600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between C min and AUC 0–24 . However, 71% of patients with C min values of 5–10 mg/L had an AUC 0–24 within the therapeutic range of 400–600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC 0–24 had a C min value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury. Conclusions Our data describe the relationship between vancomycin dose, C min , and AUC 0–24 in pediatric patients. We demonstrated the feasibility of using first‐order equations to estimate AUC 0–24 , using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC 0–24 and C min , which indicates that C min should not be used as a surrogate marker for a therapeutic AUC 0–24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC 0–24 for efficacy and safety monitoring.

Antimicrobial resistance continues to surmount increasing concern globally, and treatment of difficult‐to‐treat (DTR) Pseudomonas aeruginosa , carbapenem‐resistant (CR) Acinetobacter baumannii (CRAB), and CR Enterobacterales (CRE) remains a challenge for clinicians. Although previously rare, the incidence of multidrug‐resistant (MDR) and CR infections in pediatric patients has increased drastically in the last decade and is associated with increased morbidity and mortality. To combat this issue, 14 novel antibiotics, including three β‐lactam/novel β‐lactamase inhibitor combinations (βL‐βLIs) and two novel β‐lactams (βLs), have received approval from the United States Food and Drug Administration since 2010. Improving clinician understanding of the utility of these novel therapies is imperative to improve judicious decision‐making and prevent societal regression to a pre‐penicillin era. In this review, we summarize the pharmacokinetic/pharmacodynamic (PK/PD) properties, clinical efficacy and safety data, dosing considerations, and subsequent role in therapy for ceftazidime‐avibactam (CAZ‐AVI), meropenem‐vaborbactam (MER‐VAB), imipenem‐cilastatin‐relebactam (IMI‐REL), ceftolozane‐tazobactam (TOL‐TAZ), and cefiderocol in pediatric patients.