Critical illness, including sepsis, causes significant pathophysiologic changes that alter the pharmacokinetics (PK) of antibiotics. Ceftriaxone is one of the most prescribed antibiotics in patients admitted to the pediatric intensive care unit (PICU). We sought to develop population PK models of both total ceftriaxone and free ceftriaxone in children admitted to a single-center PICU using a scavenged opportunistic sampling approach. We tested if the presence of sepsis and phase of illness (before or after 48 hours of antibiotic treatment) altered ceftriaxone PK parameters. We performed Monte Carlo simulations to evaluate whether dosing regimens commonly used in PICUs in the United States (50 mg/kg every 12 hours vs. 24 hours) resulted in adequate antimicrobial coverage. We found that a two-compartment model best described both total and free ceftriaxone concentrations. For free concentrations, the population clearance value is 6.54 L/h/70 kg, central volume is 25.4 L/70 kg and the peripheral volume is 19.6 L/70kg. For both models, we found that allometric weight scaling, post-menstrual age, creatinine clearance and daily highest temperature had significant effects on clearance. Presence of sepsis or phase of illness did not have a significant effect on clearance or volume of distribution. Monte Carlo simulations demonstrated that to achieve free concentrations above 1 μg/mL for 100% of the dosing intervals, a dosing regimen of 50 mg/kg every 12 hours is recommended for most patients. A continuous infusion could be considered if the target is to maintain free concentrations four times above the minimum inhibitory concentrations (4 μg/mL).

BACKGROUND Communication between inpatient pediatric hospital medicine (HM) and primary care providers (PCPs) is important for quality care. As provider workload increases, it is important to focus on a means to improve communication efficiency. Our goal was to increase the percentage of HM admissions using 1-way communication from 0% to 35% over a 16-month period. METHODS HM providers and PCPs collaborated to identify 12 admission diagnoses for which 1-way communication could be used. Using quality improvement methods, we studied the implementation of “Leave a Message” (LAM) calls for 1-way communication and providing PCPs with the option to place a return call. Control charts were used to track LAM call use and balancing measures of PCP return phone calls, additional PCP communications, and 7-day readmissions over time. RESULTS A total of 778 LAM calls were placed by HM providers over 16 months. The percentage of LAM calls out of all PCP calls placed ranged from 0% to 35% during this time, increasing significantly during winter months and before the coronavirus disease 2019 pandemic. Only 0.4% (n = 3) of LAM calls were returned by PCPs. Estimated PCP return phone calls were reduced by 11.1 calls per week. CONCLUSIONS We created a system for 1-way telephone communication between HM providers and PCPs for common, simple admissions and reduced the need for PCP return phone calls. The low percentage of LAM calls returned by PCPs may suggest that 1-way communication is adequate for most simple admissions.

Introduction:Early sepsis results in pharmacokinetic (PK) changes due to physiologic alterations. PK changes can lead to suboptimal drug target attainment, risking inadequate coverage from antibiotics like ceftriaxone. Little is known about how ceftriaxone PK and target attainment quantitatively change over time in patients with sepsis or the association between target attainment and outcomes in critically ill children and young adults. Methods:A retrospective analysis of a prospective study was conducted in a singlecenter pediatric intensive care unit. Septic patients given at least one ceftriaxone dose (commonly as 50 mg/kg every 12 h) and who had blood obtained in both the first 48 h of therapy (early) and afterwards (late) were included. Normalized clearance and central volume were estimated and compared in both sepsis phases. We evaluated target attainment, defined as concentrations above 1× or 4× the minimum inhibitory concentration (MIC) for 100% of dosing intervals, and investigated the association between target attainment and clinical outcomes.Results: Fifty-five septic patients (median age: 7.5 years) were included. Normalized clearance and central volume were similar in both phases (6.18 ± 1.48 L/h/70 kg early