Neonatal sepsis (NS) remains a major cause of morbidity and mortality in neonates, but data on the etiology and antibiotic susceptibility patterns of pathogens are limited. The aim of this study was to analyze the clinical characteristics, risk factors, and the antibiotic susceptibility patterns of pathogenic microbes associated with NS at a tertiary children's hospital in Shanghai, China. Episodes of blood culture-proven sepsis in the neonatal intensive care unit (NICU) of Children's Hospital of Fudan University from January 2013 to August 2017 were retrospectively reviewed. Collected data included demographics, perinatal risk factors, clinical symptoms, laboratory values, microbiology results and their antimicrobial susceptibility. Data for early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) were compared. The 341 of 976 culture-positive cases were selected, including 161 EONS cases (47.21% of 341) and 180 LONS cases (52.79% of 341). 635 incomplete cases were excluded. There was significant difference in risk factors between the EONS group and LONS group including birth weight, gestational age, 1-minute Apgar score, respiratory support, and the use of peripherally insertion central catheter (PICC). Clinical symptoms such as fever, feeding intolerance, abdominal distension, and neonatal jaundice, and laboratory results such as hemoglobin and lymphocyte counts also showed between-group differences. Staphylococcus epidermidis (22.87%) , Escherichia coli (9.68%), Alcaligenes xylosoxidans (9.38%) and Klebsiella pneumoniae (9.09%) remain the principal organisms responsible for neonatal sepsis. Most isolates of Gram-positive bacteria were sensitive to vancomycin, linezolid, minocycline and tigecycline, of which more than 90% were resistant to penicillin. Most isolates of Gram-negative bacteria were sensitive to amikacin and imipenem and resistant to ampicillin. Fungus was sensitive to antifungal agents. Better medical decisions, especially early detection and appropriate initial antimicrobial therapy can be made after understanding the different clinical features and pathogens of EONS and LONS.

Objectives: To develop a population pharmacokinetic model of meropenem in children with sepsis receiving extracorporeal life support (ECLS) and optimize the dosage regimen based on investigating the probability of target attainment (PTA).Methods: The children with sepsis were prospectively enrolled in a pediatric intensive care unit from January 2018 to December 2019. The concentration-time data were fitted using nonlinear mixed effect model approach by NONMEM program. The stochastic simulation considering various scenarios based on proposed population pharmacokinetics model were conducted, and the PTAs were calculated to optimize the dosage regimens.Results: A total of 25 children with sepsis were enrolled, of whom13 received ECMO, 9 received CRRT, and 4 received ECMO combined with CRRT. 12 children received a two-step 3-h infusion and 13 children received 1-h infusion. Bodyweight and creatinine clearance had significant impacts on the PK parameters. ECMO intervention was not related to the PK properties. If 100%T > MIC was chosen as target, children receiving 40 mg/kg q8h over a 3 h-infusion only reached the PTA up to 77.4%. If bacteria with MIC 2 mg/L were to be treated with meropenem and the PTA target was 50%T > MIC, a dose of 40 mg/kg q8h for 1 h infusion would be necessary.Conclusions: The PK properties of meropenem in septic children receiving extracorporeal life support were best described. We recommended the opitimized dosing regimens for septic children receiving ECLS depending on the PTA of PK target 50%T > MIC and 100%T > MIC, for children with sepsis during ECLS with different body weight, estimated creatinine clearance (eCRCL) and MIC of bacteria.

The purposes of this study were to explore the population pharmacokinetics and initial dose optimization of sirolimus improving drug blood level for seizure control in pediatric patients with tuberous sclerosis complex (TSC). Eighty pediatric patients diagnosed with TSC-related epilepsy were included for analysis. Sirolimus concentrations, physiological and biochemical indexes, and drug combination were collected to build a nonlinear mixed effect (NONMEM) model. Initial dose optimization was simulated by the Monte Carlo method. The weight and concomitant medication of oxcarbazepine affected sirolimus clearance. Without oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.07, 0.06, 0.05, 0.04, and 0.03 mg/kg/day were recommended for weights of 5–7.5, 7.5–11.5, 11.5–19, 19–40, and 40–70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.05, 0.04, and 0.03 were recommended for weights of 5–8, 8–20, and 20–70 kg, respectively. With oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.09, 0.08, 0.07, 0.06, 0.05, and 0.04 mg/kg/day were recommended for weights of 5–7.5, 7.5–10, 10–13.5, 13.5–20, 20–35, and 35–70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.06, 0.05, 0.04, and 0.03 were recommended for weights of 5–7, 7–14.5, 14.5–38, and 38–70 kg, respectively. The present study was the first to establish a population pharmacokinetic model of sirolimus improving drug blood level for seizure control in pediatric patients with TSC and recommend the initial dosage regimen.

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Introduction Little is known about the relationship between exposure levels of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and comorbidities of systemic lupus erythematosus (SLE) in children. This study aims to explore this association. Methods Longitudinal data from SLE children, who were taking MMF for immunosuppression and under therapeutic drug monitoring (TDM), were retrospectively collected. Area under the concentration-time curve of mycophenolic acid (MPA) over 24 hours (AUC0–24h) was estimated with Bayesian methods. Logistic regression and random forest models were used to explore the association between comorbidities and MPA exposure levels. Results This study included 107 children with 358 times of follow-up (median age 169.02 months). The incidence of diabetes, acute kidney injury (AKI), or pneumonia was significantly associated with AUC0–24h (odds ratio [OR] 0.991, 95% confidence interval [CI] 0.982–0.999), SLE duration (OR 1.012, 95% CI 1.002–1.022), lymphocyte percentage (OR 0.959, 95% CI 0.925–0.991), plasma albumin levels (OR 0.891, 95% CI 0.843–0.940), use of aspirin (OR 0.292, 95% CI 0.126–0.633) and hydroxychloroquine (OR 0.407, 95% CI 0.184–0.906). The random forest model showed that albumin and AUC0–24h were two important predictors. The case group (with the three comorbidities) had a mean AUC0–24h of 73.63 mg · h/L, while the control group had a mean AUC0–24h of 100.39 mg · h/L. Conclusions Increased levels of MPA exposure are associated with decreased incidence odds of diabetes, AKI or pneumonia in SLE children. An AUC0–24h of 100.39 mg · h/L or an AUC0-12h of 50.20 mg · h/L could be used as the targeted exposure level for clinical practice.