ABSTRACT
OBJECTIVE@#To evaluate the efficacy and safety of C-reactive protein (CRP)-guided antibiotic treatment strategy for neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 428 neonates, with a gestational age of >35 weeks, who were admitted to the Children's Hospital of Chongqing Medical University from February to July, 2019 and were suspected of EOS were enrolled as the observation group. The effect of antibiotic treatment was prospectively observed, and if clinical symptoms were improved and CRP was 35 weeks) who were admitted to this hospital from February to July, 2018 and were suspected of EOS were enrolled as the control group, and the use of antibiotics was analyzed retrospectively. The two groups were compared in terms of duration of antibiotic treatment, length of hospital stay, incidence rate of repeated infection and clinical outcome.@*RESULTS@#Compared with the control group, the observation group had significantly shorter duration of antibiotic treatment and length of hospital stay (P0.05).@*CONCLUSIONS@#For neonates with a gestational age of >35 weeks and a suspected diagnosis of EOS, CRP-guided antibiotic treatment strategy can shorten duration of antibiotic treatment and length of hospital stay and does not increase the incidence rate of repeated infection. Therefore, it holds promise for clinical application.
Subject(s)
Humans , Infant, Newborn , Anti-Bacterial Agents , Therapeutic Uses , C-Reactive Protein , Gestational Age , Retrospective Studies , Sepsis , Drug TherapyABSTRACT
Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T>C, ABCC2 c.1249G>A, ABCC 23972C>T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T>C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T>C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.
ABSTRACT
Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×((WT)/25)K×((DD)/1.5)0.293×0.657Azole,K=(WT-30.9)/(WT-30.9+10.4-30.9). When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.
ABSTRACT
Vancomycin has been widely prescribed as the first-line antibiotic in the treatment of methicillin-resistant Staphylococcus aureus and other serious Gram-positive infections. Due to its large pharmacokinetic (PK) variability and narrow therapeutic range, it requires optimization of dosage to achieve target exposure. In this study, SmartDose, a decision support system for individualization of vancomycin dosage is developed using the maximum a posterior Bayesian estimation (MAPB) by the open-source language R combined with the population PK characteristics of vancomycin in Chinese patients. It provides initial design and adjustment of dose regimens based on the therapeutic drug monitoring (TDM) results, as well as a user-defined module to facilitate optimal vancomycin therapy. SmartDose has a high computational reliability, which is validated by NONMEM, the golden standard PK software. Meanwhile, SmartDose is established as a web-based application and its operational flexibility makes it an efficient tool for vancomycin dose optimization in routine clinical settings.