CT Quantification of Interstitial Lung Abnormalities and Changes of Agerelated Pathomorphology.

BACKGROUND: Interstitial lung abnormalities (ILA) are associated with further disease progression, increased mortality risk, and decline in lung function in the elderly, which deserves enough attention. OBJECTIVE: The objective of this study was to quantify the extent of interstitial lung abnormalities (ILA) in a non-smoking asymptomatic urban cohort in China using low-dose CT (LDCT) and to analyze the age-related pathological changes. METHODS: We retrospectively analyzed clinical data and chest LDCT images from a cohort of 733 subjects who were categorized into 3 groups: 18-39, 40-59, and ≥60 years old according to age. Furthermore, we selected 40 cases of wax-embedded lung tissue blocks archived after pulmonary bullectomy and the same age groups were categorized. Four representative CT signs of ILA, including interlobular septal thickening (ILST), intralobular interstitial thickening (ILIT), ground-glass opacity (GGO), and reticular shadow (RS), were semi-quantified based on the percentage of the affected area. The scores and distribution of four CT signs of ILA were compared between different sex and age groups. The age-related pathological changes were analyzed. RESULTS: The ILA findings were found predominantly in the lower lobes and the subpleural region. The semi-quantitative scores of four CT signs in all subjects under 40 were 0. However, in subjects over 40 years old, the scores gradually increased with age, although most of them remained low. The size of the alveoli increased, the number of alveoli decreased, the alveolar septum became thinner, and the number of ATII cells increased with age. A statistically significant difference was observed among the different age groups (χ2=50.624, P=0.033; χ2=80.000, P=0.043; χ2=33.833, P=0.000; χ2=13.525, P=0.031). The macrophage population and the percentage of collagen fibers in the alveolar septum increased, while the percentage of elastic fibers decreased with age. There was no significant difference among the different age groups (χ2=19.817, P=0.506; χ2=52.419, P=0. 682; χ2=54.868, P=0.518). CONCLUSION: When the four CT signs mentioned above are in the upper central area, and the score has a medium or high score, it is crucial to determine the underlying pathological causes. ILA may be the result of chronic lung injury.

Comparison of two multiplex PCR tests for common pathogen detection in hospitalized children with acute respiratory infection.

INTRODUCTION: Multiplex PCR methods have significantly improved the diagnosis of acute respiratory tract infections (ARTIs) in children. The ResP-CE System coupled with capillary electrophoresis is a highly specialized, automated, and expensive technology for detecting common pathogens in ARTIs. The XYRes-MCA System, a remarkably less expensive multiplex PCR instrument, employs hybridization for the detection of ARTI pathogens. Both methods detect 9 common microorganisms in ARTIs, i.e., RSV, FLUAV, FLUBV, ADV, PIV, HMPV, HBOV, HCOV, and MP. In this study, we aimed to compare the performance of these two methods in the detection of pathogens from sputum specimens collected from children with ARTIs. METHODOLOGY: Sputum specimens were collected from 237 hospitalized children with ARTIs. Nucleic acid was extracted on an automated workstation. The ResP-CE and XYres-MCA systems were applied to detect pathogens from the samples, and the test result agreement between the two methods was evaluated using Kappa statistics. RESULTS: The ResP-CE and XYres-MCA identified pathogens, single or in combination, in 151 (63.7%) and 171 (72.1%) of 237 samples, respectively. Approximately 85% of positive samples identified by either method contained a single pathogen. Moderate to almost perfect concordance between the two methods was found in detecting the following 7 pathogens: RSV, FLUAV, FLUBV, PIV, HMPV, HBOV, and MP. CONCLUSIONS: These two methods are comparable in detecting common pathogens of ARTIs in children. As XYres-MCA analysis is more cost-effective, it could play an important role in diagnosing ARTIs in children in less economically developed regions.

Carbapenem-resistant Klebsiella pneumoniae Osteoarthritis in Two Preterm Infants Treated With Ceftazidime-avibactam.

BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major threat to global public health. CRKP infections are challenging to treat owing to the limited number of antibiotic species, especially in preterm infants. Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic with activity against CRKP. At present, there have been no reports of using CAZ-AVI to treat osteoarthritis in premature infants. METHODS: We describe 2 preterm infants with CRKP osteoarthritis treated with CAZ-AVI in a tertiary children's hospital in China. Clinical characteristics, laboratory and microbiologic data, treatment and follow-up information were retrospectively collected and analyzed. RESULTS: The 2 cases were both premature infants who contracted sepsis and CRKP osteoarthritis. Meropenem and polymyxin B were initially chosen for the first infant. CAZ-AVI was then used due to persistent infection. The second infant was commenced immediately on CAZ-AVI after receipt of antimicrobial susceptibility on the 4th day after admission. Both recovered with CAZ-AVI (50 mg/kg q8h) and surgical incision and drainage. Neither had a joint deformity or limb length discrepancy at 36 and 34 months, respectively. CONCLUSIONS: This is the first report on the use of CAZ-AVI to treat CRKP osteoarthritis in premature infants. Successful treatment depends on prompt recognition of the pathogen and treatment with a combination of antibiotics with or without surgery. Further study is needed to determine the pharmacokinetics and pharmacodynamics of CAZ-AVI for treating preterm infants with serious CRKP osteoarthritis.

Living arrangements and depression of the older adults- evidence from the Chinese longitudinal healthy longevity survey.

BACKGROUND: The mental health and living arrangements of older adults are worthy of attention. Previous studies have pointed out that the living arrangements may be related to older adults' depression. However, it has not been found that studies concern the relationship between actual living arrangements, living arrangement preferences, and the fit between living arrangement preferences and reality and depression in older adults, so we carried out this study. METHODS: The data from the Chinese longitudinal healthy longevity survey were used in this study. With the older adults' depression as the dependent variable and the living arrangement related variables as the independent variable, we constructed three binary-logistic regression analysis models to explore the potential relationship between living arrangement related variables and depression in older adults. RESULTS: We found that the actual living arrangements, living arrangement preferences, and the fit between living arrangement preferences and reality are significantly correlated with depression in older adults. Specifically, older adults living alone or only with the spouse are at greater risk of depression. Older adults who prefer living alone or only with the spouse are at relatively low risk of depression. Older adults whose living arrangement preferences do not match reality have a higher risk of depression. CONCLUSION: The living arrangement related variables are significantly correlated with depression in older adults. In addition to the actual living arrangements, living arrangement preferences and whether the living arrangement preferences fit with reality are also related to the depression of older adults.

Chronic stress and turnover intention of resident physicians after experiencing COVID-19.

BACKGROUND: Previous studies have explored the stress and turnover intention of healthcare workers, but as important backup talents in the healthcare system, resident physicians have received little attention from researchers, especially after experiencing COVID-19. Therefore, this study aims to evaluate the chronic stress and turnover intention of resident physicians after experiencing COVID-19. METHODS: From June to August 2022, we conducted a questionnaire survey on resident physicians in the Children's Hospital of Hebei Province through the online platform (Wenjuanxing) to evaluate their chronic stress and turnover intention after experiencing COVID-19. For the collected data, we used frequency and percentage to make the statistical description, the Chi-square test to make a univariate analysis on the scores of chronic stress and turnover intention scale, and binary logistic regression analysis to explore the influencing factors of turnover intention. RESULTS: Out of 143 respondents, we finally received 127 questionnaires, with a response rate of 88.81%. Among 127 respondents, 80.31% of resident physicians experienced varying degrees of chronic stress (mild: 36.22%, moderate: 35.43%, severe: 8.66%), and 74.80% of resident physicians showed varying degrees of turnover intention (mild: 23.62%, moderate: 37.79%, severe: 13.39%). Moreover, age (OR = 0.772, P = 0.042), identity (OR = 8.648, P = 0.021), and chronic stress levels (mild: OR = 6.938, P = 0.003; moderate: OR = 44.049, P < 0.003; severe: OR = 46.141, P = 0.004) can significantly affect turnover intention. CONCLUSION: In this study, we reported a relatively high proportion of resident physicians with high chronic stress and high turnover intention after experiencing COVID-19. We suggest that the relevant departments should pay more attention to the resident physicians' group and formulate corresponding measures to solve the problems faced by the resident physicians and ensure the stability of the health human resources.

A Prospective Observational Study of Children with FS-Associated Hospitalization: The Implication and Outcomes of Pathogen Detection in Cerebrospinal Fluid.

Background: Febrile seizures (FS) are a common cause of paediatric emergencies, but research on their aetiology and epidemiology are limited. The aim of this study was to investigate the prevalence of central nervous system (CNS) pathogenic infections in patients with FS-associated hospitalization. Methods: A prospective observational study was conducted in children under 16 years of age with FS-associated hospitalization. Demographic, clinical and laboratory data were recorded. Multiplex-PCR was performed on cerebrospinal fluid (CSF) samples for nine viruses, nine bacteria and one fungus. Results: A total of 119 children were enrolled between June 2021 and June 2022. Of these, 83.2% had a final diagnosis of FS (69.7%) or FS plus (13.4%). In addition, epilepsy and encephalitis/meningitis were also found in 16.8% (20/119). Seven pathogens were identified from 9 CSF samples (7.6%), including viruses (EV, EBV, HHV-6) and bacteria (H. influenzae, S. pneumoniae, M. tuberculosis, S. putrefaciens). There were no significant clinical or laboratory differences between children who tested positive or negative for pathogens in the CSF, except for the presentation of herpes pharyngitis. Children with encephalitis/meningitis had longer hospital stays compared with those diagnosed with FS at discharge; abnormal EEG findings were significantly more common in patients with epilepsy. Conclusion: FS-associated hospitalized children may have viral or bacterial intracranial infections. Pathogen testing of CSF is an important basis for timely antibiotic or antiviral therapy when clinical and laboratory findings make FS indistinguishable from other CNS disorders.

Epithelial lining fluid concentrations of ceftriaxone in children with community-acquired pneumonia.

Ceftriaxone is widely used in children with community-acquired pneumonia. Currently, there are no available data regarding epithelial lining fluid (ELF) concentrations of ceftriaxone in children. Thus, blood and bronchoalveolar lavage fluids samples were collected by using an opportunistic sampling design, then we determined plasma and ELF concentrations in 22 children (0.5-11.7 years), with a total of 36 plasma and 22 ELF samples available for analysis. Ceftriaxone plasma and ELF concentrations ranged from 1.07 to 138.71 mg/L and from 0.61 to 26.69 mg/L, respectively. Ceftriaxone concentration in ELF was 12.18 ± 5.15 (mean ± standard deviation) times higher than that in plasma, ranging from 1.29 to 20.44.

Meropenem for children with severe pneumonia: Protocol for a randomized controlled trial.

Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds the minimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia. Methods: One hundred patients (aged 3 months to 15 years) will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5-1 h infusion) and a model treatment group (20 mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children's Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207). Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia. Clinical Trial Registration: http://www.chictr.org.cn identifier, ChiCTR2200061207.

Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis.

The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic−pharmacodynamic analysis in Chinese newborns with the goal to optimize meropenem dosing regimens for LOS therapy. An opportunistic sampling strategy was used to collect meropenem samples, followed by model building and validation. A Monte Carlo simulation was performed to show the probability of target attainment (PTA) for various dosages. The information from 78 newborns (postmenstrual age: 27.4−46.1 weeks) was compiled and had a good fit to a 1-compartment model that had first order elimination. The median (range) values of estimated weight−normalized volume of distribution (V)and clearance (CL) were 0.60 (0.51−0.69) L/kg and 0.16 (0.04−0.51) L/h/kg, respectively. Covariate analysis revealed that postnatal age (PNA), gestational age (GA) and current weight (CW) were the most important factors in describing meropenem PK. Simulation results showed for LOS with a minimal inhibitory concentration (MIC) of 8 mg/L, the doses of 30 mg/kg 3 times daily (TID) as a 1-h infusion for newborns with GA ≤ 37 weeks and 40 mg/kg TID as a 3-h infusion for those with GA > 37 weeks were optimal, with PTA of 71.71% and 75.08%, respectively. In conclusion, we proposed an evidence-based dosing regimen of meropenem for LOS in Chinese newborns by using the population pharmacokinetic−pharmacodynamic analysis, based on domestic common pathogens and their susceptibility patterns.

Improving the efficacy for meropenem therapy requires a high probability of target attainment in critically ill infants and children.

Probability of target attainment is the key factor influencing the outcome of meropenem therapy. The objective of the present study was to evaluate the relationship between the time in which the plasma free concentration of meropenem exceeds the minimum inhibitory concentration of pathogens (fT >MIC) during therapy and the clinical outcome of treatment to optimize meropenem therapy. Critically ill children with infections who had received intravenous meropenem monotherapy were included. The relationship between fT >MIC of meropenem and effectiveness and safety were explored. Data from 53 children (mean age ± standard deviation, 26 months ± 38) were available for final analysis. Children with fT >MIC ≥ 5.6 h (n = 14) had a more significant improvement in antibacterial efficacy in terms of decrease in fever (p = 0.02), white blood cell count (p = 0.014), and C-reactive protein (p = 0.02) compared with children with fT >MIC < 5.6 h (n = 39) after meropenem therapy completed. No drug-related adverse events were shown to have a causal association with meropenem therapy. Our study shows the clinical benefits of sufficient target attainment of meropenem therapy. Meeting a suitable pharmacodynamic target attainment of meropenem is required to ensure better antibacterial efficacy in critically ill infants and children. Clinical Trial Registration: clinicaltrials.gov, Identifier NCT03643497.

Clinical utility of a model-based amoxicillin dosage regimen in neonates with early-onset sepsis.

Early-onset sepsis (EOS) is one of the most significant causes of morbidity and mortality in neonates. Currently, amoxicillin is empirically used to treat neonates with EOS. However, data on its effectiveness in neonates with EOS are still limited. Therefore, we aimed to evaluate the pharmacodynamics (PD) target attainment and effectiveness of a model-based amoxicillin dosage regimen in these neonates. We used a previously developed model and collected additional clinical data from the EOS neonates who used the model-based dosage regimen (25 mg/kg every 12 h). The primary outcomes were PD target attainment (free drug concentration above minimum inhibitory concentration during 70% of the dosing interval) and treatment failure rate. The secondary endpoints were length of amoxicillin treatment, duration of hospitalization etc. Seventy-five neonates (postmenstrual age 28.4-41.6 wk) were enrolled. A total of 70 (93.3%) neonates reached their PD target using 1 mg/L as the minimum inhibitory concentration breakpoint. The treatment failure rate was 10.7%.

Mental Health Among Medical Students During COVID-19: A Systematic Review and Meta-Analysis.

Background: The mental health of medical students is an issue worthy of attention, especially during COVID-19. Many studies have shown that depression and anxiety are the main problems faced by medical students. To assess the pooled prevalence of depression and anxiety among medical students worldwide, we conducted this meta-analysis. Methods: According to PRISMA, we used a computerized strategy to search studies in EMBASE, PubMed, PsycArticles, Web of Science, and China Biology Medicine disc. The pooled prevalence of depression and anxiety was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis. Sensitivity analysis and publication bias were also carried out in this meta-analysis. Results: Of 1316 studies, 41 studies were selected based on 36608 medical students. The pooled depression prevalence was 37.9% (95% CI: 30.7-45.4%), and pooled anxiety prevalence was 33.7% (95% CI: 26.8-41.1%). The prevalence of depression and anxiety among medical students varied by gender, country, and continent. Conclusion: The data reported that the prevalence of depression and anxiety among medical students during COVID-19 was relatively higher than those of the general population and the healthcare workers. The impact of COVID-19 on medical students and how to protect the mental health of medical students are needed to determine through further research. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021274015], identifier [CRD42021274015].

Kawasaki disease: lncRNA Slco4a1 regulates the progression of human umbilical vein endothelial cells by targeting the miR-335-5p/POU5F1 axis.

Background: Kawasaki disease (KD) is an autoimmune disease with systemic vasculitis as the main pathological change, and is most common in children under 5. The role of long non-coding RNAs (lncRNAs) in human diseases has been highlighted. LncRNA Slco4a1 was reported to promote cell growth and act as an oncogenic regulator in cancer. However, the role of lncRNA Slco4a1 in KD remains unclear. This study aimed to investigate the role and mechanism of lncRNA Slco4a1 in KD. Methods: Enzyme linked immunosorbent assay (ELISA), qRT-PCR, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were conducted to explore the function of lncRNA Slco4a1. The interaction between POU5F1 and miR-335-5p was analyzed by the RIP assay and dual luciferase assay. Results: LncRNA Slco4a1 was significantly upregulated in the serum of KD patients compared with healthy controls. LncRNA Slco4a1 was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated with KD serum. LncRNA Slco4a1 overexpression could promote the expression of inflammatory factors and apoptosis in HUVECs. The number of inflammatory cells and the infiltration area of the coronary artery in KD rats were decreased after lncRNA Slco4a1 silencing. Furthermore, lncRNA Slco4a1 is a sponge of miR-335-5p and negatively regulated the expression of miR-335-5p. POU5F1 was the downstream target of miR-335-5p, and miR-335-5p overexpression could upregulate the expression of POU5F1. Additionally, miR-335-5p overexpression could inhibit the expression of inflammatory factors and apoptosis in HUVECs. We further investigated the effect of lncRNA Slco4a1 on the mitogen-activated protein kinase (MAPK) signaling pathway, and the results showed that lncRNA Slco4a1 could promote the activation of the MAPK signaling pathway. Conclusions: Together, these results indicated that lncRNA Slco4a1 could regulate the progression of HUVECs in KD by targeting the miR-335-5p/POU5F1 axis, providing new insights for KD treatment.

Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance.

Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine. Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program. Results: The data (n = 36) from 20 infants (age range, 0.35-1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09-0.29) L/h/kg and 0.34 (0.24-0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively. Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.

Individualized Study of Posterior Hemivertebra Excision and Short-Segment Pedicle Screw Fixation for the Treatment of Congenital Scoliosis.

OBJECTIVES: To compare the surgical effect of children with symmetrical screw fixation and asymmetric screw fixation during posterior hemivertebra excision and short-segment pedicle screw fixation for the treatment of congenital scoliosis (CS). METHODS: A total of 30 children with CS who underwent posterior hemivertebra excision and short-segment bilateral pedicle screw fixation in our hospital from 2012 to 2018 were retrospectively included and were divided into two groups: symmetric fixation group (n = 18) and asymmetric fixation group (n = 12). The total main curve, segmental main curve, cranial compensatory curve, caudal compensatory curve, coronal balance, and apical vertebra translation were measured in the coronal plane. The segmental kyphosis, thoracic kyphosis, lumbar lordosis, and sagittal balance were measured in the sagittal plane. RESULTS: Of the 30 children, 28 hemivertebrae were resected. Twenty-two children had one hemivertebra, three had two hemivertebrae, and five were rib deformities. The average operation time was 268 min (180-420 min). The average blood loss was 291 mL (150-550 mL). The average follow-up was 21.1 months (12-47 months). For symmetric fixation group and there were significant differences among postoperative and follow-up parameters including the total main curve, segmental main curve, cranial compensatory curve, caudal compensatory curve, apical vertebra translation and segmental kyphosis compared with those of preoperative parameters (P < 0.05). The postoperative coronal balance was significantly lower than preoperative coronal balance (P < 0.05). The follow-up thoracic kyphosis was significantly higher than preoperative and postoperative thoracic kyphosis (P < 0.05). For asymmetric fixation group, the postoperative and follow-up parameters including the total main curve, segmental main curve, cranial compensatory curve, caudal compensatory curve, apical vertebra translation, and segmental kyphosis had statistical differences compared with those of preoperative parameters (P < 0.05). The postoperative sagittal balance was significantly higher than preoperative postoperative (P < 0.05). There were no significant differences in the postoperative and follow-up correction rate and correction loss between the two groups (P > 0.05). There were three complications in 30 children in our study, including two cases who had poor wound healing, and the wound healed smoothly after half a month of sterile dressing change. Postoperative curve progression occurred in one case after T12 and L3 hemivertebra resection and thoracic hemivertebra resection was planned again. CONCLUSION: For pedicles which were difficult for screw fixation, adjacent segments can be chosen for screw fixation and it is safe and effective for vertebral pedicles ≤3 without internal fixation.

Prospective case-control study of enterovirus detection differences in children's cerebrospinal fluid between multiplex PCR and real-time RT-PCR assay.

BACKGROUND: Viral encephalitis is common in childhood. It is an acute brain parenchymal inflammation caused by a variety of viral infection, and enterovirus accounts for the majority. Due to atypical clinical manifestations, pathogenic testing is important for assisting clinical diagnosis. The purpose of this study was to evaluate the performance of the multiplex PCR assay compared with quantitative real-time PCR for enterovirus detection. METHODS: A prospective case-control study was performed involving 103 pediatric patients suspected for viral encephalitis and cerebrospinal fluid (CSF) samples were collected and tested for 9 pathogens using multiplex PCR assay during April to November in 2018. In parallel, an aliquot of samples was tested for enterovirus infection by real-time PCR assay. RESULTS: There were 85.4% children were confirmed as viral encephalitis on discharge, the remaining ones were diagnosed as other CNS diseases, such as epilepsy. The specificity of the two methods was the same as that of the clinical diagnosis, but the sensitivity and consistency with clinical diagnosis of multiplex PCR were both higher than the real-time PCR. Besides of enterovirus, multiplex PCR could also detect coinfection of enterovirus with Epstein-Barr virus and mumps virus. CONCLUSION: Results of multiplex PCR method are more consistent with the clinical diagnosis and are superior to real-time PCR for detecting enterovirus in CSF.

Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Chinese Infants.

Amoxicillin is used to treat various bacterial infections (eg, pneumonia, sepsis, meningitis) in infants. Despite its frequent use, there is a lack of population pharmacokinetic studies in infants, resulting in a substantial variability in dosing regimens used in clinical practice. Therefore, the objective of this study was to evaluate the population pharmacokinetics of intravenous amoxicillin in infants and suggest an optimal dosage regimen. Blood samples were collected for the determination of amoxicillin concentrations using an opportunistic sampling strategy. The amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 62 pharmacokinetic samples from 47 infants (age range, 0.09 to 2.0 years) were available for analysis. A 2-compartment model with first-order elimination was most suitable to describe the population pharmacokinetics of amoxicillin, and covariate analysis showed that only current body weight was a significant covariate. Monte Carlo simulation demonstrated that the currently used dosage regimen (25 mg/kg twice daily) resulted in only 22.4% of infants reaching their pharmacodynamic target, using a minimum inhibitory concentration (MIC) break point of 2 mg/L, whereas a dosage regimen (60 mg/kg thrice daily), as supported by the British National Formulary for Children, resulted in 80.9% of infants achieving their pharmacodynamic target. It is recommended to change antibiotics for infections caused by Escherichia coli (MIC = 8.0 mg/L) because only 27.9% of infants reached target using 60 mg/kg thrice daily.

Optimal Dosing of Ceftriaxone in Infants Based on a Developmental Population Pharmacokinetic-Pharmacodynamic Analysis.

Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT>MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.

Development and validation of a multiplex-PCR based assay for the detection of 18 pathogens in the cerebrospinal fluid of hospitalized children with viral encephalitis.

BACKGROUND: The Applied Biosystems 3500 Genetic Analyzer (ABI3500) allows for automated capillary electrophoresis on multiple targets. So far, the application of this method for detecting cerebrospinal fluid pathogens has hardly been reported. METHODS: To assess the performance of multiplex-PCR assay for 18 pathogens detection, 127 CSF samples from hospitalized children with suspected viral encephalitis were prospectively collected from April to November 2018. The Sanger sequencing was applied to verify this assay. RESULTS: All of the 18 target pathogens can be identified by multiplex-PCR assay at 104 copies (or CFU/mL) of each virus, bacterium and fungus. In contrast, 10 control microorganisms failed to be amplified. Approximately 68.5 % of the cases tested had positive results, the enterovirus accounted for the majority of the positive cases (63.8 %). Agreement between multiplex-PCR and sequencing was 91.49 %. CONCLUSIONS: Our findings suggest that the ABI3500-based multiplex-PCR detection kit could be a valuable diagnostic tool for pathogen detection in CSF of children with suspected viral encephalitis.