Population pharmacokinetics of fluconazole for prevention or treatment of invasive candidiasis in Chinese young infants.

The dosing of fluconazole for young infants remains empirical because of the limited pharmacokinetic (PK) data. We aimed to establish a population PK model and assess the systematic exposure-response of commonly used regimens of fluconazole in Chinese infants. We included infants with a postnatal age of less than 120 days and received intravenous fluconazole. Both scheduled and scavenged plasma samples were collected, and fluconzaole concentration was determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using Phoenix NLME, and then Monte Carlo simulation was conducted to predict the probability of target attainment (PTA) of empirically used regimens of both prophylactic and therapeutic purposes. Based on 304 plasma samples from 183 young infants, fluconazole concentration data was best described by a one-compartment model with first-order elimination. Gestational Age (GA), postnatal age (PNA), and body weight (BW) were included in the final model as CL = 0.02*(GA/214)2.77*(PNA/13)0.24*exp(nCL); V = 1.56*(BW/1435)0.90*exp(nV). Model validation revealed the final model had qualified stability and acceptable predictive properties. Monte Carlo simulation indicated that under the same minimum inhibitory concentration (MIC) value and administration regimen, PTA decreased with GA and PNA. The commonly used prophylactic regimens can meet the clinical need, while higher doses might be needed for treatment of invasive candidiasis. This population PK model of fluconazole discriminated the impact of GA and PNA on CL and BW on V. Dosing adjustment was needed according to the GA and PNA of infants to achieve targeted exposures.

[Analysis of IVD gene variants in four children with isovalerate acidemia].

OBJECTIVE: To detect variants of IVD gene among 4 neonates with suspected isovalerate acidemia in order to provide a guidance for clinical treatment. METHODS: 111 986 newborns and 7461 hospitalized children with suspected metabolic disorders were screened for acyl carnitine by tandem mass spectrometry. Those showing a significant increase in serum isovaleryl carnitine (C5) were analyzed for urinary organic acid and variants of the IVD gene. RESULTS: Four cases of isovalerate acidemia were detected, which included 2 asymptomatic newborns (0.018‰, 2/111 986) and 2 children suspected for metabolic genetic diseases (0.268‰, 2/7461). The formers had no obvious clinical symptoms. Analysis of acyl carnitine has suggested a significant increase in C5, and urinary organic acid analysis has shown an increase in isovaleryl glycine and 3-hydroxyisovalerate. Laboratory tests of the two hospitalized children revealed high blood ammonia, hyperglycemia, decreased red blood cells, white blood cells, platelets and metabolic acidosis. The main clinical manifestations have included sweaty foot-like odor, feeding difficulty, confusion, drowsiness, and coma. Eight variants (5 types) were detected, which included c.158G>A (p.Arg53His), c.214G>A (p.Asp72Asn), c.548C>T (p.Ala183Val), c.757A>G (p.Thr253Ala) and 1208A>G (p.Tyr403Cys). Among these, c.548C>T and c.757A>G were unreported previously. None of the variants was detected by next generation sequencing of 2095 healthy newborns, and all variants were predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The incidence of isovalerate acidemia in Liuzhou area is quite high. Screening of metabolic genetic diseases is therefore recommended for newborns with abnormal metabolism. The discovery of novel variants has enriched the mutational spectrum of the IVD gene.

Risk Identification of Bronchopulmonary Dysplasia in Premature Infants Based on Machine Learning.

Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. This disease is caused by long-time use of supplemental oxygen, which seriously affects the lung function of the child and imposes a heavy burden on the family and society. This research aims to adopt the method of ensemble learning in machine learning, combining the Boruta algorithm and the random forest algorithm to determine the predictors of premature infants with BPD and establish a predictive model to help clinicians to conduct an optimal treatment plan. Data were collected from clinical records of 996 premature infants treated in the neonatology department of Liuzhou Maternal and Child Health Hospital in Western China. In this study, premature infants with congenital anomaly, premature infants who died, and premature infants with incomplete data before the diagnosis of BPD were excluded from the data set. After exclusion, we included 648 premature infants in the study. The Boruta algorithm and 10-fold cross-validation were used for feature selection in this study. Six variables were finally selected from the 26 variables, and the random forest model was established. The area under the curve (AUC) of the model was as high as 0.929 with excellent predictive performance. The use of machine learning methods can help clinicians predict the disease so as to formulate the best treatment plan.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive diseases in China: a meta-analysis.

BACKGROUND: To summarize information about invasive pneumococcal disease (IPD) among children in mainland China. METHODS: Sixteen eligible studies were included in this systematic review and the random effect model was used to estimate the pool prevalence of IPD. RESULTS: The most predominant serotypes circulating in children were 19F (27.7, 95% confidence interval (95% CI): 17.7-37.6%), 19A (21.2%, 16.4-26.1%), 14 (16.5%, 12.8-20.1%), 6B (8.6%, 5.2-10.8%) and 23F (7.3%, 5.2-9.5%). The serotype coverage of the available pneumococcal conjugate vaccines PCV7, PCV10, and PCV13 was 60.8% (52.5-69.4%), 65.1% (57.7-72.4%), and 90.0% (87.1-92.8%), respectively. The pooled antibiotic resistance rates of Streptococcus pneumoniae revealed a resistance to penicillin prevalence rate of 32.0% (12.1-51.9%). Approximately 94.4% (90.7-98.1%) and 92.3% (87.4-97.3%) of isolates were resistant to erythromycin and clindamycin. eBURST analysis revealed great diversity among isolates, with 102 sequence types (STs) for 365 isolates. The major predominant clonal complexes (CCs) were CC271 (43.6%, 159/365), CC876 (13.4%, 49/365), CC81 (5.2%, 19/365), and CC90 (4.1%, 15/365). Long-term and regional surveillance of S. pneumoniae is necessary. CONCLUSIONS: Based on our pooled results showing that PCV13 coverage of the reported serotypes was 90% and that most serotypes contributed to the distribution of antibiotic-resistant isolates, implementation of PCV13 into the Chinese Expanded Program on Immunizations (EPI) would achieve health benefits in Chinese children.

Persistent candidemia in very low birth weight neonates: risk factors and clinical significance.

BACKGROUND: The prevalence and risk factors for persistent candidemia among very low birth weight infants are poorly understood. This study aimed to investigate the epidemiology of persistent candidemia over a 4-year period in a neonatal intensive care unit (NICU) in Liuzhou, China. METHODS: We retrospectively extracted demographic data, risk factors, microbiological results and outcomes of very low birth weight infants with candidemia in our hospital between January 2012 and November 2015. Persistent candidemia was defined as a positive blood culture for > 5 days. Logistic regression was used to identify risk factors associated with persistent candidemia. RESULTS: Of 48 neonates with candidemia, 28 had persistent candidemia. Both mechanical ventilation and intubation were significantly associated with increased rates of persistent candidemia (P = 0.044 and 0.004, respectively). The case fatality rate for the persistent candidemia group was 14.3%. CONCLUSION: The rate of persistent candidemia was high among very low birth weight neonates. Mechanical ventilation and intubation were the major factors associated with the development of persistent candidemia. This study highlights the importance of intensive prevention and effective treatment among neonates with persistent candidemia.

Epidemiology of birth defects based on surveillance data from 2011-2015 in Guangxi, China: comparison across five major ethnic groups.

BACKGROUND: The causes of birth defects (BDs) are complex and include genetic and environmental factors and/or their interactions. More research is needed to describe the epidemiology of BDs within specific regions of China. This study focused on differences in the prevalence of BDs based on ethnicity in a large city in Guangxi Province, China. METHODS: Surveillance data of infants born in 114 registered hospitals in Liuzhou between 2011 and 2015 were analyzed to determine the epidemiology of BDs across five major ethnic groups. We calculated the prevalence of BDs and relative risk of BDs by ethnicity. RESULTS: There were 260,722 perinatal infants of which 6581 had BDs, with the average prevalence of 25.24 per 1000 perinatal infants (PIs). Prevalence data showed an obvious uptrend over the past 5 years. Han had the highest prevalence of total BDs (28.98‰), followed by Zhuang (25.19‰), Yao (18.50‰), Miao (15.78‰) and Dong (14.24‰). Relative to the Han; Zhuang, Miao, Yao, and Dong had a lower risk of musculoskeletal and urogenital malformations; Miao and Yao had a lower risk of cardiovascular malformation; and Dong had a lower risk of cardiovascular and craniofacial malformation. Several maternal risk factors were found to be associated with BDs (e.g., maternal and gestational age, number of antenatal care visits). CONCLUSION: This study provided a comprehensive description of ethnic differences in the risk of BDs in Liuzhou City, China. Observed ethnic differences in the risk of BDs may be related to genetic susceptibilities, environment, cultural customs, or to potential combinations of these factors.

Epidemiology of and risk factors for neonatal candidemia at a tertiary care hospital in western China.

BACKGROUND: The prevalence and clinical characteristics of neonatal candidemia are poorly understood in western China. The aim of our study was to evaluate the epidemiological features of neonatal candidemia in the Liuzhou Maternity and Child Healthcare Hospital. METHODS: A retrospective case-control study was conducted between January 2012 and November 2015. Electronic databases were reviewed and data on Candida species were isolated from blood cultures and candidemia incidence, risk factors, and mortality were extracted. Univariate and multivariate logistic regression analysis were performed to identify risk factors associated with candidemia. RESULTS: During the 4-year period, candidemia was identified in 69 newborns, for an incidence rate of 13.6 per 1000 admissions. Prolonged antibiotic therapy duration [odds ratio (OR), 95% confidence incidence (95% CI) = 1.06, 1.01-1.10], total parenteral nutrition [OR, 95% CI = 6.03, 2.10-17.30] and neurodevelopmental impairment (OR, 95% CI = 7.34, 1.18-45.80) were all associated with increased odds of candidemia development in infants (P value was 0.010, 0.001, 0.033, respectively). The overall mortality rate was 7.2% in the candidemia group. CONCLUSIONS: Prolonged duration of antibiotic therapy, presence of total parenteral nutrition and neurodevelopmental impairment were the major risk factors associated with neonatal candidemia. This study highlights the importance of the early detection, diagnosis and treatment of neonatal candidemia.

Risk factors and clinical analysis of candidemia in very-low-birth-weight neonates.

BACKGROUND: Candidemia is the third leading cause of morbidity and mortality in preterm or very-low-birth-weight infants. The incidence and risk factors of candidemia in this population are poorly known in western China. METHODS: A case-control retrospective study of candidemia was conducted from January 2012-November 2015 in the Liuzhou Maternity and Child Healthcare Hospital. Data were analyzed by univariate analysis and multivariate logistic regression. RESULTS: Forty-eight confirmed cases of candidemia were identified during the study period, indicating an incidence of 106.9 per 1,000 admissions of very-low-birth-weight infants. Candida albicans was the most common pathogen and was isolated in 39.6% of infants with candidemia. The mortality rate of the case group was 10.4% versus 2.1% in the control group (P = .128). The multivariable logistic regression model identified that carbapenem use (odds ratio [OR], 11.39; 95% confidence interval [CI], 3.28-39.54), total parenteral nutrition (OR, 10.16; 95% CI, 2.25-45.94), and prolonged hospitalization (OR, 1.04; 95% CI, 1.01-1.07) were all associated with the risk of developing neonatal candidemia. CONCLUSION: Very-low-birth-weight infants are at a significantly high risk of developing candidemia. The local neonatal intensive care unit management teams should effectively focus on decreasing the overall use of carbapenems, improving catheter care, removing catheters early, and shortening hospitalizations to reduce the incidence of candidemia.