RESUMEN
Emergent resistance to antibiotics among Streptococcus pneumoniae isolates is a severe problem worldwide. Antibiotic resistance profiles for S pneumoniae isolates identified from pediatric patients in mainland China remains to be established.The clinical features, antimicrobial resistance, and multidrug resistance patterns of S pneumoniae were retrospectively analyzed at 10 children's hospitals in mainland China in 2016.Among the collected 6132 S pneumoniae isolates, pneumococcal diseases mainly occurred in children younger than 5 years old (85.1%). The resistance rate of S pneumoniae to clindamycin, erythromycin, tetracycline, and trimethoprim/sulfamethoxazole was 95.8%, 95.2%, 93.6%, and 66.7%, respectively. The resistance rates of S pneumoniae to penicillin were 86.9% and 1.4% in non-meningitis and meningitis isolates, while the proportions of ceftriaxone resistance were 8.2% and 18.1%, respectively. Pneumococcal conjugate vaccine was administered to only 4.1% of patients. Penicillin and ceftriaxone resistance, underling diseases, antibiotic resistant risk factors, and poor prognosis appeared more frequently in invasive pneumococcal diseases. The incidence of multidrug resistance (MDR) was 46.1% in patients with invasive pneumococcal disease which was more than in patients with non-invasive pneumococcal disease (18.3%). Patients with invasive pneumococcal disease usually have several MDR coexistence.S pneumoniae isolates showed high resistance to common antibiotics in mainland China. Penicillin and ceftriaxone resistance rate of invasive streptococcal pneumonia patients were significantly higher than that of non-invasive S pneumoniae patients. Alarmingly, 46.1% of invasive clinical isolates were multidrug resistant, so it is important to continued monitor the resistance of S pneumoniae when protein conjugate vaccine (PCV13) is coming in mainland China.
Asunto(s)
Antibacterianos/farmacología , Infecciones Neumocócicas/epidemiología , Streptococcus pneumoniae/aislamiento & purificación , Ceftriaxona/farmacología , Niño , Preescolar , China/epidemiología , Farmacorresistencia Bacteriana Múltiple , Eritromicina/farmacología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Penicilinas/farmacología , Infecciones Neumocócicas/microbiología , Estudios Retrospectivos , Streptococcus pneumoniae/efectos de los fármacos , Combinación Trimetoprim y Sulfametoxazol/farmacologíaRESUMEN
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare life threatening congenital autoimmune disorder caused by mutations in the forkhead box protein 3 (FOXP3) gene. The main typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases, which usually appear in the first months of life and cause death without treatment. Here, we report a 6-year-old boy with late-onset IPEX syndrome due to a c.1190G>A (p. R397Q) mutation in exon 11 of the FOXP3 gene. The boy had intractable diarrhea, abdominal pain, recurrent infections, and failure to thrive. However, diabetes and skin diseases were not observed in the patient. The patient was received metronidazole, teicoplanin, fluconazole, mycamine, ceftriaxone, azithromycin, and fecal microbiota transplantation for treating infections, methylprednisolone and infliximab for suspicion of Crohn's disease after admission. Finally, the boy was diagnosed as IPEX syndrome by genetic test and received hematopoietic stem cell transplantation (HSCT). Our findings suggests that IPEX should be considered in cases of late-onset, mild forms, and less typical clinical manifestations to avoid diagnostic delay.
RESUMEN
Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p < 0.001) or NHS (p < 0.001). The area under receiver operating characteristic curve for TCDCA/CDCA to differentiate BA from NHS was 0.923 (95% CI: 0.862-0.984). These findings were supported by significantly altered expression levels of bile acid transporters and nuclear receptors in liver including farnesoid X receptor (FXR), small heterodimer partner (SHP), bile salt export pump (BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants.
Asunto(s)
Ácidos y Sales Biliares/sangre , Atresia Biliar/diagnóstico , Ácido Quenodesoxicólico/sangre , Colestasis/diagnóstico , Hepatitis/diagnóstico , Ácido Tauroquenodesoxicólico/sangre , Subfamilia B de Transportador de Casetes de Unión a ATP/sangre , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Transportadoras de Casetes de Unión a ATP/sangre , Transportadoras de Casetes de Unión a ATP/genética , Alanina Transaminasa/sangre , Alanina Transaminasa/genética , Área Bajo la Curva , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/genética , Ácidos y Sales Biliares/clasificación , Atresia Biliar/sangre , Atresia Biliar/patología , Atresia Biliar/cirugía , Estudios de Casos y Controles , Colangiografía , Colestasis/sangre , Colestasis/patología , Colestasis/cirugía , Femenino , Regulación de la Expresión Génica , Hepatitis/sangre , Hepatitis/patología , Hepatitis/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Metaboloma , Receptores Citoplasmáticos y Nucleares/sangre , Receptores Citoplasmáticos y Nucleares/genética , gamma-Glutamiltransferasa/sangre , gamma-Glutamiltransferasa/genéticaRESUMEN
Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.