Antibiotic resistance and virulence genes in Helicobacter pylori strains isolated from children in Shanghai, China (2019-2022).

BACKGROUND: The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. METHODS: We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. RESULTS: Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. CONCLUSIONS: Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.

Shift in the dominant sequence type of carbapenem-resistant Klebsiella pneumonia infection from ST278-NDM-1 to ST11-KPC-2 in neonatal patients in a children's hospital in Shanghai, China, 2017-2021.

OBJECTIVES: To investigate the clinical characteristics and molecular epidemiology of CRKP infection in neonatal patients in a children's hospital in China from 2017 to 2021. METHODS: Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. The clinical data were collected from medical records. Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were investigated by antimicrobial susceptibility testing, carbapenemase genes and multilocus sequence typing. RESULTS: Six kinds of resistant genes and 23 STs were detected. BlaNDM-1 (n=83, 55.3%) was the predominant carbapenemase gene, followed by blaKPC-2 (n=45, 30.0%), blaNDM-5 (n=7, 4.7%), blaIMP-38 (n=6, 4.0%). BlaNDM-1 was predominant in 2017 and 2018, whereas blaKPC-2 increased in 2019 and became the predominant gene from 2020 to 2021. ST11 accounted for most infections (n=35, 23.3%), followed by ST278 (n=23, 15.3%), ST17 (n=17, 11. 3%) and ST2735 (n=16, 10.7%). ST278 and ST17 were predominant in 2017 and 2018, whereas ST11 increased in 2019 and became the predominant sequence type from 2020 to 2021. Compared with blaNDM-1, the CRKP strains producing blaKPC-2 were characterized by high resistance to gentamicin, amikacin and levofloxacin and the change trend of drug resistance rate before and after COVID-19 was consistent with that of blaNDM-1 and blaKPC-2. CONCLUSIONS: The main sequence type of CRKP infection changed dynamically from ST278-NDM-1 to ST11-KPC-2 during the years 2017-2021 in the newborns. Antibiotic exposure and the prevalence of COVID-19 since 2020 may have led to changes in hospital population and lead to the changes.

Carbapenem-resistant gram-negative bacterial prevention practice in nosocomial infection and molecular epidemiological characteristics in a pediatric intensive care unit.

Introduction: The increasing prevalence of carbapenem-resistant gram-negative bacilli infection has emerged as a substantial threat to human health. Methodology: In January 2017, a screening program for carbapenem-resistant gram-negative bacilli colonization was performed in a pediatric intensive care unit (PICU). Subsequently, different strategies for carbapenem-resistant gram-negative bacilli cohorting and patient placements were introduced in January 2018. Results: The increase in the single room isolation (type A) and the resettlement of the same area placement (type B) resulted in a significant decrease in the nosocomial infection rate from 2.57% (50/1945) in 2017 to 0.87% (15/1720) in 2021 (P < 0.001). Notably, the incidence of nosocomial carbapenem-resistant gram-negative bacilli infections decreased in 2019 (P = 0.046) and 2020 (P = 0.041) compared with that in the respective previous year. During 2019 and 2020, a statistically significant increasing trend of type A and type B placements was observed (P < 0.05, each), which may have contributed to the decline of carbapenem-resistant gram-negative bacilli infection. The primary carbapenemase genes identified in carbapenem-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii were blaKPC-2 from sequence type 11 and blaOXA-23 from sequence type 1712. Conclusion: The integration of various placements for patients with carbapenem-resistant gram-negative bacilli infection with active screening has been demonstrated as an effective preventive strategy in the management of carbapenem-resistant gram-negative bacilli infection.

Molecular characteristics of carbapenem-resistant gram-negative bacilli in pediatric patients in China.

BACKGROUND: Carbapenem-resistant gram-negative bacilli (CR-GNB) have been increasingly reported in China. However, dynamic monitoring data on molecular epidemiology of CR-GNB are limited in pediatric patients. RESULTS: 300 CR-GNB isolates (200 Carbapenem-resistant K. pneumoniae (CRKP), 50 carbapenem-resistant A.baumannii (CRAB) and 50 carbapenem-resistant P. aeruginosa (CRPA)) were investigated. The predominant carbapenemase gene was blaNDM-1 (73%) and blaKPC-2 (65%) in neonates and non-neonates. Meanwhile, the predominant STs were ST11 (54%) in neonates and ST17 (27.0%) and ST278 (20.0%) in non-neonates. Notably, a shift in the dominant sequence type of CRKP infections from ST17 /ST278-NDM-1 to ST11-KPC-2 was observed during the years 2017-2021 and KPC-KP showed relatively higher resistance to aminoglycosides and quinolones than NDM-KP.BlaOXA-23 was isolated from all the CRAB isolates while only one isolate expressing blaBIC and 2 isolates expressing blaVIM-2 were found in CRPA isolates. ST195 (22.0%) and ST244 (24.0%) were the most common in CRAB and CRPA isolates and all the STs of CRAB belonged to CC92 while CRPA presents ST types with diversity distribution. CONCLUSION: CRKP showed different molecular phenotypes in neonates and non-neonates and was changing dynamically and high-risk clone of ST11 KPC-KP should be paid more attention. Most CRKP and CRAB strains shared the same CCs, suggesting that intrahospital transmission may occur, and large-scale screening and more effective measures are urgently needed.

Clinical characteristics and antibiotic resistance profile of invasive MRSA infections in newborn inpatients: a retrospective multicenter study from China.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical characteristics and antibiotic resistance profiles of invasive MRSA infections and determine risk factors associated with invasive MRSA infections in newborn inpatients. METHODS: This multicenter retrospective study of inpatients from eleven hospitals in the Infectious Diseases Surveillance of Pediatrics (ISPED) group of China was performed over a two-year period (2018-2019). Statistical significance was calculated by applying the χ2 test or by Fisher's exact test in the case of small sample sizes. RESULTS: A total 220 patients were included. Among included cases, 67 (30.45%) were invasive MRSA infections, including two deaths (2.99%), while 153 (69.55%) were noninvasive infections. The invasive infections of MRSA occurred at a median age of 8 days on admission, which was significantly younger compared to 19 days in noninvasive cases. Sepsis (86.6%) was the most common invasive infection, followed by pneumonia (7.4%), bone and joint infections (3.0%), central nervous system infection (1.5%), and peritonitis (1.5%). Congenital heart disease, low birth weight infant (<2500 g), but not preterm neonates, and bronchopulmonary dysplasia, were more commonly found in invasive MRSA infections. All these isolates were susceptible to vancomycin and linezolid and were resistant to penicillin. Additionally, 69.37% were resistant to erythromycin, 57.66% to clindamycin, 7.04% to levofloxacin, 4.62% to sulfamethoxazole-trimethoprim, 4.29% to minocycline, 1.33% to gentamicin, and 3.13% were intermediate to rifampin. CONCLUSION: Low age at admission (≤8 days), congenital heart disease, and low birth weight were associated with invasive MRSA infections in neonates, and no isolates resistant to vancomycin and linezolid were found. Determining these risks in suspected neonates may help identify patients with imminent invasive infections who may require intensive monitoring and therapy.

Molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae among pediatric patients in Shanghai, China.

We retrospectively investigated CRKP isolates among 92 pediatric patients (32 neonates and 60 non­neonates) in 2019 and 2020 (59 and 33 isolates, respectively) to investigate the molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from pediatric patients,. All the CRKP isolates were subjected to antimicrobial susceptibility testing, string testing, molecular typing of virulence and carbapenemase genes, and multilocus sequence typing. Hypervirulent K. pneumoniae (Hvkp) was defined based on the detection of the regulator of mucoid phenotype A (rmpA).Sequence type 11 (ST11) accounted for the majority of infections in both neonates (37.5%) and non­neonates (43.3%) (P > 0.05), whereas it increased from 30.5% (18/59) in 2019 to 60.6% (20/33) in 2020 (P < 0.05). Carbapenemase gene KPC-2 was predominant in both neonates and non­neonates (46.9% vs. 51.7%, respectively), followed by New Delhi metallo-beta-lactamase 1 (NDM-1) (34.4% vs. 28.3%, respectively) (all P > 0.05). Compared to 2019, the proportion of blaNDM-1 decreased (44.1% vs. 6.1%) (P < 0.001), while that of blaKPC-2 increased (40.7% vs. 66.7%) (P = 0.017) in 2020. ybtS and iutA had a higher positivity rate in KPC-2 and ST11 producers (all P < 0.05); the KPC-2-, ybtS-, and iutA-positive isolates showed relatively higher resistance to fluoroquinolones and aminoglycosides, nitrofurantoin, and piperacillin/tazobactam, respectively. Furthermore, the combined expression (95.7%, 88/92) of carbapenemase and virulence-associated genes was detected, with the carbapenemase genes blaKPC-2 and blaTEM-1 combined with virulence-associated genes entB, mrkD, and ybtS accounting for the highest percentage (20.7%).Carbapenemase gene mutations in the CRKP strain from 2019 to 2020 highlight the importance of dynamic monitoring. The spread of hypervirulence-associated genes in CRKP strains and the high positivity rates of ybtS and iutA in KPC-2- and ST11-producing ones signify their high virulence potential in pediatric patients.

Antimicrobial resistance profile of methicillin-resistant Staphylococcus aureus isolates in children reported from the ISPED surveillance of bacterial resistance, 2016-2021.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health worldwide. In December 2015, the Infectious Disease Surveillance of Pediatrics (ISPED) program was organized to monitor bacterial epidemiology and resistance trends in children. Methods: This retrospective study was conducted from January 2016-December 2021 on patients at eleven ISPED-group hospitals. Results: From 2016-2021, a total of 13024 MRSA isolates were obtained from children. The most common age group for patients with MRSA infection was less than 3 years old, and newborns were an important group affected by MRSA infection. MRSA was most commonly isolated from the lower respiratory, an abscess, a secretion, or blood in neonates and from the lower respiratory, an abscess, or the upper respiratory in non-neonates. All isolates were susceptible to vancomycin and linezolid and resistant to penicillin; additionally, 76.88%, 54.97%, 22.30%, 5.67%, 5.14%, 3.63%, and 1.42% were resistant to erythromycin, clindamycin, tetracycline, levofloxacin, sulfamethoxazole-trimethoprim (TMP-SMX), gentamicin, and rifampin, respectively. Between 2016 and 2021, a significant increase was seen in the levofloxacin- and TMP-SMX-resistance rates (from 5.45% to 7.14% and from 4.67% to 6.50%, respectively) among MRSA isolates, along with a significant decrease in the rates of resistance to erythromycin (from 82.61% to 68.08%), clindamycin (from 60.95% to 46.82%), tetracycline (from 25.37% to 17.13%), gentamicin (from 4.53% to 2.82%), and rifampin (from 1.89% to 0.41%). Discussion: The antibiotic-resistance rates varied among MRSA isolated from different sources. Because of the high antibiotic resistance rate to clindamycin, this antibiotic is not recommended for empirical treatment of MRSA infections, especially in osteomyelitis.

Emergence and spread of MT28 ptxP3 allele macrolide-resistant Bordetella pertussis from 2021 to 2022 in China.

OBJECTIVES: To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China. METHODS: A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping. RESULTS: Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged <1 year) accounted for 24.7% and presented much more severe symptoms than noninfants. Pertussis was most frequently detected in infants aged 0-6 months (11.3∼14.0%) and children aged >6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx)P3/(pertactin) prn2/ptxC2/ptxA1/(fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP. CONCLUSION: The emergence and spread of MT28 ptxP3-MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3-MRBP to prevent its potential circulation.

The molecular and epidemiological characteristics of carbapenemase-producing Enterobacteriaceae isolated from children in Shanghai, China, 2016-2021.

BACKGROUND: We isolated the carbapenemase-producing Enterobacteriaceae (CPE) strains from children during 2016-2021 in Shanghai, China and investigated the antimicrobial resistance, molecular and epidemiological features of these isolates. METHODS: Antimicrobial susceptibility tests were performed to confirm the carbapenem resistance. Carbapenemase production was assessed by the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48), which were further confirmed by PCR amplification and sequencing. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. RESULTS: A total of 320 CPE strains were collected from 2016 to 2021, consisting of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn, 55.0%), Escherichia coli (CP-Eco, 24.5%) and Enterobacter cloacae (CP-Ecl, 20.4%) and others (2, 0.1%). NDM was the primary carbapenemase (67.6%) in children, followed by KPC(26.4%), IMP(5.3%) and OXA-48 (0.6%). The minimum inhibitory concentration (MIC) for imipenem has been increasing from 2016 to 2021. NDM and KPC isolates are high resistant while IMP strains show the lower resistant to imipenem. Invasive infection accounted for 10.7% of CPE-related infections and was mainly caused by CP-Kpn (70.6%). NDM-Kpn was detected in 51.8% of infants (70.8% of neonates), while KPC-Kpn was mainly isolated from non-infants (56.3%∼64.3%). ST11 was the primary clone (64.6%) of KPC-Kpn and presented an increasing trend from 2016 to 2021. CONCLUSION: NDM is widely prevalent and transfers among CPE strains in children. NDM-Kpn shows the most serious threat to infants, especially to neonates. High-risk clone of ST11 KPC-Kpn should be paid more attention and monitored continuously in children.

A multicenter investigation of 2,773 cases of bloodstream infections based on China antimicrobial surveillance network (CHINET).

Background: Bloodstream infections (BSIs), especially hospital-acquired BSIs, are a major cause of morbidity and mortality. However, the details about the pathogens and antimicrobial resistance profile of BSIs across China are still lacking. Methods: An investigation was conducted in 10 large teaching hospitals from seven geographic regions across China in 2016 based on China Antimicrobial Surveillance Network (CHINET) to profile the clinical and etiological features of BSIs. Results: A total of 2,773 cases of BSIs were identified, a majority (97.3%) of which were monomicrobial. Overall, 38.4% (1,065/2,773) were community-acquired BSIs (CABSIs), and 61.6% (1,708/2,773) were hospital-acquired BSIs (HABSIs). Of the 2,861 pathogenic BSI isolates, 67.5% were Gram-negative bacteria, 29.6% were Gram-positive bacteria, and 2.9% were fungi. The top BSI pathogens were Escherichia coli, Klebsiella pneumoniae, coagulase-negative Staphylococci (CNS), Staphylococcus aureus, Enterococci, and Acinetobacter baumannii. Escherichia coli and K. pneumoniae isolates showed low susceptibility to penicillins, cephalosporins (except ceftazidime and cefepime), and ampicillin-sulbactam (13.1%-43.4% susceptible); moderate susceptibility (about 60% susceptible) to ceftazidime, cefepime, and aztreonam; and high susceptibility (>90%) to ß-lactam/ß-lactamase inhibitor combinations other than ampicillin-sulbactam, except K. pneumoniae strains to piperacillin-tazobactam (59.2% susceptible). HABSIs were associated with significantly higher prevalence of carbapenem-resistant and extended-spectrum ß-lactamases-producing K. pneumoniae, methicillin-resistant S. aureus, methicillin-resistant CNS, and ampicillin-resistant Enterococci than CABSIs. Overall, 42.0% of the BSI due to S. aureus strains were resistant to methicillin. Conclusions: The findings about BSIs in teaching hospitals across China add more scientific evidence to inform the appropriate management of the disease.

Actively surveillance and appropriate patients placements' contact isolation dramatically decreased Carbapenem-Resistant Enterobacteriaceae infection and colonization in pediatric patients in China.

BACKGROUND: With the increasing use of carbapenems in clinic practice, carbapenem-resistant Enterobacteriaceae (CRE) has also increased, thus posing a significant threat to human health. AIM: To assess the effects of CRE colonization active screening and various CRE patient placements implemented in decreasing CRE infection risk. METHODS: CRE colonization screening and various CRE patient placements were performed across CRE high-risk departments (PICU, NICU, neonatal wards and hematology departments) between 2017 and 2018, respectively. FINDING: In 2018, more than 80% neonatal CRE positive patients were isolated using single room or same room isolation, and more than 50% non-neonatal patients were, with no cohort placement. The CRE nosocomial infection incidences decreased from 1.96% to 0.63% in NICU, and from 0.57% to 0.30% in neonatal wards (all P<0.05) while no significant changes were found in the other departments. The CRE colonization incidence at different length hospital stay (LOS) decreased at 8-14days and >14days LOS in CRE high-risk departments (all P<0.05). In addition, 62.5% clinical strains, 66.7% screening strains, and 74.1% nosocomial infection strains were belonged to CC17 complex group in neonatal isolates; while, 56.6%, 47.5% and 100% strains mentioned above were belonged to CC11 complex group in non-neonatal isolates respectively. The predominant carbapenemase gene was blaNDM-1 (98%) in neonatal and blaKPC-2 (70%) in non-neonatal CR-KP stains. CONCLUSIONS: Active CRE colonization surveillance and CRE positive patient propriety placement may decrease the CRE infection risk. Neonatal and non-neonatal CR-KP isolates showed different CRE molecular characteristics, which could further benefit CRE infection precaution and antibiotic therapy.

Epidemiology of Respiratory Pathogens in Children with Lower Respiratory Tract Infections in Shanghai, China, from 2013 to 2015.

This study aimed to explore the epidemiology of pathogens in children who were hospitalized with lower respiratory tract infections (LRTIs) at the Children's Hospital of Fudan University, Shanghai, China. Children aged less than 18 years who were hospitalized with LRTIs were enrolled from January 2013 to December 2015. Respiratory specimens were collected for the detection of common respiratory viruses, atypical bacteria, and other bacteria using current laboratory diagnostic tests. The epidemiological characteristics of the respiratory pathogens were analyzed. Of the 10,123 specimens obtained from the patients, 5,966 (58.7%) were positive for at least 1 pathogen. Mycoplasma pneumoniae (M.pneumoniae) was the most commonly detected pathogen (15.7%), followed by respiratory syncytial virus (RSV) (13.9%). Co-infections were found in 11.4% of patients. Of these co-infections, viral-bacterial co-infections were the most common. The detection rates for the respiratory pathogens varied considerably by age. RSV was the most common pathogen in children aged less than 24 months. Clear seasonal peaks were observed for RSV, M. pneumoniae, parainfluenza virus, human metapneumovirus, Moraxella catarrhalis, and Haemophilus influenza infections. Our findings demonstrate specific epidemiological patterns in children with LRTIs in Shanghai, China.

Involvement of protoporphyrin IX accumulation in the pathogenesis of isoniazid/rifampicin-induced liver injury: the prevention of curcumin.

Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively. Herein, this study focused on the role of INH/RFP in these processes. We observed PPIX accumulation in human hepatocytes (L-02) and mouse livers. FECH expression was initially found downregulated both in L-02 cells and mouse livers and expression levels of ALAS1 and BCRP were elevated in L-02 cells after INH/RFP treatment, indicating FECH inhibition and ALAS1 induction might confer a synergistic effect on PPIX accumulation. Additionally, our results revealed that curcumin alleviated INH/RFP-induced liver injury, declined PPIX levels and induced FECH expression in both L-02 cells and mice. In conclusion, our data provide a novel insight in the mechanism of INH/RFP-induced PPIX accumulation and evidence for understanding pathogenesis of INH/RFP-induced liver injury, and suggest that amelioration of PPIX accumulation might be involved in the protective effect of curcumin on INH/RFP-induced liver injury.

A case report of hepatic abscesses with soft tissue infection caused by methicillin resistant Staphylococcus aureus in a young child.

RATIONALE: Pyogenic hepatic abscess in children is a rare clinical condition. Hepatic abscesses caused by methicillin resistant Staphylococcus aureus are extremely rare. PATIENT CONCERNS: A 6-year-old boy was referred to a tertiary children's hospital for a 6-day history of right lower abdominal pain and fever. Radiographic findings showed hepatic abscesses and soft tissue abscesses around the left femur. DIAGNOSES: Bacteriology of blood, hepatic abscesses, and soft tissue abscesses showed methicillin resistant Staphylococcus aureus. INTERVENTIONS: Our patient received adequate drainage of MRSA abscesses and a complete course of antibiotics. OUTCOMES: The hepatic abscesses were healed and no recurrence has been founded until now. LESSONS: This report describes an extremely rare case of hepatic abscesses with soft tissue infection caused by MRSA. Adequate drainage and appropriate systemic antibiotics should be considered as a standard treatment of MRSA abscesses in order to reduce the mortality rate and improve the quality of life.

Clonal Spread of Enterotoxigenic Escherichia coli O128:H45 Strain in the Neonate Unit.

Enterotoxigenic Escherichia coli (ETEC) has the potential to cause nosocomial infantile diarrhea in a hospital setting. We detected 12 ETEC serotype O128:H45 isolates from diarrheal neonates in our neonatal unit from July through October 2012. These infants developed hospital-acquired and epidemiologically related diarrhea. Pulsed-field gel electrophoresis analysis and multilocus sequence typing of these 12 isolates suggested that a specific clone of ETEC serotype O128:H45-CS21-ST2332 caused nosocomial diarrhea among neonates. Of concern, this ETEC clone strain was resistant to multiple drugs, particularly third-generation cephalosporins.

[Progress in the biomarker discovery for drug-induced liver injury].

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.

Elevated serum ApoE levels are associated with bacterial infections in pediatric patients.

BACKGROUND/PURPOSE(S): We aimed to determine the variations in serum apolipoprotein E (ApoE) levels in pediatric patients with a variety of infectious diseases, and to investigate the potential mechanism of elevated ApoE serum levels during infection. METHODS: A total of 279 pediatric patients with a variety of infections and 58 normal controls were enrolled in this study. Serum ApoE levels were detected using an immunoturbidimetric assay. A mouse sepsis model was established to evaluate the expression of ApoE and its receptors by real-time polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Serum ApoE was markedly increased in cases with bacterial infections including sepsis, bacterial meningitis, and bacterial pneumonia, compared to healthy controls. No significantly elevated serum ApoE levels were observed in aseptic meningitis patients or mycoplasma pneumonia patients. The mice sepsis models showed a similar pattern of increased serum ApoE levels in the early stage of infections. We found reduced expression of ApoE and its receptors in the liver tissues in these mice models. CONCLUSION: Serum ApoE may represent a novel indicator for diagnosis of bacterial infections, especially sepsis, in pediatric patients. The decreased expression of low-density lipoprotein receptor (LDLR), LDL receptor-related protein (LRP), and heparin sulfate proteoglycan (HSPG) syndecan-1 (SDC1) may contribute to reduced ApoE clearance and accumulation in the blood.

An apolipoprotein E mimetic peptide with activities against multidrug-resistant bacteria and immunomodulatory effects.

Apolipoprotein E (apoE) mimetic peptides derived from the low-density lipoprotein receptor-binding region of apoE with both activities against multidrug-resistant bacteria and immunomodulatory effects have not previously been reported. We identified an apoE mimetic peptide analogue of the receptor-binding region of apoE (abbreviated as apoE23) with the sequence of LRKLRKRLVRLASHLRKLRKRLL, which exhibited high antibacterial effects. The minimal inhibitory concentration of apoE23 against multidrug-resistant Acinetobacter baumannii was 6 µg/ml. The antimicrobial activity of apoE23 depended on its amphipathic α-helical conformation. Moreover, apoE23 downregulated the expression of tumour necrosis factor-α, interleukin-6 and interleukin-10 in lipopolysaccharide-induced THP-1 cells. ApoE23 exhibits potential in future clinical applications.

[Clinical features and molecular characteristics of methicillin-resistant Staphylococcus aureus in children].

OBJECTIVE: To study the clinical and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infection in children. METHOD: A total of 37 MRSA strains were isolated from hospitalized patients in Children's Hospital of Fudan University from March 2009 to November 2011. The clinical characteristics were investigated by a cohort study. Furthermore, the mecA, Panton-Valentine leucocidin (PVL) genes were detected by polymerase chain reaction (PCR), and the genotypes of SCCmec were determined by multiplex PCR. RESULT: (1) Among the 37 MRSA isolates, infections with 21 were acquired from hospital (HA-MRSA), and 16 isolates were acquired from community (CA-MRSA). (2) In the study, MRSA frequently caused respiratory tract infection, and most of the strains were isolated from intensive care unit (ICU). (3) CA-MRSA was most frequently associated with skin and soft tissue infections (SSTI), suppurative tonsillitis, even pneumonia and septicemia. HA-MRSA infection was more aggressive, most frequently associated with pneumonia, septicemia, and central nervous system (CNS) infections, such as meningitis. In children with fever caused by HA-MRSA or CA-MRSA infection, HA-MRSA showed a longer duration of fever, for 10.5 days. C-reactive protein (CRP) level caused by HA-MRSA (63.00 mg/L) was higher than CA-MRSA (9.50 mg/L) , and there were statistically significant differences between the groups (t = 2.5670, P < 0.05). However, there were no statistically significant differences between the groups in white blood cell count (WBC) or procalcitonin (PCT) level. (4) Among 37 MRSA isolates, the whole isolates were mecA gene positive (100%). SCCmec genotyping results showed that the most frequent SCCmec types were type III, 17 isolates, the others including type IV 8 isolates, type II1 isolates, nontypable 11 isolates, type I and type V were not found in this group. Therein, among 21 HA-MRSA isolates, SCCmec III was the most common, 15 isolates, type IV 1 isolates, nontypable 5 isolates; among 16 CA-MRSA isolates, SCCmec type IV was the most common, 7 isolates, type III 2 isolates, type II 1 isolate, nontypable 6 isolates. (5) Among the 37 MRSA isolates, 28 were PVL gene positive; and among 21 HA-MRSA isolates, 17 were PVL gene positive; Among 16 CA-MRSA isolates, 11 were PVL gene positive; There were no statistically significant differences between the groups (χ(2) = 0.735, P > 0.05) . CONCLUSION: Compared with CA-MRSA, HA-MRSA infection was more aggressive, and induced higher C reactive protein; the dominant epidemic strains of CA-MRSA was SCCmec type IV, and HA-MRSA was SCCmec type III; the positive rate of PVL gene was high.