Geographic distribution of the major clone of extended-spectrum beta-lactamase-producing Escherichia coli infection in a pediatric community in southern Taiwan.

BACKGROUND: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. METHODS: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. RESULTS: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. CONCLUSION: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

Prevalence and household risk factors for fecal carriage of ESBL-producing, sequence type 131, and extraintestinal pathogenic Escherichia coli among children in southern Taiwan.

BACKGROUND: The rapidly increasing prevalence of antimicrobial-resistant Escherichia coli (E. coli) is a global concern. This study determined the prevalence and risk factors for the fecal carriage of drug-resistant E. coli and extraintestinal pathogenic E. coli (ExPEC) among children. MATERIALS AND METHODS: In this prospective study, stool samples from children aged 0-18 years were obtained within three days of hospitalization between April 2016 and March 2019. E. coli were selected and tested for extended-spectrum ß-lactamase (ESBL)-production and antimicrobial susceptibility. Multilocus sequence typing, blaCTX-M gene groups and ExPEC were determined using polymerase chain reactions. Questionnaires were recorded for risk factor analysis. RESULTS: Among 179 E. coli isolates, 44.1% were multi-drug resistant, 20.7% produced ESBL, and 50.3% were ExPEC. Children carrying ESBL-producing E. coli were younger than those carrying non-ESBL strains. Several anthropogenic factors, including drinking water process, pork consumption, pets and household density might be associated with ESBL-producing E. coli, sequence type (ST) 131 E. coli, or ExPEC fecal carriage. Compared with families who live in less crowded houses, participants with pets had a similar trend of higher risks of ESBL-producing E. coli, ST131 E. coli, and ExPEC fecal carriage among those living in houses accommodating relatively more people. CONCLUSIONS: Children accounted for a large proportion of instances of feces carrying ESBL E. coli. In addition to antimicrobial control for people and livestocks, avenues of exposure, such as drinking water, food, pets, household density, and socioeconomic deprivation might present potentially novel opportunities to reduce the burden of nonsusceptible E. coli and ExPEC.

Factors affecting fecal excretion time in pediatric nontyphoid Salmonella infection.

BACKGROUND: This study investigated whether the appropriate antibiotics therapy affects the fecal excretion time in pediatric salmonellosis of different severities and explored the factors associated with the fecal excretion time of nontyphoid Salmonella. METHODS: Between 2012 and 2017, admitted children with nontyphoid salmonellosis who consented to receive consecutive stool cultures every 4-7 days until 2 consecutive negative results were obtained were enrolled. Patients were stratified into no, appropriate (bacteremia or severe patients receiving antibiotics active in vitro), and inappropriate antibiotics (patients with mild or moderate severity receiving antibiotics or severe receiving antibiotics resistant in vitro) therapy groups. A previously proposed severity score was used to classify the patients into severe, moderate, and mild severity classes. The demographics, clinical manifestations, laboratory data and severity were compared among the groups. To explore the factors associated with the fecal excretion time of nontyphoid Salmonella, univariate and multivariate analyses were performed using linear regression analysis. RESULTS: This study enrolled 126 children with nontyphoid salmonellosis; 58 and 18 in the mild and severe classes, respectively. The no, appropriate and inappropriate antibiotics therapy groups comprised 69, 24 and 33 patients, respectively. The mean fecal excretion time was 12.17 days. The appropriate antibiotics therapy group had comparable fecal excretion time with that of no antibiotics group. Age <1 year, increased white blood cell count, decreased hemoglobin, and inappropriate antibiotics therapy significantly prolonged fecal excretion time in univariate analysis (p < 0.05). The multivariate analysis showed that inappropriate antibiotics therapy and decreased hemoglobin significantly prolonged the fecal excretion time. CONCLUSION: Inappropriate antibiotics therapy and decreased hemoglobin prolong the fecal excretion time of nontyphoid Salmonella, whereas appropriate antibiotics therapy does not. Continuous monitoring of antibiotic resistance and judicious use of antibiotics in children with nontyphoid salmonellosis are necessary.

Prevalence and risk factors for colonization by extended-spectrum ß-lactamase-producing or ST 131 Escherichia coli among asymptomatic adults in community settings in Southern Taiwan.

Purpose: Fecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

Fecal carriage of multidrug-resistant Escherichia coli by community children in southern Taiwan.

BACKGROUND: The emergence of multidrug-resistant (MDR) Escherichia coli (E. coli), particularly E. coli sequence type ST131, is becoming a global concern. Commensal bacteria, an important reservoir of antibiotic resistance genes, facilitate the spread of such genes to pathogenic bacterial strains. The objective of the study is to investigate the fecal carriage of MDR E. coli and ST131 E. coli in community children in Southern Taiwan. METHODS: In this prospective study, stool samples from children aged 0-18 years were obtained within 3 days of hospitalization from October 2013 to September 2014. Children with a history of underlying diseases, antibiotic treatment, or hospitalization in the 3 months before specimen collection were excluded. E. coli colonies were selected and tested for antimicrobial susceptibility, and O25b-ST131, multilocus sequence typing, and blaCTX-M gene groups were detected. RESULTS: Among 157 E. coli isolates, the rates of nonsusceptibility to ampicillin, amoxycillin + clavulanate, trimethoprim-sulfamethoxazole, and cefazolin were 70, 65.6, 47.1, and 32.5%, respectively. Twenty-nine (18.5%) isolates were nonsusceptible to ciprofloxacin. MDR E. coli accounted for 58 (37%) of all isolates. Thirteen (8.3%) isolates produced extended-spectrum ß-lactamase (ESBL). Furthermore, 26 (16.6%) and 13 (8.3%) isolates were O25b and ST131 positive, respectively. Five (38.5%) of the 13 ESBL-producing E. coli belonged to blaCTX-M group 9, among which were CTXM-14 and 4 (80%) were O25b-ST131 positive. Compared with the non-ESBL and ciprofloxacin-susceptible groups, the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b-ST131 positivity. CONCLUSIONS: The prevalence of the fecal carriage of nonsusceptible E. coli in children was high; among these E. coli, 37% were MDR, 18.5% were nonsusceptible to ciprofloxacin, and 8.3% produced ESBL. O25b-ST131 was the most common ESBL-producing E. coli clonal group present in the feces of children, and the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b-ST131 positivity.

Extended-spectrum ß-lactamase-producing Escherichia coli bacteremia: Comparison of pediatric and adult populations.

BACKGROUND/PURPOSE: The prevalence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. This study investigated the clinical features and bacteriology of pediatric patients with ESBL-producing E. coli bacteremia and compared their characteristics with those of adult patients. METHODS: Clinical and laboratory data from all of the 41 patients aged ≤18 years diagnosed with E. coli bacteremia were collected over 5 years. Patients aged >18 years diagnosed with E. coli bacteremia, matched 1:1 for calendar time, were enrolled as the adult group. All E. coli isolates were tested for their blaCTX-M group and sequence type 131 (ST131). A novel seven-single nucleotide polymorphism-based clonotyping test was applied to detect the septatypes of each isolate. RESULTS: In the adult group, patients with ESBL-producing E. coli bacteremia had more previous hospitalizations and antimicrobial agent use than did those with non-ESBL-producing E. coli bacteremia, but these differences were not found in pediatric group. In the pediatric group, the proportion of isolates producing CTX-M group 9 was higher than that in the adult group (85.7% vs. 42.9%; p < 0.05). Among both groups, there were more E. coli ST131 in ESBL isolates in than there were non-ESBL isolates. The distribution of septatypes was more homogenous in ESBL-producing E. coli among the pediatric patients than among the adult patients. CONCLUSION: ST131 was the major clone causing E. coli bacteremia in both pediatric and adult populations. The pediatric population demonstrated a higher number of isolates producing CTX-M group 9 with more homogenous septatypes compared with the adult population.

Ablation of ATG4B Suppressed Autophagy and Activated AMPK for Cell Cycle Arrest in Cancer Cells.

BACKGROUND/AIMS: ATG4B is a cysteine protease required for autophagy, which is a cellular catabolic pathway involved in energy balance. ATG4B expression is elevated during tumor growth in certain types of cancer, suggesting that ATG4B is an attractive target for cancer therapy. However, little is known about the mechanisms through which ATG4B deprivation suppresses the growth of cancer cells. METHODS: Cancer cells were transfected with either siRNA against ATG4B or an expression vector encoding wild-type ATG4BWT or encoding catalytic mutant ATG4BC74A to determine cell cycle progression by propidium iodide staining or by BrdU incorporation assay using flow cytometry. The GFP-MAP1LC3-II puncta and protein levels in the cells were determined by immunofluorescence and immunoblotting, respectively. RESULTS: Knockdown of ATG4B blocked cell proliferation, particularly at the G1-S phase transition, in various cancer cells. Moreover, knockdown of ATG4B or overexpression of the ATG4BC74A catalytic mutant reduced both autophagic flux and ATP levels and increased AMP-activated protein kinase (AMPK) phosphorylation in the cancer cells. Nevertheless, knockdown of ATG4B had only a minor effect on AMPK activation and G1 phase arrest in liver kinase B1 (LKB1)-deficient or AMPK-inhibited cancer cells. CONCLUSION: These results imply that targeting ATG4B might inhibit autophagy and trigger the LKB1-AMPK energy-sensing pathway, resulting in tumor growth suppression.

Urinary tract infection in infants caused by extended-spectrum beta-lactamase-producing Escherichia coli: comparison between urban and rural hospitals.

BACKGROUND: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management. METHODS: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012. RESULTS: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations. CONCLUSIONS: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.

Characteristics of CTX-M Extended-Spectrum ß-Lactamase-Producing Escherichia coli Strains Isolated from Multiple Rivers in Southern Taiwan.

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index (P = 0.025) and regions with a large number of chickens being raised (P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters.

Lactobacillus acidophilus attenuates Salmonella-induced intestinal inflammation via TGF-ß signaling.

BACKGROUND: Salmonella is a common intestinal pathogen that causes acute and chronic inflammatory response. Probiotics reduce inflammatory cytokine production and serve as beneficial commensal microorganisms in the human gastrointestinal tract. TGF-ß (transforming growth factor ß)/SMAD and NF-κB signaling play important roles in inflammation in intestinal cells. However, the involvement of the signaling in regulating inflammation between Salmonella and probiotics is not fully understood. METHODS: L. acidophilus and prebiotic inulin were used to treat human intestinal Caco-2 cells prior to infection with Salmonella. The cells were harvested to examine the cytokines and MIR21 expression with immunoblotting and real-time PCR. NF-κB and SMAD3/4 reporter vectors were transfected into cells to monitor inflammation and TGF-ß1 signaling, respectively. RESULTS: In this study, we showed that the probiotic L. acidophilus decreased Salmonella-induced NF-κB activation in human intestinal Caco-2 cells. Expression of the inflammatory cytokines, TNF-α and IL-8, in L. acidophilus-pretreated cells was also significantly lower than that in cells infected with Salmonella alone. Moreover, TGF-ß1 and MIR21 expression was elevated in cells pretreated with L. acidophilus or synbiotic, a combination of inulin and L. acidophilus, compared to that in untreated cells or cells infected with S. typhimurium alone. By contrast, expression of SMAD7, a target of MIR21, was accordingly reduced in cells treated with L. acidophilus or synbiotics. Consistent with TGF-ß1/MIR21 and SMAD7 expression, SMAD3/4 transcriptional activity was significantly higher in the cells treated with L. acidophilus or synbiotics. Furthermore, TGF-ß1 antibody antagonized the SMAD3/4 and NF-κB transcriptional activity modulated by L. acidophilus in intestinal cells. CONCLUSION: Our results suggest that the TGF-ß1/MIR21 signaling pathway may be involved in the suppressive effects of L. acidophilus on inflammation caused by S. typhimurium in intestinal Caco-2 cells.

Emergence of extended spectrum-ß-lactamase-producing Escherichia coli O25b-ST131: a major community-acquired uropathogen in infants.

BACKGROUND: Escherichia coli sero-group O25b-sequence type 131 (O25b-ST131), a multidrug-resistant clonal group, is a significant pathogen in adults and children. This study investigated the genotyping and role of extended spectrum ß-lactamase (ESBL)-producing E. coli O25b-ST131 and non-O25b-ST131 in urinary tract infections in infants. METHODS: Clinical and laboratory data from 111 infants less than 1 year of age, who were hospitalized for urinary tract infections caused by ESBL-producing E. coli between 2009 and 2012 were collected. Polymerase chain reactions and multi-locus sequence typing were used to identify E. coli O25-ST131 clones. The gene blaCTX-M groups 1, 2 and 9, a specific polymerase chain reaction of CTX-M 14 and 15, were also determined in ESBL-producing E. coli isolates. RESULTS: O25b-ST131 accounted for 65% of the 111 isolates, although 92 isolates belonged to the blaCTX-M group 9, of which most were CTX-M-14. Those with O25b-ST131 clones had similar risk factors, clinical features and outcomes as those with non-O25b-ST131. The E. coli O25b-ST131 isolates were more resistant to ciprofloxacin and gentamicin, but more susceptible to cefoxitin, minocycline and trimethoprim/sulfamethoxazole than the non-O25b-ST131 isolates. Most of the infants (78%) were previously healthy with no apparent risk factors. CONCLUSIONS: E. coli O25b-ST131 is a major community-acquired uropathogen in the infant population. Regardless of O25b-ST131 or non-O25b-ST131 clones, CTX-M-14 accounts for majority of the ESBL genotype. The O25b-ST131 clone is not associated with more severe clinical disease, but it may make the diagnosis and selection of antimicrobials for treatment more challenging.

Comparison of acute lobar nephronia and acute pyelonephritis in children: a single-center clinical analysis in southern taiwan.

BACKGROUND: Patients with acute lobar nephronia (ALN) require a longer duration of antimicrobial treatment than those with acute pyelonephritis (APN), and ALN is associated with renal scarring. The aim of this study was to provide an understanding of ALN by comparing the clinical features of pediatric patients with ALN and APN. METHODS: We enrolled all of the patients with ALN (confirmed by computed tomography) admitted to our hospital from 1999 to 2012 in the ALN group. In addition, each patient diagnosed with APN who was matched for sex, age, and admission date to each ALN patient was enrolled in the APN group. The medical charts of patients in these two groups were retrospectively reviewed and analyzed for comparison. RESULTS: The fever duration after hospitalization in the ALN group and the APN group were 4.85 ± 2.33 days and 2.30 ± 1.47 days respectively. The microbiological distributions and the majority of susceptibilities were similar in the ALN and APN groups. The majority of clinical manifestations are nonspecific and unreliable for the differentiation of ALN and APN. The patients with ALN were febrile for longer after antimicrobial treatment, had more nausea/vomiting symptoms, higher neutrophil count, bandemia, and C-reactive protein (CRP) levels, and lower platelet count (all p < 0.05). In multivariate analysis, initial CRP levels, nausea/vomiting symptoms, and fever duration after admission were independent variables with statistical significance to predict ALN. Severe nephromegaly occurred significantly more in the ALN group than in the APN group (p = 0.022). CONCLUSION: The majority of clinical manifestations, laboratory findings, and microbiological features are similar between patients with ALN and APN. Clinicians should keep a high index of suspicion regarding ALN, particularly for those with ultrasonographic nephromegaly, initial higher CRP, nausea/vomiting, and fever for > 5 days after antimicrobial treatment.

Infantile hepatitis B in immunized children: risk for fulminant hepatitis and long-term outcomes.

BACKGROUND: Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B. METHODS: The clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median  = 4.4 years, range 0.6-18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed. RESULTS: Among the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age <7 months) and negative maternal hepatitis B e antigen (HBeAg) were associated with FH (p = 0.03 and p = 0.01, respectively). An infantile fulminant hepatitis B risk score using maternal/infant HBeAg positivity and onset age was proposed. Among the FH cases, the rate of mortality, HBsAg clearance, and chronic HBV infection were 47.6%, 38.1%, and 14.3%, respectively. Among the NFH cases, 35% developed chronic infection. Of the 9 chronically infected children received long-term follow-up, 8 had HBeAg seroconversion before 4 years of age. One case of FH developed hepatocellular carcinoma 14 years later. CONCLUSIONS: Maternal HBsAg + /HBeAg- and early onset age were risk factors for FH in immunized infants. A significant portion of patients with FH or NFH evolve to chronic HBV infection, with HBeAg seroconversion in young childhood. Close surveillance for hepatocellular carcinoma is warranted in patients surviving infantile hepatitis B.

The clinical outcomes of antimicrobial therapy in pediatric patients with nontyphoid salmonellosis with different levels of severity.

BACKGROUND: To evaluate if a severity score could differentiate the severity of children with nontyphoid salmonellosis; clinical outcomes of antimicrobial therapy in nontyphoid salmonellosis children with different severities. METHODS: Admitted children with nontyphoid salmonellosis from 1996 to 2009 were monitored. Enrolled patients were divided into no antibiotics, concordant, and discordant therapies. Besides, the patients were classified into mild, moderate, and severe group according to the severity score. Clinical outcomes were compared among them. RESULTS: A total of 558 patients were enrolled. In no therapy subset, compared with mild group, patients had worse clinical outcomes and more complications in severe group. Patients receiving no therapy had better clinical outcomes in mild group. However, patients receiving concordant therapy (ceftriaxone) had better clinical outcomes in severe group. CONCLUSIONS: The severity score and local antibiotic susceptibility could serve as guides for antibiotic prescription for severe nontyphoid salmonellosis in children. Inappropriate antibiotic use would worsen clinical outcomes in children with mild nontyphoid salmonellosis.

Three-combination probiotics therapy in children with salmonella and rotavirus gastroenteritis.

GOALS: Quantitative Vesikari scales and qualitative severe diarrhea (Vesikari scale ≥11) assessments were used to grade the Salmonella-induced and rotavirus-induced gastroenteritis severity. A significant reduction in severe diarrhea (Vesikari score ≥11) was used to evaluate the efficacy of three-combination probiotics (BIO-THREE). BACKGROUND: Several studies have shown that rotavirus and Salmonella infections are the leading causes of infectious gastroenteritis. Although probiotics have been effective in some studies, the use of 3-combination formulation probiotics is rare. STUDY: This single-center, open-label, randomized, controlled trial included 159 patients (age range, 3 mo to 14 y) hospitalized with infectious gastroenteritis between February 2009 and October 2010. RESULTS: Patients were grouped according to the pathogen identified (48, Salmonella; 42, rotavirus; and 69, unknown origin). The total diarrhea duration was significantly shorter for children who received BIO-THREE (P<0.0001). After BIO-THREE administration, there were significantly less intervention group patients with severe diarrhea at intervention day 3. Vesikari scale or diarrhea frequency results did not reveal significant differences between groups (except for day 5 in patients with rotavirus), and there were no significant changes in other clinical parameters or the length of hospital stay. CONCLUSIONS: Seven-day BIO-THREE administration demonstrated high efficacy and safety in infants and children with severe gastroenteritis. The incidence of severe gastroenteritis was significantly reduced in the rotavirus origin and BIO-THREE intervention groups.

Infective endocarditis in children without underlying heart disease.

BACKGROUND/PURPOSE: Although pre-existing heart disease is the main predisposing factor for pediatric infective endocarditis (IE), cases of IE in children without underlying heart disease have been increasingly reported. This study reviews the clinical and laboratory characteristics of pediatric IE patients with and without underlying heart disease, and presents the unique features of patients with no apparent pre-existing heart disease. METHODS: Children who were admitted to our hospital from January 1991 to April 2011 and met the Modified Duke criteria for definite or possible IE were retrospectively analyzed. Clinical characteristics and laboratory data were collected by chart review. RESULTS: Forty-seven patients with a total of 48 episodes of IE were enrolled. Of these patients, 31 children (64.6%) had congenital heart disease (CHD), six (12.5%) had non-CHD chronic disease, and eleven (22.9%) were previously healthy adolescents. Five patients with non-CHD chronic conditions acquired infection from central catheter: two methicillin-resistant Staphylococcus aureus (MRSA), two Candida albicans and one coagulase-negative Staphylococcus (CoNS). The microbial pathogens in 11 previously healthy individuals were Streptococcus viridans (n = 3), methicillin-sensitive S. aureus (MSSA, n = 2), Haemophilus parainfluenzae (n = 2), Staphylococcus lugdunensis (n = 1), Enterococcus (n = 1), and Diphtheroid (n = 1). In total, five of 17 non-CHD patients were infected with S. aureus (two MRSA and three MSSA) and the vegetations in these five patients were detected in the right side of the heart (tricuspid valve or right atrium). The average interval between onset of symptoms and diagnosis of IE in the CHD and previously healthy groups was 18 and 31 days, respectively. Patients in the previously healthy group were older and more often required surgical interventions for removal of vegetation. CONCLUSION: Over one-third (35.4%) of cases of IE in children occurred in patients without pre-existing cardiac disease. Early identification of these patients is critical and requires a high index of suspicion. The pathogenesis of IE in previously healthy individuals is still uncertain, but previous skin infection or dental problems may contribute to potential risk.

Mechanism of [Ca2+]i rise induced by angiotensin 1-7 in MDCK renal tubular cells.

The effect of angiotensin 1-7 (Ang 1-7) on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) in MDCK renal tubular cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Ang 1-7 at concentrations of 10-50 µM induced a [Ca(2+)](i) rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). Ang 1-7 evoked store operated Ca(2+) entry that was inhibited by La(3+) and aristolochic acid. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin prevented Ang 1-7 from releasing more Ca(2+). Inhibition of phospholipase C with U73122 abolished Ang 1-7-induced [Ca(2+)](i) rise. Ang 1-7-induced [Ca(2+)](i) rise was abolished by the angiotensin type 1 receptor antagonist losartan, but was not affected by the angiotensin type 2 receptor antagonist PD 123,319. In sum, in MDCK cells, Ang 1-7 stimulated angiotensin type 1 receptors leading to a [Ca(2+)](i) rise that was composed of phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A2-sensitive store-operated Ca(2+) channels.

Clinical manifestations of nontyphoid salmonellosis in children younger than 2 years old--experiences of a tertiary hospital in southern Taiwan.

BACKGROUND: Few published studies have explored the clinical manifestations of nontyphoid salmonellosis in children <2 years of age. The aim of this study was to investigate the clinical manifestations, microbiological features, complications, fecal excretion time, and responses to treatment in children <2 years of age with nontyphoid salmonellosis. METHODS: Between January 2005 and December 2009, pediatric patients who were admitted to Kaohsiung Veterans General Hospital with positive cultures for nontyphoid Salmonella were enrolled. The following data were recorded: demographic, clinical, and microbiological features, underlying diseases, treatment regimen, complications, responses to treatment, and fecal excretion time. The clinical manifestations were compared between patients <2 years of age and patients >2 years of age. RESULTS: Of a total 279 enrolled patients, 179 were >2 years of age. Compared with the patients who were ≥2 years of age, patients <2 years of age demonstrated a significantly higher incidence of bloody stool, mixed infection, extraintestinal infection, longer course of antibiotics, longer course of diarrhea after admission, and more days spent in the hospital. The rates of insusceptibility of nontyphoid Salmonella to ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole, ceftriaxone, and ciprofloxacin in patients <2 years of age were 37.87%, 29.09%, 23.73%, 3.26%, and 2.25%, respectively. Younger patients were generally more susceptible to antibiotics than patients ≥2 years of age, although this result was not statistically significant. CONCLUSION: The clinical manifestations of nontyphoid salmonellosis are more severe in younger children <2 years of age than older children. Local susceptibility patterns could serve as a guide for the prescription of antibiotics by clinicians.