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Objectives: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. Methods: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. Results: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608–0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. Conclusions: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

Abstract Background Cytomegalovirus (CMV) colitis significantly complicates the course of inflammatory bowel disease (IBD), frequently leading to severe flare-ups and poor outcomes. The role of antiviral therapy in hospitalized IBD patients with CMV colitis is currently under debate. This retrospective analysis seeks to clarify the influence of antiviral treatment on these patients. Methods We retrospectively reviewed IBD patients diagnosed with CMV colitis via immunohistochemistry staining from colonic biopsies at a major tertiary center from January 2000 to May 2021. The study focused on patient demographics, clinical features, risk factors, prognostic indicators, and antiviral treatment outcomes. Results Among 118 inpatients, 42 had CMV colitis. Risk factors included hypoalbuminemia and antibiotic use. IBD patients with CMV colitis receiving

Background/Purpose: Precise detection of respiratory pathogens by molecular method potentially may shorten the time to diagnose and reduce unnecessary antibiotic use. Methods: Medical records of hospitalized children from January 2020 to June 2021 with acute respiratory illness who received a FilmArray RP for respiratory pathogens were reviewed and compared with data from diagnosis-matched patients without receiving the test. Results: In total, 283 patients and 150 diagnosis-matched controls were included. Single pathogen was detected in 84.3% (193/229) of the patients. The most common pathogen was human rhinovirus/enterovirus (31.6%, 84/266), followed by respiratory syncytial virus (18.8%, 50/266) and adenovirus (15%, 40/266). Although antimicrobial days of therapy (DOT) was significantly longer in FilmArray group than the control [7.1 ± 4.9 days vs 5.7 ± 2.7 days, P = 0.002], the former showed a higher intensive care unit (ICU) admission rate (3.9% vs 0%; P = 0.010). All ICU admissions were in FilmArray RP-positive group. There was no difference in antimicrobial DOT between FilmArray RP-positive and the negative groups, in all admissions, even after excluding ICU admissions. Antimicrobial DOT was shorter in the positive than negative group in patients with lower respiratory tract infections without admission to ICU [median (IQR): 6 (4–9) days vs 9 (4–12) days, P = 0.047]. Conclusions: Shorter antimicrobial DOTs were identified in children with lower respiratory tract infection admitted to general pediatric ward and with an identifiable respiratory pathogen, indicating a role of the multiplex PCR in reducing antimicrobial use for children with respiratory tract infection.

Background/purpose: Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome. Methods: A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed. Results: A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone. Conclusions: Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.

ABSTRACTClostridium innocuum is an emerging spore-forming anaerobe that is often observed in Clostridioides difficile-associated inflammatory bowel disease (IBD) exacerbations. Unlike C. difficile, C. innocuum neither produces toxins nor possesses toxin-encoding genetic loci, but is commonly found in both intestinal and extra-intestinal infections. Membrane lipid rafts are composed of dynamic assemblies of cholesterol and sphingolipids, allowing bacteria to gain access to cells. However, the direct interaction between C. innocuum and lipid rafts that confers bacteria the ability to disrupt the intestinal barrier and induce pathogenesis remains unclear. In this study, we investigated the associations among nucleotide-binding oligomerization domain containing 2 (NOD2), lipid rafts, and cytotoxicity in C. innocuum-infected gut epithelial cells. Our results revealed that lipid rafts were involved in C. innocuum-induced NOD2 expression and nuclear factor (NF)-κB activation, triggering an inflammatory response. Reducing cholesterol by simvastatin significantly dampened C. innocuum-induced cell death, indicating that the C. innocuum-induced pathogenicity of cells was lipid raft-dependent. These results demonstrate that NOD2 mobilization into membrane rafts in response to C. innocuum-induced cytotoxicity results in aggravated pathogenicity.

Background: Pseudomonas aeruginosa is not a common enteric pathogen. The association between human histo-blood group antigens (HBGAs) and P. aeruginosa enteric infection has not yet been studied. Methods: We collected stool samples from healthy children under 2 years of age for P. aeruginosa gut colonization rate. Saliva samples were collected from patients with P. aeruginosa-associated diarrheal diseases and normal healthy children. Genomic DNA was extracted from saliva samples for ABO blood group typing and FUT2 genotyping. Lewis phenotype was detected using ELISA assay. Results: A total of 85 patients with P. aeruginosa-associated diarrheal diseases and 105 healthy children were enrolled for collecting saliva specimens. The stool colonization rate was 5/101 (5%) in healthy children, 4/58 (6.9%) in infants, and 1/43 (2.3%) in children 1–2 years old, respectively. Blood group A was more frequent in patients with P. aeruginosa-associated diarrheal diseases 24/77 (31.2%) than in healthy children 18/102 (17.6%) (P = 0.035). All patients and healthy children were secretor positive. The distribution of weak-secretor genotype Se385/Se385 was 23/84 (27.4%) in patients with P. aeruginosa-associated diarrheal diseases and 17/104 (16.3%) in healthy children, respectively (P = 0.06). Patients with P. aeruginosa-associated diarrheal diseases had a higher percentage of Lea+b+ phenotype 25/81 (30.9%) than healthy children 17/105 (16.2%) (P = 0.018). There was no association between ABO or secretor or Lewis status with the clinical severity of P. aeruginosa-associated diarrheal diseases. Conclusion: Infants had a higher gut P. aeruginosa colonization rate than children. Children with blood group A and Lea+b+ phenotype are prone to P. aeruginosa-associated diarrheal diseases.

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to public health worldwide. This study aimed to determine the risk factors and outcomes for CRE colonization and infection in infants. Methods: Children aged

Objectives: This study explored the outcomes and predictors of early viral clearance among patients with COVID-19. Methods: This study recruited consecutive patients from March 1, 2020 to July 31, 2021. Early viral clearance was defined as having a duration from symptom onset to successive detection of SARS-CoV-2 polymerase chain reaction cycle threshold (Ct) value of ≥30 within 10 days. Results: Among the 239 enrolled patients, 54.4% (130 patients) had early viral clearance. A multivariate logistic regression analysis identified that dexamethasone use and day 1 Ct values were independent factors associated with late viral clearance. Patients with mild-moderate severity and who received dexamethasone therapy had a longer time to viral clearance than those who did not receive dexamethasone (17.2 ± 1.8 days vs 12.3 ± 1.1 days, P = 0.018). Patients with severe-critical severity had a similar duration from symptom onset to Ct value ≥30, regardless of dexamethasone therapy (18.3 ± 0.9 days vs 16.7 ± 4.7 days, P = 0.626). Conclusion: The study revealed that dexamethasone therapy and Ct values are independent predictors of late viral clearance. Patients with severe disease course due to older age, increased number of comorbidities, and worse clinical outcomes experienced delayed viral clearance.

BackgroundCompared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD.MethodsWe applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan.ResultsCompared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI.ConclusionFMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.

Background: Reliable clinical and laboratory predictors of coronavirus disease 2019 (COVID-19) disease progression could help to identify the subset of patients who are susceptible to severe symptoms. This study sought to identify the predictors for disease progression in patients with COVID-19. Methods: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were collected. Results: Among the 239 enrolled patients, 39.3% (94/239) experienced in-hospital disease progression. Multivariate logistic regression revealed that coronary arterial disease (CAD) (OR, 4.15; 95% C.I., 1.47–11.66), cerebrovascular attack (CVA) (OR, 12.98; 95% C.I., 1.30–129.51), platelet count median value of (OR, 2.25; 95% C.I., 1.02–4.99) were independent factors associated with COVID-19 progression. Patients who underwent disease progression at days 1, 4, and 7 presented lower lymphocyte counts and higher CRP levels, compared to patients without disease progression. Conclusions: The study revealed that in hospitalized COVID-19 patients, comorbidity with CAD and CVA, low platelet count, and elevated CRP levels were independently associated with disease progression. Compared with patients without disease progression, those with disease progression presented persistently low lymphocyte counts and elevated CRP levels.

Abstract Background Pseudomonas aeruginosa intestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. To combat intestinal dysbiosis and decolonize P. aeruginosa from gastrointestinal tract, we investigated the anti-adherence and gut microbiota modulation properties of marine prebiotic fucoidans. Methods Proteomic analysis of culture supernatant was performed by LC–MS/MS. Using lectin-based enzyme-linked immunosorbent assay, hemagglutinin domain interaction and inhibition with biomolecules were studied. We investigated the role of nutritional grade fucoidans in a mouse model and used 16S ribosomal RNA sequencing to examine fecal microbiota composition. Results Analysis of culture supernatant proteins indicated the secretion of two-partner secretion (TPS) family proteins, including TpsA1/CdiA2 and TpsA2/CdiA1. Lectin like activity at the N-terminal of TpsA due to a conserved hemagglutinin domain (Pfam identifier [ID] PF05860) mediates binding to mucins that carry multiple fucosylated glycans. Fucose-rich sulfated polysaccharides (fucoidans) and sulfated dextrans were found to be potent inhibitors of the recombinant N-terminal hemagglutinin domain of TpsA (TpsA-NT-HAD) binding to mucins. In a mouse model, antibiotic-induced dysbiosis was essential for P. aeruginosa gastrointestinal colonization. After prophylactic oral fucoidans supplementation, a higher proportion (60%) of the mice were decolonized over time and resisted re-colonization, this was associated with remarkable expansion of Bacteroides (post-infection day-3 abundance, 29–50%) and consequential reductions in bloom of Enterobacteriaceae and Enterococcaceae populations. In the non-supplemented group, Parabacteroides mediated recovery from dysbiosis but failed to decolonize P. aeruginosa. Conclusions Supplementing diet with marine prebiotic fucoidans can mediate earlier recovery from dysbiosis and decolonization of P. aeruginosa from gut by inhibiting secreted virulence factor (TpsA/CdiA) interaction with mucins and promoting the growth of beneficial Bacteroides population. We suggest the prophylactic use of nutritional grade fucoidans to decolonize P. aeruginosa from gastrointestinal tract of at-risk individuals to prevent infection and transmission of colonizing P. aeruginosa.

Background: The correlation between the clinical manifestations and fecal viral load of norovirus (NoV) infection remains unknown. Methods: We established a SYBR® Green-based real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method to quantify NoV and then sequenced its genomes from the feces of patients admitted at the Chang Gung Memorial Hospital from 2017 to 2018. Results: NoV GII.4 Sydney (n = 21, 36.2%) and GII.P16-GII.2 (n = 19, 32.8%), the two predominant genotypes found among 58 isolates, were closely related to the Taiwan variant 2012a cluster in the VP1 region and genotypes of China strain. An increase in viral load could be observed on Day 3 following the onset of NoV infection. The viral load then declined rapidly from days 10–15 but remained high for >1 month in a severe combined immunodeficiency patient. Significantly longer shedding was found in patients with fever (p = 0.03) or infected by the GII.4 Sydney strain (p 1 month in an immunodeficient patient was observed. Significantly longer shedding could be correlated with infection by the GII.4 Sydney strain and febrile patients.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Background: The genogroups GI and GII of norovirus (NoV) ribonucleic acid (RNA) genetic variants are the most prevalent cause of acute gastroenteritis outbreaks, especially in children, worldwide. A fast, accurate and convenient tool for diagnosis of NoV may be preferable to the more complicated performance of real-time reverse transcription-polymerase chain reaction (RT-PCR). Methods: In this study, we developed and evaluated a tool using insulated isothermal PCR (iiPCR)-mediated POCKIT Central NoV GI and NoV GII assay systems for diagnosis of NoV infection in pediatric patients suspected with gastroenteritis. Results: Performance of POCKIT Central Norovirus GI and GII assays using RT-iiPCR, compared to regular real-time RT-PCR showed the same diagnosis rate to NoV GI (100% of total percent agreement and 1.0 of Cohen's kappa value) and a similar detection rate to norovirus GII (96.3% of total percent agreement and 0.92 of Cohen's kappa value). In exclusivity tests, the POCKIT Central NoV GI and GII assays showed negative results to other viruses, indicating that the assays may be a NoV-specific detection tool. Conclusion: POCKIT Central NoV GI and GII Assay systems can provide a simple, rapid, sensitive, and specific point-of-need diagnostic tool for the detection of NoV GI and GII RNAs in clinical specimens from children with acute gastroenteritis.

Background/purpose: Morbidity and mortality from typhoid and paratyphoid fever remain an important problem for public health authorities in developing countries. In countries with lower incidences, most cases occur in travelers who visit regions in which typhoid and paratyphoid fever are highly endemic. The aim was to evaluate the source and transmission dynamics of typhoid and paratyphoid fever in Taiwan by using genomic analysis. Methods: During 2012–2019, 15 clinical isolates of Salmonella Typhi and S. Paratyphi A were collected. Demographic and clinical information of the infections were analyzed. We performed whole genome sequencing and evolutionary analysis on these isolates. Results: Clinical and microbiological data from 7 S. Typhi and 8 S. Paratyphi A isolates in Taiwan showed epidemiological and bacterial genomic link to the infection in South and Southeast Asia. The Taiwanese typhoidal isolates also share highly similar genomes with those collected from UK, indicating global circulation of the typhoidal clones. Local transmission of the imported but indigenized international clones was observed. Mutations occurring at gyrA 83 aa, including S83Y and S83F, were identified in the ciprofloxacin-resistant strains. Conclusion: Due to the advance of global transportation and communication, the transmission mode of infectious disease has been modified. Domestic typhoid and paratyphoid fever caused by international resistant clones can occur in low-incidence countries. Genome analysis showed that the indigenous clone originally imported from other countries has been circulating in Taiwan for over a decade.

Contaminations in frozen food imported from countries with ongoing COVID-19 epidemics have been reported in China. However, the epidemiological features of the outbreaks initiated by material-to-human transmission were less reported. The risk of this route of transmission remains unclear, and strategies to prevent resurgence could be flawed.We aimed to demonstrate the existence of cold-chain food or packaging contamination transmission and describe the time course and epidemiological features associated with the transmission in China. This review was based on the official reports or literature for resurging COVID-19 events that were related to cold-chain food or packaging contamination in China and other countries. Although SARS-CoV-2 on the material surface is not the main source of infection, the closed and humid environment for food packaging and transportation is a place favoring the material-to-human spread of SARS-CoV-2. In this transmission mode, patient zero is often hidden and difficult to detect, such that the outbreak usually can only be perceived after a period of a secret epidemic. Regular testing for high-risk populations and imported cold-chain products, proper disinfection of imported products, and protection of susceptible population while working remain an effective way to detect and prevent SARS-CoV-2 spread.

Background: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome. Methods: FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out. Results: From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT. Conclusions: FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.

Vancomycin-resistant Clostridium innocuum was recently identified as an etiologic agent for antibiotic-associated diarrhea in humans. We conducted a case–control study involving 152 C. innocuum-infected patients during 2014–2019 in Taiwan, using 304 cases of Clostridioides difficile infection (CDI) matched by diagnosis year, age (+2 years), and sex as controls. The baseline characteristics were similar between the 2 groups. C. innocuum–infected patients experienced more extraintestinal clostridial infection and gastrointestinal tract–related complications than did patients with CDI. The 30-day mortality rate among C. innocuum–infected patients was 14.5%, and the overall rate was 23.0%. Chronic kidney disease, solid tumor, intensive care unit admission, and shock status were 4 independent risk factors for death. C. innocuum identified from clinical specimens should be recognized as a pathogen requiring treatment, and because of its intrinsic vancomycin resistance, precise identification is necessary to guide appropriate and timely antimicrobial therapy.

Background/purpose: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. Methods: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case–control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015–2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. Results: Most patients (41/44, 93.2%) infected by S. Panama were

Background/Purpose: Acinetobacter baumannii is an important nosocomial pathogen. To better understand the role of CsuA/BABCDE pilus of A. baumannii in virulence, bacterial biofilm formation, adherence and carbohydrate-mediated inhibition were conducted. Methods: CsuA/BABCDE pilus-producing (abbreviated Csu pilus) operon of A. baumannii ATCC17978 was cloned for analysis of biofilm formation on an abiotic plastic plate, bacterial adherence to respiratory epithelial human A549 cells and carbohydrate-mediated inhibition. The carbohydrates used for inhibition of biofilm formation and adherence to A549 cells included monosaccharides, pyranosides, and mannose-polymers. Results: The Csu pilus of A. baumannii ATCC17978 was cloned and expressed into a non-pilus-producing Escherichia coli JM109, and was knocked out as well. The recombinant Csu (rCsu) pilus on E. coli JM109/rCsu pilus-producing clone observed by both electro-microscopy and atomic force microscopy showed abundant, while Csu-knockout A. baumannii ATCC17978 mutant appeared less or no pilus production. The E. coli JM109/rCsu pilus-producing clone significantly increased biofilm formation and adherence to A549 cells; however, the Csu-knockout mutant dramatically lost biofilm-making ability but, in contrast, increased adherence. Moreover, both of biofilm formation and adherence could be significantly inhibited by d-mannose and methyl-α-d-mannopyranoside in Csu pilus-producing E. coli JM109, whereas in A. baumannii ATCC17978, high concentration of carbohydrates was required for the inhibition, suggesting that Csu pilus is sensitive to d-mannose. Conclusion: This is the first study confirming that Csu pilus of A. baumannii belongs to mannose-sensitive type 1 pilus family and contributes to biofilm formation and bacterial adherence to human epithelial cells.

Background: Given the role of adenoid in the pathogenesis of otitis media with effusion (OME) and sleep-disordered breathing (SDB), the present study aimed to investigate the sleep quality and the impact of adenoidectomy on improvement of sleep symptoms in children with OME. Methods: Children with SDB or OME, aged 3–12 years, were prospectively enrolled before undergoing adenoidectomy in a tertiary medical center. The symptom severity of obstructive sleep apnea syndrome (OSAS) was evaluated by OSA-18 questionnaire on the day before and 6 months after surgery. Results: In total, 79 pediatric patients including 50 children with SDB and 29 children with OME were enrolled. The mean total OSA-18 score was 56.5 ± 15.1 and ten (34.5%) children experienced moderate to severe symptoms of OSAS as indicated by OSA-18 score ≥ 60 in OME group. After surgery, patients in both SDB and OME groups experienced improvement (both p

Background: Salmonella enterica serovar Typhimurium, a non-typhoidal food-borne pathogen, causes acute enterocolitis, bacteremia, extraintestinal focal infections in humans. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) contribute to invading into host cellular cytosol, residing in Salmonella-containing vacuoles for intracellular survival, and inducing cellular apoptosis. This study aimed to better understand the mechanism underlying apoptosis in Salmonella-infected macrophages. Methods: S. Typhimurium SL1344 was used to evaluate extrinsic and intrinsic apoptosis pathways in THP-1 monocyte-derived macrophages in response to Salmonella infection. Results: Activated caspase-3-induced apoptosis pathways, including extrinsic (caspase-8-mediated) and intrinsic (caspase-9-mediated) pathways, in Salmonella-infected macrophages were verified. THP-1 cells with dysfunction of TLR-4 and TLR-5 and Salmonella SPI-1 and SPI-2 mutants were constructed to identify the roles of the genes associated with programmed cell death in the macrophages. Caspase-3 activation in THP-1 macrophages was induced by Salmonella through TLR-4 and TLR-5 signaling pathways. We also identified that SPI-1 structure protein PrgH and effectors SipB and SipD, but not SPI-2 structure protein SsaV, could induce apoptosis via caspase-3 activation and reduce the secretion of inflammation marker TNF-α in the Salmonella-infected cells. The two effectors also reduced the translocation of the p65 subunit of NF-κB into the nucleus and the expression of TNF-α, and then inflammation was diminished. Conclusion: Non-typhoid Salmonella induced apoptosis of macrophages and thereby reduced inflammatory cytokine production through the expression of SPI-1. This mechanism in host–pathogen interaction may explain why Salmonella usually manifests as occult bacteremia with less systemic inflammatory response syndrome in the bloodstream infection of children.

Background: Necrotizing enterocolitis (NEC) is one of the most serious complications in preterm infants. Probiotics have been used to prevent NEC. Safety is a major concern for this practice. Methods: We reported a female preterm infant who received oral Lactobacillus rhamnosus GG but developed sepsis 12 days after the treatment. Cultures of blood and the catheter tip yielded L. rhamnosus. Next-generation sequencing was performed to analyze isolates from blood, stool, catheter, and product capsules. We also determined the capacities of these isolates to form biofilms. A literature review was performed. Results: The patient was treated with ampicillin and piperacillin/tazobactam, and she subsequently recovered without complications. The analysis of genome sequences indicated that all the isolates belonged to the clone of L. rhamnosus GG (ATCC 53103), suggesting that sepsis was a catheter-related infection caused by the oral probiotic. L. rhamnosus GG (ATCC 53103) and the probiotic strain tested formed biofilms under all growth conditions. Isolates from the blood and catheter tip also formed biofilms, but the stool isolate did not. The capacity of intrinsic biofilm formation in L. rhamnosus GG depended on environmental factors and the type of culture medium. Literature review of L. rhamnosus GG sepsis in preterm and young infants found that nearly 60% of the patients had a suspected or confirmed infected catheter. Conclusion: The study showed that the capacity of L. rhamnosus GG to form biofilms, especially in the presence of glucose, is a critical factor leading to the probiotic-related sepsis in preterm infants.

Deciphering the genotypic diversity of within-individual pathogens and verifying the evolutionary model can help elucidate resistant genotypes, virulent subpopulations, and the mechanism of opportunistic pathogenicity. However, observed polymorphic mutations (PMs) are rare and difficult to be detected in the “dominant-lineage” model of bacterial infection due to the low frequency. The four pooled group B Streptococcus (GBS) samples were collected from the genital tracts of healthy pregnant women, and the pooled samples and the isogenic controls were genomically sequenced. Using the PMcalling program, we detected the PMs in samples and compared the results between two technical duplicates, GBS-M001T and GBS-M001C. Tested with simulated datasets, the PMcalling program showed high sensitivity especially in low-frequency PMs and reasonable specificity. The genomic sequence data from pooled samples of GBS colonizing carrier pregnant women were analyzed, and few high-frequency PMs and some low-frequency PMs were discovered, indicating a dominant-lineage evolution model. The PMs mainly were nonsynonymous and enriched in quorum sensing, glycolysis/gluconeogenesis, ATP-binding cassette (ABC) transporters, etc., suggesting antimicrobial or environmental selective pressure. The re-analysis of the published Burkholderia dolosa data showed a diverse-community model, and only a few low-frequency PMs were shared between different individuals. Genes of general control non-repressible 5-related N-acetyltransferases family, major facilitator superfamily (MFS) transporter, and ABC transporter were positive selection candidates. Our findings indicate an unreported nature of the dominant-lineage model of GBS colonization in healthy women, and a formerly not observed mutation pool in a colonized microbial community, possibly maintained by selection pressure.

We investigated pneumococcal carriage between children ≦5 years old with otitis media (OM) and those without. Non-PCV13 serotypes were common in both groups; 19A remained the second most common serotype among children with OM despite high PCV13 coverage. This is important when considering a schedule with reduced vaccine doses or reduced valency, and the modification of pneumococcal immunization schedule should be followed up closely to monitor the result of protection against pneumococcal infections.

Background: Non-typhoid Salmonella infection may present as acute gastroenteritis or chronic infection, primarily in the bile-rich gallbladder. Biofilm formation is a mechanism of bile resistance in Salmonella. Our aim was to determine how Salmonella utilizes bile as a signal, and to study the relevance of the interaction between the PhoP-PhoQ two-component system and cyclic diguanosine monophosphate (c-di-GMP) signaling to biofilm formation. Methods: Two-dimensional (2-D) gel electrophoresis was used to identify genes required for Salmonella biofilm formation in bile. Quantitative real-time PCR (qRT-PCR) was used to clarify the role of the PhoP-PhoQ two-component system and its interaction with genes involved in the c-di-GMP network during biofilm formation. Results: Our result revealed that Salmonella mutants with incomplete outer membrane (△ompA), defective flagella (△flgE), or incomplete PhoP-PhoQ two-component system (△phoP), were unable to develop complete biofilms in the presence of bile. Moreover, PhoP-PhoQ two-component system-related Salmonella mutants (△phoP, △phoQ, △phoP△phoQ) had lower expression of c-di-GMP related genes (csgD, adrA) than the wild-type Salmonella strain had in the bile environment. Conclusion: Salmonella may sense and respond to bile through the PhoP-PhoQ two-component system during biofilm formation. Furthermore, the PhoP-PhoQ two-component system might activate regulators of the c-di-GMP signaling network.

Abstract Background Pneumococcus is one of the most common human airway pathogens that causes life-threatening infections. Ambient fine particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM2.5) is known to significantly contribute to respiratory diseases. PM2.5-induced airway inflammation may decrease innate immune defenses against bacterial infection. However, there is currently limited information available regarding the effect of PM2.5 exposure on molecular interactions between pneumococcus and macrophages. Results PM2.5 exposure hampered macrophage functions, including phagocytosis and proinflammatory cytokine production, in response to pneumococcal infection. In a PM2.5-exposed pneumococcus-infected mouse model, PM2.5 subverted the pulmonary immune response and caused leukocyte infiltration. Further, PM2.5 exposure suppressed the levels of CXCL10 and its receptor, CXCR3, by inhibiting the PI3K/Akt and MAPK pathways. Conclusions The effect of PM2.5 exposure on macrophage activity enhances pneumococcal infectivity and aggravates pulmonary pathogenesis.

Background: The epidemiology of nontyphoidal Salmonella (NTS) resistant to ciprofloxacin or ceftriaxone and its impact on patients’ clinical course are rarely reported. Methods: Children with culture-proven salmonellosis treated in a medical center in northern Taiwan in 2017 were enrolled. To trace the source of Salmonella, Salmonella isolated from food samples were collected from markets. Antimicrobial susceptibility and serotypes were determined. Results: Among the 453 isolates, 122 (26.9%) were highly antimicrobial-resistant, as defined by resistance to ciprofloxacin or ceftriaxone or both. The most prevalent highly resistant serotype was S. Anatum (66, 54.1%). Salmonella was detected in 94.1%, 66.7%, and 8.6% of examined pork, chicken, and vegetables examined, respectively. S. Anatum (6, 21.4%) and S. Derby (6, 21.4%) were the major serotypes isolated. Majority of the S. Anatum (5, 83.3%) were highly antimicrobial-resistant. More patients infected by highly resistant Salmonella required carbapenem treatment (OR = 23.5, 95% confidence interval [CI] 2.8–192.7, P

Background: The most severe form of pneumococcal disease is invasive pneumococcal disease (IPD), including empyema, sepsis and meningitis. Thomsen-Friedenreich antigen (TA; Galβ1-3GalNAc) activation is known to be a predictor of Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS). There have been limited data to correlate TA activation and overall disease severity of IPD in children. The study aimed to prove the positive correlation between TA activation and disease severity and to demonstrate the trend of TA level during the disease course. Methods: We retrospectively reviewed the medical records from 38 pediatric patients aged from 0 to 18 years with microbiologically-confirmed IPD between 2010 and 2015 at a medical center in Taiwan. All cases underwent TA activation testing by the fluorescence-labeled peanut lectin agglutination method. Medical information including demographic data, laboratory findings, co-morbidities, and outcome was collected and reviewed. We compared the clinical manifestations and associated co-morbidities between TA-positive and TA-negative patients. Results: Among the 38 patients, 25 (66%) showed TA activation. Compared to TA-negative patients, patients with TA activation had a statistically higher rate of prolonged anemia, thrombocytopenia, and acute kidney injury. TA-positive patients also had a longer intensive care unit stay and overall hospitalization days. The TA levels usually peaked 5–10 days after disease onset. Twenty-one pneumococcal isolates were recovered from the patients and serotyping was determined in 11 isolates: 10 serotype 19A and 1 serotype 3. Conclusions: TA determination not only helps to diagnose Sp-HUS but also is a predictor for IPD severity. Among hospitalized patients with severe pneumococcal disease, the peak of TA level usually appeared 5–10 days after disease onset.

Background: Zoonotic Salmonella enterica serovar Choleraesuis (S. Choleraesuis), causing paratyphoid in pigs and bacteremia in humans, commonly carry a virulence plasmid and sometimes a separate antimicrobial-resistant plasmid or merging together. This study aimed to analyze the likely mechanism of how to form a virulence-resistance chimera of plasmid in S. Choleraesuis. Methods: Whole plasmid sequence of pOU7519 in S. Choleraesuis strain OU7519 was determined using shotgun cloning and sequencing. Sequence annotation and comparison were performed to determine the sequence responsible for the formation of a chimeric virulence-resistance pOU7519. Other chimeric plasmids among the collected strains of S. Choleraesuis were also confirmed. Results: The sequence of pOU719, 127,212 bp long, was identified to be a chimera of the virulence plasmid pSCV50 and a multidrug-resistant plasmid pSC138 that have been found in S. Choleraesuis strain SC-B67. The pOU7519 is a conjugative plasmid carrying various mobile DNAs, including prophages, insertion sequences, integrons and transposons, especially a Tn6088-like transposon. By dissecting the junction site of the pSCV50-pSC138 chimera in pOU7519, defective sequences at integrase gene scv50 (int) and its attachment site (att) were found, and that likely resulted in a stable chimera plasmid due to the failure of excision from the pSCV50-pSC138 chimera. Similar structure of chimera was also found in other large plasmids. Conclusion: The deletion of both the int and att sties could likely block chimera excision, and result in an irreversible, stable pSCV50-pSC138 chimera. The emergence of conjugative virulence and antimicrobial-resistant plasmids in S. Choleraesuis could pose a threat to health public. KEYWORDS: Salmonella Choleraesuis, Virulence plasmid, Antimicrobial-resistant plasmid, Mobile DNA, pSCV50-pSC138 chimera

Background: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. Methods: Clinical isolates of S. pneumoniae from January 2012 to December 2015 at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. Results: During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p = 0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. Conclusions: A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone. Keywords: Non-typeable Streptococcus pneumoniae, Pneumococcal conjugate vaccine, Penicillin, Ceftriaxone

Gut dysbiosis may precede neonatal sepsis, but the association is still not well-understood. The goal of this study is to investigate the association between gut microbiota and neonatal sepsis, and to seek the evidence of colonization of pathogenic bacteria in the gut before evolving into an invasive infection. A prospective cohort study examined fecal microbiota composition in preterm infants with and without sepsis. Thirty-two very-low-birth-weight (VLBW) preterm infants and 10 healthy term infants as controls were enrolled. The fecal samples collected from the participants at the first, fourth, and seventh weeks of life underwent 16S rRNA amplicon sequencing for measurement of the diversity and composition of the microbiota. The bacterial isolates causing neonatal sepsis were genome sequenced. PCR was performed to confirm the translocation of the bacteria from the gut to the blood. The results showed that VLBW preterm infants with sepsis had lower microbial diversity in the gut at birth compared to preterm infants without sepsis and term infants. The composition of gut microbiome in preterm infants was similar to healthy terms at birth but evolved toward dysbiosis with increasing Proteobacteria and decreasing Firmicutes weeks later. The strain-specific PCR confirmed the presence of causative pathogens in the gut in 4 (40%) out of 10 VLBW preterms with sepsis before or at onset of sepsis, and persistence of the colonization for weeks after antibiotic treatment. The same bacterial strain could horizontally spread to cause infection in other infants. Prolonged antibiotic exposure significantly reduced beneficial Bifidobacterium and Lactobacillus in the gut. In conclusion, preterm infants with gut dysbiosis are at risk for neonatal sepsis, and the causative pathogens may be from the gut and persist to spread horizontally. The association of increased Proteobacteria abundance and decrease in microbiome diversity suggests the need for interventions targeting the gut microbiome to prevent dysbiosis and sepsis in VLBW preterm infants.

Background: Streptococcus agalactiae, or group B Streptococcus (GBS), remains to be one of the leading pathogens causing invasive infections in infants. Methods: The clinical GBS isolates from sterile sites of patients younger than 18 years old were collected from October 1998 to December 2014 in two hospitals in Taiwan. Medical records were retrospectively reviewed. Every isolate was serotyped with a multiplex PCR assay. Multilocus sequence typing (MLST) was performed in representative isolates of different serotypes. A total of 205 GBS isolates were collected from 181 patients with 182 infection episodes. Results: Serotype Ia was the most common in patients less than 72 h old, whereas III the most common in patients older than 72 h. In early-onset disease (0–6 days), Ia and III each caused 27.5% of the infection, followed by Ib (14.5%). In late-onset disease (7–89 days), serotype III predominated (75.3%), followed by Ia (10.1%) and Ib (6.8%). Thirty-one episodes (17%) were complicated with culture-confirmed meningitis. We compared serotype Ia and III patients, and found that serotype Ia patients were significantly younger (median age, 3 days), had more perinatal maternal fever and higher mortality. ST17 and ST19 were exclusively found in serotype III, while ST23 and ST24 comprised of 85% of serotype Ia. Conclusion: In Taiwan, serotypes Ia and III are the most common cause for early-onset and late-onset neonatal GBS infections, respectively. Some differences in the clinical features of invasive GBS infections caused by serotype Ia and III were observed. Keywords: Streptococcus agalactiae, GBS, Neonatal sepsis, serotype, MLST, GBS meningitis

Background: Group B streptococcus (GBS) infections can be life-threatening in newborns. This study aimed to analyze GBS carriage status and genotypic diversity in healthy neonates after implementation of intrapartum antibiotic prophylaxis (IAP) in Taiwan. Methods: Newborns carrying GBS were identified from a screen of 500 newborns and followed up until their cultures turned negative. Their mothers' GBS screening data were reviewed. Molecular methods, including capsular serotyping, multilocus sequence typing and pulsed-field gel electrophoresis (PFGE), were used to analyze GBS isolates. Results: GBS colonization was detected at either the nose or anus in 11 of 500 healthy neonates (2.2%). In this group of 11 neonates, 4 had GBS serotypes II and III for 4–6 months, 1 had serotype V for 2 months, 6 had serotypes Ia, II, V, and VI for less than 1 month, and 1 had 2 different serotypes (serotypes V and II) at different times. The most prevalent serotype was II (33.3%), followed by Ia (25.0%), III (16.7%), V (16.7%), and VI (8.3%). The main sequence type was ST1 (50.0%), followed by ST19 (16.7%), ST23 (8.3%), ST24 (8.3%), ST103 (8.3%), and ST 231 (8.3%). All isolates were grouped into 5 PFGE clusters F, G, J, X, and Y, and all were susceptible to β–lactam antimicrobial agents. Conclusions: GBS was carried in 2.2% (11/500) healthy newborns and persisted for 6 months in 3 neonates. This study makes clearer our understanding of GBS colonization, serotype distribution, and genotype distribution in healthy neonates. Key Words: colonization, group B Streptococcus, intrapartum antibiotic prophylaxis, PFGE, sequence type

Abstract Background Salmonella enterica consists of over 2500 serovars and displays dichotomy in disease manifestations and host range. Except for the enrichment of pseudogenes in genomes for human-restricted serovars, no hallmark has been identified to distinguish those with host-generalist serovars. The serovar Sendai is rare and human-restricted. Notably, it exhibits an O, H antigen formula as the host-generalist serovar Miami. Results We sequenced the complete genomes of the two serovars Sendai and Miami. Analysis at both nucleotide identity and gene content level demonstrates the same high degree of similarity between Sendai and Paratyphi A, but their distinct CRISPR spacers suggests a recent divergence history. A frameshift mutation occurred in rfbE for the entire lineage of Paratyphi A but not in Sendai, which may explain their distinct O antigens. The nucleotide sequence of Miami’s fliC is nearly identical to Sendai’s. The incongruent phylogeny of this gene with that of the adjacent genes suggests a recombination event responsible for Sendai and Miami possessing the same H antigen. Sendai’s even greater number of pseudogenes than that of Paratyphi A and Typhi indicates its undergoing continued genomic degradation. The phylogenetically distinct human-restricted serovars/strains share pseudogenes with the same inactivation mutations, therefore suggesting that recombination may have occurred and have been facilitated by their overlap in niches. Conclusions Analysis of Sendai’s genome and comparison with others reflect the finer evolutionary signatures of Salmonella in the process of niches changing from facultative to obligate parasite.

Background: The aim of this study was to identify risk factors for Clostridium difficile infection (CDI) and its attributable mortality and to propose methods to prevent CDI and improve patients’ outcomes. Methods: CDI was defined as diarrheal patients with stool samples that were positive for C. difficile toxin. Clinical presentations of all patients with CDI and two times as many age- and sex-matched culture-negative controls at the Chang Gung Memorial Hospital in 2014 were identified and compared by multivariate, nonparametric, and Kaplan–Meier survival analysis. Results: There were no significant differences in ages, sex, or Charlson comorbidity indexes between the CDI group (n = 42) and the control group (n = 86). The multivariate analysis indicated that underlying peptic ulcer disease and previous use of gastric acid inhibitors or third-generation cephalosporins for at least 3 days were significantly more common in patients with CDI than in the controls. Charlson scores were associated with mortality due to CDI. Recommended treatment using oral vancomycin to treat patients with Charlson score ≥ 5 and oral metronidazole or vancomycin to treat those with moderate underlying disease (Charlson score ≥ 2 and ≤ 5) significantly increased survival in these patients (p = 0.001). Conclusions: Oral vancomycin given to patients with high Charlson scores and oral metronidazole or vancomycin to patients with moderate Charlson scores decreased mortality due to CDI. Restricting the use of third-generation cephalosporins and gastric acid inhibitors is recommended to prevent CDI in hospitalized patients. Keywords: Risk factor, Clostridium difficile infection, Gastric acid inhibitor, Third-generation cephalosporin, Charlson score

Salmonella is one of the most common bacteria causing food poisoning worldwide. We evaluated the prevalence, the serotypes, and the antimicrobial resistance (AMR) of Salmonella isolates from many kinds of food, particularly pork and chicken in retail, in Taiwan between January 2017 and December 2019. The E-test was used to assess antimicrobial susceptibility and a polymerase chain reaction was performed for serotyping. A total of 459 different foods were investigated, and 117 Salmonella strains were isolated. Retail pork and chicken were the most common Salmonella-contaminated foods (64.1% and 29.1%, respectively). Of the 117 isolates, 23 serotypes were identified. The serotypes Derby (16.2%), Anatum (13.7%), and Agona (8.5%) were the most prevalent. The resistance rates to ciprofloxacin, ceftriaxone, and carbapenem were 41.9%, 11.1%, and 1.7%, respectively. The Derby and Anatum serotypes were prevalent in chicken and pork; the Anatum serotype had significantly higher ciprofloxacin and ceftriaxone resistance rates and was highly prevalent in 2017 and 2018. Multi-locus sequence typing analysis revealed that the 58 randomly chosen Salmonella isolates belonged to 18 sequence types (STs). ST64 (Anatum, 16 out of 58, 27.6%) was the most common, followed by ST321 (Muenster, 6/58, 10.3%), ST831 (Give, 5/58, 8.6%), ST155 (London, 4/58, 6.9%) and ST314 (Kentucky, 4/58, 6.9%). Multidrug-resistant Salmonella strains were remarkably observed in the serotypes Anatum (ST64) and Goldcoast (ST358). This study revealed that retail pork was commonly contaminated with antimicrobial-resistant Salmonella. Thus, periodic investigations of Salmonella serotypes and AMR are needed.

Non-typhoidal Salmonella (NTS) typically causes self-limiting diarrheal disease but may occasionally lead to invasive infection. This study investigated the epidemiology and antimicrobial resistance of children with NTS infection between 2012 and 2019. We retrospectively analyzed pediatric patients with NTS infections, confirmed by positive cultures, in a tertiary medical center in Taiwan in 2012 and 2019. Clinical features and laboratory data of the patients were collected. Changes in the serogroup category and antimicrobial resistance were also analyzed. Of the total 797 isolates collected, 55 had NTS bacteremia. Compared with the resistance rates in 2012, the rates of resistances to third-generation cephalosporin and ciprofloxacin were significantly higher in 2019 (4.1% vs 14.3%, P < 0.001; 1.9% vs 28.6%, P < 0.001), especially in groups B, D, and E. Moreover, we observed significantly higher antimicrobial resistance (25.3%) to third-generation cephalosporin, and approximately half the NTS isolates in the infant group were multidrug resistant – a higher rate than those of other age groups in 2019. Invasive NTS often presented with a longer fever duration, lower hemoglobin level and with no elevated C-reactive protein (P < 0.05). Non-invasive NTS isolates in 2019 were significantly more resistant to ceftriaxone (P < 0.001) and ciprofloxacin (P < 0.001) than those in 2012. The antimicrobial resistance of NTS in children has increased progressively in the past decade, and different serogroups exhibited different resistance patterns. During this period, infants showed the highest risk to get a third-generation cephalosporin-resistant NTS infection. The high rates of antimicrobial resistance among children with NTS in Taiwan merit continual surveillance.

Aim: Intussusception, the most common abdominal emergency in early childhood, is frequently misdiagnosed at initial presentation. The effect of using point-of-care ultrasonography (POCUS) by emergency medicine physicians on pediatric intussusception misdiagnosis rate remains unclear. Here, we summarize outcomes and misdiagnoses before and after training junior and senior physicians on using POCUS for diagnosing intussusception and compared their performance levels.Materials and Methods: This observational cohort analysis included patients with suspected intussusception who visited a pediatric emergency department (ED) between January 2017 and December 2019. All enrolled patients were evaluated by junior (

Identifying ischemic ovary as a complication of ovary torsion (OT) is a significant challenge in children. This study identified risk factors for ischemic OT among pediatric OT patients to prevent delayed treatment. This retrospective study included pediatric inpatients who underwent operation for OT over 20 years. We employed multivariable logistic regression to find the risk factors associated with ischemic OT. Among the 118 patients included in this study, 78 (66.1%) had ischemic OT. Patients with ischemic OT tended to be younger; had more frequent vomiting; and had elevated White blood cell (WBC), C-Reactive protein (CRP), and segments in comparison with non-ischemic OT patients. Multivariable regression showed increased odds of ischemic ovary torsion, associated with higher WBC (12.3 × 103/mm3 vs. 8.7 × 103/mm3, p < 0.001), CRP (50.4 mg/L vs. 8.4 mg/L, p < 0.001), and vomiting (55.1% vs. 25%, p = 0.002) than in non-ischemic patients. A receiver-operating characteristic (ROC) analysis indicated that patients with vomiting, leukocytosis, or CRP ≧ 40 mg/L were more likely to have ischemic OT (sensitivity, 92%; specificity, 54%; PPV, 79.6; NPV, 78.9%). Ischemic OT is common among pediatric OT patients. The presence of potential risk factors of vomiting, leukocytosis, and CRP more significant than 40 mg/L may assist clinicians in ensuring an expedited surgical treatment.

Background: Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial. Methods: A retrospective cohort study was designed. All patients with IPD from 2011 to 2013 admitted in a medical center were screened and collected for their clinical presentations and laboratory characteristics. Results: Approximately half of the 134 IPD isolates derived from these patients belonged to three major serotypes (19A, 6A and 3), which are included in 13-valent pneumococcal conjugate vaccine (PCV13), but not in 7-valent pneumococcal conjugate vaccine (PCV7). Ceftriaxone resistance according to non-meningitis criteria was identified in 38% of the IPD isolates, and was the major independent risk factor associated with inappropriate initial therapy that subsequently contributed to mortality of the patients. Infection by serotype 6A, 15B, 19A, 19F, or 23F was the major independent risk factor associated with ceftriaxone resistance (non-meningitis criteria). 77.6% of these isolates belonged to additional PCV13 serotypes, with more than 40% expressing resistance to ceftriaxone. In terms of serotype coverage, PCV13 covered 94.1% of the IPD isolates with ceftriaxone resistance, in comparison to 21.6% only by PCV7. Conclusions: The increase of ceftriaxone resistance in pneumococci in part driven by PCV7 vaccination in Taiwan is worrisome. The use of PCV13 in children as well as in the elderly population is likely to offer protection from the infection caused by ceftriaxone-resistant pneumococci. It is important to give an effective drug such as penicillin, fluoroquinolones or vancomycin in 2 days for improving outcome of IPD patients. Keywords: Invasive pneumococcal disease, Serotype, Pneumococcal conjugate vaccine, Ceftriaxone resistance

Background: Acinetobacter baumannii infections in neonates are not uncommon but rarely studied. Methods: Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed. Results: Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-blaOXA-80, which has never been reported in Asia before. Most infected newborns were premature (95%), with very low birth weight (70%

Background: We aimed to report the implementation of an antimicrobial stewardship program (ASP) guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. Methods: A 3-year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD), susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. Results: Average monthly length of stay of admitted patients decreased from 7.8 ± 0.5 days in 2011 to 6.9 ± 0.3 days in 2013 (p

This study identified factors associated with the recurrence of appendicitis in children with appendiceal masses after successful nonsurgical treatment. Methods: In this retrospective study, children who were diagnosed as having appendiceal masses after undergoing conservative treatment between 2000 and 2014 were enrolled and the medical records of those who did not undergo an interval appendectomy were reviewed. The clinical features and outcomes of patients with and those without recurrent appendicitis were compared. Regression analysis was used to identify risk factors of appendicitis recurrence. Results: Seventy patients were included and successfully discharged after receiving nonsurgical treatment for appendiceal masses. Of the patients, 35 (50.0%) developed recurrent appendicitis and 85.7% (30/35) recurrences developed within 3 months. Multivariate analyses showed that patients with a higher serum C-reactive protein (CRP) level and peritonitis more frequently developed recurrence. The appendicitis recurrence rate was significantly higher in the patients with CRP levels of ≥103 mg/L with an odds ratio of 16.9 or in those with peritonitis with an odds ratio of 4.9. Conclusion: Children with appendiceal masses who develop peritonitis or have CRP levels of ≥103 mg/L have a higher recurrence rate of appendicitis and should undergo an interval appendectomy.