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Background/purpose Antimicrobial resistance in Taiwan has been on the rise for two decades. The implementation of pneumococcal conjugate vaccination (PCV13) and enhanced antimicrobial control (2013–2015) by the government may have changed the antibiotic resistance. Methods Four respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis) isolated in a single medical center during 2008–2017 were studied. We defined three temporal stages: (a) the first era (2008–2012), prior to implementation of the national immunization program (PCV13 vaccination), (b) the second era (2013–2015), during which an enhanced antibiotic control strategy was implemented, and (c) the third era (2016–2017), after implementation. Antimicrobial drug sensitivities were collected from two other hospitals: one from east Taiwan, one from west-central Taiwan. Results S. pneumoniae was frequently isolated during the first era. It declined progressively during the second era of PCV13 vaccination. S. pyogenes and M. catarrhalis were not frequently isolated. The drug susceptibility of S. pneumoniae to ceftriaxone and vancomycin remained high. The antimicrobial susceptibility of H. influenzae to amoxillin/clavulante declined over the three temporal stages, from 91.9%-79.5%–58.5% (all p Conclusion Antimicrobial resistance of H. influenzae increased during the latter part of the study period. The PCV13 vaccination program reduced the invasive pneumococcal disease and reduced the stress on the emergent drug resistance. This enhanced antibiotic control strategy was effective in terms of nosocomial drug resistance but not for community-associated pathogens.

Background: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015. Methods: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung. Results: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients. Conclusion: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected. Key Words: enterovirus D68, respiratory presentation, taiwan

Chih-Cheng Lai,1 Ying-Sheng Chen,2 Nan-Yao Lee,3 Hung-Jen Tang,4,5 Susan Shin-Jung Lee,6,7 Chin-Fu Lin,8 Po-Liang Lu,9–11 Jiunn-Jong Wu,12 Wen-Chien Ko,13 Wen-Sen Lee,14 Po-Ren Hsueh15,16 1Department of Intensive Care Medicine, Chi Mei Medical Center, Liuying, Taiwan; 2Division of Infectious Diseases, Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan; 3Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; 4Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 6Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan; 8Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 11Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan; 13Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 14Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan; 15Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 16Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study aimed to determine the in vitro susceptibility of commonly encountered Gram-negative bacilli (GNB) recovered from patients admitted to intensive care units (ICUs) in Taiwan against colistin, carbapenems, and other comparative agents. Methods: In total, 758 nonduplicate GNB isolates were obtained from clinical specimens of ICU patients at seven medical centers in 2016. Minimum inhibitory concentrations (MICs) were determined using the Vitek 2 susceptibility system. The reference broth-microdilution method was performed to determine MICs of colistin. Five main carbapenemase genes among carbapenem-non-susceptible GNB and mcr-1–mcr5 genes among colistin non-wild-type or -resistant isolates were determined. Results: After exclusion 38 Proteus mirabilis and 13 Morganella morganii spp. among 361 Enterobacteriaceae isolates, 34 (9.4%) isolates were carbapenem-insusceptible, 91.1% (n=31) were colistin wild type, and three and one Klebsiella pneumoniae isolates carried blaKPC and blaOXA48-like, respectively. Carbapenem-insusceptible isolates were found in 23.4% (30 of 128) and 63.0% (87 of 138) of isolates of the Pseudomonas aeruginosa and Acinetobacter baumannii complex, respectively. mcr-1 was detected in two (1.8%) Enterobacter cloacae isolates. Very major errors between two methods of susceptibility to colistin were found in 1.5% of K. pneumoniae, 27.5% of E. cloacae, 4.7% of P. aeruginosa, and 10.1% of A. baumannii complex isolates. Conclusion: In this study, 8.7% of Enterobacteriaceae isolates from ICUs were not susceptible to carbapenem, and blaKPC and blaOXA48-like were found among three and one carbapenem-insusceptible K. pneumoniae isolates, respectively. Colistin MICs determined by Vitek 2 were not reliable, especially for E. cloacae and A. baumannii complex isolates. Keywords: colistin, carbapenems, susceptibility, carbapenemase, mcr-1, intensive care units, SMART, P. aeruginosa, A. baumannii

Objective The aim of this study was to investigate the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria from seven intensive care units in Taiwan in 2016.

TB remains a leading cause of morbidity and mortality worldwide. Approximately one-quarter of the world’s population has latent TB infection. TWEAK is a multiple-function cytokine and may be used as a target for the treatment of rheumatic diseases, cardiovascular diseases, and renal diseases. Here, we demonstrated a novel relationship between TWEAK and activation of the autophagic machinery which promotes antimycobacterial immunity. Additionally, TB infection is highly dynamic and determined by the interaction between the host and mycobacterium. We demonstrated a mechanism of fine-tuned balance between the mycobacterium and host for granuloma formation and/or maintenance in LTBI status. Once patients entered LTBI status, the upregulation of miR-889 was associated with TNF-α levels and granuloma formation to maintain mycobacterial survival. Adalimumab (a TNF-α inhibitor) reduced both TNF-α and miR-889 levels and caused LTBI reactivation and, thus, TWEAK enhancement. MiR-889 and TWEAK may become potential diagnostic biomarkers or therapeutic targets for LTBI and LTBI reactivation, respectively., Autophagy plays an important role in protecting the host against pathogens. Mycobacterium tuberculosis can suppress autophagy and then remain dormant and survive within the host for an extended period, which is responsible for latent tuberculosis infection (LTBI). Here, we explored the role of microRNAs (miRNAs) in LTBI. The miRNA profiles were explored using the next-generation sequencing approach, followed by quantitative reverse transcription-PCR validation. The biological function of candidate miRNA was evaluated using immunoblotting, immunofluorescence techniques, and enzyme-linked immunosorbent assay in an in vitro human TB granuloma model. An increased miR-889 expression was observed in patients with LTBI compared with that in patients without infection. The reporter assay identified tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the target of miR-889. Mycobacterial infection induced TWEAK upregulation in the early phase. TWEAK induced autophagy and promoted mycobacterial autophagosome maturation through activation of AMP-activated protein kinase (AMPK). Upon entry to LTBI status, elevated miR-889 levels were associated with TNF alpha (TNF-α) and granuloma formation/maintenance. MiR-889 inhibited autophagy via posttranscriptional suppression of TWEAK expression to maintain mycobacterial survival in granulomas. Adalimumab (anti-TNF-α monoclonal antibody) treatment reduced levels of both TNF-α and miR-889 and caused granuloma destruction and LTBI reactivation. The circulating miR-889 and TWEAK levels were correlated with LTBI and subsequently associated with anti-TNF-α-related LTBI reactivation in patients. We propose that miR-889 and TWEAK can act as targets that can be manipulated for antimycobacterial therapeutic purposes and act as candidate biomarkers for LTBI and LTBI reactivation, respectively.

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

Background/Purpose There are reports of an increase in vancomycin minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA) over time, a phenomenon referred to as "MIC creep", but some studies have conflicting results. The aim of this study is to evaluate the association of molecular typing, vancomycin MIC, and clinical outcome for patients with MRSA infections. Methods Thirty-two MRSA isolates from Taichung Veterans General Hospital (TCVGH), Taichung, Taiwan during the period of 2003 to 2008 were analyzed for the association of sequence typing, vancomycin MIC, and the correlated clinical outcome for patients with MRSA infections. The vancomycin MICs of 28 additional isolates from 2014 were used for the detection of MIC creep. Results Among the genotypes of 32 isolates, there were 17 (53.1%) isolates with ST239-SCC mec III, seven (21.9%) isolates with ST5-SCC mec II, six (18.8%) isolates with ST59-SCC mec IV, and two (6.2%) isolates with ST59-SCC mec V T . Two isolates had an MIC of 2 μg/mL and were identified as ST239-SCC mec III. No statistically significant change in the distribution of MICs of all isolates was observed between 2003 and 2014 ( p = 0.263). There was no significant difference in the mortality rates between two groups of patients with vancomycin MICs p = > 0.99). Conclusion There was no vancomycin MIC creep in the period from 2003 to 2014 in this study. Appropriate prognostic models for assessment of the association among sequence types, vancomycin MICs, and clinical outcome warrant further investigation.

We aimed to establish the role of MALDI-TOF MS on species discrimination of phenotypically indistinguishable A. baumannii, A. pittii and A. nosocomialis. Compared to multiplex PCR, the gold standard, MALDI-TOF MS yielded a high sensitivity for A. baumannii (97.9%) and specificity for A. pittii (98.9%) and A. nosocomialis (100%).

In this paper, we introduce a new variation of graph searching problem, namely, cooperative graph searching problem. We define that a searcher is isolated if there is no other searchers on its close neighborhood. In this variant, we add an additional constrain that every searcher would not be isolated after each searching step. Therefore, we can make sure that every searcher can be cooperated by another searcher. We prove that the cooperative graph searching problem is NP-complete on general graphs and propose polynomial-time algorithms for the problem on grid graphs.

Risk for illness and death are increased for these patients., Increasing evidence indicates that the risk of acquiring tuberculosis (TB) and nontuberculous mycobacterial disease is elevated among patients with rheumatoid arthritis (RA). To determine the epidemiology of mycobacterial diseases among RA patients in Asia, we conducted a retrospective cohort study. We used a nationwide database to investigate the association of RA with mycobacterial diseases. The risk for development of TB or nontuberculous mycobacterial disease was 2.28-fold and 6.24-fold higher among RA patients than among the general population, respectively. Among RA patients, risk for development of mycobacterial disease was higher among those who were older, male, or both. Furthermore, among RA patients with mycobacterial infections, the risk for death was increased. Therefore, RA patients, especially those with other risk factors, should be closely monitored for development of mycobacterial disease.

Background/PurposeThe emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a cause for great concern. The aim of this study was to evaluate antimicrobial susceptibility, mechanisms of carbapenem-resistance in two members of the Enterobacteriaceae family (Escherichia coli and Klebsiella pneumoniae), and clinical outcomes of their infections.MethodsThe susceptibility tests of 16 E. coli and 60 K. pneumoniae isolates, collected from 2010 to 2011, were assessed. The minimal inhibitory concentrations of eight antimicrobial agents were assessed by the broth microdilution method according to the recommendations of the Clinical and Laboratory Standards Institute. The detection of beta-lactamase genes was performed by polymerase chain reaction. The genetic relatedness of these isolates was determined by pulsed-field gel electrophoresis (PFGE) fingerprinting.ResultsThe carbapenemase genes blaKPC-2 and blaOxA were detected in one and five K. pneumoniae isolates, respectively. The genetic combinations blaSHV-5–blaDHA and blaSHV-5–blaCTx-M-G9 were prevalent in 45% and 26.7% of 60 K. pneumoniae isolates, respectively. The susceptibility rates of 60 K. pneumoniae isolates to colistin and tigecycline were 58.3% and 50.0%, respectively. The 30-day mortality rates of the patients treated with carbapenem, colistin, or tigecycline were as high as 60.6%. Nine clusters of K. pneumoniae isolates were identified by PFGE fingerprinting.ConclusionThe findings of carbapenemase genes in a few isolates and small clusters of CRE indicated the emerging problems in the hospital. The high mortality rates were observed in the patients treated by colistin and tigecycline, although they were the only alternative treatment options for CRE infections. Active surveillance and an effective infection control strategy should be implemented to control the spread of CRE infections.

Clostridium difficile PCR ribotype 027 is a hypervirulent strain that has caused significant nosocomial diarrhea in many countries but has not yet been reported or isolated in Taiwan previously. Here, we present the characteristics of a case of C. difficile PCR ribotype 027 identified in Taiwan. Taiwan is located in a key transportation center of Asia. This report is important for alerting hospitals and public health departments in Asia about the emergence of this hypervirulent strain so that close monitoring may be enacted to prevent potential outbreaks.

Objective Shewanella bacteremia is an uncommon but potentially fatal disease. Although hepatobiliary diseases have been proposed to be risk factors for various Shewanella infections, little is known about the features of Shewanella bacteremia in patients with hepatobiliary diseases. This study aims to characterize the presentation and risk factors of Shewanella bacteremia in patients with hepatobiliary diseases. Methods We retrospectively investigated the clinical features, microbiology and outcomes of patients with Shewanella bacteremia who were admitted to a tertiary medical center between January 2001 and December 2010. All isolates were confirmed to the species level using 16S rRNA sequencing analyses. The English language medical literature was searched for previously published reports. Results Fifty-nine cases of Shewanella bacteremia, including nine at the hospital, were identified, 28 (47.4%) of which involved underlying hepatobiliary diseases, representing an important risk factor. In 12 of the 28 cases, the infections involved the hepatobiliary system; with a tendency towards an Asian origin. In our case series of nine patients, Shewanella haliotis was isolated in five patients. The majority of our patients lived in coastal areas, consumed seafood regularly and developed bacteremia during the summer season. Conclusion It is recommended that the possibility for Shewanella infection be considered in patients with bacteremia and also underlying hepatobiliary diseases, particularly if patients present with hepatobiliary infections, a history of seafood, or development of the disease during the summer.

For a graph G = (V, E), a subset D of V is a total dominating set of G if every vertex in V has to be adjacent to a vertex of D. Vertex subset D is a disjunctive total dominating set if every vertex of V is adjacent to a vertex of D or has at least two vertices in D at distance 2 from it. The disjunctive total domination problem on G is to find a disjunctive total dominating set D of the minimum cardinality. The cardinality of a minimum disjunctive total dominating set of G is called the disjunctive total domination number of G. In this paper, we study the disjunctive total domination problem on grid graphs. We propose upper bounds for general grid graphs. In particular, some bounds are optimal for some special cases.

Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p trend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors.

OBJECTIVE: Infections of snake bite wounds by Shewanella are rarely discussed in the medical literature. This study aims to characterize the presentation and management of Shewanella infections in snake bite wounds. METHOD: We retrospectively investigated the microbiology, clinical features, and outcomes of patients with Shewanella infected snake bite wounds admitted to a tertiary medical center from January 1998 to December 2009. RESULTS: Ten patients with Shewanella-infected snake bite wounds were identified. All of the snake bites were caused by cobras. The majority of patients had moderate to severe local envenomation and polymicrobial infections. Shewanella isolates are susceptible to ampicillin-sulbactam, piperacillin-tazobactam, third- and fourth-generation cephalosporins, carbapenems, aminoglycosides, and quinolones but are resistant to penicillin and cefazolin. All of the patients examined had favorable outcomes. CONCLUSION: It is recommended that Shewanella infection be considered in snake bite patients, especially when patients present with moderate to severe local envenomation.

Tungsten missing was observed at the interface between contact barrier layer and W in the 28 nm node contact process. The potentiodynamic polarization scans showed that H2O2 in the W chemical-mechanical-polishing slurry increased the potential difference between the diborane (B2H6) reduced atomic layer deposited (ALD) W and TiN, suggesting that there is a high tendency for galvanic corrosion to occur. This potential difference kept constant, but the corrosion current density increased when the H2O2 concentration increased. The TEM image showed the depth of ALD W missing is proportional to the H2O2 concentration, which agrees with the electrochemical testing results. ALD W films with various pre- and post-treatments and their correlations with the degree of W missing were also investigated.

Background/Purpose Mycobacterium abscessus is the most resistant and rapidly growing mycobacterium and causes a wide range of clinical infectious diseases. The relationship between antimicrobial susceptibility and clinical outcome needs to be further evaluated. Methods Forty M. abscessus isolates were obtained from clinical specimens of 40 patients at the Taichung Veterans General Hospital from January 2006 to December 2008. Antimicrobial susceptibility testing was performed using the broth microdilution method according to the recommendations of the National Committee for Clinical Laboratory Standards. The clinical manifestations and outcomes were reviewed from medical records. Results Twenty-two patients were diagnosed with M. abscessus infection. Cough (86.3%), hemoptysis (31.8%) and fever (18.1%) were the most common symptoms. The radiographic findings included reticulonodular opacities (50.0%), consolidation (31.8%) and cavitary lesions (18.1%). The 40 isolates were susceptible to amikacin (95.0%), cefoxitin (32.5%), ciprofloxacin (10.0%), clarithromycin (92.5%), doxycycline (7.5%), imipenem (12.5%), moxifloxacin (22.5%), sulfamethoxazole (7.5%) and tigecycline (100%). The rate of treatment failure was 27.3% at the end of the 12 th month after the start of treatment, although these patients were treated with a combination of clarithromycin and other antimicrobial agents. Conclusion M. abscessus is naturally susceptible to clarithromycin and amikacin, variably susceptible to cefoxitin and imipenem, and resistant to most other antimicrobial drugs. Combination therapy with clarithromycin, amikacin and other active antimicrobial agents may lead to clinical improvement; however, the rate of treatment failure is still high.

Background/Purpose The susceptibility breakpoints of cephalosporins for Enterobacteriaceae were revised by the Clinical and Laboratory Standards Institute (CLSI) in 2010 and 2011. The clinical outcome and susceptibility data were analyzed to evaluate the impact of revised CLSI cefazolin breakpoints on the treatment of Escherichia coli bacteremia. Methods Forty-three bacteremic Escherichia coli isolates from Taichung Veterans General Hospital, Taichung, Taiwan, during the period from January 2013 to December 2013, were selected to analyze the minimum inhibitory concentration (MIC) distributions of cefazolin and the correlated clinical responses to cefazolin therapy. Results The modal cefazolin MIC among the 43 isolates was 1 μg/mL and accounted for 18 (42%) isolates. The cumulative percentage for MICs ≤ 2 μg/mL was 79%. The conventional dosing regimens achieved clinical cure in 33 (97%) of 34 patients with bacteremia due to E. coli with a cefazolin MIC ≤ 2 μg/mL, in all of the six patients with a cefazolin MIC of 4 μg/mL, and all of the three patients with a cefazolin MIC of 8 μg/mL. Conclusion The microbiological data support the revised CLSI breakpoints of cefazolin. The conventional cefazolin dosing regimens can still achieve satisfactory clinical cure rates for bacteremia of E. coli with a cefazolin MIC ≤ 2 μg/mL in patients without severe septic shock. Before the approval of the efficacy of cefazolin for the treatment of E. coli isolates with a cefazolin MIC of 4 μg/mL, it is prudent to use cefazolin only when a high drug level can be achieved in the infection site, such as the urinary tract.

Optimization of the polishing and cleaning steps during the copper chemical mechanical polishing (Cu CMP) process can be accomplished by modification of Cu trench profile, control of Cu surface roughness, and reduction of residual Cu ions on the ultra-low k (ULK) surface. For the tuning of the polishing process, the optimized profile will improve the sheet resistance (Rs) and TDDB (time-dependent dielectric breakdown). The cleaning effectiveness would be influenced by the clean chemicals and clean process. The correlation between cleaning effectiveness and voltage ramp dielectric breakdown (VRDB) was investigated. In addition, inductively coupled plasma mass spectrometry (ICP-MS) was found to be a useful tool for the evaluation of post cleaning performance.

Clostridium difficile PCR ribotype 027 is a hypervirulent strain that has caused significant nosocomial diarrhea in many countries but has not yet been reported or isolated in Taiwan previously. Here, we present the characteristics of a case of C. difficile PCR ribotype 027 identified in Taiwan. Taiwan is located in a key transportation center of Asia. This report is important for alerting hospitals and public health departments in Asia about the emergence of this hypervirulent strain so that close monitoring may be enacted to prevent potential outbreaks.

BackgroundUrinary tract infections (UTIs) in children with vesicoureteral reflux (VUR) are often caused by uropathogens with a high rate of drug resistance and are associated with a high rate of recurrence with a single pathogen. In this study, we evaluated the incidence of recurrent UTI and the drug resistance pattern of Escherichia coli in children with VUR. We also evaluated whether combination therapy comprising fosomycin plus one other antimicrobial agent is effective for treatment of recurrent UTIs.MethodsWe retrospectively reviewed the medical records of all children with VUR who developed at least one episode of UTI during the period January 1, 2003 to December 31, 2013 at a single medical center. The effectiveness of fosfomycin plus amikicin for Enterobacteriaceae or ceftazidime for Pseudomonas aeruginosa infections was prospectively studied in six children with recurrent relapsing UTIs.ResultsThe study population comprised 129 children (age range, from 1month to 15 years; mean ± standard deviation, 2.37 ± 2.91 years) with VUR who developed at least one UTI during the 10-year study period; 68 (52.7%) had recurrent UTIs. The presence of an underlying urinary tract anomaly was predictive of recurrence (p = 0.028). The rates of susceptibility of E. coli to cefazolin (p

Background/purpose The isoniazid (INH) resistance of Mycobacterium tuberculosis is caused by mutations in the katG and inhA genes encoding for catalase-peroxidase and inhA, respectively. Sequences of the katG and inhA gene of 70 isolates were analyzed to identify the mutations and to compare the mutations with their related susceptibilities. Methods Sequences of the katG and inhA genes and the resistance profiles were analyzed for the 70 M. tuberculosis isolates, collected from nine hospitals in Taiwan during the period from 1999 to 2011. Results Fifteen alleles were identified in the katG gene and two alleles were identified in the inhA gene. Among the 15 alleles identified in the katG gene, 14 alleles were found in isolates resistant to isoniazid, while only three alleles were found in isolates susceptible to isoniazid. The mutations of the katG gene and their frequencies of 41 INH-resistant isolates were Arg463Leu (51%), Ser315Thr (29%), Ser315Asn (9.8%), and other loci (22%). The sensitivity and specificity of the Ser315Thr mutation for the detection of INH-resistant isolates were 29% and 100%, respectively. The frequency of inhA gene mutation was low (2.44%) in the 41 INH-resistant isolates. Conclusion The diverse alleles of the katG gene associated with INH resistance are present in the M. tuberculosis isolates in Taiwan. These data may be applied to develop new probes for various alleles associated with INH resistance in order to increase the sensitivity for the detection of genetically diverse M. tuberculosis isolates in different geographic areas. The diversity of mutations can also provide information for investigating the evolutional lineages of M. tuberculosis isolates.

We report a case of acute purulent meningitis caused by Streptococcus sanguinis after endoscopic ligation for oesophageal variceal haemorrhage in a cirrhotic patient without preceding symptoms of meningitis. Initial treatment with flomoxef failed. The patient was cured after 20 days of intravenous penicillin G. This uncommon infection due to S. sanguinis adds to the long list of infectious complications among patients with oesophageal variceal haemorrhage.

Shewanella bacteremia is an uncommon but potentially fatal disease. Although hepatobiliary diseases have been proposed to be risk factors for various Shewanella infections, little is known about the features of Shewanella bacteremia in patients with hepatobiliary diseases. This study aims to characterize the presentation and risk factors of Shewanella bacteremia in patients with hepatobiliary diseases.We retrospectively investigated the clinical features, microbiology and outcomes of patients with Shewanella bacteremia who were admitted to a tertiary medical center between January 2001 and December 2010. All isolates were confirmed to the species level using 16S rRNA sequencing analyses. The English language medical literature was searched for previously published reports.Fifty-nine cases of Shewanella bacteremia, including nine at the hospital, were identified, 28 (47.4%) of which involved underlying hepatobiliary diseases, representing an important risk factor. In 12 of the 28 cases, the infections involved the hepatobiliary system; with a tendency towards an Asian origin. In our case series of nine patients, Shewanella haliotis was isolated in five patients. The majority of our patients lived in coastal areas, consumed seafood regularly and developed bacteremia during the summer season.It is recommended that the possibility for Shewanella infection be considered in patients with bacteremia and also underlying hepatobiliary diseases, particularly if patients present with hepatobiliary infections, a history of seafood, or development of the disease during the summer.

Introduction: The Clinical and Laboratory Standards Institute (CLSI) updated its antimicrobial susceptibility testing interpretation criteria for Enterobacteriaceae . This study assessed the effects of clinical breakpoint changes in the CLSI 2009 to 2012 guidelines on antibiotic susceptibility testing reports. Methodology: In total, 2,076 non-duplicate clinical isolates of Enterobacteriaceae were analyzed. The disk diffusion method was used for susceptibility testing. The CLSI 2009-12 clinical breakpoints were applied to determine susceptibility of cefotaxime and ertapenem. Combined-disk testing was used for phenotypic confirmation of extended-spectrum beta–lactamase (ESBL) production. Results: In total, Enterobacteriaceae resistance rates to cefotaxime increased from 13.1% using the CLSI 2009 guidelines to 23.6% with the CLSI 2010-12 guidelines, and the resistance rates to ertapenem were 0.4%, 1.0% and 0.8% with CLSI 2009, 2011 and 2012, respectively. Based on the 2010-12 CLSI criteria, all ESBL-producing Escherichia coli and Klebsiella pneumoniae were resistant to cefotaxime. Marked differences in susceptibility to ertapenem between the 2009 CLSI criteria and 2012-12 CLSI criteria were noted in ESBL-producing K. pneumoniae . Conclusions: Breakpoints changes in the updated CLSI guidelines resulted in higher resistance rates to cefotaxime and ertapenem. In addition, the effects were different in individual Enterobacteriaceae species. As a result, clinicians may opt to use alternative antimicrobial agents. Upon implementation of the newer CLSI guidelines, laboratories should be aware of the possible consequences and closely monitor the effects.

This study examined the anti-herpes simplex virus type I activity of the major constituents of several essential oils. Plaque reduction assays were performed to evaluate anti-herpes simplex virus type I activity. Thymol and carvacrol both possessed significant antiviral activity with an IC₅₀ of 7 µM, and herpes simplex virus type I was 90 % inactivated within 1 hr. The mode of antiviral action was shown to affect the virion directly. Evidence was also observed by electron microscopy. Evaluation of the structural requirements for antiviral activity of thymol-related monoterpenoids revealed that aliphatic side chains had a minor effect, while a hydrophilic group on the benzene ring was sufficient for activity. Our results suggest that thymol and carvacrol are potential candidates for topical therapeutic application to reduce herpes simplex virus transmission.

A CMOS bandgap reference generator with switched-capacitor and corresponding double sampling techniques is presented. The proposed circuit uses a low-gain amplifier to generate an accurate reference voltage so that this structure can be implemented in low-voltage environment. With proper design, the circuit can produce any output voltage between supply voltage and ground. The circuit was designed and implemented in 0.18-µm CMOS process. The core circuit occupies about 0.065 mm2 (240 µm × 271 µm). Measurement results show that the temperature coefficient of the output is 47.3 ppm/°C in the temperature range from −40 °C to 100 °C. The average power consumption is about 48.1 µW.

Background/Purpose A growing number of β-lactamases have been reported in Pseudomonas aeruginosa isolates. The aims of this study were to survey the types of extended-spectrum β-lactamases (ESBLs) by polymerase chain reaction (PCR), to evaluate the reliability of phenotypic tests for ESBLs, and to identify the clonal distribution by pulsed-field gel electrophoresis (PFGE) among P. aeruginosa isolates resistant to expanded-spectrum cephalosporins (ceftazidime, aztreonam, or cefepime). Methods The antimicrobial susceptibility of 57 P. aeruginosa isolates from blood specimens were examined according to the recommendations of the Clinical Laboratory Standards Institute. ESBL phenotypes were determined by using cloxacillin-containing double disc synergy test (DDST). The existence of 11 β-lactamase genes was detected by PCR. Results Of the 57 P. aeruginosa isolates, 35 (61.4%) isolates were PCR-positive for β-lactamase genes. Twelve of 35 isolates were PCR-positive for combination of ampC and ESBL genes, including TEM, GES, SHV, VEB and OXA-I genes. The sensitivity and specificity of cloxacillin-containing DDST (using the criteria of ceftazidime zone diameter increased ≧5 mm) were 84.1% and 54.5%, respectively. Nine clusters were classified among 35 PCR-positive isolates by PFGE. Isolates of clusters B and C were distributed in different wards of this hospital during a period of 3–4 years. Conclusion ESBL genes are not uncommon in P. aeruginosa isolates. Cloxacillin-containing DDST can enhance the sensitivity and has a potential role for phenotypic detection of ESBL-producing P. aeruginosa , and PCR is also helpful for the identification of specific β-lactamase genes. These P. aeruginosa isolates were classified into several diverse clones which could continue to spread in the hospital over a long period of time.

This study was conducted to detect the genes encoding extended-spectrumβ-lactamases (ESBLs) and determine the epidemiological relatedness of 69Escherichia coliand 33Klebsiella pneumoniaeisolates collected from a regional hospital in central Taiwan, mostly from inpatients (E. coli87.0 %;K. pneumoniae88.0 %). The phenotypes of these isolates were examined according to the combination disc method recommended by the Clinical and Laboratory Standards Institute. Most of the ESBL-producingE. coliandK. pneumoniaeisolates (98.6 % and 97 %, respectively) could be detected using cefotaxime discs with and without clavulanate. Genotyping was performed by PCR with type-specific primers. CTX-M-14 type (53.6 %) was the most prevalent ESBL amongE. coliisolates while SHV type (57.6 %) was the most dominant amongK. pneumoniaeisolates. SixE. coliand threeK. pneumoniaeisolates did not carry genes encoding ESBLs of types TEM, SHV, CTX-M-3, CTX-M-14, CMY-2 and DHA-1. The co-existence of two or more kinds of ESBL in a single isolate was common, occurring in 40.6 % and 72.7 % ofE. coliandK. pneumoniaeisolates, respectively. PFGE analysis revealed that ESBL producers isolated in this setting were genetically divergent.

A 4-year-old sexually intact male German shepherd with a 3-month history of chronic watery diarrhea was referred to the Veterinary Medical Teaching Hospital. Dehydration and serum biochemistry revealed hypoalbuminemia, and fecal material contained a large quantity of round arthroconidia that were microscopically observed. A specimen was submitted for fungal culture and yielded a white to cream-colored subsurface colony. Microorganisms derived from the colony exhibited chains of smooth, septate hyaline hyphae that were producing 1-celled arthroconidia. Geotrichum candidum was thus identified. Colonoscopic features included erythema, edema, and loss of the usual fine vascular pattern, with granularity of the mucosa of the descending column. Treatment consisted of oral administration of ketoconazole and metronidazole for 3 weeks, while oral prednisolone was tapered after 1 week of therapy. The dog’s feces gradually softened after the first treatment. Fecal smear examination revealed no trace of the yeast-like microbes 7 days after treatment was administered, and 2 weeks post-treatment the dog passed well-formed stools and had regained its normal body weight. The previously observed clinical signs did not reoccur, even after oral medication was withdrawn.

Background/Purpose The emergence of multiple drug resistance in Enterobacteriaceae is of particular concern. The aim of this study was to evaluate the antimicrobial susceptibility and screen for the ampC gene in three members of the Enterobacteriaceae family ( Enterobacter cloacae , Citrobacter freundii , and Serratia marcescens ) found at Taichung Veterans General Hospital during the past 5 years using multiplex polymerase chain reaction (PCR). Methods The susceptibility of thirty isolates from each of the three Enterobacteriaceae family members to five antimicrobial agents (ceftazidime, flomoxef, imipenem, moxifloxacin, and colistin) was assessed. The susceptibility was analyzed by disk diffusion, screening and confirmatory tests for extended-spectrum β-lactamases (ESBL) and minimum inhibitory concentration tests according to the recommendations of the Clinical and Laboratory Standards Institute. The detection of ampC genes (3 families, including DHA, EBC and CIT) was performed by multiplex PCR. To detect the coexistence of ESBL genes, PCR was performed using five primer pairs: TEM, SHV, SHV-5, CTX-M-3, and CTX-M-14. Results Of the 90 isolates, 53 (58.9%) were positive in the screening test for ESBL. Resistance genes were detected in 12 (22.6%) of these isolates: ampC gene of DHA type in one E. cloacae isolate and EBC type in three E. cloacae isolates; ampC gene of CIT type in four C. freundii isolates; CTX-M-3-like in one C. freundii isolate and one S. marcescens isolate; TEM in three E. cloacae isolates, three C. freundii isolates and two S. marcescens isolates; SHV in one C. freundii isolate. Conclusion Antibiotic phenotypes cannot accurately distinguish the resistance mechanisms caused by ampC or ESBL, and especially in ESBL- ampC combinations. However, PCR is a useful technique for the identification of the different types of resistance genes.

A limited range of antibiotic classes are available for treatment of Chryseobacterium meningosepticum infections. Although the role of C. meningosepticum in newborn infections and immunocompromised hosts has been recognized, clinical data detailing these infections remain limited. This retrospective study investigated the risk factors for mortality in patients with C. meningosepticum infections and the antibiotic susceptibility of clinical isolates.Information on demographic characteristics, clinical parameters, antibiotic treatment, and outcomes was collected. Statistical significance of potential prognostic parameters was analyzed by Fisher's exact test. The antimicrobial susceptibility of 19 isolates to seven antibiotics was determined, and susceptibility results were presented as minimal inhibitory concentration (MIC) range, MIC at which 50% of isolates were inhibited (MIC(50)), and MIC at which 90% of isolates were inhibited (MIC(90)).Hypoalbuminemia (2.5 g/dL) [p=0.02] and increased pulse rate (p=0.008) at the onset of infection, and presence of an indwelling central venous line (p=0.04) were associated with poor outcomes. Use of appropriate antibiotics was not significantly associated with the clinical outcome (p=0.21). MIC values of levofloxacin (MIC(50)/(90), 0.12/2 microg/mL) were lower than those of ciprofloxacin (0.5/4 microg/mL).Hypoalbuminemia, increased pulse rate at the onset of infection and presence of central venous line infection were associated with a poor outcome in patients with C. meningosepticum.