2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China.

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.

MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK.

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.IMPORTANCE 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.

Respiratory pathogens - Some altered antibiotic susceptibility after implementation of pneumococcus vaccine and antibiotic control strategies.

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 < 0.05). 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.

Respiratory presentation of patients infected with enterovirus D68 in Taiwan.

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.

Susceptibility rates of clinically important bacteria collected from intensive care units against colistin, carbapenems, and other comparative agents: results from Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

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 bla KPC and bla OXA48-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 bla KPC and bla OXA48-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.

Antimicrobial activities of ceftazidime-avibactam, ceftolozane-tazobactam, and other agents against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolated from intensive care units in Taiwan: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan in 2016.

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. MATERIALS AND METHODS: In total, 300 non-duplicate isolates of Escherichia coli (n=100), Klebsiella pneumoniae (n=100), and Pseudomonas aeruginosa (n=100) collected from 300 patients were studied. The minimum inhibitory concentrations (MICs) of these isolates to antimicrobial agents were determined using the broth microdilution method. Carbapenemase-encoding genes (bla KPC, bla NDM, bla IMP, bla VIM, and bla OXA-48-like) were studied for the isolates that were not susceptible to any carbapenems. Sequencing analysis of the mcr genes (mcr-1-5) was conducted for all isolates with colistin MICs ≥4 mg/L. RESULTS: Ertapenem non-susceptibility was detected in 3% (n=3) E. coli and 12% (n=12) K. pneumoniae isolates. The susceptibility rates of imipenem, ceftazidime-avibactam (CAZ-AVB), and ceftolozane-tazobactam (CLZ-TAZ) were 99%, 99%, and 88%, respectively, for E. coli, 91%, 100%, and 80%, respectively, for K. pneumoniae, and 66%, 91%, and 93%, respectively, for P. aeruginosa. Carbapenemase-encoding genes were not detected in E. coli, were detected in four (33.3%) K. pneumoniae isolates that were not susceptible to ertapenem (three harboring bla KPC and one harboring bla OXA-48-like), and were not detected in P. aeruginosa isolates that were not susceptible to imipenem. One K. pneumoniae isolate was resistant to colistin (MIC 4 mg/L) and negative for mcr genes. CONCLUSION: CAZ-AVB exhibited excellent activity against carbapenem-resistant Enterobacteriaceae, and CLZ-TAZ exhibited good activity against imipenem-resistant P. aeruginosa.

Sensitivity and specificity of Matrix-Associated Laser Desorption/Ionization - Time of Flight Mass Spectrometry (MALDI-TOF MS) in discrimination at species level for Acinetobacter bacteremia.

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%).

The association of molecular typing, vancomycin MIC, and clinical outcome for patients with methicillin-resistant Staphylococcus aureus infections.

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-SCCmecIII, seven (21.9%) isolates with ST5-SCCmecII, six (18.8%) isolates with ST59-SCCmecIV, and two (6.2%) isolates with ST59-SCCmecVT. Two isolates had an MIC of 2 µg/mL and were identified as ST239-SCCmecIII. 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 < 2 µg/mL and ≥ 2 µg/mL (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.

Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area.

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 < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5- < 10 mg/day aOR = 2.51, Ptrend = 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.

Impact of revised susceptibility breakpoints on bacteremia of Klebsiella pneumoniae: Minimum inhibitory concentration of cefazolin and clinical outcomes.

BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised the susceptibility breakpoints of cephalosporins for Enterobacteriaceae in 2010 and 2011. However, there is a lack of clinical data about the correlation of minimum inhibitory concentrations (MICs) and clinical outcome. Data for the distribution of MICs and clinical outcomes were analyzed in this study to evaluate the impact of changes in the CLSI breakpoints on the treatment of Klebsiella pneumoniae bacteremia. METHODS: Ninety-seven bacteremic K. pneumoniae isolates from Taichung Veterans General Hospital, Taichung, Taiwan were collected for study during the period 2009-2011. The cefazolin MIC was determined by the broth microdilution method according to the recommendations of the CLSI. The MIC distribution of cefazolin and the clinical responses to definitive cefazolin treatment were analyzed. RESULTS: The modal cefazolin MIC among the 97 isolates was 1 µg/mL and accounted for 73 (75.3%) isolates. There were 18 (18.6%) isolates with a cefazolin MIC of 2 µg/mL. The conventional dosage regimens of cefazolin (1 g every 6 hours or 8 hours) achieved a clinical cure in 70 (97.2%) of 72 patients in the group with a cefazolin MIC ≤1 µg/mL and in 14 (87.5%) of 16 patients in the group with a cefazolin MIC of 2 µg/mL. With the conventional dose, the cumulative clinical cure rate for K. pneumoniae bacteremia with cefazolin MIC ≤2 µg/mL was 95.5% (84/88 patients). CONCLUSION: The conventional cefazolin dose still can result in satisfactory clinical cure rates for bacteremic episodes due to K. pneumoniae with cefazolin MIC ≤2 µg/mL, the revised susceptible breakpoint of CLSI 2011.

Treatment of recurrent complicated urinary tract infections in children with vesicoureteral reflux.

BACKGROUND: Urinary 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. METHODS: We 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. RESULTS: The 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 < 0.001) and cefotaxime (p < 0.001) were significantly lower in patients with recurrent UTIs. Combination therapy with fosfomycin plus amikacin or ceftazidime was shown to be an effective therapeutic option for recurrent UTIs due to a single uropathogen. CONCLUSION: The rates of susceptibility of E. coli to commonly used antimicrobials were significantly lower in children who developed more than one episode of UTI. The empiric choice of cefazolin or cefotaxime was usually ineffective. Administration of fosfomycin plus amikacin or ceftazidime was an effective therapeutic and preventive strategy in children with VUR and recurrent relapsing UTI.

The impact of revised CLSI cefazolin breakpoints on the clinical outcomes of Escherichia coli bacteremia.

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.

Risk for Mycobacterial Disease among Patients with Rheumatoid Arthritis, Taiwan, 2001-2011.

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.

Clostridium difficile PCR Ribotype 027 Emerges in Taiwan.

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.

The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan.

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.

Antimicrobial resistance to cefotaxime and ertapenem in Enterobacteriaceae: the effects of altering clinical breakpoints.

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.

Molecular surveillance and clinical outcomes of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae infections.

BACKGROUND/PURPOSE: The 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: The 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.

Clinical and microbiological features of shewanella bacteremia in patients with hepatobiliary disease.

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.

Streptococcus sanguinis meningitis following endoscopic ligation for oesophageal variceal haemorrhage.

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.

Resistance profiles and rpoB gene mutations of Mycobacterium tuberculosis isolates in Taiwan.

BACKGROUND/PURPOSE: The rifampicin resistance of Mycobacterium tuberculosis is caused by mutations in the 81-base pair region of the rpoB gene encoding the ß-subunit of RNA polymerase. Sequences of the rpoB gene of 68 isolates were analyzed to identify the mutations and to compare the mutations with their related susceptibilities. METHODS: Susceptibility tests of 68 M. tuberculosis isolates, collected in Taiwan during the period from 1999 to 2011, were performed by the modified agar proportion method according to Clinical and Laboratory Standards Institute recommendations. Sequences of the rpoB gene and the resistance profiles were analyzed and compared with the data from different geographic regions. RESULTS: Seven alleles were identified. Among 47 isolates of allele 1 (without mutations of rpoB), 46 were rifampicin-susceptible. The other 21 isolates (alleles 2 to 7, with mutations of rpoB) were rifampicin-resistant, including 18 isolates that were multidrug-resistant. Five mutated alleles demonstrated a single mutation. The mutations occurred in the codons 531 (68.2%), 513 (9.1%), 533 (9.1%), 516 (4.5%), and 526 (4.5%). The sensitivity and specificity of rpoB mutations for predicting the rifampicin-resistance of M. tuberculosis were 95.5% and 100%, respectively. CONCLUSION: The most prevalent mutations of the rpoB gene were missense mutations in the critical codons, encoding Ser-531, Gln-513, Leu-533, Asp-516, and His-526. These mutations had high sensitivity and specificity for predicting the rifampicin-resistance of M. tuberculosis isolates. The resistance profiles and the frequencies of mutated codons of the rpoB gene varied in different geographic regions, indicating that resistance evolved under the selective pressure of the therapeutic regimens and the spread of different genetic clones.