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Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

The aim of this study was to investigate the susceptibility of respiratory Gram-negative bacteria to ceftolozane/tazobactam and other antibiotics in the Asia-Pacific region during 2015-2016. MICs were determined using the CLSI standard broth microdilution method and interpreted accordingly. Pseudomonas aeruginosa (1574 isolates), Klebsiella pneumoniae (1226), Acinetobacter baumannii (627) and Escherichia coli (476) accounted for 73.1% of 5342 Gram-negative respiratory pathogens. Susceptibility to ceftolozane/tazobactam of individual Enterobacteriaceae was >80%, except for Enterobacter cloacae (76.6%). Ceftolozane/tazobactam inhibited 81.9% of K. pneumoniae and 91.9% of E. coli, with respective MIC50/MIC90 values of 0.5/>32 and 0.25/2 mg/L. For carbapenem-susceptible, ESBL-producing K. pneumoniae and E. coli, susceptibility was 65.5% and 93.3%, respectively, and respective MIC50/MIC90 values were 2/>32 and 0.5/2 mg/L. BlaCTX-M-1 group was most prevalent in selected ESBL-producing K. pneumoniae (40 of 54 isolates) and E. coli (15 of 22 isolates), with ceftolozane/tazobactam susceptibility rates of 50% and 80%, respectively. BlaSHV-ESBL was the second most prevalent, and ceftolozane/tazobactam inhibited 20% of 20 K. pneumoniae isolates with blaSHV-ESBL. The only effective antibiotics for carbapenem-non-susceptible K. pneumoniae (111 isolates) and E. coli (24 isolates) were amikacin and colistin. Ceftolozane/tazobactam was effective against almost all tested P. aeruginosa and carbapenem-non-susceptible strains, with susceptibility of 92.3% and 72.8%, respectively; the respective MIC50/MIC90 values were 1/4 and 2/>32 mg/L. The high susceptibility of ceftolozane/tazobactam remained in different age groups, patient locations, recovery times and countries, except Vietnam. In conclusion, ceftolozane/tazobactam was effective against most respiratory Gram-negative pathogens in the Asia-Pacific region; however, the emergence of carbapenem resistance mandates ongoing surveillance.

Carbon monoxide poisoning is the most commonly seen cause of poisoning in the emergency room (ER). The high affinity between carbon monoxide and hemoglobin and their complex biological characteristics greatly increase the risks of cardiac, nervous, muscular, and kidney diseases. In severe cases, patients may lose consciousness or die in just a few minutes. In recent years, hyperbaric oxygen therapy has been applied extensively in patients with severe conditions such as carbon monoxide poisoning and cerebral hypoxia. Hyperbaric oxygen accelerates the decomposition of carbon monoxide in hemoprotein. Therefore, treating patients with similar conditions in the ER with hyperbaric oxygen as soon as possible will improve their cognitive disorder and postpone their neuropsychological sequelae. ER nurses typically play a decisive role in saving patients with carbon monoxide poisoning. This research scrutinizes a case analysis of using hyperbaric oxygen to treat carbon monoxide poisoning and offers general rules for the use of hyperbaric oxygen. Further, the research elaborates from the perspective of ER nursing staffs the management and care of acute carbon monoxide poisoning and hyperbaric oxygen therapy nursing care. The aim of this research is to offer references for members of the ER nursing team and to enable this team to provide accurate and effective medical measures to patients during the "golden hours" of nursing care. Achieving this will help ensure that patients receive comprehensive nursing and care, thus reducing the harm suffered by patients and increasing the rate of survival.高壓氧治療與急性一氧化碳中毒.一氧化碳中毒是急診室最常見的中毒類型急症，因一氧化碳與血紅素具有高親和力與複雜的生物學特性，導致一氧化碳中毒會造成心臟、神經、肌肉、腎臟等組織病變，嚴重者數分鐘內失去知覺或死亡。近年來，高壓氧廣泛應用在急重症病人（如一氧化碳中毒、腦組織缺氧），因為高壓氧可以加速一氧化碳結合血紅素的分解，故這類病人送達急診室，若能盡早接受高壓氧治療，可以改善或降低認知障礙及延遲神經心理學後遺症。急診護理是影響一氧化碳中毒病人能否獲救的關鍵。本文探討高壓氧對一氧化碳中毒的實證分析，提出高壓氧的使用通則；繼而由護理人員角度闡述急性一氧化碳中毒的處置與照護，及高壓氧治療的護理，期能提供給急診照護團隊參考，在救護的黃金時刻給予正確有效的醫護措施，使病人得到完善的護理照顧，減低對病人的傷害，及提高存活率。.

Amidst the ever-rising threat of antibiotics resistance, colistin, a decade-old antibiotic with lingering toxicity concern, is increasingly prescribed to treat many drug-resistant, gram-negative bacteria. With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. Subsequent stabilization by DSPE-PEG and homogenization through micro-fluidization of the liquid coacervates yielded nanoparticles 8 nm in diameter. In vitro assessment showed that the colistin antimicrobial activity against multiple drug-resistant bacterial strains was retained and, in some cases, enhanced following the nanoparticle assembly. In vivo administration in mice demonstrated improved safety of the colistin nanoparticle, which has a maximal tolerated dose of 12.5 mg/kg compared to 10 mg/kg of free colistin. Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin. In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin. These results demonstrate coacervation-induced nanoparticle assembly as a promising approach towards improving colistin treatments against bacterial infections. Statement of Significance Improving the safety of colistin while retaining its antimicrobial activity has been a highly sought-after objective toward enhancing antibacterial treatments. Herein, we demonstrate formation of stabilized colistin nanocomplexes in the presence of anionic polypeptides and DSPE-PEG stabilizer. The nanocomplexes retain colistin’s antimicrobial activity while demonstrating improved safety upon in vivo administration. The supramolecular nanoparticle assembly of colistin presents a unique approach towards designing antimicrobial nanoparticles.

ObjectiveTo investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas.DesignCommunity-based comparison study.SettingOutpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants.ParticipantsA total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled.Primary and secondary outcome measuresThe interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis.ResultsDiabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95% CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95% CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95% CI 1.03 to 1.55) and history of TB (aOR=2.08; 95% CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95% CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI.ConclusionThere was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.

Purpose: To investigate the increasing prevalence of colistin resistance in animal Escherichia coli isolates and their mcr-1-carrying plasmids, especially those shared by isolates from human and retail meats. Methods: E. coli from diseased swine and poultry recovered between 2012 and 2016 were studied. Susceptibility was determined using broth microdilution method or Vitek II system. Fifty-eight mcr-1-positive isolates were randomly selected for further testing, including pulsed-field gel electrophoresis (PFGE) for clonality determination, S1- or I-CeuI-PFGE and Southern blotting for localization of mcr-1, and conjugation for transmissibility. Whole genome sequencing (WGS) was performed for the genetic structure of plasmids. Results: Among the 1234 E. coli isolates from diseased swine, colistin resistance increased from 14.6% (14/96) in 2012 to 43.8% (63/144) in 2016 with a paralleled increase in mcr-1-positivity from 12.5% (12/96) to 33.3% (48/144) in 2016 (P

The emergence of antibiotic-resistant bacteria has threatened our health worldwide. There is an urgent need for novel antibiotics. Previously, we identified a novel 37-mer antimicrobial peptide (AMP), HBcARD, with broad spectrum antimicrobial activity. Here, we improved the efficacy of HBcARD, by re-engineering the peptide, including the addition of a new cysteine to its C-terminus (CTC). The new 28-mer derivative, D-150-177C, contains all D-form arginines, in addition to a C-terminal cycteine. This peptide can kill antibiotic-resistant clinical isolates of Gram-negative bacteria, and is more potent than the parental HBcARD peptide in a mouse sepsis model. In another lung infection mouse model, D-150-177C showed protection efficacy against colistin-resistant Acinetobacter baumannii. Unlike colistin, we observed no acute toxicity of D-150-177C in vivo. Interestingly, we found that CTC modification could enhance the antibacterial activity of several other AMPs, such as buforinII and lysin. The potential application and mechanism of this CTC method as a general approach to improving drug efficacy, warrants further investigation in the future.

Endotoxicity originating from a dangerous debris (i.e., lipopolysaccharide, LPS) of Gram-negative bacteria is a challenging clinical problem, but no drugs or therapeutic strategies that can successfully address this issue have been identified yet. In this study, we report a subnanometer gold cluster that can efficiently block endotoxin activity to protect against sepsis. The endotoxin blocker consists of a gold nanocluster that serves as a flakelike substrate and a coating of short alkyl motifs that act as an adhesive to dock with LPS by compacting the intramolecular hydrocarbon chain-chain distance ( d-spacing) of lipid A, an endotoxicity active site that can cause overwhelming cytokine induction resulting in sepsis progression. Direct evidence showed the d-spacing values of lipid A to be decreased from 4.19 Å to either 3.85 or 3.54 Å, indicating more dense packing densities in the presence of subnanometer gold clusters. In terms of biological relevance, the concentrations of key pro-inflammatory NF-κB-dependent cytokines, including plasma TNF-α, IL-6, and IL-1β, and CXC chemokines, in LPS-challenged mice showed a noticeable decrease. More importantly, we demonstrated that the treatment of antiendotoxin gold nanoclusters significantly prolonged the survival time in LPS-induced septic mice. The ultrasmall gold nanoclusters could target lipid A of LPS to deactivate endotoxicity by compacting its packing density, which might constitute a potential therapeutic strategy for the early prevention of sepsis caused by Gram-negative bacterial infection.

Objectives Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan. Methods A total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing. Results The relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern. Conclusion This study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis.

The rate of recovery of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates has increased significantly in recent decades in Taiwan. This study investigated the molecular epidemiology of CRAB with a focus on the mechanisms of resistance and spread in isolates with bla OXA-23-like or bla OXA-24-like . All 555 CRAB isolates in our multicenter collection, which were recovered from 2002 to 2010, were tested for the presence of class A, B, and D carbapenemase genes. All isolates with bla OXA-23-like or bla OXA-24-like were subjected to pulsed-field gel electrophoresis, and 82 isolates (60 isolates with bla OXA-23-like and 22 isolates with bla OXA-24-like ) were selected for multilocus sequence typing to determine the sequence type (ST) and clonal group (CG) and for detection of additional β-lactamase and aminoglycoside resistance genes. The flanking regions of carbapenem and aminoglycoside resistance genes were identified by PCR mapping and sequencing. The localization of bla OXA was determined by S1 nuclease and I-CeuI assays. The numbers of CRAB isolates carrying bla OXA-23-like or bla OXA-24-like , especially those carrying bla OXA-23-like , increased significantly from 2008 onward. The bla OXA-23-like gene was carried by antibiotic resistance genomic island 1 (AbGRI1)-type structures located on plasmids and/or the chromosome in isolates of different STs (CG92 and novel CG786), whereas bla OXA-24-like was carried on plasmids in CRAB isolates of limited STs (CG92). No class A or B carbapenemase genes were identified. Multiple aminoglycoside resistance genes coexisted in CRAB. Tn 6180 -borne armA was found in 74 (90.2%) CRAB isolates, and 58 (70.7%) isolates had Tn 6179 upstream, constituting AbGRI3. bla TEM was present in 38 (46.3%) of the CRAB isolates tested, with 35 (92.1%) isolates containing bla TEM in AbGRI2-type structures, and 61% of ampC genes had IS Aba1 upstream. We conclude that the dissemination and spread of a few dominant lineages of CRAB containing various resistance island structures occurred in Taiwan.

Elizabethkingia species are ubiquitous bacteria that uncommonly cause human infection. Elizabethkingia anophelis was first identified in 2011 from the mosquito Anopheles gambiae. The currently available bacterial typing systems vary greatly with respect to labour, cost, reliability, and ability to discriminate among bacterial strains. Polymerase chain reaction (PCR)-based fingerprinting using random amplified polymorphic DNA (RAPD) is commonly used to identify genetic markers. To our knowledge, no system coupling RAPD-PCR and capillary gel electrophoresis (CGE) has been utilized for the epidemiological typing of E. anophelis. Thus, the aim of the present study was to establish a reliable and reproducible molecular typing technique for E. anophelis isolates based on a multi-centre assessment of bacteraemia patients. Here, we used a rapid CGE-light-emitting diode-induced fluorescence (LEDIF)-based method in conjunction with RAPD-PCR to genotype E. anophelis with a high level of discrimination. All clinical isolates of E. anophelis were found to be typeable, and isolates from two hospitals formed two distinct clusters. The results demonstrated the potential of coupling RAPD and CGE as a rapid and efficient molecular typing tool, providing a reliable method for surveillance and epidemiological investigations of bacterial infections. The proposed method shows promise as a novel, cost-effective, high-throughput, first-pass typing method.

OBJECTIVES To investigate the link between two NDM-1-positive Acinetobacter isolates from the same hospital, the plasmid profiles of the isolates were examined. These two isolates were found from a surveillance programme within 3 months from two patients without obvious physical contact or hospitalization time overlap. METHODS Antimicrobial susceptibility tests, genome sequencing of both isolates and plasmid transfer experiments were performed. A comparative study of similar plasmids was performed using BLAST analysis. RESULTS The antimicrobial susceptibility of the isolates (Acinetobacter soli M131 and Acinetobacter pittii MS32) and their Escherichia coli transconjugants revealed a conjugative plasmid that carried the carbapenem resistance determinant. Eleven plasmids were observed in M131 and three in MS32. Each isolate shared an identical plasmid that carried the blaNDM-1 gene. This 47 271 bp plasmid harbours a conserved blaNDM-1-containing region that is flanked by ISAba125 and ISAba11 elements, and also contains a Ti-type conjugative operon. The plasmid is nearly identical in sequence to those of Acinetobacter isolates from China. In contrast to the mobilization of the blaNDM-1 sequence in Enterobacteriaceae, which is mainly by transposition, this plasmid moves as a whole among Acinetobacter species. Consistently, this plasmid was found to transfer effectively by in vitro conjugation to several Acinetobacter species. CONCLUSIONS The clinical and laboratory findings suggest that Acinetobacter species may serve as a reservoir of this blaNDM-1 plasmid. Our study demonstrates the potential of applying genome sequencing to the surveillance of antimicrobial-resistant bacteria.

We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of those receiving other appropriate antimicrobial agents (13.8%, 9/65; P = 0.018). However, the percentages of end-stage renal disease and congestive heart failure were higher in the tigecycline cohort. The efficacy of tigecycline was contingent upon the illness severity and bacterial species. Tigecycline should be applied cautiously for treatment of Acinetobacter bacteremia.

Background Extended-spectrum β-lactamase (ESBL)-producing pathogens have been increasingly identified in community-onset urinary tract infection (UTI). This study was conducted to determine the epidemiology and risk factors of community-onset UTI caused by ESBL-producing pathogens, and to determine the correlation of antimicrobial resistance with ESBL detected by phenotypic and genotypic methods. Methods The study was conducted from December 2010 to January 2012. Patients with community-onset UTI caused by Enterobacteriaceae were enrolled from the emergency department. The production of ESBL was determined by the phenotypic method (using the combined disk test) or by the genotypic method (using polymerase chain reaction detection). The patients' medical records were reviewed and risk factors were analyzed by multivariate analysis. Results A total of 376 patients were enrolled and 393 isolates from urine culture were analyzed. Escherichia coli was the most commonly isolated species (259/393 isolates; 65.9%), followed by Klebsiella pneumoniae (42/393 isolates; 10.7%). Fifty-three (13.5%) isolates were phenotypically positive for ESBL production. Nine (2.3%) isolates were phenotypically positive for both ESBL and AmpC β-lactamase (AmpC) production. Nasogastric tube placement [odds ratio (OR) 2.230; 95% confidence interval (CI) 1.244–3.997; p = 0.007] and hospitalization within the previous 3 months (OR 2.567, 95% CI 1.448–4.551, p = 0.001) were independently associated with the acquisition of ESBL-producing pathogens in community-onset UTI. The ESBL phenotype had a better correlation with resistance to third-generation cephalosporins, compared to the ESBL-positive genotype. Conclusion In our study, nasogastric tube placement and hospitalization within the previous 3 months were significantly associated with the acquisition of ESBL-producing pathogens in community-onset UTI.

Acinetobacter baumannii (Ab) is a global emerging bacterium causing nosocomial infections such as pneumonia, meningitis, bacteremia and soft tissue infections especially in intensive care units. Since Ab is resistant to almost all conventional antibiotics, it is now one of the 6 top-priorities of the dangerous microorganisms listed by the Infectious Disease Society of America. The development of vaccine is one of the most promising and cost-effective strategies to prevent infections. In this study, we identified potential protective vaccine candidates using reverse vaccinology. We have analyzed 14 on-line available Ab genome sequences and found 2752 homologous core genes. Using information obtained from immuno-proteomic experiments, published proteomic information and the bioinformatics PSORTb v3.0 software to predict the location of extracellular and/or outer membrane proteins, 77 genes were identified and selected for further studies. After excluding those antigens have been used as vaccine candidates reported by the in silico search-engines of PubMed and Google Scholar, 13 proteins could potentially be vaccine candidates. We have selected and cloned the genes of 3 antigens that were further expressed and purified. These antigens were found to be highly immunogenic and conferred partial protection (60%) in a pneumonia animal model. The strategy described in the present study incorporates the advantages of reverse vaccinology, bioinformatics and immuno-proteomic platform technologies and is easy to perform to identify novel immunogens for multi-component vaccines development.

BackgroundCarbapenem-resistant Acinetobacter baumannii has emerged as an important cause of nosocomial infections with high morbidity and mortality. The carbapenemases, especially class D carbapenem-hydrolyzing oxacillinases (CHDLs), play an important role, but the relationship between their prevalence trend and carbapenem resistance remains unclear.Materials and methodsBetween 1995 and 2012, we collected 667 isolates of A. baumannii from a single medical center in northern Taiwan. Pulsed-field gel electrophoresis (PFGE) was used to determine clonality. Antimicrobial susceptibility was determined. Carbapenemase genes and associated genetic structures were detected by polymerase chain reaction.ResultsIsolates were heterogeneous on PFGE. Susceptibility to carbapenem decreased steadily over the study period from 88.1% (2001–2003) to

Summary Objective The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. Methods A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000–2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. Results The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs . 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08–2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02–2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37–4.72) compared to the matched cohort. Conclusions HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.

Background— Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results— A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion— Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.

Breakthrough Acinetobacter bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough Acinetobacter bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough Acinetobacter bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant Acinetobacter bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively; P = 0.025 by bivariate analysis) and a higher 30-day mortality ( P = 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough Acinetobacter bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis ( P = 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough Acinetobacter bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465; P < 0.001). Patients with breakthrough Acinetobacter bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough Acinetobacter bacteremia that develops during carbapenem therapy.

The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) offer different recommendations for carbapenem MIC susceptibility breakpoints for Acinetobacter species. In addition, the clinical efficacy of the intermediate category remains uncertain. This study was designed to determine the optimal predictive breakpoints based on the survival of patients with Acinetobacter bacteremia treated with a carbapenem. We analyzed the 30-day mortality rates of 224 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia at 4 medical centers over a 5-year period, according to the carbapenem MICs of the initial isolates. The 30-day mortality was about 2-fold greater in patients whose isolates had carbapenem MICs of ≥8 mg/liter than in those with isolates with MICs of ≤4 mg/liter. The differences were significant by bivariate analysis (53.1% [60/113] versus 25.2% [28/111], respectively; P < 0.001) and on survival analysis by the log rank test ( P < 0.001). Classification and regression tree analysis revealed a split between MICs of 4 and 8 mg/liter and predicted the same difference in mortality, with a P value of Acinetobacter bacteremia caused by isolates with carbapenem MICs of ≥8 mg/liter was an independent predictor of 30-day mortality (odds ratio, 4.218; 95% confidence interval, 2.213 to 8.039; P < 0.001). This study revealed that patients with Acinetobacter bacteremia treated with a carbapenem had a more favorable outcome when the carbapenem MICs of their isolates were ≤4 mg/liter than those with MICs of ≥8 mg/liter.

The higher 14-day mortality rate for patients with Acinetobacter bacteremia receiving tigecycline appropriately compared to other appropriate antibiotics (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for isolates with a minimum inhibitory concentration of 2 μg/mL (63.6% of 11 versus 14.2% of 127, P = 0.001).

The rate of recovery of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates has increased significantly in recent decades in Taiwan. This study investigated the molecular epidemiology of CRAB with a focus on the mechanisms of resistance and spread in isolates with blaOXA-23-like or blaOXA-24-like. All 555 CRAB isolates in our multicenter collection, which were recovered from 2002 to 2010, were tested for the presence of class A, B, and D carbapenemase genes. All isolates with blaOXA-23-like or blaOXA-24-like were subjected to pulsed-field gel electrophoresis, and 82 isolates (60 isolates with blaOXA-23-like and 22 isolates with blaOXA-24-like) were selected for multilocus sequence typing to determine the sequence type (ST) and clonal group (CG) and for detection of additional β-lactamase and aminoglycoside resistance genes. The flanking regions of carbapenem and aminoglycoside resistance genes were identified by PCR mapping and sequencing. The localization of blaOXA was determined by S1 nuclease and I-CeuI assays. The numbers of CRAB isolates carrying blaOXA-23-like or blaOXA-24-like, especially those carrying blaOXA-23-like, increased significantly from 2008 onward. The blaOXA-23-like gene was carried by antibiotic resistance genomic island 1 (AbGRI1)-type structures located on plasmids and/or the chromosome in isolates of different STs (CG92 and novel CG786), whereas blaOXA-24-like was carried on plasmids in CRAB isolates of limited STs (CG92). No class A or B carbapenemase genes were identified. Multiple aminoglycoside resistance genes coexisted in CRAB. Tn6180-borne armA was found in 74 (90.2%) CRAB isolates, and 58 (70.7%) isolates had Tn6179 upstream, constituting AbGRI3. blaTEM was present in 38 (46.3%) of the CRAB isolates tested, with 35 (92.1%) isolates containing blaTEM in AbGRI2-type structures, and 61% of ampC genes had ISAba1 upstream. We conclude that the dissemination and spread of a few dominant lineages of CRAB containing various resistance island structures occurred in Taiwan.

Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection.

Acinetobacter baumannii, Acinetobacter nosocomialis and Acinetobacter pittii are clinically relevant members of the Acinetobacter calcoaceticus–A. baumannii (Acb) complex and important nosocomial pathogens. These three species are genetically closely related and phenotypically similar; however, they differ in their epidemiology, antibiotic resistance and pathogenicity. In this study, we investigated the use of a multiplex PCR-based assay designed to detect internal fragments of the 16S–23S rRNA intergenic region and the gyrB and recA genes. The assay was capable of differentiating A. baumannii, A. nosocomialis and A. pittii in a reliable manner. In 23 different reference strains and 89 clinical isolates of Acinetobacter species, the assay accurately identified clinically relevant Acb complex species except those ‘between 1 and 3’ or ‘close to 13TU’. None of the non-Acb complex species was misidentified. In an analysis of 1034 positive blood cultures, the assay had a sensitivity of 92.4 % and specificity of 98.2 % for Acb complex identification. Our results show that a single multiplex PCR assay can reliably differentiate clinically relevant Acb complex species. Thus, this method may be used to better understand the clinical differences between infections caused by these species.

Background The emergence of imipenem-nonsusceptible (INS) Acinetobacter baumannii complex has had a great impact on healthcare systems worldwide. Understanding the risk factors related to INS infection is useful for infection control. The risk factors for INS A. baumannii have been well documented; however, the risk factors related to INS Acinetobacter nosocomialis infection lack documentation. The purpose of this study was to identify the risk factors associated with INS A. nosocomialis bacteremia. Methods This retrospective 9-year study included 329 adults with A. nosocomialis bacteremia in a tertiary medical center in Taiwan. Acinetobacter nosocomialis was identified using a multiplex polymerase chain reaction method and sequence analysis of a 16S–23S intergenic spacer. Results Among 329 patients with A. nosocomialis bacteremia, 67 had INS isolates (20.4%). Patients with INS isolates tended to have a more severe form of the diseases [with ICU admission and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score], specific underlying diseases (associated with chronic lung diseases and end-stage renal diseases, but less commonly alcoholism and chemotherapy), multiple invasive procedures, pneumonia as a primary focus of infection, and prior antimicrobial use (sulbactam, antipseudomonal penicillins, aminoglycosides, and carbapenems). Multivariable analysis showed that ICU admission, chronic lung diseases, arterial line catheterization, total parenteral nutrition, and prior use of carbapenems were independent risk factors; prior use of carbapenems was found to be the most influential (odds ratio 6.36, 95% confidence interval 2.00–20.21; p = 0.002). Conclusion To our knowledge, this is the first study describing the risk factors associated with INS A. nosocomialis bacteremia. Regulated antibiotic control policy, especially for carbapenem, and infection control measures targeting patients hospitalized in ICU, with chronic lung diseases and multiple invasive procedures, may be helpful in reducing INS A. nosocomialis infection.

Summary Previous research revealed a 6-fold higher incidence of tuberculosis (TB) amongst aborigines compared to Han Chinese in Taiwan. To investigate the reasons for this disparity, we genotyped Mycobacterium tuberculosis (MTB) strains obtained from members of different aboriginal tribes in different geographical regions of Taiwan by using molecular methods. In total, 177 isolates of MTB collected from patients at four hospitals in Taiwan from January 2006 to December 2011 were analysed by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem-repeat (MIRU-VNTR) typing. The most prevalent strains in the eastern and central regions of Taiwan were Beijing (45.7% in eastern) and Haarlem (39.1% in eastern, 37.1% in central) lineages, whereas in southern regions the most prevalent strains were EAI (47.7%) and Haarlem (20.5%) lineages. The high prevalence of EAI in southern Taiwan aborigines may be closely associated with Austronesian culture. This study provides a first overview of the M. tuberculosis strains circulating in aboriginal populations in Taiwan. The high prevalences of certain MTB lineages within aboriginal sub-populations suggest that transmission of MTB may have been restricted to close contacts.

Background and objectives We aimed to investigate the benefits and risks of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in patients undergoing hemodialysis. Design, setting, participants, & measurements A nested case-control analysis of patients on hemodialysis after receipt of DES and DAPT treatment was conducted using data from Taiwan’s National Health Insurance Research Database for the period 2007–2011. Cases of myocardial infarction or death within 1 year after DES implantation were matched one-to-one with control patients. Odds ratios were calculated to compare DAPT continuation with discontinuation. Additionally, a propensity score–adjusted 6-month landmark cohort analysis was also conducted to evaluate the long-term benefits and risks of prolonged (>6 months) compared with ≤6 months of DAPT use. The primary outcomes were death and myocardial infarction. The secondary outcomes were ischemic stroke, revascularization, and major bleeding. Results In the nested case-control analysis, patients who continued DAPT had a lower rate of death or myocardial infarction within 1 year after receipt of a DES (adjusted odds ratio, 0.54; 95% confidence interval, 0.36 to 0.81; P =0.003), whereas this association became statistically nonsignificant when compared with patients who discontinued DAPT for the period between 6 and 12 months after receipt of a DES (adjusted odds ratio, 1.51; 95% confidence interval, 0.75 to 3.04). In the propensity score–adjusted cohort analysis, >6 months of DAPT use was not associated with different primary or secondary outcomes than shorter-term use. Conclusions Our findings support that the clinical effectiveness of extended DAPT in a hemodialysis population may be tempered after 6 months post-DES implantation.

Purpose: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that. Methods: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity. Results: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits. Conclusion: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted.

Background Large-scale and long-term studies are not sufficient to determine the efficiency that IT solutions can bring to transfusion safety. Objective This quality-improvement report describes our continuous efforts to implement and upgrade a bar code–based transfusion management (BCTM) system since 2011 and examines its effectiveness and sustainability in reducing blood transfusion errors, in a 3000-bed tertiary hospital, where more than 60,000 prescriptions of blood transfusion are covered by 2500 nurses each year. Methods The BCTM system uses barcodes for patient identification, onsite labeling, and blood product verification, through wireless connection to the hospital information systems. Plan-Do-Study-Act (PDSA) cycles were used to improve the process. Process maps before and after implementation of the BCTM system in 2011 were drawn to highlight the changes. The numbers of incorrect labeling or wrong blood in tube incidents that occurred quarterly were plotted on a run chart to monitor the quality changes of each intervention introduced. The annual occurrences of error events from 2011 to 2017 were compared with the mean occurrence of 2008-2010 to determine whether implementation of the BCTM system could effectively reduce the number of errors in 2016 and whether this reduction could persist in 2017. Results The error rate decreased from 0.03% in 2008-2010 to 0.002% in 2016 (P Conclusions This report demonstrates that continuous efforts to upgrade the existing process is critical to reduce errors in transfusion therapy, with support from information technology.

The present study aimed to evaluate the association between influenza vaccination and the secondary prevention of cardiovascular disease (CVD) among elderly persons. This retrospective cohort study used the Geriatric Dataset of Taiwan’s National Health Insurance Research Database (2000–2013). Patients aged ≥ 65 years who had been hospitalized for the first episodes of myocardial infarction were eligible. The vaccinated cohort comprised patients who received one dose of influenza vaccine within 180 days after discharge. The unvaccinated cohort included those who did not receive influenza vaccination and was propensity score–matched (1:1) for known CVD risk factors. All-cause death, acute myocardial infarction or cardiovascular death, and hospitalization for heart failure were assessed 1 year after the 181st day after hospital discharge. Compared with the matched cohort (n = 4,350), the vaccinated cohort (n = 4,350) had significantly lower incidences of all-cause death (hazard ratios [HR] 0.82, 95% CI [confidence interval] 0.73–0.92), myocardial infarction or cardiovascular death (HR 0.84, 95% CI 0.74–0.96), and hospitalization for heart failure (HR 0.83, 95% CI 0.74–0.92). The association between influenza vaccination and reduction of CVDs was similar across different subgroups. Cumulative incidence curves of the CVDs of interest for the two cohorts separated within the initial 3 months of follow-up (P < 0.05). Influenza vaccination was associated with a reduced risk of CVD in the elderly population with previous myocardial infarction.

Background An association between use of oral fluoroquinolones (FQs) and retinal detachment remains controversial. This study was to determine the association of recent use of oral FQs and rhegmatogenous retinal detachment (RRD) after adjustment for confounding factors known to be associated with RRD. Methods This retrospective population-based cohort study with parallel groups included adults treated with an oral FQ (FQ cohort = 178 179 prescriptions) and propensity score-matched adults treated with oral amoxicillin (amoxicillin cohort = 178 179 prescriptions). The data were extracted from the Taiwan National Health Insurance Research Database from 1998 to 2010. Interaction terms were used to identify populations at risk. RRD was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results During the 90-day follow-up period, 96 patients (0.054%) in the FQ cohort developed RRD compared to 46 (0.026%) among the matched amoxicillin cohort. The overall adjusted hazard ratio (HR) for FQ use and RRD was 2.07 (95% confidence interval [CI], 1.45-2.96). The interval between use of oral FQs and onset of RRD was 35.5 days (interquartile range, 14-57 days). Interaction terms were not significant for age, sex, diabetes, indications for antimicrobials, or underlying ophthalmic conditions. The adjusted HRs differed for specific FQs. These were 10.68 (95% CI, 3.28-34.82) for ciprofloxacin, 2.41 (95% CI, .76-7.68) for levofloxacin, 2.00 (95% CI, 1.06-3.79) for norfloxacin, and 1.17 (95% CI, .59-2.31) for ofloxacin. Conclusions The use of oral FQs was associated with the subsequent occurrence of RRD. The FQ risk was independent of age, sex, diabetes, indications for antimicrobials, and underlying ophthalmic conditions. Certain FQs carried higher risk of RRD.

Background: In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections. Methods: Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections. Results: After a follow-up period of 28 866 person–years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90–2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54–1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin's disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis. Conclusion: Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.

The argument of this study is that social capital is a key factor of health literacy. Data came from an island-wide sample. Position generator was adopted to measure social capital. A regression model is constructed to test the social capital which is known as a robust predictor of health literacy after controlling gender, age, education, income, and health communication ability. The results reveal that female, higher education, and better health communication ability are also correlated with health literacy. Implications for public health are discussed.

The carbapenem breakpoints set by different organizations for Acinetobacter are discordant, but supporting clinical data are lacking. This study aimed to provide the first clinical outcome data to support the carbapenem breakpoints for Acinetobacter baumannii (Ab) group in patients with bacteremia. This study included 117 adults who received carbapenems for treatment of Ab group bacteremia in Taipei Veterans General Hospital over an 8-year period. We analyzed 30-day mortality rates among patient groups acquiring isolates with different carbapenem minimal inhibitory concentrations (MICs). The carbapenem MIC breakpoint derived from classification and regression tree (CART) analysis to delineate the risk of 30-day mortality was between MICs of ≤ 4 mg/L and ≥ 8 mg/L. Mortality rate was higher in patients acquiring isolates with carbapenem MIC ≥ 8 mg/L than ≤ 4 mg/L, by bivariate (54.9% [28/51] vs 25.8% [17/66]; P = 0.003) and survival analysis (P = 0.001 by log-rank test). Multivariate analysis using logistic regression and Cox regression models including severity of illness indices demonstrated that treating patients with Ab group bacteremia caused by isolates with a carbapenem MIC ≥ 8 mg/L with carbapenem was an independent predictor of 30-day mortality (odds ratio, 5.125; 95% confidence interval [CI], 1.946–13.498; P = 0.001, and hazard ratio, 2.630; 95% CI, 1.431–4.834; P = 0.002, respectively). The clinical outcome data confirmed that isolates with MIC ≤ 4 mg/L were susceptible to carbapenem, and those with MIC ≥ 8 mg/L were resistant in patients with Ab group bacteremia.

Background: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. Methods: We conducted a propensity score–matched cohort study using Taiwan’s National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. Results: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87–1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87–1.04), including myocardial infarction (HR 1.03, 95% CI 0.88–1.20), ischemic stroke (HR 0.94, 95% CI 0.85–1.04) and cardiovascular death (HR 1.01, 95% CI 0.88–1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91–1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86–1.18). Results were similar in as-treated analyses. Interpretation: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy.

OBJECTIVES According to our previous study, OXA-58 translocates to the periplasm via the Sec pathway in carbapenem-resistant Acinetobacter baumannii (CRAb). In the present study, carbapenem-hydrolysing class D β-lactamases (CHDLs) belonging to the OXA-23, OXA-40 and OXA-51 families were examined to determine whether they are also Sec-dependent. Additionally, the effects of SecA inhibitors combined with carbapenems against CHDL-producing CRAb were examined. METHODS Cell fractionation and western blot analyses were performed to detect periplasmic His-tagged CHDLs. A chequerboard analysis with pairwise combinations of carbapenems (imipenem or meropenem) and SecA inhibitors (rose bengal, sodium azide or erythrosin B) was performed using six clinical CRAb isolates harbouring different CHDL genes. The fractional inhibitory concentration (FIC) index was determined. The combination with the lowest FIC index was subjected to a time-kill analysis to examine synergistic effects. RESULTS In an in silico analysis, the CHDLs OXA-23, OXA-40 and OXA-51 were preferentially translocated via the Sec system. The SecA inhibitor rose bengal decreased periplasmic translocation of His-tagged OXA-23 and OXA-83 (belonging to the OXA-51 family), but not OXA-72 (belonging to the OXA-40 family) from ATCC 15151 transformants. Imipenem or meropenem with rose bengal showed synergistic effects (FIC index, ≤0.5) for six and four clinical isolates, respectively. Imipenem or meropenem with sodium azide showed no interactions (FIC index, 0.5-4) against all clinical isolates. Imipenem and rose bengal had the lowest FIC index and showed synergy at 24 h in the time-kill assay. CONCLUSIONS Combinations of SecA inhibitors and carbapenems have synergistic effects against CHDL-producing CRAb.

Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26–6302.18, p

S. aureus bacteremia (SAB) is a severe systemic illness, which is associated with high mortality and healthcare cost. It has been reported that older age per se is a poor prognostic factor of SAB, but little is known whether poor clinical outcomes is related to conservative attitudes of treating physicians. A retrospective cohort of 126 patients (mean age: 73.7 ± 13.6 years, 72.2% males) with community-onset SAB during 2004–2008 in a tertiary medical center in Taiwan was obtained for study. Demographic data, clinical characteristics, primary infectious focus, metastatic lesions, access to critical care units, performance of invasive procedures, Charlson comorbidity index (CCI) and in-hospital mortality for all study subjects were collected. The overall in-hospital mortality was 32.5%, which was not significantly different between adult and elderly groups. SAB of elderly patients was more likely to be primary than that of the adult patients (20.4% vs. 3.6%, p = 0.043). Deep-seated abscess, osteomyelitis and metastatic lesion with central nervous system (CNS) involvement were more common infection foci in the adult patient group. Chronic obstructive pulmonary disease and cerebrovascular accident were more common underlying conditions of the elderly group. Chances of patients admitted to intensive care unit and employment of invasive procedures were not different between groups although elderly patients were supposed to be of a greater risk of mortality. In conclusion, the overall in-hospital mortality of community-onset SAB was 32.5%, which was not different between age groups. In general, older patients were of similar chance to receive critical care and invasive procedures except arterial line and non-tunneled central venous catheters. Further prospective investigation is needed to clarify whether physicians hold different attitudes to older patients with SAB and the differences in treatment attitude resulting in poorer clinical outcomes.

The efficacy of antimicrobial therapy for Acinetobacter baumannii bacteremia has been difficult to establish because of confounding by underlying diseases, severity of infection, and differences in the pathogenicity of Acinetobacter species. This retrospective study was conducted to evaluate the effect of appropriate antimicrobial therapy on 14-day mortality after adjustment for multiple risk factors.The population consisted of 252 patients with monomicrobial A. baumannii bacteremia admitted to a large teaching hospital in Taiwan. The isolates were identified to species level using reference molecular methods. Predictors of 14-day mortality were determined by logistic regression analysis. The influence of severity of infection, determined by Acute Physiology and Chronic Health Evaluation (APACHE) II score, on the impact of appropriate use of antimicrobials on 14-day mortality was assessed by including an interaction term.The overall 14-day mortality rate was 29.8% (75 of 252 patients). The unadjusted mortality rate for appropriate antimicrobial therapy was 13.2% (12 of 91 patients). Appropriate therapy was independently associated with reduced mortality (odds ratio [OR], 0.22; 95% confidence interval [CI], .01-.50; P.001), and the effect was influenced by APACHE II score (OR for interaction term, 0.90; 95% CI, .82-.98; P= .02). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with high APACHE II scores (OR for patients with scores25 and ≤ 35, 0.16 [95% CI, .07-.37]; OR for those with scores35, 0.06; 95% CI, .01-.25).Appropriate antimicrobial therapy significantly reduced 14-day mortality for A. baumannii bacteremia in severely ill patients.

Background Acinetobacter baumannii complex (Abc) comprises at least three phenotypically undifferentiated species, including A baumannii , Acinetobacter genomic species 3 (AGS 3) and Acinetobacter genomic species 13TU (AGS 13TU). Abc bacteremia had rarely been described in patients receiving total parenteral nutrition (TPN). In this study, we aimed to determine any differences in the clinical features of patients having TPN and bacteremia due to A baumannii and those due to non baumannii Abc (including AGS 3 and AGS 13TU). Methods The data of patients who had received TPN and had Abc bacteremia in Taipei Veterans General Hospital between August 1998 and December 2007 were retrospectively reviewed. The Acinetobacter isolates were identified to genomic species level. Results A total of 23 patients with A baumannii and 23 patients with non baumannii Abc (15 AGS 13TU and 8 AGS 3) bacteremia were identified. The two groups of the patients were comparable regarding their gender, age and APACHE II score at the onset of bacteremia. However, several clinical features were different between the two groups of the patients in the univariate analysis. Furthermore, A baumannii isolates were resistant to more classes of antibiotics than non baumannii Abc isolates. The multivariate analysis showed that a higher number of patients with A baumannii bacteremia had received TPN for≥15 days before their onset of bacteremia [odds ratio (OR) 7.214, 95% confidence interval (CI) (1.108–46.989), p = 0.039]. Nevertheless, the 14-day (30.4% vs. 21.7%, p = 0.737) and all-cause in-hospital mortality rate (60.9% vs. 39.1%, p = 0.238) did not differ significantly between these two groups. Conclusion The patients with A baumannii bacteremia demonstrated a longer timeframe in the treatment of TPN prior to the onset of bacteremia than those with non baumannii Abc bacteremia, however the clinical outcomes between the two groups of the patients did not differ significantly.

Although the association of hyperuricemia and cardiovascular diseases is well established by previous research studies, the relationship between gout and deep vein thrombosis (DVT) remains unclear. We conducted a nationwide longitudinal cohort study to investigate the relationship between gout and DVT. We used the Taiwan National Health Insurance Research Database to identify patients with gout diagnosed in Taiwan during 2000–2011, and we followed up these patients to determine the incidence of DVT among them. The association between gout and DVT was analyzed by cox proportional hazard model. The study cohort included 35,959 patients with history of gout attack and 35,959 matched controls without gout attack. During the median follow-up of 7.5 ± 3.6 years, the incidence rate of DVT was significantly higher in patients with gout than that in control group (13.48 versus 9.77 per 104 person-years, p

Objectives The elderly (aged ≥65 years) population with type 2 diabetes (T2D) is growing substantially, but evidence for associations between the use of dipeptidyl peptidase-4 inhibitors (DPP-4is), novel incretin-based antidiabetic drugs, and clinical hard endpoints in this group remains inconclusive. We aimed to assess the safety and cardiovascular effects of DPP-4i use in a nationally representative sample of elderly adults with T2D. Design, setting, and participants We conducted a nationwide, observational, propensity score–matched study using Taiwan's National Health Insurance Research Database. Of a total of 414,213 patients aged ≥65 years with T2D, 58,485 patients receiving initial DPP-4i prescriptions between March 1, 2009, and June 31, 2013, were included. Each DPP-4i user was matched with a nonuser control using propensity scores. The endpoints were all-cause mortality and major adverse cardiovascular events (MACEs), including ischemic stroke and myocardial infarction. Potential adverse effects of hospitalization for heart failure and hypoglycemia were also evaluated. Results Compared with the matched control cohort, the risks of all-cause mortality (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.52–0.56), MACEs (HR 0.79, 95% CI 0.75–0.83), myocardial infarction (HR 0.79, 95% CI 0.72–0.87), and ischemic stroke (HR 0.79, 95% CI 0.75–0.84) were lower in the DPP-4i cohort. DPP-4i use did not affect the risks of hospitalization for heart failure and hypoglycemia. Stratified analyses produced consistent results across age, sex, and comorbidity subgroups. Conclusions Prescription of DPP-4is was associated with reduced risks of all-cause mortality and MACEs in patients aged ≥65 years with T2D.

To disclose the association between diabetes mellitus (DM) and cryptococcosis in HIV-uninfected patients.Case patients' diagnoses with cryptococcosis and cryptococcal meningitis were based on data from the Taiwan National Health Insurance Research Database from 2000 to 2010, and diagnoses were defined using the International Classification of Disease, Ninth Revision, Clinical Modification. A case-control study comprising inpatient and outpatient populations was conducted using 4 controls for each patient (4587 case patients and 18,348 controls) matched for age, sex, monthly income, and urbanization level.Human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis were more likely to have diabetes than matched control patients (adjusted odds ratio [OR], 1.45; 95% confidence interval [95% CI], 1.36-1.64; p 0.001). A diagnosis of DM was also associated with 1-year and overall mortality from cryptococcosis (hazard ratio [HR], 1.39; 95% CI, 1.17-1.65; p 0.001, HR, 1.47; 95% CI, 1.29-1.67; p 0.001; respectively) and cryptococcal meningitis (p = 0.018).Diabetes was associated with the occurrence of cryptococcosis and cryptococcal meningitis in HIV-uninfected patients. DM was also associated with 1-year and overall mortality for these patients.

Background JX594 is an oncolytic poxvirus derived from Wyeth strain vaccinia virus. We reported the presentation of cutaneous and mucosal pustules containing laboratory-confirmed JX594 in a patient following injection of JX594. Case presentation A 36-year-old man was diagnosed hepatitis B virus-associated hepatocellular carcinoma on September 19, 2011. Despite treatment with entecavir, radiofrequency ablation and transarterial chemoembolization for recurrent local tumors, the tumors recurred in both lobes and lung metastases were detected by computed tomography on September 12, 2012. The patient was treated with JX594 (Pexa-vec®) via intravenous injection on December 19, 2012. No apparent adverse effects were observed following intravenous injection other than a single fever episode. However, pustular lesions were detected on both sides of the tongue dorsum and on the proximal interphalangeal joint of the right middle finger on December 25, 1012. Biopsy samples analyzed by PCR identified the presence of the JX-594-specific hGM-CSF transgene and the disrupted viral thymidine kinase gene. Following aspiration of the lesion a scab formed that resolved within 14 days without necessitating additional treatment. Conclusion Our case completely recovered and did not develop systemic or recurrent disease, the presentation of a few pustules may not necessarily require that treatment with JX594 be interrupted for patients with advanced hepatocellular carcinoma.

Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and Acinetobacter genomic species sensu Tjernberg and Ursing (AGS 13TU) are phenotypically indistinguishable and are often reported together as the A. baumannii complex (ABC). Few studies have investigated the difference in outcome caused by these different species, and all involved heterogeneous groups of patients. This study aimed to delineate whether there are differences in the clinical characteristics and outcome among patients with solid tumors and bacteremia caused by A. baumannii or two other non-baumannii ABC species (AGS 3 plus AGS 13TU).Patients with solid tumors and ABC bacteremia over a period of 5 years in a medical center were identified. The patient data were retrospectively reviewed and analyzed.We identified 103 patients with ABC bacteremia during the study period. Bacteremia was due to A. baumannii in 30 patients, AGS 3 in 24 patients, and AGS 13TU in 49 patients. Among the 103 patients with ABC bacteremia, recent stay in the intensive care unit (ICU) (p = 0.008) was independently associated with the acquisition of A. baumannii bacteremia. Multivariate analysis revealed that bacteremia caused by A. baumannii (hazard ratio [HR] 2.990, 95% confidence interval [CI], 1.021-8.752, p = 0.046) and Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥21 (HR 4.623, 95% CI 1.348-15.859, p = 0.015) were independent factors associated with 14-day mortality.Infection with A. baumannii and a high APACHE II score (≥21) might be associated with poor outcome in patients with solid tumors and ABC bacteremia.

Background We aim to evaluate the efficacy of polymerase chain reaction (PCR) to detect Acinetobacter baumannii in endotracheal aspirates. Methods Endotracheal aspirates and clinical data were collected from patients who were admitted to the intensive care unit of Taipei Veterans General Hospital between April 1 and August 31 in 2006. Bacterial isolates from endotracheal aspirate cultures were phenotypically identified as Acinetobacter calcoaceticus – A baumannii complex using the API ID 32GN system. The presence of A baumannii in the aspirate was also directly detected by multiplex PCR. Results Ten of the 114 endotracheal aspirate cultures were positive for A calcoaceticus – A baumannii complex, and only nine of the isolates were confirmed as A baumannii by the multiplex PCR. Direct PCR detection showed that 40 (35.1%) of the endotracheal aspirates were positive for A baumannii . Using positive culture of A baumannii as the gold standard, the sensitivity of direct PCR detection was 100% (6 of 6), the specificity was 70.4% (38 of 54), the positive predictive value was 27.3% (6 of 22), and the negative predictive value (NPV) was 100% (38 of 38) among patients with A baumannii pneumonia. Among patients with A baumannii colonization, the sensitivity of direct PCR detection was 100% (3 of 3), the specificity was 70.6% (36 of 51), the positive predictive value was 16.7% (3 of 18), and the NPV was 100% (36 of 36). Conclusion Direct PCR detection of A baumannii in endotracheal aspirates has a high sensitivity and NPV as compared with culture-based methods. Further studies are needed to determine the clinical applicability of this rapid detection test.

Objective Acinetobacter baumannii is an important nosocomial pathogen associated with a high mortality rate. However, no objective and quantitative severity scores are available for the severity stratification. We aimed to assess the effectiveness of SOFA and APACHE II scores calculated at the onset of bacteremia in predicting the mortality of patients with A. baumannii bacteraemia. Patients and Methods A total of 110 patients with A. baumannii bacteremia were included in this retrospective study during the 40-month study period. Information including clinical and laboratory data was collected. Results Multivariate analysis showed that both SOFA and APACHE II scores were independent outcome predictors after adjustment for other parameters. Goodness-of-fit was good for SOFA and APACHE II, and both models displayed excellent AUROCs (SOFA: 0.83 ± 0.06, APACHE II: 0.82 ± 0.08 in predicting 14-day mortality; SOFA: 0.85 ± 0.04, APACHE II: 0.81 ± 0.04 in predicting in-hospital mortality). There was no significant difference in the predictions of the two scoring systems, and the scores were highly correlated (r2=0.724, p 8, APACHE II >29 and SOFA >7, APACHE II >23 are associated with significantly higher 14-day and in-hospital mortality rates, respectively. Conclusion SOFA and APACHE II scores assessed at the onset of bacteremia are reliable risk stratifying tools in predicting 14-day and in-hospital mortality in A. baumannii bacteremia. For ease of calculation, the use of SOFA rather than APACHE II score to predict mortality of A. baumannii bacteremia might have clinical application.