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1.  Molecular Epidemiology of Tuberculosis in Kaohsiung City Located at Southern Taiwan, 2000-2008 
PLoS ONE  2015;10(1):e0117061.
Background
We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates.
Methods
All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed.
Results
The percentage of EAI (East African-Indian) strains increased across sampling years (2000–2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p<0.0001) when compared to Beijing genotypes. Notably, MTB resistance to streptomycin (STR) had significantly increased over time, but resistance to other antibiotics, including multidrug resistance, had not. Three major genes (gidB, rpsL and rrs) implicated in STR resistance were sequenced and specific mutations identified.
Conclusions
This study revealed that EAI strains were highly transmissible and that STR resistance has increased between 2000 and 2008 in Kaohsiung, Taiwan.
doi:10.1371/journal.pone.0117061
PMCID: PMC4309396  PMID: 25629610
2.  Sheltering Effect and Indirect Pathogenesis of Carbapenem-Resistant Acinetobacter baumannii in Polymicrobial Infection 
The role of carbapenem-resistant Acinetobacter baumannii (CRAb) in polymicrobial infection remains elusive. Having observed the ability of CRAb to shelter other susceptible bacteria from carbapenem killing, we sought to determine the factors contributing to this sheltering effect by transforming different recombinant plasmids into recipient A. baumannii cells. The sheltering effects of CRAb were reproduced in recipient A. baumannii cells that highly expressed carbapenem-hydrolyzing class D β-lactamases (CHDLs) through their associated strong promoter. With the use of Western blot analysis and a bioassay, the highly expressed CHDLs were found to be extracellularly released and led to hydrolysis of carbapenem. The level of extracellular CHDLs increased after challenge with a higher concentration of CHDL substrates, such as carbapenem and ticarcillin. This increased CHDL may, in part, be attributed to cell lysis, as indicated by the presence of extracellular gyrase. In the planktonic condition, the sheltering effect for the cocultured susceptible bacteria might represent an indirect and passive effect of the CRAb self-defense mechanism, because coculture with the susceptible pathogen did not augment the amount of the extracellular CHDLs. Polymicrobial infection caused by CRAb and a susceptible counterpart exerted higher pathogenicity than monomicrobial infection caused by either pathogen alone in mice receiving carbapenem therapy. This study demonstrated that CHDL-producing CRAb appears to provide a sheltering effect for carbapenem-susceptible pathogens via the extracellular release of CHDLs and, by this mechanism, can enhance the pathogenesis of polymicrobial infection in the presence of carbapenem therapy.
doi:10.1128/AAC.02636-13
PMCID: PMC4068520  PMID: 24798276
3.  Distinct Modes of Transmission of Tuberculosis in Aboriginal and Non-Aboriginal Populations in Taiwan 
PLoS ONE  2014;9(11):e112633.
Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ≤20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR) = 5.98, p<0.0001). MTB lineages with high clustering were EAI (54.9%) among southern people, and Beijing (62.5%) and Haarlem (52.9%) among eastern aborigines. Resistance to first-line drugs and multidrug resistance (MDR) were significantly higher among eastern aborigines (≥15%) than in any other geographic and ethnic group (p<0.05); MDR was detected in 5 of 28 eastern aboriginal patients ≤20 years old. Among patients from the eastern region, clustered strains (p = 0.01) and aboriginal ethnicity (p = 0.04) were independent risk factors for MDR. The lifestyles of aborigines in eastern Taiwan may explain why the percentage of infected aborigines is much higher than for their Han Chinese counterparts. The significantly higher percentage of the MDR-MTB strains in the aboriginal population warrants close attention to control policy and vaccination strategy.
doi:10.1371/journal.pone.0112633
PMCID: PMC4231046  PMID: 25393403
4.  The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study 
BMC Medicine  2014;12(1):169.
Background
Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD.
Methods
This nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients ≥70 years old with advanced CKD and serum creatinine levels >6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality.
Results
During a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities.
Conclusions
In older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ≥70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0169-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-014-0169-3
PMCID: PMC4189680  PMID: 25315422
Advanced chronic kidney disease; Dialysis; Conservative care; Older people
5.  Genetic Diversity of the Mycobacterium tuberculosis Beijing Family Based on SNP and VNTR Typing Profiles in Asian Countries 
PLoS ONE  2012;7(7):e39792.
The Mycobacterium tuberculosis (MTB) Beijing strain is highly virulent, drug resistant, and endemic over Asia. To explore the genetic diversity of this family in several different regions of eastern Asia, 338 Beijing strains collected in Taiwan (Republic of China) were analyzed by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and compared with published MIRU-VNTR profiles and by the Hunter-Gaston diversity index (HGDI) of Beijing strains from Japan and South Korea. The results revealed that VNTR2163b (HGDI>0.6) and five other loci (VNTR424, VNTR4052, VNTR1955, VNTR4156 and VNTR 2996; HGDI>0.3) could be used to discriminate the Beijing strains in a given geographic region. Analysis based on the number of VNTR repeats showed three VNTRs (VNTR424, 3192, and 1955) to be phylogenetically informative loci. In addition, to determine the geographic variation of sequence types in MTB populations, we also compared sequence type (ST) data of our strains with published ST profiles of Beijing strains from Japan and Thailand. ST10, ST22, and ST19 were found to be prevalent in Taiwan (82%) and Thailand (92%). Furthermore, classification of Beijing sublineages as ancient or modern in Taiwan was found to depend on the repeat number of VNTR424. Finally, phylogenetic relationships of MTB isolates in Taiwan, South Korea, and Japan were revealed by a minimum spanning tree based on MIRU-VNTR genotyping. In this topology, the MIRU-VNTR genotypes of the respective clusters were tightly correlated to other genotypic characters. These results are consistent with the hypothesis that clonal evolution of these MTB lineages has occurred.
doi:10.1371/journal.pone.0039792
PMCID: PMC3395628  PMID: 22808061
6.  Levofloxacin-Resistant Haemophilus influenzae, Taiwan, 2004–2010 
Emerging Infectious Diseases  2014;20(8):1386-1390.
Levofloxacin resistance in Haemophilus influenzae has increased significantly in Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular investigations of 182 levofloxacin-resistant isolates revealed that the increase was mainly the result of the spread of several clones in the elderly population in different regions.
doi:10.3201/eid2008.140341
PMCID: PMC4111205  PMID: 25061696
Haemophilus influenzae; fluoroquinolone resistance; GyrA; ParC; Taiwan; respiratory infections; bacteria; antimicrobial resistance; levofloxacin
7.  The Pattern of Cytokine Production In Vitro Induced by Ancient and Modern Beijing Mycobacterium tuberculosis Strains 
PLoS ONE  2014;9(4):e94296.
It is unclear to what extent the host-responses elicited by Beijing versus non-Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the predominance of modern Beijing strains in Taiwan and some other Asian countries. The purpose of this study was to compare the expression profiles of virulence-related genes in human monocyte-derived macrophages infected in vitro with Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB that are epidemic in Taiwan. We found that modern Beijing strains induced lower levels of pro-inflammatory cytokines, whereas EAI strains induced higher levels. Notably, the most prevalent modern Beijing sub-lineage, possessing intact RD150 and RD142 chromosomal regions, induced very low levels of pro-inflammatory cytokines, especially interleukin-1β. Moreover, in an intracellular growth assay, the survival of the same modern Beijing strain in human monocyte-derived macrophages was significantly higher than that of an ancient Beijing strain and an EAI strain. Taken together, these results may explain why modern Beijing strains of MTB predominate in Taiwan.
doi:10.1371/journal.pone.0094296
PMCID: PMC3984122  PMID: 24728339
8.  Incidence and outcome of newly-diagnosed tuberculosis in schizophrenics: a 12-year, nationwide, retrospective longitudinal study 
BMC Infectious Diseases  2013;13:351.
Background
To control tuberculosis (TB), it is critical to identify at risk populations. Schizophrenia is recognized as an important risk factor for TB. However, previous studies have been confounded by comorbidities, and reports of TB infection outcomes are rare. Therefore, the current nation-wide study aimed to compare the adjusted incidence and outcome of TB diseases in schizophrenics and the general population.
Method
Using the National Health Insurance Research Database from 1998 to 2009, this retrospective longitudinal study included 60,409 schizophrenics and general population matched for age, Charlson’s score, and comorbidities. Diagnosis of TB was based on the international classification of disease, ninth revision and use of anti-TB drugs. Unfavorable outcome for TB was defined as death, loss to follow-up, or use of anti-TB treatment for more than 9 months.
Results
The adjusted incidence of TB in schizophrenics was significantly higher than in the general population [hazard ratio, 1.52; 95% confidence interval (CI), 1.29-1.79; p < 0.001; Kaplan-Meier log-rank test, p < 0.001]. Cox regression revealed age and male gender as risk factors for newly-diagnosed TB. The outcome of TB was comparable in schizophrenics and the general population [odds ratio (OR), 0.78; 95% CI, 0.55-1.09; p =0.144]. Logistic regression revealed a statistical trend for diabetes mellitus to predict poor outcome in schizophrenics with TB (OR, 2.30; 95% CI, 0.96-5.74; p = 0.062).
Conclusions
Schizophrenics are at increased risk for TB, and screening may be warranted for those living in areas with high prevalence of TB.
doi:10.1186/1471-2334-13-351
PMCID: PMC3729604  PMID: 23895638
Schizophrenia; Tuberculosis; Incidence; Outcome
9.  Dissemination of imipenem-resistant Acinetobacter baumannii with new plasmid-borne blaOXA-72 in Taiwan 
BMC Infectious Diseases  2013;13:319.
Background
The systemic surveillance of imipenem-resistant Acinetobacter baumannii (IRAB) from multicenters in Taiwan revealed the emergence of isolates with blaOXA-72. This study described their genetic makeup, mechanism of spread, and contribution to carbapenem resistance.
Methods
Two hundred and ninety-one non-repetitive isolates of A. baumannii were collected from 10 teaching hospitals from different geographical regions in Taiwan from June 2007 to September 2007. Minimal inhibitory concentrations (MICs) were determined by agar dilution. Clonality was determined by pulsed-field gel electrophoresis. Plasmid was extracted and digested by restriction enzymes, and subsequently analyzed by electrophoresis and Southern blot for blaOXA-72. The flanking regions of blaOXA-72 were determined by inverse PCR. The contribution of blaOXA-72 to imipenem MIC was determined by transforming plasmids carrying blaOXA-72 into imipenem-susceptible A. baumannii.
Results
Among 142 IRAB in Taiwan, 27 harbored blaOXA-72; 22 originated from Southern Taiwan, 5 from Central Taiwan, and none from Northern Taiwan. There were two major clones. The blaOXA-72 was identified in the plasmids of all isolates. Two genetic structures flanking plasmid-borne blaOXA-72 were identified and shared identical sequences in certain regions; the one described in previous literature was present in only one isolate, and the new one was present in the remaining isolates. Introduction of blaOXA-72 resulted in an increase of imipenem MIC in the transformants. The overexpression of blaOXA-72 mRNA in response to imipenem further supported the contribution of blaOXA-72.
Conclusions
In conclusion, isolates with new plasmid-borne blaOXA-72 were found to be disseminated successfully in Southern Taiwan. The spread of the resistance gene depended on clonal spread and dissemination of a new plasmid. BlaOXA-72 in these isolates directly led to their imipenem-resistance.
doi:10.1186/1471-2334-13-319
PMCID: PMC3728158  PMID: 23849336
Imipenem-resistant; Acinetobacter baumannii; Carbapenemase; BlaOXA-72
10.  Comparison between bacteremia caused by carbapenem resistant Acinetobacter baumannii and Acinetobacter nosocomialis 
BMC Infectious Diseases  2013;13:311.
Background
It is unknown whether there are differences between bacteremia caused by carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Acinetobacter nosocomialis (CRAN). This study aims to investigate the differences, especially in clinical outcomes, between patients with bacteremia caused by CRAB or CRAN.
Methods
This is a 9-year retrospective study comparing the clinical manifestations, antimicrobial susceptibilities, and clinical outcomes of 71 patients with CRAB bacteremia and 64 patients with CRAN bacteremia.
Results
Patients with CRAB were more likely to have hematologic malignancies and presented with more shock episodes than those with CRAN. CRAB isolates were more resistant to various classes of antimicrobials except colistin, and therefore the patients with CRAB bacteremia were more likely to receive inappropriate antimicrobial therapies. The 14-day mortality was significantly higher in patients with CRAB (40.8% vs. 14.1%; p = 0.001), and in this study, acquisition of CRAB was identified as an independent risk factor for mortality (odds ratio = 4.003; 95% confidence interval = 1.566-10.231; p = 0.004).
Conclusions
CRAB and CRAN bacteremia are different in clinical characteristics, antimicrobial susceptibilities, and mortality rates. Genomic species identification should be performed in the study of carbapenem resistant Acinetobacters to better delineate the role of different species.
doi:10.1186/1471-2334-13-311
PMCID: PMC3710499  PMID: 23841753
Acinetobacter; Bacteremia; Carbapenem resistant; Risk factor; Mortality
11.  Acinetobacter baumannii nosocomial pneumonia: is the outcome more favorable in non-ventilated than ventilated patients? 
BMC Infectious Diseases  2013;13:142.
Background
Acinetobacter baumannii hospital-acquired pneumonia (HAP) is associated with a high mortality worldwide. Non-ventilated patients with HAP (NVHAP) caused by nosocomial pathogens are reported to have a more favorable outcome than those with ventilator-associated pneumonia (VAP). The current study was designed to determine whether bacteremic patients with A. baumannii NVHAP also have a lower mortality than those receiving assisted ventilation.
Methods
This retrospective 10-year study was conducted at a 2900-bed teaching hospital located in Northern Taiwan. The population consisted of 144 patients with A. baumannii bacteremia and HAP. Of these 96 had VAP and 48 had NVHAP. Charts were reviewed for demographic characteristics, comorbidities, clinical manifestations, antimicrobial susceptibility, and 14-day mortality. Clonal relationships were determined by molecular typing.
Results
There were no significant differences between the two groups in comorbidities (Charlson scores). Patients with NVHAP were more likely to have developed bacteremia earlier, outside the ICU and undergone fewer invasive procedures. They had significantly lower APACHE II scores, fewer bilateral pneumonias and lower rates of antimicrobial resistance. No specific clones were identified in either group. The unadjusted (crude) 14-day mortality rates were not significantly different between the groups (NVHAP 43.8% vs. VAP 31.3%, p = 0.196). The adjusted 14-day mortality risk was significantly lower in ventilator-assisted patients (odds ratio = 0.201; 95% confidence interval = 0.075-0.538; p = 0.001).
Conclusions
Patients with bacteremic NVHAP and VAP caused by A. baumannii had similar crude mortality rates, but on logistic regression analysis those receiving ventilator assistance had a significantly lower mortality. This may have been due to better airway protection, more intensive monitoring with earlier diagnosis and treatment in patients with VAP, greater innate susceptibility to infection in those with NVHAP and differences in the virulence of A. baumannii.
doi:10.1186/1471-2334-13-142
PMCID: PMC3605360  PMID: 23509931
Acinectobacter baumannii; Pneumonia; Hospital acquired; Ventilator
12.  Emergence of extensively drug-resistant Acinetobacter baumannii complex over 10 years: Nationwide data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program 
BMC Infectious Diseases  2012;12:200.
Background
Acinetobacter baumannii complex (ABC) has emerged as an important pathogen causing a variety of infections. Longitudinal multicenter surveillance data on ABC from different sources in Taiwan have not been published. Using data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) conducted biennially, we investigated the secular change in resistance of 1640 ABC from 2002 to 2010 (TSAR period III to VII) to different antimicrobial agents and identified factors associated with imipenem-resistant and extensively drug-resistant ABC (IRABC and XDRABC).
Methods
Isolates were collected by TSAR from the same 26 hospitals located in all 4 regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. Isolates nonsusceptible to all tested aminoglycosides, fluoroquinolones, β-lactam, β-lactam/β-lactam inhibitors, and carbapenems were defined as extensively drug-resistant (XDR). Multivariate logistic regression analysis was performed to assess the relationship between predictor variables among patients with resistant ABC and patients with non-resistant ABC.
Results
The prevalence of IRABC increased from 3.4% in 2002 to 58.7% in 2010 (P < 0.001; odds ratio [OR], 2.138; 95% confidence interval [CI], 1.947 to 2.347) and that of XDRABC increased from 1.3% in 2002 to 41.0% in 2010 (P < 0.001; OR, 1.970; 95% CI, 1.773-2.189). The rates of non-susceptibility to other antimicrobial agents remained high (>55%) over the years with some fluctuations before and after TSAR V (2006) on some agents. Multivariate analysis revealed that recovery from elderly patients, origins other than blood, from ICU settings, or geographic regions are independent factors associated with IRABC and XDRABC. Although the prevalence of XDRABC increased in all four regions of Taiwan over the years, central Taiwan had higher prevalence of XDRABC starting in 2008. Susceptibility to polymyxin remained high (99.8%).
Conclusions
This longitudinal multicenter surveillance program revealed significant increase and nationwide emergence of IRABC and XDRABC in Taiwan over the years. This study also identified factors associated with IRABC and XDRABC to help guide empirical therapy and at-risk groups requiring more intense interventional infection control measures with focused surveillance efforts.
doi:10.1186/1471-2334-12-200
PMCID: PMC3462144  PMID: 22929085
Extensively drug-resistant; Acinetobacter baumannii complex; Antimicrobial resistance
13.  Clonal Expansion of Both Modern and Ancient Genotypes of Mycobacterium tuberculosis in Southern Taiwan 
PLoS ONE  2012;7(8):e43018.
We present the first comprehensive analysis of Mycobacterium tuberculosis isolates circulating in the Kaohsiung region of southern Taiwan. The major spoligotypes found in the 224 isolates studied were Beijing lineages (n = 97; 43.3%), EAI lineages (n = 72; 32.1%) and Haarlem lineages (n = 18; 8.0%). By 24 MIRU-VNTR typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. The combination of spoligotyping and 12-MIRU-VNTR revealed that 129 (57.6%) of the 224 isolates were clustered in 18 genotypes. Moreover, 63.6% (7/11) of infected persons younger than 30 years had a Beijing strain, which could suggest recent spread among younger persons by this family of TB strains in Kaohsiung. Among the 94 Beijing family (SIT1, SIT250 and SIT1674) isolates further analyzed for SNPs by mass spectrometry, the most frequent strain found was ST10 (n = 49; 52%), followed by ST22 (n = 17; 18%) and ST19 (n = 11; 12%). Among the EAI-Manila family isolates analyzed by region deletion-based subtyping, the most frequent strain found was RD type 1 (n = 63; 87.5%), followed by RD type 2 (n = 9; 12.5%). In our previous study, the proportion of modern Beijing strains (52.5%) in northern Taiwan was significantly higher than the proportion of EAI strains (11%). In contrast, in the present study, EAI strains comprised up to 32% of Beijing strains in southern Taiwan. In conclusion, both ‘modern’ (Beijing) and ‘ancient’ (EAI) M. tuberculosis strains are prevalent in the Kaohsiung region, perhaps suggesting that both strains are somehow more adapted to southern Taiwan. It will be interesting to investigate the dynamics of the lineage composition by different selection pressures.
doi:10.1371/journal.pone.0043018
PMCID: PMC3427295  PMID: 22937008
14.  Emergence of Carbapenem-Resistant Non-baumannii Species of Acinetobacter Harboring a blaOXA-51-Like Gene That Is Intrinsic to A. baumannii 
The blaOXA-51-like gene, originally intrinsic to Acinetobacter baumannii, had been detected in two clones of Acinetobacter nosocomialis and one clone of Acinetobacter genomic species “Close to 13TU.” These blaOXA-51-like genes, all preceded by ISAba1, were located on plasmids that might have originated with A. baumannii. The plasmid-borne ISAba1--blaOXA-51-like confers a high level of carbapenem resistance and affects the accuracy of using blaOXA-51-like detection as a tool for differentiating A. baumannii from other Acinetobacter species.
doi:10.1128/AAC.00622-11
PMCID: PMC3264228  PMID: 22083478
15.  Establishing and evaluating bar-code technology in blood sampling system: a model based on human centered human-centered design method 
This study intended to use a human-centered design study method to develop a bar-code technology in blood sampling process. By using the multilevel analysis to gather the information, the bar-code technology has been constructed to identify the patient’s identification, simplify the work process, and prevent medical error rates. A Technology Acceptance Model questionnaire was developed to assess the effectiveness of system and the data of patient’s identification and sample errors were collected daily. The average scores of 8 items users’ perceived ease of use was 25.21(3.72), 9 items users’ perceived usefulness was 28.53(5.00), and 14 items task-technology fit was 52.24(7.09), the rate of patient identification error and samples with order cancelled were down to zero, however, new errors were generated after the new system deployed; which were the position of barcode stickers on the sample tubes. Overall, more than half of nurses (62.5%) were willing to use the new system.
PMCID: PMC3799121  PMID: 24199057
16.  High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin-nonsusceptible Staphylococcus aureus: Case report 
BMC Infectious Diseases  2011;11:152.
Background
Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus.
Case presentation
We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin.
Conclusions
Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.
doi:10.1186/1471-2334-11-152
PMCID: PMC3119071  PMID: 21612672
Daptomycin-nonsusceptible; fosfomycin; ICD device-related endocarditis
17.  Emergence and Distribution of Plasmids Bearing the blaOXA-51-Like Gene with an Upstream ISAba1 in Carbapenem-Resistant Acinetobacter baumannii Isolates in Taiwan ▿  
Antimicrobial Agents and Chemotherapy  2010;54(11):4575-4581.
The blaOXA-51-like gene with an upstream ISAba1 (ISAba1-blaOXA-51-like gene) was originally found on the chromosomes of carbapenem-resistant or -susceptible Acinetobacter baumannii isolates. However, a plasmid-borne ISAba1-blaOXA-51-like gene has recently been identified in Acinetobacter genomic species 13TU and several A. baumannii isolates in Taiwan, and all of the isolates are carbapenem resistant. This study aimed to characterize the plasmids bearing the ISAba1-blaOXA-51-like gene and their significance in A. baumannii. Among the 117 ISAba1-blaOXA-51-like-harboring isolates collected from 10 hospitals in Taiwan, 58 isolates (49.6%) from 24 clones had the genes located on plasmids that likely originated from a common progenitor. Among the 58 isolates, four had additional copy of the ISAba1-blaOXA-51-like gene on their chromosomes. Based on the analysis of these four isolates, the plasmid-located ISAba1-blaOXA-51-like gene appeared to be acquired via one-ended transposition (Tn6080). The isolates with a plasmid bearing the ISAba1-blaOXA-51-like gene had higher rates of resistance to imipenem (98% versus 46.6%; P < 0.001) and meropenem (98% versus 69%; P = 0.019) than those with the genes chromosomally encoded, which is most likely due to increased gene dosage provided by the higher copy number of associated plasmids. Transformation with a recombinant plasmid harboring only the ISAba1-blaOXA-51-like gene was enough to confer a high level of carbapenem resistance to A. baumannii, eliminating the possible contribution of other factors on the original plasmids. This study demonstrated that the carbapenem resistance-associated plasmids carrying the ISAba1-blaOXA-51-like gene are widespread in A. baumannii strains in Taiwan.
doi:10.1128/AAC.00764-10
PMCID: PMC2976157  PMID: 20713680
18.  Deterioration of the liver biochemistry due to reactivation of chronic hepatitis B during etanercept treatment for rheumatoid arthritis 
BMJ Case Reports  2009;2009:bcr09.2008.0873.
To report a hepatitis B virus (HBV) reactivation during the treatment of etanercept for rheumatoid arthritis (RA).
The chronological course of a patient with RA who developed HBV reactivation associated with etanercept treatment was recorded.
A Taiwanese woman with RA was treated by etanercept. A severe deterioration of liver biochemistry occurred soon after the start of the biologicals because of the previously unrecognised HBV carrier status. The condition was successfully alleviated by oral lamivudine administration.
In the prevalent area of HBV, viral titre monitoring and pre-emptive antiviral treatment may be fundamentally important to avoid serious complications of HBV reactivation whenever a new treatment modality such as biologicals is started for patients with RA.
doi:10.1136/bcr.09.2008.0873
PMCID: PMC3029840  PMID: 21686590
19.  Contribution of a Plasmid-Borne blaOXA-58 Gene with Its Hybrid Promoter Provided by IS1006 and an ISAba3-Like Element to β-Lactam Resistance in Acinetobacter Genomic Species 13TU ▿  
The contribution of the blaOXA-58 gene and its promoter to β-lactam resistance has not been validated in Acinetobacter spp. other than Acinetobacter baumannii. We identified a multidrug-resistant (including carbapenem resistance) Acinetobacter genomic species 13TU in which blaOXA-58 was the only detected carbapenemase gene. The blaOXA-58 gene was plasmid located, flanked by ISAba3 (downstream) and an ISAba3-like element (upstream). An IS1006 element was inserted into ISAba3-like (IS1006-ΔISAba3-like) to generate a hybrid promoter for blaOXA-58, with a −35 promoter located in IS1006 and a −10 promoter in ISAba3-like. The reference strain of Acinetobacter genomic species 13TU, ATCC 17903, revealed higher MICs of amoxicillin, ticarcillin, and piperacillin and heteroresistance to imipenem and meropenem when it was transformed with a shuttle vector containing a fragment encompassing ΔISAba3-like-blaOXA-58, compared to the same host containing only blaOXA-58. When the fragment was changed from ΔISAba3-like-blaOXA-58 to IS1006-ΔISAba3-like-blaOXA-58, the ATCC 17903 transformant revealed a markedly higher level of blaOXA-58 transcription (12-fold), increased cefuroxime and piperacillin-tazobactam MICs, and homoresistance to imipenem and meropenem. Different roles of the insertion elements preceding the blaOXA-58 gene in Acinetobacter genomic species 13TU are demonstrated. The ISAba3-like--blaOXA-58 construct can mediate resistance to penicillin derivatives but only heteroresistance to carbapenems. The insertion of IS1006 into ISAba3-like, generating a hybrid promoter, could further enhance the transcription of blaOXA-58 and mediate homoresistance to carbapenems and also enhanced resistance to piperacillin-tazobactam.
doi:10.1128/AAC.00128-10
PMCID: PMC2916316  PMID: 20516281
20.  Bacteremia Due to Acinetobacter Genomic Species 10▿  
Journal of Clinical Microbiology  2009;48(2):586-590.
Six patients with Acinetobacter genomic species 10 bacteremia were identified. The clinical features of the patients, phenotypic and genotypic identifications, antimicrobial susceptibilities, and genes flanking ISAba1 of the bacteria were described. The results revealed that this bacterium is a potentially lethal pathogen that can cause health care-associated infections in debilitated patients.
doi:10.1128/JCM.01857-09
PMCID: PMC2815618  PMID: 19955266

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