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1.  Complete Sequences of Two Plasmids in a blaNDM-1-Positive Klebsiella oxytoca Isolate from Taiwan 
Genetic determinants of a blaNDM-1-positive, multidrug-resistant bacterial isolate that caused active infection was investigated by DNA sequencing. Two plasmids, pKOX_NDM1 and pKOX-R1, were identified for the Klebsiella oxytoca strain E718. Sequence annotation revealed a blaNDM-1 gene in pKOX_NDM1 and two extended-spectrum β-lactamase producers (blaCTX-M-3 and blaSHV-12) and a wide array of resistance genes in pKOX-R1. These findings highlight the difficulty in treating multidrug-resistant bacterial infections and the potential danger of emerging resistant enterobacteria.
doi:10.1128/AAC.02266-12
PMCID: PMC3719732  PMID: 23752513
3.  Staphylococcal Cassette Chromosome mec in MRSA, Taiwan 
Emerging Infectious Diseases  2007;13(3):494-497.
To determine the predominant staphylococcal cassette chromosome (SCC) mec element in methicillin-resistant Staphylococcus aureus, we typed 190 isolates from a hospital in Taiwan. We found a shift from type IV to type III SCCmec element during 1992–2003, perhaps caused by selective pressure from indiscriminate use of antimicrobial drugs.
doi:10.3201/eid1303.060247
PMCID: PMC2725918  PMID: 17552111
Methicillin-resistant Staphylococcus aureus; multilocus sequence typing; SCCmec; dispatch
4.  Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis 
Emerging Infectious Diseases  2004;10(7):1213-1219.
Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis.
The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 102 to 5.93 x 106 copies/mL) and saliva (7.08 x 103 to 6.38 x 108 copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.
doi:10.3201/eid1007.031113
PMCID: PMC3323313  PMID: 15324540
severe acute respiratory syndrome; SARS; coronavirus; CoV; Taiwan; perspective
5.  Clinical Manifestations, Laboratory Findings, and Treatment Outcomes of SARS Patients 
Emerging Infectious Diseases  2004;10(5):818-824.
Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.
doi:10.3201/eid1005.030640
PMCID: PMC3323212  PMID: 15200814
severe acute respiratory syndrome; C-reactive protein; intravenous immunoglobulin
6.  SARS in Hospital Emergency Room 
Emerging Infectious Diseases  2004;10(5):782-788.
Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.
doi:10.3201/eid1005.030579
PMCID: PMC3323223  PMID: 15200809
Severe acute respiratory syndrome; healthcare workers; environmental contamination; real-time reverse transcriptase–polymerase chain reaction
7.  Early Defervescence and SARS Recovery 
Emerging Infectious Diseases  2004;10(3):544-545.
doi:10.3201/eid1003.030500
PMCID: PMC3322783  PMID: 15116707
SARS; atypical presentation; temporary defervescence
8.  Daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bacteremia: systematic review and meta-analysis 
BMC Infectious Diseases  2014;14(1):687.
Background
Linezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Meanwhile, daptomycin exerts bactericidal activity against VRE, but is not approved for the treatment of VRE bacteremia. Only a few studies with small sample sizes have compared the effectiveness of these drugs for treatment of VRE bacteremia.
Methods
PubMed, EMBASE, and the Cochrane Library were searched for studies of VRE bacteremia treatment published before January 1, 2014. All studies reporting daptomycin and linezolid treatment outcomes simultaneously were included. The endpoints were mortality and microbiological cure. The adjusted odds ratios (aORs) of mortality in daptomycin- and linezolid-treated patients were extracted if available. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for all outcomes using a random-effects model.
Results
Thirteen studies (532 patients receiving daptomycin, 656 patients receiving linezolid) met the selection criteria. All studies had retrospective cohort designs and relatively small sample sizes. Eight studies compared the aORs of mortality in daptomycin- and linezolid-treated patients. Four studies were published as conference papers and there was significant heterogeneity among these studies (I2 = 63%, p = 0.04). Daptomycin use was not associated with better microbiological cure (daptomycin vs. linezolid, OR: 0.67, 95% CI: 0.42–1.06, p = 0.09). However, mortality was higher in patients receiving daptomycin (OR: 1.43, 95% CI: 1.09–1.86, p = 0.009). Subgroup analysis of studies that reported aORs indicated that daptomycin was associated with higher mortality (OR: 1.59, 95% CI: 1.02–2.50, p = 0.04). There was no evidence of publication bias, but all enrolled studies were retrospective, had small sample sizes, and had substantial limitations.
Conclusions
Although limited data is available, the current meta-analysis shows that linezolid treatment for VRE bacteremia was associated with a lower mortality than daptomycin treatment. However, the results should be interpreted cautiously because of limitations inherent to retrospective studies and the high heterogeneity among studies. A large randomized trial is needed to confirm the present results.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0687-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-014-0687-9
PMCID: PMC4269951  PMID: 25495779
Daptomycin; Linezolid; Meta-analysis; Vancomycin-resistant enterococci
9.  Antimicrobial susceptibilities of Proteus mirabilis: a longitudinal nationwide study from the Taiwan surveillance of antimicrobial resistance (TSAR) program 
BMC Infectious Diseases  2014;14(1):486.
Background
Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) β-lactam breakpoints on susceptibility rates and on detecting extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues.
Methods
Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC β-lactamases gene detection by PCR. Univariate and multivariate analyses were performed.
Results
Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P < 0.01). The revised CLSI breakpoints had significant impact on susceptibility to cefazolin (2009 vs. current breakpoints, 71.9% vs. 0.9%) and imipenem (99.8% vs. 55.1%) (P < 0.001 for both). However, using the 2014 cefazolin breakpoints for urinary tract infections, 81.2% of the urine isolates were susceptible. Susceptibilities of isolates from different specimen types were mostly similar but outpatient isolates were more susceptible than inpatient isolates. The overall prevalence of ESBL- and AmpC- producers was 8.2% and 4.7%, respectively, but AmpC carriage increased significantly over the years (from 0 to 7.0%, P < 0.001). ESBL and AmpC β-lactamase-producers were more likely to be found in elderly and ICU patients. The predominant ESBL and AmpC β-lactamase genes were CTX-M- and CMY- types, respectively.
Conclusions
A significant decrease in susceptibility to 3rd-generation cephalosporins and ciprofloxacin occurred in P. mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC β-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these β-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.
doi:10.1186/1471-2334-14-486
PMCID: PMC4162950  PMID: 25192738
Drug resistance; Extended-spectrum β-lactamase; AmpC β-lactamase; Proteus mirabilis; Clinical and Laboratory Standards Institute (CLSI)
10.  Two distinct Do-Not-Resuscitate protocols leaving less to the imagination: an observational study using propensity score matching 
BMC Medicine  2014;12(1):146.
Background
Do-Not-Resuscitate (DNR) patients tend to receive less medical care after the order is written. To provide a clearer approach, the Ohio Department of Health adopted the Do-Not-Resuscitate law in 1998, indicating two distinct protocols of DNR orders that allow DNR patients to choose the medical care: DNR Comfort Care (DNRCC), implying DNRCC patients receive only comfort care after the order is written; and DNR Comfort Care-Arrest (DNRCC-Arrest), implying that DNRCC-Arrest patients are eligible to receive aggressive interventions until cardiac or respiratory arrest. The aim of this study was to examine the medical care provided to patients with these two distinct protocols of DNR orders.
Methods
Data were collected from August 2002 to December 2005 at a medical intensive care unit in a university-affiliated teaching hospital. In total, 188 DNRCC-Arrest patients, 88 DNRCC patients, and 2,051 non-DNR patients were included. Propensity score matching using multivariate logistic regression was used to balance the confounding variables between the 188 DNRCC-Arrest and 2,051 non-DNR patients, and between the 88 DNRCC and 2,051 non-DNR patients. The daily cost of intensive care unit (ICU) stay, the daily cost of hospital stay, the daily discretionary cost of ICU stay, six aggressive interventions, and three comfort care measures were used to indicate the medical care patients received. The association of each continuous variable and categorical variable with having a DNR order written was analyzed using Student’s t-test and the χ2 test, respectively. The six aggressive interventions and three comfort care measures performed before and after the order was initiated were compared using McNemar’s test.
Results
DNRCC patients received significantly fewer aggressive interventions and more comfort care after the order was initiated. By contrast, for DNRCC-Arrest patients, the six aggressive interventions provided were not significantly decreased, but the three comfort care measures were significantly increased after the order was initiated. In addition, the three medical costs were not significantly different between DNRCC and non-DNR patients, or between DNRCC-Arrest and non-DNR patients.
Conclusions
When medical care provided to DNR patients is clearly indicated, healthcare professionals will provide the medical care determined by patient/surrogate decision-makers and healthcare professionals, rather than blindly decreasing medical care.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0146-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-014-0146-x
PMCID: PMC4156651  PMID: 25175307
Medical care; Cardiopulmonary resuscitation; Do-Not-Resuscitate
11.  Epidemiology and Molecular Characterization of Macrolide-Resistant Streptococcus pyogenes in Taiwan 
Journal of Clinical Microbiology  2014;52(2):508-516.
Our multicenter nationwide surveillance data indicated that erythromycin (ERY) resistance among group A Streptococcus (GAS) isolates in Taiwan declined from 53.1% in 1998 and 2000 to 14.6% in 2002 and 2004 and 10.7% in 2006 to 2010 (P < 0.01). The present study aimed to assess the epidemiology of GAS in Taiwan and identify factors associated with ERY resistance. All 127 ERY-resistant (ERYr) isolates and 128 randomly selected ERY-susceptible (ERYs) isolates recovered from 1998 to 2010 were emm typed. ERYr isolates were also characterized by ERY resistance phenotype and mechanisms and pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing was performed on selected ERYr isolates. The predominant emm types in ERYr isolates were emm22 (n = 33, 26.0%), emm12 (n = 24, 18.9%), emm4 (n = 21, 16.5%), and emm106 (n = 15, 11.8%). In ERYs isolates, emm12 (n = 27, 21.9%), emm1 (n = 18, 14.1%), emm106 (n = 16, 12.5%), and emm11 (n = 9, 7.1%) predominated. The most common ERY resistance phenotype was the M phenotype (resistant to macrolides) (70.9%), with all but one isolate carrying mef(A), followed by the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype (26.8%), with isolates carrying erm(B) or erm(TR). ERYr isolates of the emm12-sequence type 36 (ST36) lineage with the cMLSB phenotype were mostly present before 2004, while those of the emm22-ST46 lineage with the M phenotype predominated in later years. Recovery from respiratory (throat swab) specimens was an independent factor associated with ERY resistance. emm1 and emm11 GAS isolates were significantly associated with ERYs, while emm22 was detected only in ERYr GAS. In addition, emm106 isolates were prevalent among the abscess/pus isolates, whereas emm12 isolates were strongly associated with a respiratory (throat) origin. In addition to identifying factors associated with ERY resistance in GAS, our study provides helpful information on the changing GAS epidemiology in Taiwan.
doi:10.1128/JCM.02383-13
PMCID: PMC3911310  PMID: 24478481
12.  Differential Impact of Resistance-Associated Mutations to Protease Inhibitors and Nonnucleoside Reverse Transcriptase Inhibitors on HIV-1 Replication Capacity 
AIDS Research and Human Retroviruses  2013;29(8):1117-1122.
Abstract
The effects of drug resistance on HIV-1 replication capacity have been studied, but data from clinical isolates are few. We accessed the patients with HIV-1 infection at the National Taiwan University Hospital who experienced virological failure. Genotypic susceptibility and replication capacity of clinical HIV-1 isolates were measured. There were 80 patients enrolled between September 2007 and August 2010. The HIV-1 replication capacity declined significantly with the increasing number of major resistance-associated mutations (RAMs) to protease inhibitors (PIs) (p<0.001); however, it did not decline significantly with the increasing RAMs to first-line nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) (p=0.098). Regarding the effects of resistance to antiretroviral drugs in salvage therapy, decreased replication capacity was noted with the increasing RAMs to darunavir/ritonavir (p<0.001) and specific RAMs (L100I, K101P, and Y181C/I/V) to etravirine (p<0.001). Although NNRTI-related RAMs have less remarkable effects, both PI- and NNRTI-related RAMs reduced replication capacity, especially RAMs to darunavir/ritonavir and etravirine, which are commonly used in salvage therapy for treatment of patients infected with highly resistant HIV. Thus, decreased viral fitness during the emergence of RAMs suggests the importance of continued optimal antiretroviral treatment even when virological failure was noted.
doi:10.1089/aid.2013.0038
PMCID: PMC3715794  PMID: 23594266
13.  Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example 
BMC Medical Ethics  2014;15:21.
Background
Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan.
Methods
Taiwan’s extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan’s crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression.
Results
The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan’s crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan’s and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan’s trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance.
Conclusions
Significant social events, such as a well-known person’s successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of life-sustaining treatment such as extracorporeal membrane oxygenation.
doi:10.1186/1472-6939-15-21
PMCID: PMC3975881  PMID: 24592981
Life-sustaining treatment; Extra-corporeal membrane oxygenation; Cardiopulmonary resuscitation; Media; Trend
14.  Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis 
BMC Infectious Diseases  2014;14:102.
Background
Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.
Methods
The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009–2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.
Results
A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% – 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).
Conclusions
Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.
doi:10.1186/1471-2334-14-102
PMCID: PMC3936940  PMID: 24564226
Acinetobacter baumannii; Pneumonia; Colistin; Tigecycline; Mortality; Nephrotoxicity
15.  Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy 
Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART).
Methods: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes.
Results: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23–4.78] and 3.58 [95% CI. 1.76–7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60–3.64] and 3.62 [95% CI, 1.11–11.81], respectively).
Conclusions: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses.
doi:10.4161/hv.22836
PMCID: PMC3859763  PMID: 23291936
Streptococcus pneumoniae; pneumococcal conjugate vaccine; pneumococcal polysaccharide vaccine; HIV infection; immunogenicity; combination antiretroviral therapy
16.  Slow immunological progression in HIV-1 CRF07_BC-infected injecting drug users 
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused serious HIV-1 epidemics among injecting drug users (IDUs) in East Asia. Little is known about the characteristics of the virus and its impact on disease progression among the infected individuals. In this study, we compared immunological progression between 423 IDUs infected with CRF07_BC and 194 men who have sex with men (MSM) with primary subtype B infection, and a representative full-length CRF07_BC molecular clone, pCRF07_BC, was constructed to characterize the virus. We found that IDUs infected with CRF07_BC had significantly slower immunological progression in the Cox proportional hazards model (hazard ratio: 0.30; 95% confidence interval: 0.13–0.69; P=0.004). The constructed recombinant CRF07_BC viruses had a reduced processing of the Gag/Gag-Pol polyproteins, a decreased incorporation of Vpr in the virus particle, tethering of virus particles on the plasma membrane and decreased virus growth kinetics. These phenotypes are related to the unique 7-amino acid deletion in the p6 of CRF07_BC, since complementation of the 7-amino acid in pCRF07_BC could improve the defective phenotypes. In summary, compared with MSM infected with HIV-1 subtype B, IDUs infected with CRF07_BC had slower immunological progression, which is likely correlated with interference of virus particle maturation by the 7-amino acid deletion in p6.
doi:10.1038/emi.2013.83
PMCID: PMC3880871
disease progression; growth kinetics; HIV subtype; injecting drug use; men who have sex with men; primary HIV infection
17.  Excess Mortality and Long-Term Disability from Healthcare-Associated Staphylococcus aureus Infections: A Population-Based Matched Cohort Study 
PLoS ONE  2013;8(8):e71055.
Background
Staphylococcus aureus is a leading cause of healthcare-associated infections (HAIs), but the impact of S. aureus HAIs on the long-term survival and functional status of hospitalized patients remain unknown. This study aimed to examine whether S. aureus HAIs increase the risks for long-term mortality and disability.
Methods
We conducted a retrospective population-based matched cohort study of inpatients at 8 medical centers, 43 regional hospitals, and 63 local hospitals which participated in the Taiwan Nosocomial Infection Surveillance (TNIS). We individually matched 3070 patients with S. aureus HAIs to 6140 inpatients without HAIs at a 1∶2 ratio by age, gender, hospital, specialty, underlying diseases, and the length of stay before onset of the S. aureus HAI. Main outcome measures are one-year excess risks for mortality, new-onset chronic ventilator dependence, and new-onset dialysis-dependent end-stage renal disease.
Results
We found that patients with S. aureus HAIs had an excess one-year mortality of 20.2% compared with matched uninfected inpatients (P<0.001). The excess risk for new-onset chronic ventilator dependence and dialysis-dependent end-stage renal disease was 7.3% and 2.6%, respectively (Ps<0.001). S. aureus HAIs were also associated with an excess hospital stay of 12 days and an extra cost of $5978 (Ps<0.001).
Conclusion
S. aureus HAIs have substantial negative effect on the long-term outcome of hospitalized patients in terms of both mortality and disability, which should be taken into consideration in future cost-effectiveness studies of the control and prevention interventions for S. aureus HAIs.
doi:10.1371/journal.pone.0071055
PMCID: PMC3735502  PMID: 23940689
18.  Clinical and Microbiological Characteristics of Perianal Infections in Adult Patients with Acute Leukemia 
PLoS ONE  2013;8(4):e60624.
Background
Perianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed.
Method
The medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed.
Result
The prevalence of perianal infection was 6.7% (74 of 1102) in adult patients with acute leukemia. Twenty-three (31%) of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028). More than half (n = 61, 53%) of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%), anaerobes (n = 18, 15%) and Candida (n = 1, 1%) from pus culture. Eighteen patients experienced bacteremia (n = 24) or candidemia (n = 1). Overall 41 (68%) of 60 patients had polymicrobial infection. Escherichia coli (25%) was the most common micro-organism isolated, followed by Enterococcus species (22%), Klebsiella pneumoniae (13%), and Bacteroides species (11%). Twenty-five (34%) of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067). Four (5%) patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years) (p = 0.015) and patients with shock (p<0.001) had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016).
Conclusion
Perianal infections were common and had high recurrence rate in adult patients with acute leukemia. Empirical broad-spectrum antibiotics with anaerobic coverage should be considered. Shock independently predicted 30-day crude mortality. Surgical intervention for perianal infection remains challenging in patients with acute leukemia.
doi:10.1371/journal.pone.0060624
PMCID: PMC3618431  PMID: 23577135
19.  Complete Genome Sequence of Klebsiella oxytoca E718, a New Delhi Metallo-β-Lactamase-1-Producing Nosocomial Strain 
Journal of Bacteriology  2012;194(19):5454.
We report the complete genome sequence of Klebsiella oxytoca E718, a New Delhi metallo-β-lactamase-1 (NDM-1)-producing strain isolated from a renal transplant patient. The genome contains a 6,097,032-bp chromosome and two multidrug resistance plasmids with sizes of 324,906 bp and 110,781 bp.
doi:10.1128/JB.01216-12
PMCID: PMC3457199  PMID: 22965083
20.  Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients 
Background
Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.
Methods
A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.
Results
A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3–53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.
Conclusions
Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.
doi:10.1186/1471-2334-13-66
PMCID: PMC3571896  PMID: 23379510
Daptomycin; High dose; Creatine phosphokinase; Treatment outcomes
21.  Compliance of Health Care Workers with Hand Hygiene Practices: Independent Advantages of Overt and Covert Observers 
PLoS ONE  2013;8(1):e53746.
Background
Evaluation and feedback of hand hygiene (HH) compliance are important elements of the WHO multimodal strategy for hospital infection control. Overt observation is recommended, but it may be confounded by Hawthorne effect. Covert observation offers the opportunity to decrease observer bias. In this study we conducted a one year hospital-wide HH promotion program that included medical students (MS) as covert observers.
Methods
HH compliance for the five WHO indications was determined by trained and validated observers. The overt observers consisted of eleven infection control nurses (ICNs) and two unit HH ambassadors (UAs) in each of 83 wards. The covert observers consisted of nine MS during their rotating clinical clerkships. Feedback was provided to department heads and staff each quarter.
Results
Of the 23,333 HH observations 76.0% were by MS, 5.3% by ICNs and 18.7% by UAs. The annual compliance rates were MS 44.1%, ICNs 74.4% and UAs 94.1%; P<0.001. The MS found significantly lower annual compliance rates for 4/5 HH indications compared to ICNs and UAs; P<0.05. The ICNs reported significantly improvement from the first to the fourth quarter; P<0.001. This was associated with feedback from the MS of very poor compliance by nurses during the first quarter.
Conclusions
Based on these findings we recommend a two-pronged approach to HH programs. The role of ICNs and UAs is to educate, serve as role models, establish, sustain good HH practices and provide direct feedback. The role of the covert observers is to measure compliance and provide independent feedback.
doi:10.1371/journal.pone.0053746
PMCID: PMC3544847  PMID: 23341991
22.  Incidence of and Risk Factors for Infection or Colonization of Vancomycin-Resistant Enterococci in Patients in the Intensive Care Unit 
PLoS ONE  2012;7(10):e47297.
The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1st April 2008 to 31st March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4–29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.
doi:10.1371/journal.pone.0047297
PMCID: PMC3468570  PMID: 23071778
23.  Recent Hepatitis C Virus Infections in HIV-Infected Patients in Taiwan: Incidence and Risk Factors 
Journal of Clinical Microbiology  2012;50(3):781-787.
Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-infected men who have sex with men (MSM) in Europe, Australia, and North America. Little is known concerning whether this also occurs in other Asia-Pacific countries. Between 1994 and 2010, a prospective observational cohort study was performed to assess the incidence of recent HCV seroconversion in 892 HIV-infected patients (731 MSM and 161 heterosexuals) who were not injecting drug users. A nested case-control study was conducted to identify associated factors with recent HCV seroconversion, and phylogenetic analysis was performed using NS5B sequences amplified from seroconverters. During a total followup duration of 4,270 person-years (PY), 30 patients (3.36%) had HCV seroconversion, with an overall incidence rate of 7.03 per 1,000 PY. The rate increased from 0 in 1994 to 2000 and 2.29 in 2001 to 2005 to 10.13 per 1,000 PY in 2006 to 2010 (P < 0.05). After adjustment for age and HIV transmission route, recent syphilis remained an independent factor associated with HCV seroconversion (odds ratio, 7.731; 95% confidence interval, 3.131 to 19.086; P < 0.01). In a nested case-control study, seroconverters had higher aminotranferase levels and were more likely to have CD4 ≥ 200 cells/μl and recent syphilis than nonseroconverters (P < 0.05). Among the 21 patients with HCV viremia, phylogenetic analysis revealed 7 HCV transmission clusters or pairs (4 within genotype 1b, 2 within genotype 2a, and 1 within genotype 3a). The incidence of HCV seroconversion that is associated with recent syphilis is increasing among HIV-infected patients in Taiwan.
doi:10.1128/JCM.06014-11
PMCID: PMC3295121  PMID: 22189113
24.  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
25.  Increase of Carbapenem-Resistant Acinetobacter baumannii Infection in Acute Care Hospitals in Taiwan: Association with Hospital Antimicrobial Usage 
PLoS ONE  2012;7(5):e37788.
Objective
Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as an important pathogen causing healthcare-associated infections (HAIs) in Taiwan. The present study is aimed to investigate the epidemiology of HAIs caused by CRAB and the association of CRAB infection and hospital usage of different antimicrobials.
Methods
Two nationwide databases in the period 2003 to 2008, the Taiwan Nosocomial Infection Surveillance System and National Health Insurance claim data, were used for analysis. A total of 13,811 healthcare-associated A. baumannii infections and antimicrobial usage data from 121 hospitals were analyzed.
Results
There was a significant increase in the proportion of number of HAIs caused by CRAB over that by all A. baumannii (CRABpAB), from 14% in 2003 to 46% in 2008 (P<0.0001). The greatest increase was in central Taiwan, from 4% in 2003 to 62% in 2008 (P<0.0001). Use of anti-pseudomonal carbapenems, but not other classes of antibiotics, was significantly correlated with the increase of CRABpAB (r = 0.86, P<0.0001).
Conclusions
We suggested that dedicated use of anti-pseudomonal carbapenems would be an important intervention to control the increase of CRABpAB.
doi:10.1371/journal.pone.0037788
PMCID: PMC3357347  PMID: 22629456

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