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s Background Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. Methods This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. Results A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. Conclusion Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Background: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited. Methods: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided. Keywords: Clostridium difficile, Diarrhea, CDI, Infectious diarrhea

Yu-Ting Tseng,1,2 Pei-Yun Chou,1 Ming-Hong Tai,2,3 Chia-Yen Dai,4– 6 Susan Shin-Jung Lee,1,7 Yao-Shen Chen,1,7 Hung-Chin Tsai,1,3,7,8,* Yen-Hsu Chen2,6,9– 13,* 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 8Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanEmail hctsai1011@yahoo.com.twYen-Hsu ChenGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanEmail infchen@gmail.comBackground: The Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.Methods: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.Results: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986– 19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033– 26,150 ng/mL] vs 3489 ng/mL [IQR 924– 160,640] ng/mL, p = 0.0059, 95% CI 4002– 17,098 ng/mL, area under the curve 0.799, 95% CI 0.632– 0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).Conclusion: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.Keywords: C-reactive protein, Jarisch-Herxheimer reaction, syphilis

Background: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. Methods: Medical records of adult JE patients with acute encephalitis syndrome during 2001–2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. Results: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. Conclusion: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients. Keywords: Adult, Japanese encephalitis, Outcome, Prognostic factor

Purpose The role of pathogenic Escherichia coli colonization in asymptomatic pregnant women is not well understood. The purpose of this work was to determine the prevalence, antimicrobial susceptibility, and neonatal outcomes of pathogenic E. coli colonization in pregnant women. Patients and methods A total of 137 women from southern Taiwan with singleton pregnancies were enrolled between March 2016 and June 2017. The women were prospectively screened for E. coli colonization in the rectovaginal region during prenatal examination. The exclusion criteria are twin pregnancy of the mother and major anomaly of the neonate. All E. coli isolates were identified as either pathogenic or commensal strains, and their susceptibility to various antimicrobials was investigated. Clinical data of the infants were retrieved from their medical records. Results Results showed that 35.8% of asymptomatic pregnant women had pathogenic E. coli colonization in the rectovaginal region. Neonates born to such mothers showed significant morbidities, including hospitalization (OR= 3.74, 95% CI= 1.18~11.87), hyperbilirubinemia (OR= 2.81, 95% CI= 1.24~6.38), and gastrointestinal symptoms (OR= 5.53, 95% CI= 1.39~21.94). Maternal colonization with pathogenic E. coli at rectoanal site was a risk factor for neonatal hyperbilirubinemia after Benjamini-Hochberg (BH) adjustment (52% vs 24%, adjusted P= 0.048). Conclusion The prevalence of pathogenic E. coli colonization in Taiwanese asymptomatic pregnant women was high, and the neonates born to colonized mothers exhibited potential neonatal morbidities. Larger studies are necessary to confirm these findings.

Background: The incidence of non-tuberculous mycobacterial (NTM) infections of the skin, soft tissue, and musculoskeletal system (SSTI) has increased over the past two decades, however, re...

Background The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. Methods TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. Results Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012–2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007–2011) and period 2 (2012–2015). Conclusions A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.

Purpose: Fecal carriage of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

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

BackgroundMycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB.MethodsWe performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010–2017 at seven hospitals across Taiwan.ResultsIn total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%.ConclusionsThe dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.

Background: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichiacoli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichiacoli (NESBLEC). Methods: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. Results: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p &lt, 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1&ndash, 18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). Conclusion: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.

Hung-Chin Tsai,1– 4 I-Tzu Chen,1 Kuo-Wang Tsai,5 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, TaiwanCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, #386 Ta-Chung 1st Road, Kaohsiung 813, TaiwanTel +886 7 3422121 ext. 2029Fax +886 7 346 8292Email hctsai1011@yahoo.com.twPurpose: Integrase strand transfer inhibitors (INSTIs) are used as first-line therapy for HIV-1-infected patients. Next-generation sequencing (NGS) can detect low-frequency mutants; however, the clinical value of NGS to detect resistance variants is unknown. This study aimed to evaluate the prevalence of INSTI resistance in southern Taiwan and determine the clinical implications of using NGS to detect integrase region low-level resistant variants.Patients and Methods: This retrospective cohort study included antiretroviral therapy-naïve HIV-1-infected individuals at Kaohsiung Veterans General Hospital, Taiwan, from 2013 to 2017. Drug-resistance mutations were determined, and an in-house polymerase chain reaction was used for genotyping INSTI resistance. NGS was used to assess INSTI resistance (≧1%), and the results were compared with those from population sequencing. Drug resistance-associated mutations were defined according to the 2019 IAS-USA HIV drug resistance-associated mutations list, and accessory mutations by a Stanford HIVdb score ≥ 10 to at least one INSTI.Results: A total of 224 patients were included. Subtype B HIV-1 strains were found in 96% of the individuals and subtype CRF01_AE in 4%. The prevalence rates for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and INSTI resistance were 4%, 5.8%, 0.4% and 0.9%, respectively. The most common INSTI resistance-associated mutations were G163K (0.4%) and E138A (0.4%). Of the 38 patients diagnosed in 2017 who had both NGS and population sequencing data, none had INSTI resistance-associated mutations by population sequencing; however, NGS detected four more INSTI resistance-associated mutations with low frequencies (G163R 3.25%, S153F 3.21%, S153Y 1.36% and Y143H 2.06%). Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy, and none had virological failure by week 48.Conclusion: Our findings showed a low rate of HIV drug resistance to INSTIs (0.9%) in treatment-naïve patients. NGS detected more INSTI resistance-associated mutations at a low frequency. Low-level drug resistance-associated mutations to INSTIs identified by NGS did not have an impact on the treatment response to INSTI-based first-line therapy.Keywords: HIV, integrase strand transfer inhibitor, drug resistance, next-generation sequencing

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC–lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC–lung disease.

Background/Purpose: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. This study investigated the clinical features and bacteriology of pediatric patients with ESBL-producing E. coli bacteremia and compared their characteristics with those of adult patients. Methods: Clinical and laboratory data from all of the 41 patients aged ≤18 years diagnosed with E. coli bacteremia were collected over 5 years. Patients aged >18 years diagnosed with E. coli bacteremia, matched 1:1 for calendar time, were enrolled as the adult group. All E. coli isolates were tested for their blaCTX-M group and sequence type 131 (ST131). A novel seven-single nucleotide polymorphism-based clonotyping test was applied to detect the septatypes of each isolate. Results: In the adult group, patients with ESBL-producing E. coli bacteremia had more previous hospitalizations and antimicrobial agent use than did those with non-ESBL-producing E. coli bacteremia, but these differences were not found in pediatric group. In the pediatric group, the proportion of isolates producing CTX-M group 9 was higher than that in the adult group (85.7% vs. 42.9%; p

Hung-Chin Tsai,1–3 I-Tzu Chen,1 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan Purpose: Sparse data are available on the prevalence of resistance among HIV-1-infected patients with virological failure to a single-tablet regimen (STR). This study aimed to evaluate the prevalence of HIV genotypic drug resistance in HIV-1-infected patients with virological failure to STRs in southern Taiwan. Patients and methods: This retrospective study investigated drug resistance in patients with virological failure to STR from January 2016 to September 2017. Antiretroviral resistance mutations were defined using the 2017 International AIDS Society-USA HIV drug resistance algorithm, and drug resistance was compared using the HIVdb program of the Stanford University HIV Drug Resistance Database. Variables between resistance and non-resistance groups were compared. Results: Thirty-nine HIV-1-infected patients with treatment failure were tested for resistance, of whom 89% were infected by men who have sex with men. Subtype B HIV-1 strains were found in 90% of the patients. Eight patients were treatment naïve and initiated STRs, while 31 patients experienced treatment failure after switching to STRs. Eighty-seven percent of the patients harbored any of four classes of resistance (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors (PIs), and integrase strand transfer inhibitors). The prevalence rates of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, PI, and integrase strand transfer inhibitor resistance were 72%, 82%, 10%, and 3%, respectively. Patients with PI resistance were more likely to respond to treatment with a non-tenofovir disoproxil fumarate/emtricitabine/efavirenz-based STR (P=0.004) and a longer duration of antiretroviral therapy (101 months [72.0–123.3] vs 11 months [7–44], P=0.007). There were no associations between different STRs and transmission risk factors, HIV subtype, duration of antiretroviral therapy, and resistance to tenofovir disoproxil fumarate. Conclusion: A high rate of antiretroviral drug resistance was found in the patients who failed STR treatment. The presence of PI resistance in these patients represented an inappropriate switch from a multiple tablet regimen to an STR. These findings should remind clinicians that detailed drug resistance history and close monitoring are mandatory after switching to an STR. Keywords: HIV, single-tablet regimen, drug resistance, treatment failure, antiretroviral therapy

Background Observation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings. Methods A prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables. Results A total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p

Background Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real-world setting. Methods We conducted a 2-year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity ( P Conclusions The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large-scale observation.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform β and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 β, γ, e, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

BackgroundThe risk of tuberculosis (TB) is higher in human immunodeficiency virus (HIV)-infected patients and intravenous drug users (IDUs). We determined the prevalence and risk factors of latent TB infection (LTBI) in individuals with or without HIV infection, including IDUs, in a country with a low HIV prevalence, an intermediate TB burden, and a high Bacillus Calmette-Guérin (BCG) vaccine coverage using two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST).MethodsFor this prospective, cross-sectional study, HIV-infected and -uninfected patients from a regional hospital and medical center in Taiwan were enrolled. Results of the two IGRAs [QuantiFERON-TB Gold (QFT-G) and QuantiFERON-TB Gold In-Tube (QFT-GIT)] and the TST were compared. Risk factors for positivity were analyzed.ResultsWe recruited 233 patients [198 (85%) men; mean age, 39.4 years]. Most patients (74%) were BCG vaccinated. The prevalence of LTBI was estimated to be 22.8% by TST, 15.9% by QFT-G, and 20.6% by QFT-GIT. HIV-infected individuals had fewer positive QFT-GIT [7.0% vs. 28.6%, p

Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management.A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012.Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations.The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.

Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and β-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 μg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any β-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations ( P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 μg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.

Hand hygiene (HH) is considered to be the most simple, rapid, and economic way to prevent health care-associated infection (HAI). However, poor HH compliance has been repeatedly reported. Our objective was to evaluate the impact of implementing the updated World Health Organization (WHO) multimodal HH guidelines on HH compliance and HAI in a tertiary hospital in Taiwan.We conducted a before-and-after interventional study during 2010-2011. A multimodal HH promotion campaign was initiated. Key strategies included providing alcohol-based handrub dispensers at points of care, designing educational programs tailored to the needs of different health care workers, placement of general and individual reminders in the workplace, and establishment of evaluation and feedback for HH compliance and infection rates.Overall HH compliance increased from 62.3% to 73.3% after 1 year of intervention (P .001). The rate of overall HAI decreased from 3.7% to 3.1% (P .05), urinary tract infection rate decreased from 1.5% to 1.2% (P .05), and respiratory tract infection rate decreased from 0.53% to 0.35% (P .05). This campaign saved an estimated $940,000 and 3,564 admission patient days per year.The WHO multimodal HH guidelines are feasible and effective for the promotion of HH compliance and are associated with the reduction of HAIs.

This case report describes a methicillin-resistant Staphylococcus aureus isolated repeatedly from the blood of a patient with community-acquired endocarditis who developed a four-fold increase in the minimal inhibitory concentration of vancomycin and daptomycin 7 months after his last exposure to glycopeptide antibiotics. This is contrary to the expected situation in which antimicrobial resistance tends to decrease after a patient is no longer exposed to vancomycin.

Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a significant pathogen causing healthcare-associated infections. Matrix-assisted laser desorption/ionisation mass spectrometry time-of-flight mass spectrometry (MALDI-TOF MS) is used by clinical microbiology laboratories to address the need for rapid, cost-effective and accurate identification of microorganisms. We evaluated application of machine learning methods for differentiation of drug resistant bacteria from susceptible ones directly using the profile spectra of whole cells MALDI-TOF MS in 46 CRKP and 49 CSKP isolates. Methods We developed a two-step strategy for data preprocessing consisting of peak matching and a feature selection step before supervised machine learning analysis. Subsequently, five machine learning algorithms were used for classification. Results Random forest (RF) outperformed other four algorithms. Using RF algorithm, we correctly identified 93% of the CRKP and 100% of the CSKP isolates with an overall classification accuracy rate of 97% when 80 peaks were selected as input features. Conclusions We conclude that CRKPs can be differentiated from CSKPs through RF analysis. We used direct colony method, and only one spectrum for an isolate for analysis, without modification of current protocol. This allows the technique to be easily incorporated into clinical practice in the future.

Executive Summary: Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia. Keywords: Pneumonia, Guidelines, Treatment, Taiwan

BACKGROUND Escherichia coli sero-group O25b-sequence type 131 (O25b-ST131), a multidrug-resistant clonal group, is a significant pathogen in adults and children. This study investigated the genotyping and role of extended spectrum β-lactamase (ESBL)-producing E. coli O25b-ST131 and non-O25b-ST131 in urinary tract infections in infants. METHODS Clinical and laboratory data from 111 infants less than 1 year of age, who were hospitalized for urinary tract infections caused by ESBL-producing E. coli between 2009 and 2012 were collected. Polymerase chain reactions and multi-locus sequence typing were used to identify E. coli O25-ST131 clones. The gene blaCTX-M groups 1, 2 and 9, a specific polymerase chain reaction of CTX-M 14 and 15, were also determined in ESBL-producing E. coli isolates. RESULTS O25b-ST131 accounted for 65% of the 111 isolates, although 92 isolates belonged to the blaCTX-M group 9, of which most were CTX-M-14. Those with O25b-ST131 clones had similar risk factors, clinical features and outcomes as those with non-O25b-ST131. The E. coli O25b-ST131 isolates were more resistant to ciprofloxacin and gentamicin, but more susceptible to cefoxitin, minocycline and trimethoprim/sulfamethoxazole than the non-O25b-ST131 isolates. Most of the infants (78%) were previously healthy with no apparent risk factors. CONCLUSIONS E. coli O25b-ST131 is a major community-acquired uropathogen in the infant population. Regardless of O25b-ST131 or non-O25b-ST131 clones, CTX-M-14 accounts for majority of the ESBL genotype. The O25b-ST131 clone is not associated with more severe clinical disease, but it may make the diagnosis and selection of antimicrobials for treatment more challenging.

Background The epidemiology and impact of hepatitis δ virus (HDV) on hepatic outcomes and virological and immunological responses to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients coinfected with hepatitis B virus (HBV) in northern Taiwan have been reported. However, the epidemiology and impact of HDV infection in HIV–HBV coinfection patients in southern Taiwan remains uncertain. Methods In this cohort study, a total of 64 HIV patients coinfected with HBV were identified between January 1, 2009 and May 30, 2012. The seroprevalence of anti-HDV antibodies, HDV genotyping, clinical manifestations and hepatic outcomes were compared between the patients with and without HDV coinfection, and laboratory examinations and hepatic outcomes were recorded. Results Among the 64 HIV patients coinfected with HBV, seven were seropositive for HDV (10.9%). There were no statistically significant differences in risk factors for acquiring HIV infection. During a median observation period of 27.8 months, the adjusted hazard ratio of HDV and HBV genotype (type B vs. non-type B) on hepatitis flare-ups were 62.132 ( p = 0.04) and 0.028 ( p = 0.01), respectively. All seven patients had genotype II and were HDV viremic. The phylogenetic tree analysis and clinical history evaluation did not identify any clusters of HDV infection. Conclusion HDV infection resulted in higher rate of hepatitis flare-ups, but it did not have a statistical significance on HIV progression and immunological response to HAART. Whether higher rate of HDV viremia has worse impact on the hepatic outcomes requires further investigation.

Background Rapid identification of mycobacteria is important for timely treatment and the implementation of public health measures. The MGIT system ensures rapid detection of mycobacteria, but identification is usually delayed by days to weeks due to further subculture on solid medium. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) was demonstrated to effectively identify mycobacteria isolates subcultured from solid or liquid media. Reports of identification directly from MGIT broths of both sterile and non-sterile clinical specimens, omitting the subculture step, were limited and not satisfactory before. Our identification method dramatically shortened delay from detection to identification of mycobacteria. Methodology We assessed the performance of the Vitek MS IVD version 3.0 for direct identification of NTM and M.tuberculosis from primary MGIT cultures, and assessed two sample preparation methods. Results Direct identification of NTM from positive MGIT broths, using MALDI-TOF VITEK MS with IVD v.3.0, generated high rates of acceptable results reaching 96.4% (80/83), and up to 100% (83/83) for sample preparations including a 0.1% SDS washing step. The sensitivity of VITEK MS to identify M.tuberculosis from MGIT tubes was 58/72 (80.6%), when using immunochromatography (ICA) test as gold standard. A characteristic colony clumping, wool-like appearance was observed in 48, and all 58 (100%) were correctly identified as M.tuberculosis using MALDI-TOF. The detection rate of M.tuberculosis complex was low (10/24, 41.6%) in the 24 MGIT tubes that was polymicrobial. Our method significantly reduced both the reagent cost and turnaround time. Conclusions Based on a simplified protocol, we showed that MALDI-TOF MS can be used for rapid identification of NTM directly from primary MGIT cultures within the routine clinical laboratory workflow. However, we recommend an initial ICA test to screen for M.tuberculosis complex, due to a low identification rate of M. tuberculosis in the presence of polymicrobial cultures using MALDI-TOF.

Hung-Chin Tsai,1–3 I-Tzu Chen,1 Kuan-Sheng Wu,1,2 Yu-Ting Tseng,1 Cheng-Len Sy,1 Jui-Kuang Chen,1 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Department of Medicine, Division of Infectious Diseases, Kaohsiung Veterans General Hospital, Kaohsiung, 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. Objectives: This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy.Materials and methods: Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model.Results: From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/µL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p

Background Dengue fever is an important arboviral disease. The clinical manifestations vary from a mild non-specific febrile syndrome to severe life-threatening illness. The virus can usually be detected in the blood during the early stages of the disease. Dengue virus has also been found in isolated cases in the cerebrospinal fluid, urine, nasopharyngeal sections and saliva. In this report, we describe the isolation of dengue virus from the upper respiratory tract of four confirmed cases of dengue. Methods We reviewed all laboratory reports of the isolation of dengue virus from respiratory specimens at the clinical microbiology laboratory of the Kaohsiung Veterans General Hospital during 2007 to 2015. We then examined the medical records of the cases from whom the virus was isolated to determine their demographic characteristics, family contacts, clinical signs and symptoms, course of illness and laboratory findings. Results Dengue virus was identified in four patients from a nasopharyngeal or throat culture. Two were classified as group A dengue (dengue without warning signs), one as group B (dengue with warning signs) and one as group C (severe dengue). All had respiratory symptoms. Half had family members with similar respiratory symptoms during the period of their illnesses. All of the patients recovered uneventfully. Conclusions The isolation of dengue virus from respiratory specimens of patients with cough, rhinorrhea and nasal congestion, although rare, raises the possibility that the virus is capable of transmission by the aerosol route among close contacts. This concept is supported by studies that show that the virus can replicate in cultures of respiratory epithelium and can be transmitted through mucocutaneous exposure to blood from infected patients. However, current evidence is insufficient to prove the hypothesis of transmission through the respiratory route. Further studies will be needed to determine the frequency of respiratory colonization, viable virus titers in respiratory secretions and molecular genetic evidence of transmission among close contacts., Author summary Dengue virus is rarely identified in respiratory specimens. We retrospectively identified four patients with dengue fever who had the virus isolated from their nose or throat. All the patients had respiratory signs or symptoms. Half had family members who also had respiratory symptoms. Further studies are needed to evaluate the possibility of respiratory transmission of this virus.

Background/PurposeHuman immunodeficiency virus (HIV) and syphilis coinfection is a common phenomenon. A percentage of neurosyphilis cases is asymptomatic in HIV-infected patients. The diagnosis of neurosyphilis is more difficult because of the alteration of cerebrospinal fluid (CSF) presentation by the HIV itself. The CSF levels of the degradation products of nitric oxide (NO; e.g., nitrate and nitrite) are reportedly elevated in animals and patients with bacterial meningitis. We hypothesized that an elevated CSF nitrite concentration may be present in patients coinfected with HIV and neurosyphilis.MethodsThis cohort study was conducted from January 2007 to June 2008. Forty patients were enrolled and included seven patients in the control group and 33 HIV-infected patients with or without syphilis. Nitrite levels in the serum and the CSF were measured by using the Griess assay.ResultsThe CSF nitrite levels were significantly higher in HIV-infected patients with neurosyphilis, compared to the control group or patients with HIV infection only or patients with HIV and syphilis coinfection (p = 0.026). The CSF nitrite levels were correlated with the CSF white blood cell counts (Spearman correlation test, r2 = 0.324; p

The potential mechanisms for blood–brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80 %) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21–68) years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92–434) cells/μl. Eight patients (24 %) had neurosyphilis based on a reactive CSF VDRL test (n = 5) or increased CSF white blood cell counts of ≧20 cells/μl (n = 3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p = 0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p = 0.017), CSF white blood cell count (p = 0.001), and CSF protein levels (p = 0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients.

Background Cellulitis is a common infectious disease. Although blood culture is frequently used in the diagnosis and subsequent treatment of cellulitis, it is a contentious diagnostic test. To help clinicians determine which patients should undergo blood culture for the management of cellulitis, a diagnostic scoring system referred to as the Bacteremia Score of Cellulitis was developed. Methods Univariable and multivariable logistic regression analyses were performed as part of a retrospective cohort study of all adults diagnosed with cellulitis in a tertiary teaching hospital in Taiwan in 2013. Patients who underwent blood culture were used to develop a diagnostic prediction model where the main outcome measures were true bacteremia in cellulitis cases. Area under the receiver operating characteristics curve (AUC) was used to demonstrate the predictive power of the model, and bootstrapping was then used to validate the performance. Results Three hundred fifty one cases with cellulitis who underwent blood culture were enrolled. The overall prevalence of true bacteremia was 33/351 cases (9.4 %). Multivariable logistic regression analysis showed optimal diagnostic discrimination for the combination of age ≥65 years (odds ratio [OR] = 3.9; 95 % confidence interval (CI), 1.5–10.1), involvement of non-lower extremities (OR = 4.0; 95 % CI, 1.5–10.6), liver cirrhosis (OR = 6.8; 95 % CI, 1.8–25.3), and systemic inflammatory response syndrome (SIRS) (OR = 15.2; 95 % CI, 4.8–48.0). These four independent factors were included in the initial formula, and the AUC for this combination of factors was 0.867 (95 % CI, 0.806–0.928). The rounded formula was 1 × (age ≥65 years) + 1.5 × (involvement of non-lower extremities) + 2 × (liver cirrhosis) + 2.5 × (SIRS). The overall prevalence of true bacteremia (9.4 %) in this study could be lowered to 1.0 % (low risk group, score ≤1.5) or raised to 14.7 % (medium risk group, score 2–3.5) and 41.2 % (high risk group, score ≥4.0), depending on different clinical scores. Conclusions Determining the risk of bacteremia in patients with cellulitis will allow a more efficient use of blood cultures in the diagnosis and treatment of this condition. External validation of this preliminary scoring system in future trials is needed to optimize the test. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1907-2) contains supplementary material, which is available to authorized users.

Background Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens. Methods We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events. Results During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group (82.9% vs. 85.7%; P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response (hazard ratio: 0.940; P = 0.754). Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients (5145.0 ng/mL vs. 6775.0 ng/mL; P = 0.267). The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups. Conclusions We found that switching from NVP-IR to NVP-XR appeared to have similar safety and efficacy compared with continuing NVP-IR among virologically suppressed, HIV-infected Taiwanese patients. Our finding of higher Ctrough levels in both groups compared with other studies conducted in Caucasian populations and the high prevalence of CYP2B6 516 GT requires further investigation in a larger Taiwanese cohort. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2371-3) contains supplementary material, which is available to authorized users.

Background The transmission of drug-resistant HIV-1 strains might compromise the efficacy of antiretroviral treatment. The aim of this study was to monitor the prevalence of transmitted drug resistance (TDR) in Taiwan, where free highly active antiretroviral therapy (HAART) was provided since 1997. Methods A cohort study on TDR was conducted in antiretroviral therapy -naïve HIV-1 ¡Vinfected voluntary counseling and testing (VCT) clients from 2007 to 2016 in southern Taiwan. Genotypic drug resistance testing to PR/RT (pol gene) were determined by ViroSeqTM system and drug resistance testing to integrase inhibitors (INSTI) was done by in house PCR. Antiretroviral resistance was interpreted using the HIVdb program of the Stanford University HIV Drug Resistance Database. The patients classified as having low-level resistance, intermediate resistance and high-level resistance were defined as having drug resistance. Resistance-associated mutations were defined by the presence of at least one mutation included in the 2017 drug resistance mutation list of the International AIDS Society-USA consensus guidelines. Results A total of 29384 individuals received a free HIV anonymously screening test during 2007 to 2016. The positive rate for HIV-1 infection was 2%. Sequences were obtained from 407 individuals, of whom 90% were infected by MSM, and 10% were infected by heterosexually. Subtype B HIV-1 strains were found in 97%, subtype C in 0.3% and subtype CRF01_AE in 2.7%. A total of 6% was found to harbor drug resistance strains. The most common NRTI resistance associated mutation was D67N, M184V, K219N, Y118I and T215S/P. The most common NNRTI resistance associated mutation was Y181C, K103N, V179D and Y318F. No any one harbored resistance to INSTI inhibitors (n = 188). Conclusion The resistance prevalence (6%) in this study supported the WHO guideline to prescribe pol resistance testing before initiation of HAART therapy in the treatment naïve patients. Disclosures All authors: No reported disclosures.

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p

Background/Purpose Mycobacterium avium complex (MAC) is frequently considered to be a contaminant or transient colonizer. To the best of our knowledge, there have been very few reports regarding the clinical significance of MAC isolates in respiratory specimens, and the associated disease spectrum in Taiwan. The purpose of this study was to investigate the clinical significance of MAC isolates in respiratory specimens. Methods We retrospectively reviewed the medical records of patients in a medical center in Southern Taiwan from whom MAC isolates were recovered from respiratory specimens, and analyzed their clinical features, chest imaging findings, treatment and prognosis. We also performed an antibiotic susceptibility test on our MAC isolates. Results The 64 isolates used in this study were recovered from April to October 2001 from respiratory specimens in 54 patients admitted to Kaohsiung Veterans General Hospital, Taiwan. According to the 2007 criteria of the American Thoracic Society, a total of 12 patients (22.2%) had clinically significant MAC pulmonary disease. Conclusion Despite the increased frequency of recovering MAC from respiratory specimens, most cases did not meet the criteria of American Thoracic Society for clinically significant nontuberculous pulmonary disease. The minimum inhibitory concentrations of drugs against these MAC isolates might help to guide treatment, but further studies should be done.

Cellulomonas spp. are often believed to be of low virulence and have never been reported as a pathogen causing human disease before. We report the first case of endocarditis caused by Cellulomonas and complicated with osteomyelitis of the lumbar spine in a 78-year-old woman. General weakness and aggravated lower back pain followed by sudden-onset of fever and chills were the major presentation. The diagnosis of infective endocarditis in this case was definitely using the Duke criteria. The magnetic resonance imaging of the lumbar spine revealed infective spondylodisciitis at an early stage. After a full course of antibiotics treatment, the patient's fever subsided but her lower back pain persisted. A slow clinical response to appropriate antimicrobial agents was characteristic of Gram-positive bacillary endocarditis.

To quantitate cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase 9 (MMP-9) in adult patients with Klebsiella pneumoniae meningitis and to correlate levels of MMP-9 with parameters of intrathecal inflammation and analyze the kinetic changes of MMP-9. In a prospective cohort study, levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1) concentrations were measured in the CSF of six adult patients with meningitis and 11 controls. MMP-9 and TIMP-1 were detected in all of the six patients at presentation and follow up lumbar puncture. CSF levels of MMP-9 (6.71+/-7.29 ng/ml) and TIMP-1(454.3+/-242.9 ng/ml) were higher in patients than in the control group (0.07+/-0.11 ng/ml and 27.14+/-39.34 ng/ml, respectively). Levels of MMP-9 correlated with CSF concentrations of protein, cell count and lactate. Repeated lumbar punctures showed that levels of MMP-9 decrease during clinical recovery, although the levels of MMP-9 in the CSF are variable because of the small number of cases. The relative change in gelatin zymography is comparable to the changes of MMP-9 levels found in ELISA. MMP-9 levels in CSF may be a useful tool in follow-up in patients with K. pneumoniae meningitis.

Background/Purpose: To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. Methods: During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). Results: Nearly all of the RGM were susceptible to amikacin and ofloxacin (≥90%) and resistant to doxycycline (＜3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and ＜40% of the RGM isolates remained susceptible to imipenem (21-38%). Conclusion: The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time. [J Formos Med Assoc 2008; 107(4):281-287]

Reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates carrying Panton-Valentine leukocidin (PVL) gene that causes infective endocarditis in injection drug users (IDUs) with human immunodeficiency virus (HIV) infection are rare in the English language literature. We present a case of CA-MRSA infective endocarditis with bilateral septic lung emboli in a previously healthy 45-year-old IDU. This case suggests that PVL gene-positive CA-MRSA should be considered as a potential pathogen in IDUs with infective endocarditis.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of vascular endothelial growth factor in eosinophilic meningitis, vascular endothelial growth factor was measured in the cerebrospinal fluid (CSF) and blood of 9 patients with eosinophilic meningitis in a cohort study. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45-2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. These results indicate that vascular endothelial growth factor may be associated with blood-brain barrier disruption in patients with eosinophilic meningitis.

Background The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. Methods We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. Results Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p

Background Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS. Methods A retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs. Results Fifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1 st 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40–10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52–12.14; p = 0.006) were independently associated with ADRs. Conclusion We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

The human immunodeficiency virus type 1 (HIV-1) epidemic in Taiwan is rapidly escalating because of an increasing number of injection drug users (IDUs). A molecular epidemiological study of HIV-1-infected IDUs in Taiwan was conducted from January 2004 to April 2005. Of the 131 HIV-1-positive specimens collected all contained detectable sequences including 105 from the C2-V3 region of env and 87 from the protease and reverse transcriptase genes of pol. Phylogenetic analysis of these sequences indicated that 128 individuals harbored CRF07_BC which resembles the dominant strains circulating among IDUs in China. Twenty-three individuals had a history of travel to the southwest provinces of China and shared needles or apparatuses there. This suggests that CRF07_BC might have been transmitted from China into Taiwan thereby causing an outbreak among IDUs in Taiwan. This is the first report in the English literature of the appearance of HIV-1 CRF07_BC in Taiwan. These provide information relevant to the development of antiviral therapy and vaccine in Taiwan and may assist public health workers in the prevention of HIV-1 spread. (authors)

Invasive aspergillosis is a devastating infection in immunocompromised hosts. The lung is the most common site of primary infection, and the central nervous system is the most common secondary site of invasive disease. Invasive aspergillosis in autoimmunopathies treated with corticosteroids has rarely been reported in the literature. Herein, we report the case of a 48-year-old female patient with idiopathic thrombocytopenic purpura complicated with fatal invasive pulmonary and cerebral aspergillosis. She had been given 1,016 g intravenous amphotericin B empirically for lung infection during a previous admission. At presentation, she had fever, cough, and shortness of breath for 4 weeks. Chest radiography revealed a huge cavity over the left upper lung field. Bronchoscopic biopsy and culture showed Aspergillus species. She was initially treated with intravenous amphotericin B (0.9 mg/kg/day), and intravenous hydrocortisone for her idiopathic thrombocytopenic purpura. However, deterioration of consciousness occurred 12 days after hospitalization. Computed tomography of the brain showed ring-like cystic mass lesions in the right side basal ganglion. Stereotactic aspiration of the brain revealed Aspergillus species. Her condition exacerbated despite combination treatment with high-dose amphotericin B (1.2 mg/kg/day) and itraconazole (400 mg/day). She died 24 days after admission. This case suggests that treatment with corticosteroids and premature discontinuation of antifungal drugs bear the risk of fatal cerebral involvement in patients with invasive pulmonary aspergillosis.