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Hung-Chin Tsai,1– 5 I-Tzu Chen,1 Hui-Min Chang,6– 8 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 Chiao Tung University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; 6Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, TaiwanCorrespondence: Hung-Chin Tsai, Division of Infectious Diseases, Department of Medicine Kaohsiung Veterans General Hospital, #386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan, Tel +886 7 3422121 ext. 2029, Fax +886 7 346 8292, Email hctsai1011@yahoo.com.tw; tsaihungchin@gmail.comPurpose: This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment.Patients and Methods: Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann–Whitney U-test, and categorical variables were compared using the chi-square test or Fisher’s exact test.Results: A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001).Conclusion: Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.Keywords: HIV, doravirine, drug resistance, single-tablet regimen, virological failure

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Candidemia is a life-threatening condition; however, the predictive markers for candidemia and mortality are inadequate in cirrhotic patients. This study was conducted to propose candidate predictors for the occurrence of candidemia and 30-day mortality in hospitalized cirrhotic patients with bloodstream infection (BSI) and review the related literature.Cirrhotic patients with BSI between January 2011 and March 2020 were screened from the databank of a medical center and eligible patients were enrolled. Patients were separated into candidemia and bacteremia groups according to the results of blood cultures. Baseline characteristics, clinical presentation, and biochemistry data were collected at this time, as were microbiological data, medical management, use of antimicrobial agents, and outcome of the patients. The parameters and 30-day mortality were compared between candidemia and bacteremia groups. A combination of the MeSH terms and text terms related to candidemia and cirrhosis was searched in the electronic databases.Four hundred and sixty cirrhotic patients with BSI were enrolled. Thirty-five patients with candidemia (7.6%) were identified. Nosocomial infection, intensive care unit (ICU) admission, antibiotics exposure ≥14 days, white cell count10 K/mm3, and model for end-stage liver disease (MELD) score24 were associated with candidemia. The 30-day mortality was 65.7% in the candidemia group and 37.9% in the bacteremia group (p = 0.001). Nosocomial infection, ICU admission, hepatoma, hepatic encephalopathy, international normalized ratio ≥1.2, platelet ≤150 K/mm3, estimated glomerular filtration rate60 mL/min/1.73m2, and MELD score24 were associated with 30-day mortality. Six studies were identified. The results were consistent with our findings regarding low incidence of candidemia, and relevant risk factors are listed.Candidemia had low incidence but high mortality in hospitalized cirrhotic patients with BSI. New predictors were proposed for the occurrence of candidemia and 30-day mortality in these patients.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Hung-Chin Tsai,1– 5 I-Tzu Chen,1 Hui-Min Chang,6– 8 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 Chiao Tung University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; 6Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, TaiwanCorrespondence: Hung-Chin Tsai, Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan, Tel +886 7 3422121 ext. 2029, Fax +886 7 346 8292, Email hctsai1011@yahoo.com.tw; tsaihungchin@gmail.comBackground: The prevalence of transmitted drug resistance (TDR) after the universal implementation of STRs is unknown in Taiwan.Objective: This study aimed to investigate the prevalence of TDR in patients with HIV-1 infection, clarify the risk factors for pol resistance, and compare differences in HIV drug resistance before and after the implementation of STRs in Taiwan.Methods: Adult patients infected with HIV-1 were enrolled in this study from 2013 to 2021. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database edition 9. A logistic regression model was used to analyze the risk factors for pol resistance, and the differences in the prevalence of drug resistance from 2013– 2016 to 2017– 2021 were compared using the Mann–Whitney U-test. General linear regression was used to analyze temporal changes in the annual proportion of TDR overall and by type of antiretroviral drugs.Results: A total of 369 patients were included. The prevalence rate of pol resistance was 9.8% (36/369). The resistance rates to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 3.3%, 6.9%, 0% and 1.8%, respectively. The patients with hepatitis C infection were more likely to have pol resistance (aHR 5.767, CI 1.232– 26.991, p=0.026). The prevalence rate of pol resistance did not decrease after the implementation of STRs as first-line therapy in 2017 (11.2% vs 8.7%, aHR 1.329, CI 0.667– 2.645, p=0.480), and no significant temporal changes were shown in the annual proportion of TDR overall or by type of antiretroviral drug.Conclusion: Our findings showed a stable prevalence rate of transmitted drug resistance despite the implementation of STRs as the first-line therapy in June 2016.Keywords: HIV, transmitted drug resistance, single-tablet regimen

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

Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

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

BackgroundVarious bacterial putative virulence factors are involved in the pathogenesis of bacterial infection. However, the effect of comorbidities or infection syndrome in the association of virulence factors and mortality remains inconclusive.MethodThis study addressed whether specific sequence type (ST) and virulence factors of extended-spectrum beta-lactamase–producingEscherichia coli(ESBL-EC) are associated with different outcomes in patients with bloodstream infection.121 adults from southern Taiwan with ESBL-producingE. colibloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing.ResultPositivity for the virulence genes iha,hlyD,sat,iut,fyu,malX,ompT,uspandtraTwas associated with ST131 positivity (PiroNandisswas significantly associated with increased 30-day mortality (death within 30 days) on univariate analysis (PiroNpositivity.ConclusionIn bacteremic patients with UTI, and the ST131 clone was borderline associated with mortality. Positivity for the virulence geneiroNmay be linked to mortality in bacteremic patients without UTI.

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.

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,&ast; Yen-Hsu Chen2,6,9– 13,&ast; 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&ast;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

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

Chih-Cheng Lai,1 Ying-Sheng Chen,2 Nan-Yao Lee,3 Hung-Jen Tang,4,5 Susan Shin-Jung Lee,6,7 Chin-Fu Lin,8 Po-Liang Lu,9–11 Jiunn-Jong Wu,12 Wen-Chien Ko,13 Wen-Sen Lee,14 Po-Ren Hsueh15,16 1Department of Intensive Care Medicine, Chi Mei Medical Center, Liuying, Taiwan; 2Division of Infectious Diseases, Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan; 3Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; 4Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 6Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan; 8Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 11Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan; 13Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 14Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Medical Center, Taipei Medical University, Taipei, Taiwan; 15Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 16Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study aimed to determine the in vitro susceptibility of commonly encountered Gram-negative bacilli (GNB) recovered from patients admitted to intensive care units (ICUs) in Taiwan against colistin, carbapenems, and other comparative agents. Methods: In total, 758 nonduplicate GNB isolates were obtained from clinical specimens of ICU patients at seven medical centers in 2016. Minimum inhibitory concentrations (MICs) were determined using the Vitek 2 susceptibility system. The reference broth-microdilution method was performed to determine MICs of colistin. Five main carbapenemase genes among carbapenem-non-susceptible GNB and mcr-1–mcr5 genes among colistin non-wild-type or -resistant isolates were determined. Results: After exclusion 38 Proteus mirabilis and 13 Morganella morganii spp. among 361 Enterobacteriaceae isolates, 34 (9.4%) isolates were carbapenem-insusceptible, 91.1% (n=31) were colistin wild type, and three and one Klebsiella pneumoniae isolates carried blaKPC and blaOXA48-like, respectively. Carbapenem-insusceptible isolates were found in 23.4% (30 of 128) and 63.0% (87 of 138) of isolates of the Pseudomonas aeruginosa and Acinetobacter baumannii complex, respectively. mcr-1 was detected in two (1.8%) Enterobacter cloacae isolates. Very major errors between two methods of susceptibility to colistin were found in 1.5% of K. pneumoniae, 27.5% of E. cloacae, 4.7% of P. aeruginosa, and 10.1% of A. baumannii complex isolates. Conclusion: In this study, 8.7% of Enterobacteriaceae isolates from ICUs were not susceptible to carbapenem, and blaKPC and blaOXA48-like were found among three and one carbapenem-insusceptible K. pneumoniae isolates, respectively. Colistin MICs determined by Vitek 2 were not reliable, especially for E. cloacae and A. baumannii complex isolates. Keywords: colistin, carbapenems, susceptibility, carbapenemase, mcr-1, intensive care units, SMART, P. aeruginosa, A. baumannii

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.