BACKGROUND:Chlamydia trachomatis infection is one of the most common sexually transmitted infections (STIs). This study investigated the prevalence and genotype distribution of C. trachomatis, and treatment response, focusing on the recent emergence of genovariant L2b in Taiwan. METHODS:This prospective study was conducted from August 2021 to September 2023, enrolling 1023 participants, including 492 people who received pre-exposure prophylaxis (PrEP) for HIV and 531 people with HIV (PWH). Multiple-site sampling and genotyping of C. trachomatis identified were performed. Participants testing positive for C. trachomatis received a 7-day course of doxycycline and test-of-cure (TOC) assessments were conducted post-treatment. RESULTS:Among the participants, mostly MSM (92.7%), 26.4% tested positive for C. trachomatis, with 77.8% identified in the rectum. The prevalent genotypes were J (26.4%), G (24.0%), and B (17.7%). Treatment with a 7-day course of doxycycline resulted in clearance for most cases (91.1%). Genotyping investigations for those repeatedly testing positive (8.9%) showed reinfections with different genotypes. Eighteen cases of asymptomatic rectal carriage of genovariant L2b were detected, predominantly in PWH (88.9%). The L2b genovariant was cleared with 7 days of doxycycline on TOC assessments. The prevalence of L2b increased over time, with multi-locus sequence typing showing ST53 as the predominant strain. CONCLUSIONS:C. trachomatis was prevalent among PWH and PrEP users and the prevalence of L2b genovariant was increasing in Taiwan. A 7-day course of doxycycline was effective in clearing L2b genovariant in asymptomatic participants. Continued surveillance to monitor the evolving epidemiology of chlamydia in Taiwan is warranted.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased in recent years, and it is highly associated with metabolic diseases, as well as the development of hepatocellular carcinoma. However, effective therapeutic strategies for the treatment of NAFLD are still scarce. Although hydrogen-rich water shows beneficial effects for hepatic steatosis, the inconvenience limits the application of this antioxidant. In light of this, hydrogen-rich coral calcium (HRCC) was developed due to its convenience and quantifiable characteristics. However, the effects of HRCC on NAFLD are still unknown. In the present study, we found that HRCC treatment improved methionine-and-choline-deficient diet (MCD)-induced hepatic steatosis, increased aspartate aminotransferase and alanine aminotransferase levels, and elevated hepatic inflammatory factor expressions in mice. In addition to the increased expressions of antioxidative enzymes, we found that HRCC increased the expressions of bile acid biosynthesis-related genes, including Cyp8b1 and Cyp27a1. Increased hepatic bile acid contents, such as muricholic acids, 23 nor-deoxycholic acid, glycoursodeoxycholic acid, and cholic acids, were also confirmed in MCD mice treated with HRCC. Since the biogenesis of bile acids is associated with the constitution of gut microbiome, the alterations in gut microbiome by HRCC were evaluated. We found that HRCC significantly changed the constitution of gut microbiome in MCD mice and increased the contents of Anaerobacterium, Acutalibacter, Anaerosacchariphilus, and Corynebacterium. Taken together, HRCC improved MCD-induced NAFLD through anti-inflammatory mechanisms and by increasing antioxidative activities. Additionally, HRCC might alter gut microbiome to change hepatic bile acid contents, exerting beneficial effects for the treatment of NAFLD.

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

While the incidence of shigellosis has decreased in developed nations due to improved living conditions and healthcare systems, it remains prevalent in economically developing regions. In recent years, a resurgence of shigellosis has been observed in the United States, Europe, and Taiwan, primarily among men having sex with men and people living with human immunodeficiency virus, along with a rise in antimicrobial resistance. This study aims to review the historical epidemiological trends and drug resistance in shigellosis, with a focus on Taiwan. A comprehensive search was conducted using various databases and sources, including non-English literature in Japanese and Chinese. In developed countries, Shigella sonnei and Shigella flexneri are the most common species, while Shigella dysenteriae infections are sporadic. In Taiwan, the classification and prevalence of Shigella species have evolved over time, with S. flexneri and S. sonnei being the predominant strains. Fluoroquinolone resistance and azithromycin non-susceptibility are the ongoing threat. In conclusion, shigellosis remains a significant global health concern, with recent increases in certain populations and antimicrobial resistance. Further research is necessary to understand the clinical significance and risk factors associated with asymptomatic carriers and to assess the impact of behavioral modifications and interventions in high-risk populations.

OBJECTIVES:Currently recognized risk factors for sexually transmitted enteric infections (STEIs) among men who have sex with men (MSM) include oroanal sex, multiple sexual partners, and chemsex. This study aimed to investigate the prevalence of the asymptomatic carriage of enteric pathogens in men who have sex with men (MSM) and to identify the associated risk factors. METHODS:Questionnaires were completed by 375 MSM in Taiwan from December 2019 to November 2022. Fecal samples were analyzed by multiplex PCR to determine whether seven enteric pathogens, including Entamoeba histolytica, Giardia duodenalis, Shiga toxin-producing Escherichia coli, Cryptosporidium, Campylobacter, Salmonella, and Shigella species, were present. RESULTS:Among 375 fecal samples from asymptomatic MSM, 27 (7.2%) fecal samples tested positive for at least one enteric pathogen. The recent use of proton pump inhibitors (PPIs) was significantly associated with asymptomatic fecal carriage (22.2% vs. 2.0%, P < 0.001). G. duodenalis (2.1%, 8 cases), E. histolytica (1.6%, 6 cases), and Shigella species (1.3%, 5 cases) were commonly detected. Oroanal sex and PPI use were associated with the asymptomatic carriage of enteric pathogens. Specifically, Shigella, Salmonella, or Campylobacter carriage was significantly correlated with PPI use. In contrast, rectal gonorrhea was associated with multiple sexual partners and prior syphilis. CONCLUSIONS:Recent use of PPIs was associated with the asymptomatic carriage of enteric pathogens. Therefore, targeted education about the appropriate use of PPIs is necessary to mitigate the risk of STEIs among MSM.

OBJECTIVES:WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS:We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS:At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS:SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

BACKGROUND:Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with human immunodeficiency virus (PWH). METHODS:From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment; secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS:During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSIONS:Combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

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.

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.

BACKGROUND:The clinical burden of Clostridioides difficile infections (CDIs) remains substantial globally. This study aimed to investigate the ribotypes (RTs) and antimicrobial susceptibility of C. difficile isolates collected in Taiwan. METHODS:C. difficile isolates were prospectively collected from four medical centers in Taiwan from 2019 to 2021. In a reference laboratory, in vitro susceptibility to clindamycin, moxifloxacin, metronidazole, vancomycin, fidaxomicin, and rifaximin were tested, and ribotyping was conducted to determine their genetic diversity. RESULTS:A total of 568 C. difficile isolates were included. Metronidazole resistance was not observed, and the susceptibility rate of vancomycin was 99.5 %. Clindamycin showed poor activity against these isolates, with a resistance rate of 74.8 %. Fidaxomicin exhibited potent activity and 97.4 % of isolates were inhibited at 0.25 μg/mL. Rifaximin MIC90 increased from 0.015 μg/mL in 2019 to 0.03 μg/mL in 2020 and 2021. Of 40 RTs identified, two predominant RTs were RT 078/126 (78, 14 %) and 014/020 (76, 13 %). RT 017, traditional harboring truncated tcdA, accounted for 3 % (20 isolates) and there was no isolate belonging to RT 027. The proportions of RT 078 increased from 11.2 % in 2019 to 17.1 % in 2021, and the predominance of RT 078/126 was more evident in central Taiwan. CONCLUSIONS:Vancomycin, fidaxomicin, and metronidazole remain in vitro effective against clinical C. difficile isolates in Taiwan. The reservoirs and genetic relatedness of two major RTs with zoonotic potentials, RT 078/126 and 014/020, warrant further investigations.

BACKGROUND:The short-term impact of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) combined with antiretroviral therapy (ART) on renal function in patients with HIV/HCV-coinfection remains controversial. METHODS:This multicenter, retrospective study aimed to sequentially record the estimated glomerular filtration rate (eGFR) at baseline, end of therapy (EOT), 12 weeks off-treatment (SVR12), and at time points after SVR12 (post-SVR12) and to identify the factors associated with an eGFR decline to <60 ml/min/1.73 m2 in HIV/HCV-coinfected patients receiving DAAs. The evolution of mean eGFRs between different ART and DAAs combinations among patients of different HIV transmission routes were compared using a generalized linear mixed effects model. The periods between baseline and EOT, between EOT and post-SVR12, and between baseline and post-SVR12 were defined as the on-treatment, post-treatment, and all-course periods, respectively. Acute kidney disease (AKD) was defined as a decline of eGFR to <60 ml/min/1.73 m2. RESULT:A total of 445 patients with baseline eGFRs >60 ml/min/1.73 m2 were included. We found that eGFRs declined during the on-treatment period in the tenofovir-containing ART and SOF-based DAA groups. There were no differences in the slope coefficient during the on-treatment and post-treatment periods among all risk groups except for people who inject drug. Increasing age and plasma HIV RNA >20 copies/ml before DAA treatment were factors independently associated with AKD during the on-treatment period while increasing age was independently associated with AKD during the all-course period. CONCLUSION:Only increasing age was an independent factor associated with AKD among HIV/HCV-coinfected patients during and after DAA treatments.

Background: The prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East. Material and methods: From January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire.Medical records of those who took regular medical visits for HIV were recorded. Multiplex po-lymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample.Results: Among 341 MSM during 2020-2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44-31.91, P = 0.015) and mul-tiple sexual partners (AOR 1.373, 95% CI 1.002-1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline.Conclusions: Rectal gonorrhea and multiple sexual partners are risk factors for rectal chla-mydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis. Copyright 2023, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Same-day antiretroviral therapy (SDART) initiation is recommended for newly diagnosed people with HIV (PWH) by the WHO; however, higher attrition rates were noted after SDART initiation in developing countries.Methods: To compare the clinical outcomes with SDART versus rapid ART initiation, we included newly diagnosed PWH from 2018 to 2022 in Taiwan, where the program of rapid ART initiation was implemented in 2018. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid ART initiation as starting ART within 14 days of diagnosis. A composite unfavorable clinical outcome was assessed, defined as any deaths after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failures or rebounds at 12 months.Findings: The rate of SDART initiation increased from 15·8% in 2018 to 34·1% in 2021-2022. At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with viral suppression (87·5% vs 87·7%) and the composite unfavorable outcome (7·7% vs 7·7%). Age >30 years (adjusted hazard ratio [aHR] 0·44, 95% CI 0·28-0·70) was the only independent factor associated with LTFU. PWH aged >30 years (aHR 0·59, 95% CI 0·41-0·85) and GBMSM (aHR 0·50, 95% CI 0·32-0·79) were less likely to have composite unfavorable outcomes.Interpretation: Programs of SDART and rapid ART initiation demonstrated comparable clinical outcomes and viral suppression rates for newly diagnosed PWH. Strategies are needed for PWH 30 years or younger and those other than GBMSM to improve the post-engaging care continuum.Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Declaration of Interest: C.-C. H has received honoraria and research funding from Gilead Sciences. Other authors have no conflict of interest to declare.Ethical Approval: This study was reviewed and approved by the Research Ethics Committee of the National Taiwan University Hospital (202101016RIND). Due to the retrospective study design, patients were not involved in research development, recruitment, study conduction, or outcome measurement.

BACKGROUND:A comprehensive study of respiratory pathogens was conducted in an area with a low prevalence of COVID-19 among the adults quarantined at a tertiary hospital.METHODS:From March to May 2020, 201 patients suspected lower respiratory tract infection (LRTI) were surveyed for etiologies by multiplex polymerase chain reaction (PCR: FilmArray TM Respiratory Panel) test combination with cultural method, viral antigen detection and serologic surveys.RESULTS:Total 201 patients tested with FilmArray TM Respiratory Panel were enrolled, of which 68.2% had sputum bacterial culture, 86.1% had pneumococcus and Legionella urine antigen test. Their median age was 72.0 year-old with multiple comorbidities, and 11.4% were nursing home residents. Bacteria accounted for 59.7% of identified pathogens. Atypical pathogens were identified in 31.3% of total pathogens, of which viruses accounted for 23.9%. In comparison to patients with bacterial infection, patients with atypical pathogens were younger (median= 77.2 vs 67.1, years, P = 0.017) and had shorter length of hospital (8.0 vs 4.5, days, P = 0.007).CONCLUSIONS:Patients with LRTI caused by atypical pathogens was indistinguishable from those with bacterial pathogens by clinical manifestations or biomarkers. Multiplex PCR providing rapid diagnosis of atypical pathogens enhance patient care and decision making when rate of sputum culture sampling was low in quarantine ward during pandemic.

The threat of antibiotic-resistant bacteria to public health may originate from public restrooms. To better understand the community burden of antimicrobial-resistantEscherichia coliand sequence type complex 131E. coli(STc131) in the public restroom, we performed a surveillance in public restrooms in southern Taiwan. Swabs were sampled from randomly selected public restrooms in Tainan, Taiwan in 2019. Antimicrobial susceptibility, phylogenetic grouping, and multiplex PCR were performed for the major ST complex in the B2 phylogenetic group. If STc131 isolates were identified, the whole-genome sequencing was performed. A total of 613 collection sites found 132 sites (21.5%) positive forE. coli. The most common phylogenetic group was A (30.9%) followed by B2 (30.3%). Ceftriaxone-resistantE. coliand extended-spectrum β-lactamases–producingE. coliwere found in 2.4 and 1.0% of total public restrooms, respectively. The isolates in rural areas had higher ceftriaxone non-susceptibility than those in the city centers (3.9 vs. 1.2%,P= 0.038). Nine STc131 isolates were found in public restrooms, and most (77.8%) belonged to the subtype fimH41, whereas 22.2% belonged to fimH30. With the inclusion of STc131 isolates from human and dog fecal colonization in Taiwan, whole-genome sequencing was performed in 35 isolates. A large cluster of fimH41 in SNP-tree and GrapeTree was found from different sources (human, dog, and environment) and geographical areas. In conclusion, our surveillance of antimicrobial-resistantE. colishowed a higher prevalence ofE. colidetected in public restrooms in the rural areas compared to those in city centers. The whole-genome sequence implies that fimH41 STc131 strains are successfully circulated in the community in Taiwan.

This is the first report to discover Clostridiodes difficile (C. difficile) ribotype RT126 and RT598 (both ribotypes belong to RT078-lineage) in a river water system in southern Taiwan. Fluoroquinolone resistance was also found. The connection between clinical isolates and those from the environment needs further investigation.