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Li-Na Guo,1,2 Shu-Ying Yu,1– 3 Meng Xiao,1,2 Chun-Xia Yang,4 Chun-Mei Bao,5 Yan-Hua Yu,6 Li-Yan Ye,7 Yang Yang,1,2 Ge Zhang,1,2 Jie Liu,8 Guo-Wei Liang,9 Rong Min,10 Yu Zhu,11 Hong Lei,12 Yu-Lei Liu,13 Lin-Juan Liu,14 Yun-Jian Hu,15 Po-Ren Hsueh,16 Ying-Chun Xu1,2 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447); 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences; 4Department of Infectious Diseases & Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University; 5Clinical Laboratory Medical Center, The Fifth Medical Center of Chinese PLA General Hospital; 6Department of Clinical Laboratory, You’an Hospital, Capital Medical University; 7Center for Clinical Laboratory Medicine, Chinese PLA General Hospital; 8Department of Clinical Laboratory, Seventh Medical Center, PLA General Hospital; 9Department of Clinical Laboratory, Aerospace Center Hospital; 10Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University; 11Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; 12Department of Clinical Laboratory, The 8th Medical Center of Chinese PLA General Hospital; 13Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University; 14Department of Clinical Laboratory, Peking University Cancer Hospital and Institute; 15Department of Clinical Laboratory, Beijing Hospital, Beijing, People’s Republic of China; 16Departments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanCorrespondence Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/ Fax +86 106 915 9766Email xycpumch@139.comPo-Ren HsuehDepartments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanTel +886-2-23224262 ext. 65355Fax +886-2-23955072Email hsporen@ntu.edu.twObjective: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017.Materials and Methods: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted.Results: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012– 2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P< 0.05) compared with that observed in 2012– 2013, while micafungin resistance rates were < 5% for all tested Candida species.Conclusion: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.Keywords: invasive fungal infections, Candida, species distribution, antifungal resistance, surveillance, Beijing

Pin-Chieh Wu,1,2,* Jiun-Ling Wang,3,4,* Po-Ren Hsueh,5 Po-Hsiang Lin,6 Ming-Fang Cheng,7–10 I-Fei Huang,7 Yao-Shen Chen,8,11 Susan Shin-Jung Lee,8,11 Mar Guang-Yuan,1,11 Hsien-Chung Yu,1,8,11–12 Chiao-Lin Hsu,1,2 Fu-Wei Wang,2,13 Chi-Shen Chen,1 Chih-Hsin Hung,9 Wen-Chien Ko3,41Department of Physical Examination Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Nursing, Meiho University, Pingtung, Taiwan; 3Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 4Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8School of Medicine, National Yang-Ming University, Taipei, Taiwan; 9Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 10Department of Nursing, Fooyin University, Kaohsiung, Taiwan; 11Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 12Institute of Health Care Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan; 13Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workPurpose: 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.Keywords: fecal colonization, extended-spectrum β-lactamase, sequence type, MCR1, Escherichia coli

Chia-Jung Liu,1 Tai-Fen Lee,2 Sheng-Yuan Ruan,1 Chong-Jen Yu,1 Jung-Yien Chien,1 Po-Ren Hsueh1,21Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 2Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanObjectives: The incidence of Pneumocystis pneumonia (PCP) has been increasing among non-HIV-infected patients. Here, we investigated the clinical characteristics, treatment outcomes, and prognostic factors of PCP in non-HIV-infected patients.Patients and methods: Information on clinical characteristics, treatment outcomes, and prognostic factors of PCP patients who were treated at a medical center in northern Taiwan from October 2015 to October 2016 were retrieved from medical records and evaluated.Results: Among the patients with PCP included in the study, 84 were non-HIV-infected and 25 were HIV-infected. Non-HIV-infected patients with PCP had a longer duration between radiographic findings and treatment (P

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

Chun-Hsing Liao,1,2 Na-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 Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Yang-Ming University, Taipei, 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 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. Materials and methods: In total, 300 non-duplicate isolates of Escherichia coli (n=100), Klebsiella pneumoniae (n=100), and Pseudomonas aeruginosa (n=100) collected from 300 patients were studied. The minimum inhibitory concentrations (MICs) of these isolates to antimicrobial agents were determined using the broth microdilution method. Carbapenemase-encoding genes (blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48-like) were studied for the isolates that were not susceptible to any carbapenems. Sequencing analysis of the mcr genes (mcr-1–5) was conducted for all isolates with colistin MICs ≥4 mg/L. Results: Ertapenem non-susceptibility was detected in 3% (n=3) E. coli and 12% (n=12) K. ­pneumoniae isolates. The susceptibility rates of imipenem, ceftazidime–avibactam (CAZ–AVB), and ceftolozane–tazobactam (CLZ–TAZ) were 99%, 99%, and 88%, respectively, for E. coli, 91%, 100%, and 80%, respectively, for K. pneumoniae, and 66%, 91%, and 93%, respectively, for P. aeruginosa. Carbapenemase-encoding genes were not detected in E. coli, were detected in four (33.3%) K. pneumoniae isolates that were not susceptible to ertapenem (three harboring blaKPC and one harboring blaOXA-48-like), and were not detected in P. aeruginosa isolates that were not susceptible to imipenem. One K. pneumoniae isolate was resistant to colistin (MIC 4 mg/L) and negative for mcr genes. Conclusion: CAZ–AVB exhibited excellent activity against carbapenem-resistant Enterobacteriaceae, and CLZ–TAZ exhibited good activity against imipenem-resistant P. aeruginosa. Keywords: carbapenem resistance, second-generation, β-lactam, β-lactamase inhibitor combinations, carbapenemase-encoding genes, mcr

Shio-Shin Jean,1,2 Min-Chi Lu,3 Zhi-Yuan Shi,4 Shu-Hui Tseng,5 Ting-Shu Wu,6 Po-Liang Lu,7 Pei-Lan Shao,8 Wen-Chien Ko,9 Fu-Der Wang,10,11 Po-Ren Hsueh12,13 1Department of Emergency Medicine and Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan; 4Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Center for Disease Control and Prevention, Ministry of Health and Welfare, Taiwan; 6Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 7Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Pediatrics, Hsin-Chu Branch, National Taiwan University Hospital, Hsin-Chu, Taiwan; 9Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; 10Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 11School of Medicine, National Yang-Ming University, Taipei, Taiwan; 12Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 13Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017. Materials and methods: Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase, imipenemase, OXA-48-like, and mcr-1-5 genes were detected by molecular methods in Enterobacteriaceae isolates. Results: Five (0.7%) E. coli isolates harbored mcr-1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla KPC, bla OXA-48-like, mcr-1, and bla NDM, respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr-1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane–tazobactam (CLZ–TAZ) NS (40.2%, 16.3%, and 71%–80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%–28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime–avibactam (CAZ–AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ–AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ–TAZ than hospital-acquired E. coli isolates. Conclusion: Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella, and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan. Keywords: Enterobacteriaceae, Neisseria gonorrhoeae, extended-spectrum β-lactamases, carbapenemase, ceftolozane–tazobactam, ceftazidime–avibactam

Shio-Shin Jean,1,2 Wen-Sen Lee,3,4 Po-Ren Hsueh5,6 on behalf of the SMART Asia-Pacific Group 1Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Departments of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated the prevalence rates of carbapenemase positivity, antibiotic susceptibility, and independent predictors of carbapenemase producers among the Enterobacteriaceae isolates recovered from patients with intra-abdominal infections (IAI) in the Asia-Pacific region between 2008 and 2014.Materials and methods: Multiplex PCR was used for the detection of specific β-lactamases, while the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibiotics among the IAI-related Enterobacteriaceae isolates. We studied the abovementioned parameters in 484 ertapenem-non-susceptible (Erta-NS) isolates and explored the independent predictors of carbapenemase-producing Enterobacteriaceae (CPE) isolates.Results: Eighty (16.5%) Erta-NS-IAI Enterobacteriaceae isolates were found to be CPE. Vietnam and the Philippines had the highest CPE prevalence rates. The IAI isolates of Enterobacter species and Klebsiella pneumoniae followed by Escherichia coli were the three major pathogens with 77.4%, 40.9%, and 11.7% Erta-NS prevalence rates, respectively. Furthermore, the highest CPE prevalence (35%) was noted among the Erta-NS-K. pneumoniae isolates. The CPE isolates harboring the blaNDM, blaKPC, or blaOXA-48-like alleles had higher imipenem MIC levels than those harboring the blaIMP alleles. Using multivariate logistic regression analysis, we concluded that Erta-NS-IAI isolates with an imipenem non-susceptible phenotype (OR, 56.4), with cefepime MIC >8 µg/mL (OR, 4.4), cultured from the peritoneal space samples (tissue or abscess; OR, 3.3), and harboring the extended-spectrum β-lactamase encoding allele (OR, 11.5) are independent predictors of CPE.Conclusion: Imipenem non-susceptibility, cefepime MIC >8 μg/mL, and the peritoneal space as a culture site are independent clinical predictors of CPE among the Erta-NS-IAI Enterobacteriaceae isolates in the Asia-Pacific region. Keywords: intra-abdominal infection, antimicrobial susceptibility, ertapenem-non-susceptible, carbapenemase-producing Enterobacteriaceae

Yu-Tsung Huang,1–3 Chun-Hsing Liao,1,4 Shey-Ying Chen,5 Chia-Jui Yang,1,4 Hsin-Sui Hsu,1 Lee-Jene Teng,2,3 Po-Ren Hsueh2,6 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 3Department of Clinical Laboratory Science and Medical Biotechnology College of Medicine, National Taiwan University, Taipei, Taiwan; 4Department of Internal Medicine, College of Medicine, Yang-Ming University, Taipei, Taiwan; 5Department of Emergency Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated molecular characteristics of rifampin (RIF)-resistant (RIF-R) Staphylococcus aureus isolates recovered from patients receiving RIF-containing regimens for tuberculosis (TB). Patients and methods: Patients with TB who received RIF-containing regimens from November 2009 to May 2011 at a medical center were enrolled. Nasal swabs for S. aureus culture were obtained at the time of enrollment, and then every two months until two months after RIF treatment had been completed. Genetic relatedness of the isolates was determined using pulsed-field gel electrophoresis, multilocus sequence typing, and gene typing of spa and SCCmec. The presence of RIF resistance-associated mutations in rpoB, and fusidic acid resistance genes fusB and fusC in the S. aureus isolates were analyzed. Results: Among the 200 patients enrolled in this study, 152 completed follow-ups during treatment, and 114 completed two months of follow-up after discontinuing use of RIF. At enrollment, ten patients (5%) had nasal colonization with S. aureus, namely eight with methicillin-susceptible S. aureus (MSSA), and two with methicillin-resistant S. aureus (MRSA, ST59-SCCmecIV-RIF-susceptible). All these patients were decolonized after RIF usage. Two patients with MSSA colonization at enrollment showed recolonization with genetically unrelated MSSA strains two months after completion of RIF treatment. There were five ST45-SCCmecVT-RIF-R strains from two patients isolated during RIF exposure. Sequencing of rpoB in the RIF-R S. aureus isolates revealed different mutation sites between the MSSA and MRSA isolates. Conclusion: RIF-R S. aureus strains are more likely to result in persistent nasal carriage in TB patients receiving RIF treatment. Monitoring of emergence and possible dissemination of the MRSA ST45 strains among TB patients treated with RIF in Taiwan is warranted. Keywords: Staphylococcus aureus, methicillin-resistant S. aureus, rifampin resistance, tuberculosis, nasal carriage, Taiwan

Yuan-Pin Hung,1–3,* Pei-Jane Tsai,4,* Yuan-Ti Lee,5,6 Hung-Jen Tang,7 Hsiao-Ju Lin,1–3 Hsiu-Chuan Liu,1 Jen-Chieh Lee,2 Bo-Yang Tsai,4 Po-Ren Hsueh,8 Wen-Chien Ko2,9,10 1Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 2Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 3Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Institute of Medicine and School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6Division of Infectious Diseases, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 7Department of Internal Medicine, Chi-Mei Hospital, Tainan, Taiwan; 8Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 9Center of Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan; 10Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan *These authors contributed equally to this work Objectives: The information of antimicrobial susceptibility, toxin gene, and ribotype distribution of toxigenic Clostridium difficile isolates in Taiwan remain limited. Patients and methods: The study was conducted from January 2015 to December 2016 in 5 hospitals in Taiwan. Adults aged ≥20 years with a hospital stay for >5 days were included, and those with colectomy or intestinal infection due to other enteropathogens were excluded. Multiplex PCR was used to detect tcdA, tcdB, cdtA, cdtB, and tcdC deletions, and antimicrobial susceptibility for metronidazole, vancomycin, doxycycline, and tigecycline was investigated. Ribotypes of those isolates with tcdC deletion and tcdA+/tcdB+ were determined. Results: Of 1112 C. difficile isolates collected from adults at 5 hospitals, 842 were toxigenic, including 749 (89.0%) tcdA+/tcdB+ isolates and 93 (11.0%) tcdA−/tcdB+. Of the toxigenic isolates, 76 (9.0%) had a tcdC deletion and were cdtA+/cdtB+, indicative of hypervirulence, and RT078 lineage, including RT126, RT127, and RT078, predominated (n=53, 76.3%). Similar to the susceptibility data in Asia countries, metronidazole or vancomycin resistance was rare, noted in 1.2% or 2.1%, respectively. Reduced doxycycline susceptibility (minimum inhibitory concentration [MIC] of ≥8 mg/L) was more common among RT078 lineage than non-RT078 lineage (75.9%, 44/58 vs 6.0%, 47/784; P

Objectives: This study was intended to delineate the clinical and microbiological characteristics of patients with bacteremia caused by Campylobacter species.Methods: Twenty-four patients with Campylobacter bacteremia were treated at the National Taiwan University Hospital from 1998 to 2008. All isolates from the 24 patients were confirmed to the species level by multiplex PCR (cadF, hipO and asp gene) and 16S RNA gene sequencing.Results: Bacteremia was caused by Campylobacter coli in 15 (62.5%) patients, Campylobacter fetus in 6 (25%), and Campylobacter jejuni in 3 (12.5%). Of the 24 patients, 16 were male. The major underlying conditions included chronic renal insufficiency (41.7%), liver cirrhosis (37.5%), malignancy (33.3%), and previous abdominal surgery (33.3%). The most common infections were intra-abdominal infection (54.2%), followed by primary bacteremia (41.7%), and cellulitis (4.2%). The mean Pittsburgh bacteremia score was 2.5 (range, 0-9). During the bacteremic episodes, six (25%) patients developed septic shock. Third-generation cephalosporins were administered to 12 (50%) patients as empirical therapy. All-cause mortality was 4.2% at 14 days and 12.5% at 30 days. The majority of the isolates were resistant to third-generation cephalosporins and quinolones, with minimum inhibitory concentration (MIC(90)) values of 32 mg/L for cefotaxime, 128 mg/L for ceftriaxone, and 32 mg/L for both ciprofloxacin and levofloxacin. All isolates possessed a parC mutation (Arg-139-Gln) and 15 exhibited an additional gyrA mutation (Thr-86-Ile). Among these isolates, 20.8% were susceptible to erythromycin (MIC≤0.5 mg/L).Conclusion: Bacteremia caused by antimicrobial resistant Campylobacter species is alarming although the mortality rate is low. [ABSTRACT FROM AUTHOR]

To characterize the distribution of nontuberculous mycobacteria (NTM) species isolated from pulmonary samples from persons in Asia and their association with pulmonary infections, we reviewed the literature. Mycobacterium avium complex bacteria were most frequently isolated (13%-81%) and were the most common cause of pulmonary NTM disease (43%-81%). Also pathogenic were rapidly growing mycobacteria (M. chelonae, M. fortuitum, M. abscessus). Among all NTM isolated from pulmonary samples, 31% (582/1,744) were considered clinically relevant according to American Thoracic Society diagnostic criteria. Most patients were male (79%) and had a history of tuberculosis (37%). In Asia, high prevalence of rapidly growing mycobacteria and a history of tuberculosis are distinct characteristics of pulmonary NTM disease. This geographic variation is not well reflected in the American Thoracic Society criteria for NTM infections and could be incorporated in future guidelines. [ABSTRACT FROM AUTHOR]

Two hundred and four Salmonella enterica serotype Typhi (S. Typhi) isolates were collected from seven Asian countries during 2002-2004. Multidrug-resistant S. Typhi (resistant to > or = 3 antibiotics) was detected in 84 (41.2%) isolates and 142 (69.6%) showed reduced susceptibility to ciprofloxacin (minimum inhibitory concentration=0.125-1.0 mg/l). This study highlights the worsening situation of antimicrobial resistance of S. Typhi in Asia. [ABSTRACT FROM AUTHOR]

To assess the species distribution and epidemiologic trends of nontuberculous mycobacteria, we examined isolates from patients in Taiwan. During 2000-2008, the proportion increased significantly from 32.3% to 49.8%. Associated disease incidence increased from 2.7 to 10.2 cases per 100,000 patients. Mycobacterium avium complex and M. abscessus were most frequently isolated. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic is a persistent challenge, with continued breakthrough infections despite vaccination efforts. This has spurred interest in alternative preventive measures, including dietary and herbal interventions. Previous research has demonstrated that herbal medicines can not only inhibit cancer progression but also combat viral infections, including COVID-19 by targeting SARS-CoV-2, indicating a multifaceted potential to address both viruses and cancer. Here, we found that the Kang Guan Recipe (KGR), a novel herbal medicine formula, associates with potent inhibition activity against the SARS-CoV-2 viral infection. We demonstrate that KGR exhibits inhibitory activity against several SARS-CoV-2 variants of concern (VOCs). Mechanistically, we found that KGR can block the interaction of the viral spike and human angiotensin-converting enzyme 2 (ACE2). Furthermore, we assessed the inhibitory effect of KGR on SARS-CoV-2 viral entry in vivo, observing that serum samples from healthy human subjects having taken KGR exhibited suppressive activity against SARS-CoV-2 variants. Our investigation provides valuable insights into the potential of KGR as a novel herbal-based preventive and therapeutic strategy against COVID-19., Competing Interests: Declaration of Competing Interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have a patent related to the subject matter of this manuscript. Mien-Chie Hung, Sheng-Teng Huang, Wei-Jan Wang and Shi-Chen Ou are co-inventors of a patent entitled “Herbal compositions for treating and preventing SARS-CoV-2 virus infection”., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs)., Methods: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analyzed in both models., Results: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analyzed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, p < 0.001 in Model 1; 23.5% vs. 58.6%, p = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2)., Conclusion: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy., Competing Interests: Declaration of competing interest None declared, (Copyright © 2024. Published by Elsevier Ltd.)

Background: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD)., Methods: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry., Results: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group., Conclusion: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO., (© 2024. The Author(s).)

Background: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies., Methods: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023., Results: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention., Conclusions: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes., Competing Interests: Declaration of competing interests All authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Aspergillus is a common filamentous fungus found in various natural environments, with spores frequently inhaled by humans. While healthy individuals typically resist infection, immunocompromised individuals and those with pre-existing lung diseases are at higher risk for aspergillosis. Chronic pulmonary aspergillosis (CPA) often develops in individuals with conditions like tuberculosis and chronic obstructive pulmonary disease. Recent studies in Taiwan reveal a significant incidence of CPA among elderly patients with these underlying conditions. The most common clinical manifestations include cavitation, nodules, and consolidation in the lungs. Aspergillus-specific IgG antibodies have emerged as key diagnostic markers, with varying optimal cut-off values across different regions. Studies indicate a strong correlation between high IgG levels and severe CPA, alongside associations with specific radiographic features. Additionally, elevated inflammatory markers such as IL-1β and TNF-α are linked to poor outcomes, emphasizing the need for early detection and intervention. The preferred treatment regimen consists of itraconazole, voriconazole, posaconazole, and isavuconazole, with itraconazole and voriconazole being the most extensively documented in the context of CPA. Overall, this review underscores the importance of localized diagnostic validation and comprehensive studies to improve the understanding and treatment of CPA in Taiwan., (Copyright © 2024. Published by Elsevier B.V.)

Background: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored., Methods: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists., Results: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results., Conclusions: In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU., (Copyright © 2024. Published by Elsevier B.V.)

The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines., Competing Interests: Declaration of competing interest Yu-Lin Lee: Consulting fees from GSK; Fees from GSK for participation in this expert meeting. Szu Min Hsieh: Consulting fees from GSK; Fees from GSK for participation in this expert meeting. Yi-Tsung Lin: Consulting fees from GSK; Fees from GSK for participation in this expert meeting. Shian Sen Shie: Consulting fees from GSK; Fees from GSK for participation in this expert meeting. Chia-Jui Yang: Consulting fees from Gilead Science, GSK, Johnson & Johnson, and Pfizer; Fees from GSK for participation in this expert meeting. Po Ren Hsueh: Consulting fees from GSK; Fees from GSK for participation in this expert meeting., (Copyright © 2024. Published by Elsevier B.V.)

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015-2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: In the Asia-Pacific region, Mycoplasma pneumoniae (MP) could be a notable pathogen responsible for adult community-acquired pneumonia (CAP), with varying prevalence rates. This comprehensive review aimed to explore the epidemiology, clinical manifestations, macrolide resistance, and molecular characteristics of MP in adults across several countries in Asia., Methods: PubMed, Embase, and Google Scholar were searched for relevant articles from 2010-2023 based on the following keywords: adult and Mycoplasma pneumoniae., Results: The prevalence of MP in CAP patients in these countries ranged from 2.1% in Korea to 25.5% in Japan. Macrolide resistance was prominent, particularly in China, with rates ranging 26.9-100%. Clinical manifestations of MP infection included protean extrapulmonary manifestations, and complications such as rhabdomyolysis and thrombocytopenia. Molecular characteristics, especially the multiple locus variable-number tandem-repeat analysis type 4/5/7/2, remained predominant across various countries, emphasising the importance of ongoing surveillance., Conclusions: This review highlights the urgent need for continued monitoring of MP infections, macrolide resistance, and molecular characteristics to inform effective prevention and treatment strategies in the Asia-Pacific region., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Mitigation measures aimed at curbing the transmission of the severe acute respiratory syndrome coronavirus 2 effectively suppressed the occurrence of many respiratory infections other than coronavirus disease 2019. Several infections experienced a resurgence following the relaxation of non-pharmaceutical interventions, surpassing pre-pandemic levels in Taiwan. This phenomenon, known as immune debt, primarily affected respiratory infections in young children, including respiratory syncytial virus (RSV) infection. Infections transmitted by means other than droplets or contact did not exhibit significant changes in their epidemic patterns, such as varicella and Japanese encephalitis. Alterations in seasonality were noted for RSV infection and influenza, and these changes are also linked to immune debt. The recent emergence of severe pediatric pneumonia in northern China may be associated with immune debt and the rise of macrolide-resistant Mycoplasma pneumoniae associated with severe illness., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes., Methods: Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018-2021. Comprehensive antimicrobial susceptibility testing and β-lactamase gene detection were also conducted, along with statistical analysis of the collected data., Results: Among the 72 244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (P < 0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018-2021., Conclusions: This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In Taiwan, sequence type (ST) 239 and ST59 were two major clones among meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates in the past two decades. USA300 (ST8) prevailed in the Americas but not in outside areas. Recently USA300 (ST8) emerged and was increasingly identified in Taiwan; we thus conducted an island-wide study to explore the role of USA300 among MRSA isolates., Methods: One hundred MRSA bloodstream isolates identified in 2020 from each of the six participating hospitals in Taiwan were collected and characterized. The first 10 ST8 isolates from each hospital were further analysed by whole-genome sequencing., Results: Of the 590 confirmed MRSA isolates, a total of 22 pulsotypes and 21 STs were identified. The strain of pulsotype AI/ST8 was the most common lineage identified, accounting for 187 isolates (31.7%) and dominating in five of six hospitals, followed by pulsotype A/ST239 (14.7%), pulsotype C/ST59 (13.9%) and pulsotype D/ST59 (9.2%). Of the 187 pulsotype AI/ST8 isolates, 184 isolates were characterized as USA300 and clustered in three major sub-pulsotypes, accounting for 78%. Ninety per cent of the 60 ST8 isolates for whole-genome sequencing were clustered in three major clades., Conclusions: In 2020, USA300 became the most common clone of MRSA in Taiwan, accounting for >30% of MRSA bloodstream isolates island wide. Most of USA300 isolates circulating in Taiwan might have been imported on multiple occasions and evolved into at least three successful local clades. MRSA USA300 has successfully established its role in Taiwan, an area outside of the Americas., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Actinobacillus pleuropneumoniae infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of A. pleuropneumoniae in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017-2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of A. pleuropneumoniae for the first time in Taiwan using NGS.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to assess the performance of three commercial panels, the ERIC Carbapenem-Resistant Enterobacteriaceae Test (ERIC CRE test), the NG-Test CARBA 5 (NG CARBA 5), and the BD Phoenix CPO Detect Panel (CPO panel), for the detection of main types of carbapenemases among carbapenem-resistant Enterobacterales (CRE)., Methods: We collected 502 isolates of carbapenem-resistant Enterobacterales (CRE) demonstrating intermediate or resistant profiles to at least one carbapenem antibiotic (ertapenem, imipenem, meropenem, or doripenem). Carbapenemase genes and their specific types were identified through multiplex PCR and sequencing methods. Subsequently, the ERIC CRE test, CPO panel, and NG CARBA 5 assay were conducted on these isolates, and the results were compared with those obtained from multiplex PCR., Results: The results indicated that the ERIC CRE test exhibited an overall sensitivity and specificity of 98.1% and 93.6%, respectively, which were comparable to 99.1% and 90.6% for the NG CARBA 5. However, the CPO panel demonstrated a sensitivity of only 56.2% in identifying Ambler classes, exhibiting the poorest sensitivity for class A. Moreover, while the ERIC CRE test outperformed the NG CARBA 5 in identifying multi-gene isolates with multiple carbapenemase-encoding genes, the CPO panel failed to accurately classify these isolates., Conclusions: Our findings support the utilization of the ERIC CRE test as one of the methods for detecting carbapenemases in clinical laboratories. Nonetheless, further optimization is imperative for the CPO panel to enhance its accuracy in determining carbapenemase classification and address limitations in detecting multi-gene isolates., (Copyright © 2024. Published by Elsevier B.V.)

Background: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship., Methods: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP., Results: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results., Conclusions: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits., Competing Interests: Declaration of competing interest No conflicts exist for the specified authors., (Copyright © 2024. Published by Elsevier B.V.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales., Methods: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021)., Results: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC β-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel β-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam., Conclusions: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA)., Methods: A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated., Results: The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013)., Conclusions: Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)