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Reduced mortality in patients with extended duration of methadone maintenance treatment: a five-year retrospective nationwide study

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PSYCHOLOGICAL MEDICINE 2023年第3期53卷 722-730页

作者： Huang, Chieh-Liang Tsai, I-Ju Lin, Wen-Chi Lin, Cheng-Li Ho, Ing-Kang Wang, Ruey-Yun Lee, Cynthia Wei-Sheng China Med Univ Coll Med PhD Program Aging Taichung Taiwan China Med Univ Sch Med Taichung Taiwan Minist Hlth & Welf Tsaotun Psychiat Ctr Nantou City Nan Tou County Taiwan China Med Univ China Med Univ Hosp Ctr Drug Abuse & Addict Taichung Taiwan China Med Univ China Med Univ Hosp Management Off Hlth Data Taichung Taiwan China Med Univ Grad Inst Biomed Sci Taichung Taiwan China Med Univ Dept Publ Hlth Taichung Taiwan

Background The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration. Methods A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012-2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1-364 and > 365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve. Results The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67;95% confidence interval 0.60-0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury. Conclusions Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

关键词： Alcoholic liver disease cardiovascular disease (CVD) cohort study depression hepatitis C virus human immunodeficiency virus methadone maintenance treatment mortality

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SerpinE1 drives a cell-autonomous pathogenic signaling in Hutchinson-Gilford progeria syndrome

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CELL DEATH & DISEASE 2022年第8期13卷 1-12页

作者： Catarinella, Giorgia Nicoletti, Chiara Bracaglia, Andrea Procopio, Paola Salvatori, Illari Taggi, Marilena Valle, Cristiana Ferri, Alberto Canipari, Rita Puri, Pier Lorenzo Latella, Lucia IRCCS Fdn Santa Lucia Rome Italy Sanford Burnham Prebys Med Discovery Inst Dev Aging & Regenerat Program La Jolla CA 92037 USA Univ Roma Tor Vergata Dept Biol PhD Program Cellular & Mol Biol Rome Italy Univ Roma La Sapienza Dept Expt Med I-00161 Rome Italy Sapienza Univ Rome Unit Histol & Med Embryol DAHFMO Rome Italy Natl Res Council Italy Inst Translat Pharmacol Rome Italy Philipps Univ Marburg Pharmakol Inst BPC Marburg Germany

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal disease caused by Lamin A mutation, leading to altered nuclear architecture, loss of peripheral heterochromatin and deregulated gene expression. HGPS patients eventually die by coronary artery disease and cardiovascular alterations. Yet, how deregulated transcriptional networks at the cellular level impact on the systemic disease phenotype is currently unclear. A genome-wide analysis of gene expression in cultures of primary HGPS fibroblasts identified SerpinE1, also known as Plasminogen Activator Inhibitor (PAI-1), as central gene that propels a cell-autonomous pathogenic signaling from the altered nuclear lamina. Indeed, siRNA-mediated downregulation and pharmacological inhibition of SerpinE1 by TM5441 could revert key pathological features of HGPS in patient-derived fibroblasts, including re-activation of cell cycle progression, reduced DNA damage signaling, decreased expression of pro-fibrotic genes and recovery of mitochondrial defects. These effects were accompanied by the correction of nuclear abnormalities. These data point to SerpinE1 as a novel potential effector and target for therapeutic interventions in HGPS pathogenesis.

关键词： Atherosclerosis DNA damage response Mechanisms of disease Senescence Target identification

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Geographic variations in distributions of carbapenemase-encoding genes, susceptibilities, and minimum inhibitory concentrations of inpatient meropenem-resistant Enterobacterales to ceftazidime-avibactam, meropenem-vaborbactam, and aztreonam-avibactam across four global regions: 2020-2022 data from the Antimicrobial Testing Leadership and Surveillance

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INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 2025年第1期66卷 107500-107500页

作者： Jean, Shio-Shin Lai, Chih-Cheng Ho, Sung-Jung Liu, I-Min Hsieh, Po-Chuen Hsueh, Po-Ren Tajen Univ Dept Pharm Coll Pharm & Hlth Care Pingtung 90741 Taiwan Min Sheng Gen Hosp Dept Internal Med & Crit Care Med Taoyuan Taiwan Chi Mei Med Ctr Div Hosp Med Dept Internal Med Tainan Taiwan Natl Sun Yat Sen Univ Coll Med Sch Med Kaohsiung Taiwan Min Sheng Gen Hosp Dept Internal Med Div Pulm Med Taoyuan Taiwan China Med Univ Hosp China Med Univ Dept Lab Med & Internal Med Taichung Taiwan China Med Univ Sch Med PhD Program Aging Taichung Taiwan China Med Univ Sch Med Dept Lab Med Taichung Taiwan

Purpose: To evaluate the susceptibility profiles of regional inpatient meropenem-resistant (MEM-R) carbapenemase-producing Enterobacterales (CPE) isolates and their MIC values to ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB), and aztreonam-avibactam (ATM-AVI) Methods: The 2020-2022 Antimicrobial Testing Leadership and Surveillance database were analyzed. Carbapenemase-encoding genes in CPE isolates were identified using multiplex PCR and Sanger sequencing. Susceptibility breakpoints for CZA and MVB recommended by CLSI 2024 and EUCAST 2025 against Enterobacterales were applied. Results: A total of 2,318 CPE isolates (78.2% were Klebsiella pneumoniae ) were tested globally. Notable diversity in carbapenemase-encoding gene distributions was observed among CPE isolates from Africa/the Middle East (10 countries;n = 361), Asia (7 countries, excluding India and Pakistan;n = 182), Europe (17 countries;n = 1,002), and Latin America (10 countries;n = 773). Metallo- beta-lactamase-encoding genes, predominantly blaNDM-1 , were more frequently detected in CPE isolates from Africa/the Middle East (75.3%, except blaNDM-5 in Kuwait) and Asia (67%, except blaIMP-8 in Taiwan) compared to other regions. Among KPC variants, the KPC-2 enzyme was the predominant one in CPE isolates in Europe (43.4%, except for KPC-3 prevalent specifically in Italy) and in Latin America (62.1%). The susceptibility rates of all analyzed CPE isolates harboring only a single blaKPC gene to CZA and MVB were 99.4% and 93.5%, respectively, based on the CLSI 2024 susceptibility breakpoints. The MIC50/90 values of CPE isolates to ATM-AVI were 0.12/0.25 mg/L and 0.5/1 mg/L, respectively, regardless of collection region, dual carbapenemase production, or infection source. Conclusions: The trends in resistance to novel antibiotics among contemporary CPE isolates need close monitoring. (c) 2025 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those fo

关键词： Carbapenemase-producing Enterobacterales Ceftazidime-avibactam Meropenem-vaborbactam Aztreonam-avibactam Susceptibility rates Surveillance Antimicrobial Testing Leadership and

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Safety and the probiotic potential of Bifidobacterium animalis CP-9

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JOURNAL OF FOOD SCIENCE 2022年第5期87卷 2211-2228页

作者： Tsai, Hui-Yun Wang, Ya-Chin Liao, Chorng-An Su, Chia-Yan Huang, Cheng-Hsieh Chiu, Min-Hsi Yeh, Yao-Tsung Fooyin Univ Dept Nutr & Hlth Sci Kaohsiung Taiwan Fooyin Univ Aging & Dis Prevent Res Ctr 151 Jinxue Rd Kaohsiung 831301 Taiwan Fooyin Univ Dept Med Lab Sci & Biotechnol Kaohsiung Taiwan Fooyin Univ Hosp Biomed Anal Ctr Pingtung Taiwan Kaohsiung Med Univ Sch Pharm Kaohsiung Taiwan Kaohsiung Med Univ Coll Med PhD Program Environm & Occupat Med Kaohsiung Taiwan Natl Hlth Res Inst Kaohsiung Taiwan

Bifidobacterium animalis CP-9 was a commensal strain isolated from human breast milk. In this study, genetic and 90-day oral toxicity were assessed in rodents for its safety. Ames test as well as in vivo bone marrow micronucleus and spermatocyte chromosomal aberration were surveyed in mice. B. animalis CP-9 exhibited no mutagenic activity in the Ames test at the highest tested dosage (5000 mu g/plate) with or without metabolic activation. No evidence of in vivo genetic toxicity was observed at the maximum tested dosage of 10 g/kg body weight (BW). Furthermore, there was no statistically significant difference of the biochemical and histological parameters in the rats administrated with B. animalis CP-9 at dosages of 0, 0.25, 0.5, or 1.5 g/kg BW/day. No indication of concern for pathogenicity was exhibited during evaluation of Bifidobacterium ssp. generally, or B. animalis specifically. It was noted that B. animalis CP-9 was able to survive in gastric acid-like and high bile salt environment, and showed strong adhesion to the intestinal epithelial cells, Caco-2. Intriguingly, B. animalis CP-9 decreased olic acid-induced triglyceral (TG) accumulation in the Caco-2 cells, and viable B. animalis CP-9 had a better bacteriostatic activity compared to another well-documented B. animalis ssp. lactis, BB-12. Based on the present study, B. animalis CP-9 can be a safe probiotic supplement and may improve the health of host.

关键词： Bifidobacterium animalis CP-9 probiotic safety rodent

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The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens

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JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION 2024年第4期57卷 580-593页

作者： Chen, Hsu-Yuan Tseng, How-Yang Chen, Chieh-Lung Lin, Yu-Chao Liang, Shinn-Jye Tu, Chih-Yen Chen, Wei-Cheng Hsueh, Po-Ren China Med Univ China Med Univ Hosp Dept Internal Med Div Pulm & Crit Care Taichung Taiwan China Med Univ Coll Med Sch Med Taichung Taiwan China Med Univ Grad Inst Biomed Sci Coll Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med 2 Yude Rd Taichung 40447 Taiwan China Med Univ China Med Univ Hosp Dept Internal Med 2 Yude Rd Taichung 40447 Taiwan China Med Univ Sch Med PhD Program Aging Taichung Taiwan China Med Univ Sch Med Dept Lab Med Taichung Taiwan

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 (c) 2024, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open

关键词： Critically ill Drug-resistant pathogen Intensive care units Multiplex polymerase chain reactio Antimicrobial stewardship Bloodstream infection Antimicrobial stewardship Bloodstream infection Critically ill Drug-resistant pathogen Intensive care units Multiplex polymerase chain reactio

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Exposure to autoimmune disorders is associated with increased Alzheimer's disease risk in a multi-site electronic health record analysis

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CELL REPORTS MEDICINE 2025年第3期6卷 101980-101980页

作者： Ramey, Grace D. Tang, Alice Phongpreecha, Thanaphong Yang, Monica M. Woldemariam, Sarah R. Oskotsky, Tomiko T. Montine, Thomas J. Allen, Isabel Miller, Zachary A. Aghaeepour, Nima Capra, John A. Sirota, Marina UCSF Biol & Med Informat PhD Program San Francisco CA USA UCSF Bakar Computat Hlth Sci Inst San Francisco CA 94143 USA UCSF Sch Med San Francisco CA USA Stanford Univ Dept Pathol Palo Alto CA USA Stanford Univ Dept Anesthesiol Perioperat & Pain Med Palo Alto CA USA Stanford Univ Dept Biomed Data Sci Palo Alto CA USA UCSF Dept Med Div Rheumatol San Francisco CA USA UCSF Dept Pediat San Francisco CA 94143 USA UCSF Dept Epidemiol & Biostat San Francisco CA 94143 USA UCSF Memory & Aging Ctr San Francisco CA USA Stanford Univ Dept Pediat Palo Alto CA USA

Autoimmunity has been proposed to increase Alzheimer's disease (AD) risk, but evaluating the clinical connection between autoimmune disorders and AD has been difficult in diverse populations. We investigate risk relationships between 26 autoimmune disorders and AD using retrospective observational case-control and cohort study designs based on electronic health records for >300,000 individuals at the University of California, San Francisco (UCSF) and Stanford University. We discover that autoimmune disorders are associated with increased AD risk (odds ratios [ORs] 1.4-1.7) across study designs, primarily driven by endocrine, gastrointestinal, dermatologic, and musculoskeletal disorders. We also find that autoimmune disorders associate with increased AD risk in both sexes, but the AD sex disparity remains in those with autoimmune disorders: women exhibit higher AD prevalence than men. This study identifies consistent associations between autoimmune disorders and AD across study designs and two real-world clinical databases, establishing a foundation for exploring how autoimmunity may contribute to AD risk.

关键词： autoimmunity Alzheimer’s bioinformatics case-control cohort electronic health records risk analysis sex differences statistical epidemiology

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Social and health disparities associated with healthy brain ageing in Brazil and in other Latin American countries

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LANCET GLOBAL HEALTH 2025年第2期13卷 e277-e284页

作者： Da Ros, Lucas U. Borelli, Wyllians Vendramini Aguzzoli, Cristiano Schaffer De Bastiani, Marco Antonio Schilling, Lucas Porcello Santamaria-Garcia, Hernando Pascoal, Tharick A. Rosa-Neto, Pedro Souza, Diogo O. da Costa, Jaderson Costa Ibanez, Agustin Suemoto, Claudia Kimie Zimmer, Eduardo R. Univ Fed Rio Grande do Sul Grad Program Biol Sci Biochem Porto Alegre Brazil Univ Fed Rio Grande do Sul Grad Program Biol Sci Biochem Porto Alegre Brazil Univ Fed Rio Grande do Sul Dept Pharmacol BR-90035003 Porto Alegre Brazil Hosp Moinhos Vento Memory Ctr Porto Alegre RS Brazil Pontifical Univ Rio Grande do Sul Brain Inst Rio Grande do Sul Porto Alegre Brazil Pontifical Univ Rio Grande do Sul Sch Med Dept Pediat Tokat Brazil Pontifical Univ Rio Grande do Sul Grad Program Biomed Gerontol Porto Alegre Brazil Univ Calif San Francisco Hosp Univ San Ignacio Ctr Brain & Cognit Intellectus PhD Program NeurosciPontificia Univ Javeriana San Francisco CA USA Univ Calif San Francisco Gobal Brain Hlth Inst Memory & Aging Ctr Francisco CA USA Univ Pittsburgh Dept Psychiat & Neurol Pittsburgh PA USA McGill Ctr Studies Aging Montreal PQ Canada McGill Univ Montreal Neurol Inst Dept Neurol & Neurosurg Montreal PQ Canada Douglas Hosp Res Ctr Montreal PQ Canada Univ Sao Paulo Med Sch Dept Internal Med Div Geriatr Sao Paulo Brazil Univ Adolfo Ibanez Latin Amer Brain Hlth Inst BrainLat Santiago Chile Trinity Coll Dublin Global Brain Hlth Inst Dublin Ireland Univ San Andres Cognit Neurosience Ctr Buenos Aires Argentina

Background Latin American countries present major health-related inequities due to historical, cultural, and social aspects. Recent evidence highlights that factors related to social and health disparities outweigh classic demographic factors in determining healthy brain aging in these populations. However, these analyses have not been conducted with the Brazilian population, the largest and most ethnically diverse population in Latin America. Methods Here, we evaluated demographic, social, and health factors for healthy brain ageing using a machine learning model in a Brazilian population-based cohort (n=9412) and in additional cohorts from other Latin American countries, including Colombia (n=23 694), Chile (n=1301), Ecuador (n=5235), and Uruguay (n=1450). Findings In the Brazilian population and other Latin American countries, social and health disparities were more influential than demographic factors for cognition and functional ability. Uniquely in Brazil, education emerged as the primary risk factor impacting cognitive outcomes, diverging from other Latin American countries where mental health symptoms played more prominent roles. In terms of functional ability, Brazil displayed a distinct pattern, with mental health symptoms identified as the primary contributing factor. Interpretation Our findings indicate that Brazil converges with other Latin American countries to show that heterogeneous factors impacted more than demographic factors, but also showed a unique set of health factors when compared with other Latin American countries. Therefore, our study emphasises that social and health disparity factors are relevant predictors of healthy brain ageing in Latin America, but population-specific analyses are necessary to identify the specific risk profiles of each country.

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Enlarged perivascular space burden predicts declines in cognitive and functional performance

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JOURNAL OF THE NEUROLOGICAL SCIENCES 2024年 466卷 123232-123232页

作者： Libecap, T. J. Pappas, Colleen A. Bauer, Christopher E. Zachariou, Valentinos Raslau, Flavius D. Gold, Brian T. Univ Kentucky Coll Med MD PhD Program Lexington KY USA Univ Kentucky Coll Med Dept Neurosci Lexington KY USA Univ Kentucky Coll Med Dept Radiol Lexington KY USA Univ Kentucky Magnet Resonance Imaging & Spect Ctr Lexington KY USA Univ Kentucky Sanders Brown Ctr Aging Lexington KY USA

Introduction: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline. Methods: 83 community-dwelling, older adults (aged 56-86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR (R)) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD neuroimaging biomarkers. Results: At baseline, high basal ganglia ePVS counts were associated with lower executive function scores and episodic memory scores. Moreover, baseline basal ganglia ePVS predicted worse longitudinal CDR-SB scores over the study period. Discussion: Basal ganglia ePVS burden is a promising biomarker for cSVD-related cognitive and functional decline.

关键词： Enlarged perivascular spaces Magnetic resonance imaging Neuroimaging biomarkers Cerebral small vessel disease Clinical dementia rating (CDR (R)) dementia staging instrument

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Navigating medication-taking after kidney transplant

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RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY 2022年第10期18卷 3846-3854页

作者： Balakrishnan, Aparna Weinmeyer, Richard Serper, Marina Bailey, Stacy Cooper Kaiser, Karen Wolf, Michael Northwestern Univ Feinberg Sch Med Chicago IL USA Univ Penn Perelman Sch Med Div Gastroenterol & Hepatol Philadelphia PA USA Northwestern Univ Inst Publ Hlth & Med Ctr Appl Hlth Res Aging Chicago IL USA Northwestern Univ Feinberg Sch Med Hlth Sci Integrated PhD Program 633 N St Clair20th Floor Chicago IL 60611 USA

Background: Mixed methods are valuable in understanding multifaceted health behaviors like medication adherence. Kidney transplant recipients (KTRs) have complex medication regimens and are more vulnerable to nonadherence relative to other transplant recipients. Yet mixed methods have not been widely applied to examine adherence among KTRs, especially in relation to prescribed medications beyond ***: As part of a sequential approach, we used in-depth interviews to better understand findings from a previous quantitative study and to describe additional factors that influence prescription medication-taking among adult ***: Semi-structured interviews were conducted with a purposive sample of 14 adult KTRs recruited from a transplant center in Chicago, IL. Deductive and inductive content analysis was used to code transcripts and identify key ***: Across the sample, we identified insurance challenges, disruptions in routine, and poor mental well-being as barriers to adherence at the patient level. For Black and Hispanic KTRs, poor communication between pro-viders and disjointed care transitions posed additional barriers at the health system level. Compared with White KTRs, Black and Hispanic KTRs experienced greater medication burden due to comorbidities, while medication and digital literacy challenges were unique to Hispanic ***: KTRs are often motivated to take medications as prescribed, but sometimes lack the capacity or support to do so. Eliciting KTR perspectives is necessary in addressing knowledge and resource gaps at the patient and health system levels to improve adherence. In addition, recognizing the relative burden of taking comor-bidity medications compared with immunosuppressants may important, particularly for Black and Hispanic KTRs.

关键词： Kidney transplant Medication -taking Medication adherence Post -transplant experience Qualitative research Mixed methods

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High diversity of strain clonality and metallo-β-lactamases genes among carbapenem-resistant Enterobacterales in Taiwan

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EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 2025年第2期44卷 251-262页

作者： Lee, Jia-Arng Kuo, Yao-Wen Du, Shin-Hei Lee, Tai-fen Liao, Chun-Hsing Huang, Yu-Tsung Hsueh, Po-Ren Natl Taiwan Univ Coll Med Dept Lab Med Natl Taiwan Univ Hosp Taipei Taiwan Natl Taiwan Univ Grad Inst Clin Lab Sci & Med Biotechnol Taipei Taiwan Natl Taiwan Univ Coll Med Natl Taiwan Univ Hosp Dept Integrated Diagnost & Therapeut Taipei Taiwan Far Eastern Mem Hosp Dept Internal Med New Taipei City Taiwan Natl Yang Ming Univ Coll Med Taipei Taiwan Natl Taiwan Univ Coll Med Dept Internal Med Natl Taiwan Univ Hosp Taipei Taiwan China Med Univ Coll Med PhD Program Aging Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Internal Med Taichung Taiwan

PurposeThis study aimed to investigate the genetic and clinical characteristics of carbapenem-resistant Enterobacterales (CRE) isolates carrying metallo-beta-lactamases (MBLs) *** total of 146 non-duplicated isolates of CRE were collected in 2022. Their ceftazidime/avibactam (CZA) susceptibilities were determined using the E test. The phenotypic identification of carbapenemases was conducted using the modified carbapenem inactivation method, followed by sequencing of the five common carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48). Multilocus sequence typing of selected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae complex isolates were *** the 146 CRE isolates, 52 (35.6%) were resistant to CZA. MBL-encoding genes were detected in 46 (31.5%) of all tested CRE isolates, with 82.6% (n = 38) of them exhibiting resistance to CZA. Fourteen isolates were resistant to CZA without any detected MBL genes. The most commonly identified MBL genes were blaIMP (n = 20), followed by blaNDM (n = 19), and blaVIM (n = 5). In CZA-R, the most common definite antibiotic before the CZA E test was CZA (n = 18), followed by tigecycline (n = 13), and fluroquinolone (n = 10). The 14-day and 30-day mortality rates were 9.0% (n = 13) and 22.8% (n = 34), and were associated with intensive care unit admission at onset (P = 0.029 and P = 0.001, respectively). The sequence types of CRE isolates carrying MBLs were diverse without major *** continuous emergence of MBL gene-encoding CRE with multiple clones has led to reduced CZA susceptibilities and worse outcomes.

关键词： Enterobacterales Klebsiella oxytoca Enterobacter cloacae complex Carbapenem-resistant Metallo-beta-lactamases

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