Pub Date : 2024-08-22DOI: 10.1016/j.jmii.2024.08.007
Vanesa Garrido-Rodríguez, Ángel Bulnes-Ramos, Israel Olivas-Martínez, María Del Mar Pozo-Balado, Ana Isabel Álvarez-Ríos, Félix Gutiérrez, Rebeca Izquierdo, Federico García, Juan Manuel Tiraboschi, Francisco Vera-Méndez, Joaquim Peraire, Anna Rull, Yolanda María Pacheco
Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression.
Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/β-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350).
Results: R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased β2-microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNγ/IL-2 secretion. However, comparing N ≤ 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern.
Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches.
{"title":"The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function.","authors":"Vanesa Garrido-Rodríguez, Ángel Bulnes-Ramos, Israel Olivas-Martínez, María Del Mar Pozo-Balado, Ana Isabel Álvarez-Ríos, Félix Gutiérrez, Rebeca Izquierdo, Federico García, Juan Manuel Tiraboschi, Francisco Vera-Méndez, Joaquim Peraire, Anna Rull, Yolanda María Pacheco","doi":"10.1016/j.jmii.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.08.007","url":null,"abstract":"<p><strong>Background: </strong>Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression.</p><p><strong>Methods: </strong>CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/β-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350).</p><p><strong>Results: </strong>R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased β2-microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNγ/IL-2 secretion. However, comparing N ≤ 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern.</p><p><strong>Conclusion: </strong>Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Data describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited.
Methods: This study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections.
Results: From January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections.
Conclusions: ALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy.
背景:描述急性淋巴细胞白血病(ALL)患者在诱导化疗后发生严重感染的风险因素以及预防性粒细胞集落刺激因子(G-CSF)在抗菌药物预防时代的作用的数据十分有限:本研究招募了188名年龄小于18岁的新确诊ALL患儿,他们在2010年1月1日至2021年6月30日期间接受了台湾儿科肿瘤学组ALL-2002和2013治疗。自2015年6月1日以来,患者在获得首次骨髓缓解后,如果继续出现中性粒细胞减少症,则会使用预防性G-CSF。对临床因素与严重感染的关系进行了评估:从2010年1月到2015年5月,80名儿童共发生了11次(13.5%)严重感染;而在108名接受预防性G-CSF的患者中,据报告发生了10次(9.2%)严重感染。在ALL患者预防性使用G-CSF期间,严重感染发生率的降低并没有统计学意义。与未使用 G-CSF 预防性治疗的 ALL 高危(HR)和极高危患者相比,使用 G-CSF 预防性治疗可显著减少发热性中性粒细胞减少症的发生。发生III-IV级肠回肠炎、II-III级口腔粘膜炎、中性粒细胞减少时间延长、中心静脉导管(CVC)置入或因高血糖需要胰岛素治疗与较高的血流感染风险有关:结论:ALL-HR患者接受G-CSF预防治疗可减少发热性中性粒细胞减少症的发生。在接受诱导化疗的ALL患者中,出现严重回肠炎、口腔黏膜炎、高血糖、CVC置入或中性粒细胞减少时间延长与严重感染有关。
{"title":"The clinical impact of primary granulocyte-colony stimulating factor prophylaxis in children with acute lymphoblastic leukemia who underwent induction chemotherapy.","authors":"Yi-An Lu, Hsi-Che Liu, Jen-Yin Hou, Nan-Chang Chiu, Ting-Huan Huang, Ting-Chi Yeh","doi":"10.1016/j.jmii.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.08.004","url":null,"abstract":"<p><strong>Background: </strong>Data describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited.</p><p><strong>Methods: </strong>This study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections.</p><p><strong>Results: </strong>From January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections.</p><p><strong>Conclusions: </strong>ALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/purpose: There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients.
Methods: From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment.
Results: Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026).
Conclusion: For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.
{"title":"Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals.","authors":"Ming-Han Hsieh, Tzu-Yu Kao, Ting-Hui Hsieh, Chun-Chi Kao, Cheng-Yuan Peng, Hsueh-Chou Lai, Hsing-Hung Cheng, Mao-Wang Ho, Chih-Yu Chi, Jung-Ta Kao","doi":"10.1016/j.jmii.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.08.005","url":null,"abstract":"<p><strong>Background/purpose: </strong>There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients.</p><p><strong>Methods: </strong>From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment.</p><p><strong>Results: </strong>Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 10<sup>3</sup>/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m<sup>2</sup> (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 10<sup>3</sup>/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026).</p><p><strong>Conclusion: </strong>For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 10<sup>3</sup>/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m<sup>2</sup>, sofosbuvir/ribavirin use, platelet counts <119 10<sup>3</sup>/μL, or the absence of early ALT normalization at 4 weeks after baseline.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Unveiling the dynamics of respiratory infections revealed by multiplex PCR testing during the COVID-19 pandemic in Taiwan, 2020-2023.","authors":"Hung-Chieh Su, Yu-Chang Chang, Chih-Hao Chen, Meng-Yu Cheng, Wen-Hsin Hsih, Yi-Jhen Chen, Chia-Huei Chou, Yu-Chao Lin, Chiung-Tzu Hsiao, Hong-Mo Shih, Mao-Wang Ho, Po-Ren Hsueh","doi":"10.1016/j.jmii.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.08.003","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.jmii.2024.08.002
Chou-Jui Lin , Jin-Hua Chen , Shun-Tien Chien , Yi-Wen Huang , Chih-Bin Lin , Jen-Jyh Lee , Chih-Hsin Lee , Ming-Chih Yu , Chen-Yuan Chiang
Background
Bedaquiline, delamanid and fluoroquinolones are associated with increased QTcF. Whether clofazimine is associated with QTcF prolongation is less clear.
Methods
All patients with rifampicin-resistant TB enrolled between May 2017 and Dec 2019 were included. ECGs were performed at baseline, month 1, month 3 and month 6 for patients treated with conventional regimens, and at additional timepoint for patients treated with bedaquiline, delamanid and short regimen. We estimated the maximum increase of QTcF and constructed cox proportional hazards models to assess factors associated with QTcF≥501ms.
Results
Among 321 patients, 59 (18.4%) patients had QTcF≥501ms during a mean follow-up of 242 days (median 189, range 4–1091). The median maximum increase of QTcF was 43.4 ms (IQR 31.3–65.9) in patients treated with clofazimine. Treatment with clofazimine was significantly associated with QTcF≥501ms as compared to without clofazimine (adjusted hazards ratio (adjHR) 4.35, 95% confidence interval (CI) 2.01–9.44). Among patients not treated with bedaquiline and delamanid, those treated with clofazimine and a fluoroquinolone (adjHR 3.43, 95% CI 1.61–7.34) and those treated with clofazimine and high dose moxifloxacin (adjHR 6.54, 95% CI 2.43–17.60) had a significantly higher risk of QTcF≥501ms as compared to those treated with a fluoroquinolone without other QTcF prolonging agents. Four (1.6%) patients had documented ventricular tachycardia, in which one was Torsade de pointes. One patient was found to have sudden death during hospitalization.
Conclusions
Clofazimine was significantly associated with an increased risk of QTcF prolongation. QTcF≥501ms was potentially associated with fatal event and needed to be managed cautiously.
{"title":"Clofazimine and QT prolongation in the treatment of rifampicin-resistant tuberculosis: Findings of aDSM in Taiwan","authors":"Chou-Jui Lin , Jin-Hua Chen , Shun-Tien Chien , Yi-Wen Huang , Chih-Bin Lin , Jen-Jyh Lee , Chih-Hsin Lee , Ming-Chih Yu , Chen-Yuan Chiang","doi":"10.1016/j.jmii.2024.08.002","DOIUrl":"10.1016/j.jmii.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><p>Bedaquiline, delamanid and fluoroquinolones are associated with increased QTcF. Whether clofazimine is associated with QTcF prolongation is less clear.</p></div><div><h3>Methods</h3><p>All patients with rifampicin-resistant TB enrolled between May 2017 and Dec 2019 were included. ECGs were performed at baseline, month 1, month 3 and month 6 for patients treated with conventional regimens, and at additional timepoint for patients treated with bedaquiline, delamanid and short regimen. We estimated the maximum increase of QTcF and constructed cox proportional hazards models to assess factors associated with QTcF≥501ms.</p></div><div><h3>Results</h3><p>Among 321 patients, 59 (18.4%) patients had QTcF≥501ms during a mean follow-up of 242 days (median 189, range 4–1091). The median maximum increase of QTcF was 43.4 ms (IQR 31.3–65.9) in patients treated with clofazimine. Treatment with clofazimine was significantly associated with QTcF≥501ms as compared to without clofazimine (adjusted hazards ratio (adjHR) 4.35, 95% confidence interval (CI) 2.01–9.44). Among patients not treated with bedaquiline and delamanid, those treated with clofazimine and a fluoroquinolone (adjHR 3.43, 95% CI 1.61–7.34) and those treated with clofazimine and high dose moxifloxacin (adjHR 6.54, 95% CI 2.43–17.60) had a significantly higher risk of QTcF≥501ms as compared to those treated with a fluoroquinolone without other QTcF prolonging agents. Four (1.6%) patients had documented ventricular tachycardia, in which one was Torsade de pointes. One patient was found to have sudden death during hospitalization.</p></div><div><h3>Conclusions</h3><p>Clofazimine was significantly associated with an increased risk of QTcF prolongation. QTcF≥501ms was potentially associated with fatal event and needed to be managed cautiously.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224001464/pdfft?md5=09591c0da3b02e01c30cbeef369b0c1b&pid=1-s2.0-S1684118224001464-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.jmii.2024.07.009
Li-Kuo Kuo , Hou-Tai Chang , Shun-Chung Hsueh , I-Min Liu , Po-Chuen Hsieh , Shio-Shin Jean
Objectives
To understand the microbial profile and investigate the independent predictors for healthcare-associated pneumonia (HCAP) pertinaciously caused by isolates of multidrug-resistant (MDR) Gram-negative bacteria (GNB).
Methods
Multicenter ICU patients who received appropriate antibiotic treatments for preceding pneumonia due to MDR GNB isolates and subsequently developed HCAP caused by either MDR GNB (n = 126) or non-MDR GNB (n = 40) isolates in Taiwan between 2018 and 2023 were enrolled. Between the groups of patients with HCAP due to MDR GNB and non-MDR GNB, the proportions of the following variables, including demographic characteristics, important co-morbidities, nursing home residence, physiological severity, intervals between two hospitalizations, steroid use, the tracheostomy tube use alone, ventilator support, and the predominant GNB species involving HCAP, were analyzed using the chi-square test. Logistic regression was employed to explore the independent predictors for HCAP persistently caused by MDR GNB in the aforementioned variables with a P-value of <0.15 in the univariate analysis.
Results
MDR-Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii complex were the three predominant species causing HCAP. Chronic structural lung disorders, diabetes mellitus, intervals of ≤30 days between two hospitalizations, use of the tracheostomy tube alone, and prior pneumonia caused by MDR A. baumannii complex were shown to independently predict the HCAP tenaciously caused by MDR GNB. Conversely, the preceding pneumonia caused by MDR P. aeruginosa was a negative predictor.
Conclusion
Identifying predictors for HCAP persistently caused by MDR GNB is crucial for prescribing appropriate antibiotics.
{"title":"Bacterial profile, and independent predictors for healthcare-associated pneumonia persistently caused by multidrug-resistant Gram-negative bacteria for patients with the preceding multidrug-resistant Gram-negative pneumonia in Taiwan","authors":"Li-Kuo Kuo , Hou-Tai Chang , Shun-Chung Hsueh , I-Min Liu , Po-Chuen Hsieh , Shio-Shin Jean","doi":"10.1016/j.jmii.2024.07.009","DOIUrl":"10.1016/j.jmii.2024.07.009","url":null,"abstract":"<div><h3>Objectives</h3><p>To understand the microbial profile and investigate the independent predictors for healthcare-associated pneumonia (HCAP) pertinaciously caused by isolates of multidrug-resistant (MDR) Gram-negative bacteria (GNB).</p></div><div><h3>Methods</h3><p>Multicenter ICU patients who received appropriate antibiotic treatments for preceding pneumonia due to MDR GNB isolates and subsequently developed HCAP caused by either MDR GNB (n = 126) or non-MDR GNB (n = 40) isolates in Taiwan between 2018 and 2023 were enrolled. Between the groups of patients with HCAP due to MDR GNB and non-MDR GNB, the proportions of the following variables, including demographic characteristics, important co-morbidities, nursing home residence, physiological severity, intervals between two hospitalizations, steroid use, the tracheostomy tube use alone, ventilator support, and the predominant GNB species involving HCAP, were analyzed using the chi-square test. Logistic regression was employed to explore the independent predictors for HCAP persistently caused by MDR GNB in the aforementioned variables with a <em>P</em>-value of <0.15 in the univariate analysis.</p></div><div><h3>Results</h3><p>MDR-<em>Klebsiella pneumoniae</em>, <em>Pseudomonas aeruginosa</em>, and <em>Acinetobacter baumannii</em> complex were the three predominant species causing HCAP. Chronic structural lung disorders, diabetes mellitus, intervals of ≤30 days between two hospitalizations, use of the tracheostomy tube alone, and prior pneumonia caused by MDR <em>A. baumannii</em> complex were shown to independently predict the HCAP tenaciously caused by MDR GNB. Conversely, the preceding pneumonia caused by MDR <em>P. aeruginosa</em> was a negative predictor.</p></div><div><h3>Conclusion</h3><p>Identifying predictors for HCAP persistently caused by MDR GNB is crucial for prescribing appropriate antibiotics.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S168411822400121X/pdfft?md5=1df95c0509fa51081cc6f881e4d055d5&pid=1-s2.0-S168411822400121X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.jmii.2024.07.010
Ruibing Yang, Meiyining Xu, Lichao zhang, Yao Liao, Yuheng Liu, Xiaoyan Deng, Lifu Wang
is an important soil-transmitted helminth occurring world-wide and affecting 30–100 million people. Because many cases are asymptomatic and sensitive diagnostic methods are lacking, infection is frequently underdiagnosed. The increasing incidence of autoimmune and wasting diseases and increased use of immunosuppressive agents, as well as the increased use of immunosuppressants and cytotoxic drugs, have increased infection and their mortality. This review provides information about epidemiology, life cycle, aetiology, pathology, comorbidities, immunology, vaccines, diagnosis, treatment, prevention, control and makes some recommendations for future prevention and control of this important parasite.
{"title":"Human Strongyloides stercoralis infection","authors":"Ruibing Yang, Meiyining Xu, Lichao zhang, Yao Liao, Yuheng Liu, Xiaoyan Deng, Lifu Wang","doi":"10.1016/j.jmii.2024.07.010","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.07.010","url":null,"abstract":"is an important soil-transmitted helminth occurring world-wide and affecting 30–100 million people. Because many cases are asymptomatic and sensitive diagnostic methods are lacking, infection is frequently underdiagnosed. The increasing incidence of autoimmune and wasting diseases and increased use of immunosuppressive agents, as well as the increased use of immunosuppressants and cytotoxic drugs, have increased infection and their mortality. This review provides information about epidemiology, life cycle, aetiology, pathology, comorbidities, immunology, vaccines, diagnosis, treatment, prevention, control and makes some recommendations for future prevention and control of this important parasite.","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We validated a modified enrichment broth that changes its color when group B Streptococcus (GBS) grows. No GBS was detected in any of the non-yellow samples. Thus, the non-yellow samples were considered GBS-negative without conducting further examinations, potentially reducing medical costs and workload.
我们验证了一种改良的富集肉汤,当 B 群链球菌(GBS)生长时,肉汤会变色。在非黄色样本中均未检测到 GBS。因此,非黄色样本被认为是 GBS 阴性样本,无需进行进一步检查,从而降低了医疗成本和工作量。
{"title":"Validation of a modified enrichment broth for efficient screening of group B Streptococcus in pregnant women.","authors":"Daiki Tanno, Kyoichi Saito, Yasuaki Tomii, Yukari Nakatsuka, Kohei Uechi, Kazutaka Ohashi, Yukio Yamadera, Atsuko Hata, Masahiro Toyokawa, Hiroki Shimura","doi":"10.1016/j.jmii.2024.07.015","DOIUrl":"https://doi.org/10.1016/j.jmii.2024.07.015","url":null,"abstract":"<p><p>We validated a modified enrichment broth that changes its color when group B Streptococcus (GBS) grows. No GBS was detected in any of the non-yellow samples. Thus, the non-yellow samples were considered GBS-negative without conducting further examinations, potentially reducing medical costs and workload.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.jmii.2024.07.007
Yu-Fang Chang , Yi-Ping Huang , Chia-Huei Chou , Mao-Wang Ho , Hwai-Jeng Lin , Chun-Ya Chen , Hui-Yu Wu , Yi-Ru Lai , Yuan-Haw Lee , Cheng-Hsun Chiu , Chih-Ho Lai
Background
Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated.
Methods
Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells.
Results
In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis.
Conclusion
Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by C. jejuni CDT.
{"title":"RAGE participates in the intracellular transport of Campylobacter jejuni cytolethal distending toxin","authors":"Yu-Fang Chang , Yi-Ping Huang , Chia-Huei Chou , Mao-Wang Ho , Hwai-Jeng Lin , Chun-Ya Chen , Hui-Yu Wu , Yi-Ru Lai , Yuan-Haw Lee , Cheng-Hsun Chiu , Chih-Ho Lai","doi":"10.1016/j.jmii.2024.07.007","DOIUrl":"10.1016/j.jmii.2024.07.007","url":null,"abstract":"<div><h3>Background</h3><p>Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to <em>Campylobacter jejuni</em>-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated.</p></div><div><h3>Methods</h3><p>Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells.</p></div><div><h3>Results</h3><p>In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis.</p></div><div><h3>Conclusion</h3><p>Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by <em>C. jejuni</em> CDT.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S168411822400118X/pdfft?md5=a3484fdd0b8722779904c781aae8d6e9&pid=1-s2.0-S168411822400118X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.jmii.2024.07.014
Geng-Lou Lin , Po-Hsun Chang , Ing-Kit Lee , Yi-Chun Chen , Chen-Hsiang Lee
Background
In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan.
Methods
The incidence of candidemia and fluconazole susceptibility of Candida species before (2015–2019) and during COVID-19 pandemic (2020–2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136).
Results
Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01–1.03), ICU stay (AOR = 1.84, 95% CI: 1.29–2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03–1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04–2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29–0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38–0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar.
Conclusion
While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.
{"title":"Clinical characteristics and outcomes of patients with candidemia during the COVID-19 pandemic: Insights from experience in the Omicron era","authors":"Geng-Lou Lin , Po-Hsun Chang , Ing-Kit Lee , Yi-Chun Chen , Chen-Hsiang Lee","doi":"10.1016/j.jmii.2024.07.014","DOIUrl":"10.1016/j.jmii.2024.07.014","url":null,"abstract":"<div><h3>Background</h3><p>In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan.</p></div><div><h3>Methods</h3><p>The incidence of candidemia and fluconazole susceptibility of <em>Candida</em> species before (2015–2019) and during COVID-19 pandemic (2020–2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136).</p></div><div><h3>Results</h3><p>Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01–1.03), ICU stay (AOR = 1.84, 95% CI: 1.29–2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03–1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04–2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29–0.74) and infected by <em>Candida parapsilosis</em> (AOR = 0.61, 95% CI: 0.38–0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar.</p></div><div><h3>Conclusion</h3><p>While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224001257/pdfft?md5=723511a1fb812240f021457f122de9e3&pid=1-s2.0-S1684118224001257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}