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Description of clinical cases and available diagnostic tools of oropharyngeal syphilis: a systematic review of the literature. 口咽梅毒临床病例和可用诊断工具的描述:文献系统回顾。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-06 DOI: 10.1186/s12879-024-10129-1
Pierre Guarino, Francesco Chiari, Carlo Carosi, Giustino Parruti, Claudio Donadio Caporale, Livio Presutti, Gabriele Molteni

Introduction: Syphilis is a systemic bacterial infection caused by the spirochete Treponema pallidum. Head and neck mucosal manifestations of syphilis can be observed in each and all of primary, secondary and tertiary syphilis, especially in the secondary one. Therefore, oropharynx is an unusual localization of syphilitic lesions, mainly represented by ulcerous lesions, tissue hypertrophy, mucosal patches and cancer-like lesions. Serology is routinely considered the gold standard for the screening and diagnosis of syphilis. However, direct detection is routinely used during polymerase chain reaction (PCR) of oropharyngeal tissue and suspicious cervical lymphadenopathies.

Methods: PRISMA 2020 guidelines were applied to make a systematic literature review with the aim to make an overview of clinical manifestations and diagnostic tools of oropharyngeal syphilitic infection. A computerized MEDLINE search was performed using the PubMed, Web of Science and Cochrane databases.

Results: The intended analysis was based on 38 papers, including a total of 55 cases. The main localization of oropharyngeal infection was the tonsil (71%), followed by lateral and posterior wall of oropharynx (16%). Ulcerous lesions were the most frequently encountered lesions in the primary syphilis (56%) and secondary syphilis (36%), whereas gumma's lesions were encountered in the tertiary syphilis (57%). Diagnosis based on serological assays was used in combination with non-treponemal methods to determine disease activity (80% cases).

Conclusions: Oropharyngeal syphilis has historically been referred to as the "great imitator" due to its highly variable manifestations, which can resemble malignancies. Physicians have to recognize oropharyngeal luetic features early, in order to set up an effective diagnostic and therapeutic work-up.

导言:梅毒是由苍白螺旋体引起的全身性细菌感染。梅毒的头颈部黏膜表现在原发性、二期和三期梅毒中均可见到,尤其是二期梅毒。因此,口咽部是梅毒病变的不常见部位,主要表现为溃疡性病变、组织肥大、粘膜斑块和癌样病变。血清学通常被认为是筛查和诊断梅毒的金标准。然而,在对口咽组织和可疑宫颈淋巴结病进行聚合酶链反应(PCR)时,通常会使用直接检测法:方法:采用 PRISMA 2020 指南进行系统性文献综述,旨在概述口咽部梅毒感染的临床表现和诊断工具。利用PubMed、Web of Science和Cochrane数据库对MEDLINE进行了计算机检索:预期分析基于 38 篇论文,共包括 55 个病例。口咽感染的主要部位是扁桃体(71%),其次是口咽侧壁和后壁(16%)。溃疡是一期梅毒(56%)和二期梅毒(36%)中最常见的病变,而在三期梅毒(57%)中则会出现古马病变。根据血清学检测进行诊断,并结合非抗梅毒法确定疾病的活动性(80%的病例):口咽梅毒的表现千变万化,可能与恶性肿瘤相似,因此历来被称为 "伟大的模仿者"。医生必须及早识别口咽梅毒的特征,以便制定有效的诊断和治疗方案。
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引用次数: 0
Antimicrobial stewardship programs in a Mexican private healthcare system: a self-assessment of core elements. 墨西哥私立医疗系统的抗菌药物管理计划:核心要素自我评估。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-06 DOI: 10.1186/s12879-024-09601-9
José Iván Castillo Bejarano, Dzoara Laura Lugo Ondarza, Juan O Galindo Galindo, Daniel Siller Rodríguez, Sara Paulina Rosales-González, Susana Patricia Cantú González, Jorge Alberto Vera Delgado

Background: Antimicrobial stewardship programs (ASPs) refer to a set of coordinated actions that improve the quality of care and combat antimicrobial resistance. Currently, information regarding the status of ASPs in Mexico is scarce. We aimed to describe the status of ASPs in 12 hospitals from Christus Muguerza Healthcare System.

Methods: A cross-sectional study was conducted in 12 hospitals, with a previously developed self-assessment tool to calculate each hospital's ASP development score. The self-assessment tool includes 7 standards with 23 items. Score categories were defined as; high, medium, low, or none. The overall ASP development score was calculated using the proportional weight of each standard. Participating hospitals were divided into 2 groups according to their bed count. Statistical analysis was conducted in Excel program (Microsoft, Redmont, Washington).

Results: 12 hospitals completed the self-assessment survey. The median overall ASP development score was 32.3%. The highest overall development scores were observed for hospitals with > 40 beds. The core elements with the lowest development scores were Education and training, and Reporting and feedback. Unlike hospitals with over 40 beds, those with 40 beds or less had a low development score for Hospital leadership support. The core element with the highest development score was Infection prevention and control.

Conclusions: This is the first multicenter assessment of ASPs in Mexico, revealing a high proportion of low-score hospitals. National implementation of ASPs is required to combat antimicrobial resistance.

背景:抗菌药物监管计划(ASPs)是指一整套协调行动,旨在提高医疗质量并对抗抗菌药物耐药性。目前,有关墨西哥抗菌药物管理计划现状的信息很少。我们旨在描述克里斯特斯-穆格萨医疗保健系统的 12 家医院的 ASPs 情况:在 12 家医院开展了一项横断面研究,使用之前开发的自我评估工具来计算每家医院的 ASP 发展得分。自我评估工具包括 7 项标准和 23 个项目。得分类别被定义为:高、中、低或无。ASP 发展总分是根据每项标准的权重比例计算得出的。根据床位数将参与医院分为两组。统计分析在 Excel 程序(Microsoft,Redmont,Washington)中进行:12 家医院完成了自我评估调查。ASP 总体发展得分的中位数为 32.3%。床位数大于 40 张的医院总体发展得分最高。发展得分最低的核心要素是教育和培训以及报告和反馈。与拥有 40 张以上床位的医院不同,拥有 40 张以下床位的医院在医院领导支持方面的发展得分较低。发展得分最高的核心要素是感染预防与控制:这是墨西哥首次对 ASP 进行多中心评估,发现低分医院的比例很高。需要在全国范围内实施 ASPs,以对抗抗菌药耐药性。
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引用次数: 0
Neuro-leishmaniasis with cauda equina syndrome and cranial nerve palsy: a rare manifestation of recurrent atypical visceral leishmaniasis. 神经利什曼病伴有马尾综合征和颅神经麻痹:复发性非典型内脏利什曼病的罕见表现。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-06 DOI: 10.1186/s12879-024-10082-z
Karthick Kumar Vaitheeswaran, Baidhnath Kumar Gupta, Rahul Krishnan G, Manish Soneja, Naval K Vikram, Upendra Baitha, Amandeep Singh, Naveet Wig, Mudsser Azam, Ruchi Singh, Ajay Garg, Nishikant Damle, Yamini Dharmashaktu

Background: Visceral leishmaniasis (VL) is a neglected tropical disease primarily affecting Brazil, East Africa, and India, with India accounting for 18% of the global burden. While VL typically presents with systemic symptoms like fever, weight loss, and splenomegaly, it can occasionally manifest atypically, posing significant diagnostic challenges. Neurological presentations of VL are extremely rare, making them difficult to suspect and diagnose. Cases where VL predominantly presents with neurological symptoms are particularly novel, underscoring the need for heightened awareness of such atypical manifestations in endemic regions.

Clinical case: A 38-year-old man with history of recurrent atypical VL presented with diffuse lower back pain, progressive tingling, numbness, weakness in the lower extremities, and double vision for one month. Clinical and radiological evaluations suggested cauda equina syndrome and cranial nerve palsy, accompanied by generalized lymphadenopathy, subcutaneous nodules, and skin papules. The differential diagnosis initially included disseminated tuberculosis, histoplasmosis, and lymphoma. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. Histopathology of lymph node and bone marrow revealed Leishmania amastigotes and subcutaneous nodule and skin biopsy revealed inflammatory cells with granulomas. Furthermore, the qPCR test on DNA from a subcutaneous nodule, lymph node, and CSF was positive for Leishmania kinetoplast DNA. The species was further confirmed as Leishmania donovani through ITS-based PCR amplification and sequencing. Finally, a diagnosis of relapse of VL with lymph node, cutaneous, and neurological involvement, including abducens nerve palsy and cauda equina syndrome, was established. He was treated with combination of liposomal amphotericin B and miltefosine, along with intrathecal hyaluronidase, resulting in significant improvement.

Conclusion: Unlike previously reported cases with both systemic and neurological symptoms, our patient predominantly presented with neurological manifestations, making this a unique and novel presentation of VL. This case highlights diagnostic challenges and management of atypical VL, emphasizing neurological involvement and successful therapeutic strategies.

背景:内脏利什曼病(VL)是一种被忽视的热带疾病,主要影响巴西、东非和印度,其中印度的发病率占全球发病率的 18%。虽然内脏利什曼病通常表现为发热、体重减轻和脾肿大等全身症状,但偶尔也会有不典型的表现,这给诊断带来了巨大挑战。VL 的神经系统表现极为罕见,因此难以怀疑和诊断。VL主要表现为神经系统症状的病例尤为新颖,突出表明在流行地区需要提高对此类不典型表现的认识:临床病例:一名 38 岁的男子曾反复出现非典型 VL,并伴有弥漫性下背痛、进行性刺痛、麻木、下肢无力和复视一个月。临床和放射学评估提示马尾综合征和颅神经麻痹,伴有全身淋巴结病、皮下结节和皮肤丘疹。最初的鉴别诊断包括播散性结核、组织胞浆菌病和淋巴瘤。脑脊液(CSF)分析表明患者患有炎症综合征。淋巴结和骨髓的组织病理学检查发现了利什曼原虫,皮下结节和皮肤活检发现了带有肉芽肿的炎性细胞。此外,对皮下结节、淋巴结和 CSF 的 DNA 进行的 qPCR 检测显示,利什曼原核 DNA 呈阳性。通过基于 ITS 的 PCR 扩增和测序,进一步确认了该病原体为多诺万利什曼病。最后,他被确诊为 VL 复发,并伴有淋巴结、皮肤和神经系统受累,包括外展神经麻痹和马尾综合征。他接受了两性霉素 B 脂质体和米替福新的联合治疗,并使用了鞘内透明质酸酶,结果病情明显好转:结论:与之前报道的同时伴有全身症状和神经系统症状的病例不同,我们的患者主要表现为神经系统症状,因此是一种独特而新颖的 VL 表现。本病例突出了非典型 VL 的诊断挑战和管理,强调了神经系统受累和成功的治疗策略。
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引用次数: 0
Prospective clinical surveillance for severe acute respiratory illness and COVID-19 vaccine effectiveness in Kenyan hospitals during the COVID-19 pandemic. COVID-19 大流行期间肯尼亚医院对严重急性呼吸道疾病和 COVID-19 疫苗有效性的前瞻性临床监测。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10140-6
Ruth Khadembu Lucinde, Henry Gathuri, Lynda Isaaka, Morris Ogero, Livingstone Mumelo, Dennis Kimego, George Mbevi, Conrad Wanyama, Edwin Onyango Otieno, Stella Mwakio, Metrine Saisi, Elizabeth Isinde, Irene Njeri Oginga, Alvin Wachira, Evans Manuthu, Hazel Kariuki, Jared Nyikuli, Cyprian Wekesa, Amos Otedo, Hannah Bosire, Steve Biko Okoth, Winston Ongalo, David Mukabi, Wilber Lusamba, Beatrice Muthui, Isaac Adembesa, Caroline Mithi, Mohammed Sood, Nadia Ahmed, Bernard Gituma, Matiko Giabe, Charles Omondi, Rashid Aman, Patrick Amoth, Kadondi Kasera, Fred Were, Wangari Nganga, James A Berkley, Benjamin Tsofa, Jospeh Mwangangi, Philip Bejon, Edwine Barasa, Mike English, John Athony Gerard Scott, Samuel Akech, Eunice Wangeci Kagucia, Ambrose Agweyu, Anthony Oliwa Etyang

Background: There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic.

Methods: We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) and progression to inpatient mortality among patients admitted with SARI, using a test-negative case control design.

Results: Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77).

Conclusion: We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.

背景:撒哈拉以南非洲地区描述 COVID-19 大流行期间公立医院收治的严重急性呼吸道感染患者的人口统计学特征、临床特征和预后的数据非常有限:2020年5月至2022年12月期间,我们在肯尼亚16家公立医院开展了一项前瞻性纵向医院哨点监测。所有在参与医院成人内科病房住院的 18 岁以上患者均被纳入监测范围。我们收集了有关人口统计学和临床特征、SARS-CoV-2 感染和 COVID-19 疫苗接种情况以及入院结果的数据。我们采用试验阴性病例对照设计,确定了 COVID-19 疫苗对 SARS-CoV-2 阳性严重急性呼吸道疾病(SARI)(即 COVID-19)入院的有效性(VE),以及 SARI 入院患者的住院死亡率:在纳入研究的 52,636 名患者中,17,950 人(34.1%)因 SARI 入院。中位年龄为 50 岁。男女患者人数相当。出院时最常见的诊断是肺炎。高血压、人类免疫缺陷病毒(HIV)感染和糖尿病是最常见的慢性并发症。在接受检测的 8471 名患者中,有 2364 人(27.9%)的 SARS-CoV-2 检测结果呈阳性。在对年龄、性别和是否存在慢性并发症进行调整后,与非 SARI 患者相比,无论其 SARS-CoV-2 感染状况如何,SARI 患者都更有可能发展为住院病人死亡(SARI 和 SARS-CoV-2 阴性患者的调整赔率(aOR)为 1.22,95% CI 为 1.10-1.37;SARI 和 SARS-CoV-2 阳性患者的调整赔率(aOR)为 1.32,95% CI 为 1.24-1.40)。在对年龄、性别和是否存在慢性并发症进行调整后,COVID-19 VE 对已确认接种疫苗的 SARI 患者入院后的住院死亡率的影响为 0.59(95% CI 0.27-0.77):我们全面描述了 COVID-19 大流行期间肯尼亚医院收治的 SARI 患者的人口和临床模式以及这些患者的 COVID-19 VE。这些数据有助于了解肯尼亚大流行头三年的情况,并为国家应对措施提供信息。
{"title":"Prospective clinical surveillance for severe acute respiratory illness and COVID-19 vaccine effectiveness in Kenyan hospitals during the COVID-19 pandemic.","authors":"Ruth Khadembu Lucinde, Henry Gathuri, Lynda Isaaka, Morris Ogero, Livingstone Mumelo, Dennis Kimego, George Mbevi, Conrad Wanyama, Edwin Onyango Otieno, Stella Mwakio, Metrine Saisi, Elizabeth Isinde, Irene Njeri Oginga, Alvin Wachira, Evans Manuthu, Hazel Kariuki, Jared Nyikuli, Cyprian Wekesa, Amos Otedo, Hannah Bosire, Steve Biko Okoth, Winston Ongalo, David Mukabi, Wilber Lusamba, Beatrice Muthui, Isaac Adembesa, Caroline Mithi, Mohammed Sood, Nadia Ahmed, Bernard Gituma, Matiko Giabe, Charles Omondi, Rashid Aman, Patrick Amoth, Kadondi Kasera, Fred Were, Wangari Nganga, James A Berkley, Benjamin Tsofa, Jospeh Mwangangi, Philip Bejon, Edwine Barasa, Mike English, John Athony Gerard Scott, Samuel Akech, Eunice Wangeci Kagucia, Ambrose Agweyu, Anthony Oliwa Etyang","doi":"10.1186/s12879-024-10140-6","DOIUrl":"10.1186/s12879-024-10140-6","url":null,"abstract":"<p><strong>Background: </strong>There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic.</p><p><strong>Methods: </strong>We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) and progression to inpatient mortality among patients admitted with SARI, using a test-negative case control design.</p><p><strong>Results: </strong>Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77).</p><p><strong>Conclusion: </strong>We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.</p>","PeriodicalId":8981,"journal":{"name":"BMC Infectious Diseases","volume":"24 1","pages":"1246"},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk factors affecting the development of pneumothorax in patients followed up in intensive care with a diagnosis of COVID-19. 影响诊断为 COVID-19 的重症监护随访患者发生气胸的风险因素。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10147-z
Yasemin Bozkurt Turan
<p><strong>Background: </strong>Pneumothorax is a little known and reported complication of COVID-19. These patients have poorer general outcomes and greater respiratory support requirements, longer hospitalization times, and higher mortality rates. The purpose of this study was to determine which factors predict mortality in patients with tube thoracostomy diagnosed with COVID-19, admitted to the COVID-19 intensive care unit (ICU), and developing pneumothorax.</p><p><strong>Methods: </strong>This respective, observational study was conducted in all COVID-19 ICUs at the Marmara University Pendik Training and Research Hospital, Türkiye. Patients admitted to the ICU with diagnoses of COVID-19 pneumonia and with chest tubes inserted due to pneumothorax were investigated retrospectively.</p><p><strong>Results: </strong>One hundred patients with tube thoracostomy were included in the study. Their median age was 68 (57-78), and 63% were men. The median follow-up time was 20 [10-29] days, and the median time from initial reverse transcriptase polymerase chain reaction (RT-PCR) results to tube thoracostomy was 17 [9-23] days. Initial RT-PCR results were positive in 90% of the patients, while 8% were negative, and 2% were unknown. Half the patients exhibited pulmonary involvement at thoracic computed tomography (CT) (n = 50), while 22 patients had COVID-19 reporting and data system (CO-RADS) scores of 5 (22%). Sixty-two patients underwent right tube thoracostomy, 24 left side placement, and 14 bilateral placement. The patients' mean positive end expiratory pressure (PEEP) level was 10.31 (4.48) cm H<sub>2</sub>O, with a mean peak inspiratory pressure (PIP) level of 26.69 (5.95) cm H<sub>2</sub>O, a mean fraction of inspired oxygen (FiO2) level of 80.06 (21.11) %, a mean respiratory rate of 23.71 (5.62) breaths/min, and a mean high flow nasal cannula (HFNC) flow rate of 70 (8.17) L/min. Eighty-seven patients were intubated (87%), six used non-rebreathable reservoir masks, four HFNC, two non-invasive mechanical ventilation (NIV), and one a simple face mask. Comorbidity was present in 70 patients, 25 had no comorbidity, and the comorbidity status of five was unknown. Comorbidities included hypertension (38%), diabetes mellitus (23%), cardiovascular disease (12%), chronic obstructive pulmonary disease (5%), malignancy (3%), rheumatological diseases (3%), dementia (2%) and other diseases (9%). Twelve of the 100 patients survived. The median survival time was 20 (17.82-22.18) days, and the median 28-day overall survival rate was 29% (20-38%). The multivariate Cox proportional hazards model indicated that age over 68 (HR = 2.23 [95% CI: 1.39-3.56]; p = 0.001), oxygenation status other than by intubation (HR = 2.24 [95% CI: 1.11-4.52]; p = 0.024), and HCO3- below 22 compared with a normal range of 22 to 26 (HR = 1.95 [95% CI: 1.08-3.50]; p = 0.026) were risk factors associated with mortality in patients in the ICU.</p><p><strong>Conclusions: </strong>Age over 68,
背景:气胸是 COVID-19 鲜为人知的并发症。这些患者的总体预后较差,需要更多的呼吸支持,住院时间较长,死亡率较高。本研究旨在确定哪些因素可预测被诊断为 COVID-19、入住 COVID-19 重症监护病房(ICU)并发生气胸的管式胸腔造口术患者的死亡率:这项观察性研究在土耳其马尔马拉大学彭迪克培训与研究医院的所有 COVID-19 重症监护室进行。对被诊断为 COVID-19 肺炎并因气胸而插入胸腔管的重症监护病房入院患者进行了回顾性调查:结果:100 名患者接受了胸腔插管手术。他们的中位年龄为 68 岁(57-78 岁),63% 为男性。随访时间的中位数为 20 [10-29] 天,从最初的逆转录酶聚合酶链反应(RT-PCR)结果到胸廓切开术的中位数为 17 [9-23] 天。90% 的患者最初的 RT-PCR 结果为阳性,8% 为阴性,2% 结果不明。半数患者在胸部计算机断层扫描(CT)中显示肺部受累(n = 50),22 名患者的 COVID-19 报告和数据系统(CO-RADS)评分为 5(22%)。62 名患者接受了右侧管式胸腔造口术,24 名患者接受了左侧造口术,14 名患者接受了双侧造口术。患者的平均呼气末正压 (PEEP) 为 10.31 (4.48) cm H2O,平均吸气峰压 (PIP) 为 26.69 (5.95) cm H2O,平均吸入氧饱和度 (FiO2) 为 80.06 (21.11) %,平均呼吸频率为 23.71 (5.62) 次/分钟,平均高流量鼻插管 (HFNC) 流速为 70 (8.17) L/分钟。87 名患者进行了插管(87%),6 名患者使用了非再通气储气罐面罩,4 名患者使用了高流量鼻导管,2 名患者使用了无创机械通气 (NIV),1 名患者使用了简易面罩。70 名患者有合并症,25 名患者无合并症,5 名患者合并症状况不明。合并症包括高血压(38%)、糖尿病(23%)、心血管疾病(12%)、慢性阻塞性肺病(5%)、恶性肿瘤(3%)、风湿病(3%)、痴呆(2%)和其他疾病(9%)。100 名患者中有 12 人存活。中位存活时间为20天(17.82-22.18),28天总存活率中位数为29%(20-38%)。多变量考克斯比例危险模型显示,年龄超过 68 岁(HR = 2.23 [95% CI: 1.39-3.56];P = 0.001)、除插管外的氧合状态(HR = 2.24 [95% CI: 1.11-4.52]; p = 0.024)、HCO3- 低于 22(正常范围为 22 至 26)(HR = 1.95 [95% CI: 1.08-3.50]; p = 0.026)是与 ICU 患者死亡率相关的风险因素:结论:COVID-19 肺炎患者的年龄超过 68 岁、接受插管以外的氧合治疗以及 HCO3- 值低于 22,是与气胸死亡率相关的预后因素。
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引用次数: 0
NLRP3 inflammasome activation contributes to acute liver injury caused by CVA6 infection in mice. NLRP3炎症小体活化是CVA6感染小鼠造成急性肝损伤的原因之一。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10136-2
Yaqi Xie, Quanman Hu, Guangcai Duan, Fang Wang, Feifei Feng, Dong Li, Wenjie Jiang, Wangquan Ji, Peiyu Zhu, Xiaolong Zhang, Jinzhao Long, Huifen Feng, Haiyan Yang, Shuaiyin Chen, Yuefei Jin

Background: Coxsackievirus (CV) A6 has emerged as an important causative agent in global outbreaks of hand, foot, and mouth disease (HFMD), which typically presents as a mild illness with a large generalized rash, herpes. However, some patients can develop encephalitis, pneumonia, myocarditis and liver injury. Our previous study took the view that CVA6 could replicate in mouse liver, leading to acute liver injury; however, the precise underlying mechanism remains elusive.

Methods: 10-day-old wild-type (WT, C57BL/6J) and NLRP3 knock-out (KO) mice were intraperitoneal (i.p.) inoculated with a lethal dose of the CVA6 strain. The muscle homogenate supernatant from normal mice was used to inoculate mock-infected mice. At 5 days post infection (dpi), the mouse liver was taken out for histopathological analyses and molecular biology experiments.

Results: Our in vivo experiments demonstrated that CVA6 caused severe liver injury in mice, as evidenced by pathological changes in liver slices, elevated liver injury markers (e.g., AST, ALT, LDH) and pro-inflammatory cytokines (e.g., IL-6, MCP-1, TNF-α, IL-1β). Further results revealed the activation of NLRP3 inflammasome characterized by the increase in the expression of NLRP3, Cleaved-Casp-1 (p20), mature IL-1β and IL-18. Importantly, upon CVA6 infection, NLRP3 KO mice exhibited attenuated pathological damage and reduced levels of pro-inflammatory cytokines production (e.g., TNF-α and IL-1β) compared with WT mice. Finally, increased levels of blood ALT, AST, LDH were strongly correlated with the severity of CVA6 patients.

Conclusion: Collectively, our findings suggest that the activation of NLRP3 inflammasome is involved in CVA6 infection-induced acute liver injury, providing novel insights into CVA6 infection associated adverse clinical outcomes.

背景:柯萨奇病毒(CV)A6 已成为全球爆发的手足口病(HFMD)的重要致病因子,手足口病通常表现为轻微疾病,伴有大面积全身性皮疹和疱疹。然而,有些患者会发展成脑炎、肺炎、心肌炎和肝损伤。我们之前的研究认为,CVA6可在小鼠肝脏中复制,导致急性肝损伤;然而,其确切的内在机制仍难以确定。方法:给10天大的野生型(WT,C57BL/6J)和NLRP3基因敲除(KO)小鼠腹腔注射致死剂量的CVA6菌株。正常小鼠的肌肉匀浆上清液用于接种模拟感染小鼠。感染后 5 天,取出小鼠肝脏进行组织病理学分析和分子生物学实验:我们的体内实验表明,CVA6 会造成小鼠严重的肝损伤,表现为肝切片的病理变化、肝损伤标志物(如 AST、ALT、LDH)和促炎细胞因子(如 IL-6、MCP-1、TNF-α、IL-1β)的升高。进一步的结果显示,NLRP3 炎性体被激活,其特征是 NLRP3、裂解-Casp-1(p20)、成熟 IL-1β 和 IL-18 的表达增加。重要的是,与 WT 小鼠相比,NLRP3 KO 小鼠在感染 CVA6 后病理损伤减轻,促炎细胞因子(如 TNF-α 和 IL-1β)产生水平降低。最后,血液中 ALT、AST 和 LDH 水平的升高与 CVA6 患者的严重程度密切相关:总之,我们的研究结果表明,NLRP3 炎性体的激活参与了 CVA6 感染诱导的急性肝损伤,为 CVA6 感染相关不良临床结局提供了新的见解。
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引用次数: 0
Antimicrobial susceptibility of enterobacterales causing bloodstream infection in United States medical centres: comparison of aztreonam-avibactam with beta-lactams active against carbapenem-resistant enterobacterales. 美国医疗中心中引起血流感染的肠杆菌的抗菌药敏感性:阿曲南-阿维菌素与对耐碳青霉烯类肠杆菌有效的β-内酰胺类药物的比较。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10133-5
Helio S Sader, John H Kimbrough, Rodrigo E Mendes, Mariana Castanheira

Background: Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.

Objectives: To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI.

Methods: 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020-2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase-encoding genes using Next-generation sequencing.

Results: Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48-like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48-like and MBL producers. The most active non-β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible).

Conclusions: Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.

背景:血流感染(BSI)与不良预后有关,尤其是当有效的抗菌治疗和感染源控制被延误时。由于在美国一些医疗中心,产生金属-β-内酰胺酶(MBL)和/或 OXA-48 类碳青霉烯酶的肠杆菌的频率正在增加,因此迫切需要有效的抗菌药物来治疗由这些微生物引起的感染。氨曲南-阿维巴坦正在临床开发中,用于治疗革兰氏阴性菌(包括 MBL 生产者)引起的感染:评估美国医疗中心引起 BSI 的肠杆菌的抗菌药敏感性,并比较唑来南-阿维巴坦与头孢唑肟-阿维巴坦、美罗培南-瓦硼巴坦、亚胺培南-雷巴坦、头孢克肟和其他用于治疗 BSI 的抗菌药的活性。方法:2020-2022 年期间,从美国 72 个医疗中心连续收集了 4802 个肠杆菌(每个病人 1 个),并通过肉汤微量稀释法进行了药敏试验。氨曲南-阿维菌素与固定浓度为 4 毫克/升的阿维菌素一起进行了测试。为进行比较,唑来南-阿维菌素的药代动力学/药效学易感性断点为≤ 8 mg/L。使用新一代测序技术检测了耐碳青霉烯类肠杆菌(CRE)分离物中的β-内酰胺酶编码基因:结果:氨曲南-阿维菌素对肠杆菌具有很高的活性;只有 2 个分离株的氨曲南-阿维菌素 MIC > 8 mg/L:1 个是对美罗培南敏感的大肠杆菌,1 个是产气荚膜杆菌(CRE)。所有碳青霉烯酶生产者和 98.0% 的 CRE 在唑氯南-阿维菌素 MIC ≤ 8 mg/L 时均受到抑制。头孢唑肟-阿维巴坦对 CRE 的敏感率为 81.6%,美罗培南-瓦巴坦为 65.3%,亚胺培南-雷巴坦为 61.2%,头孢克肟为 87.8%。氨曲南-阿维巴坦对所有(100.0%)美罗培南-伐巴内酰胺不敏感菌株(n = 17)、99.5%亚胺培南-雷巴内酰胺不敏感菌株(n = 206)和 90.0%头孢他啶-阿维巴坦不敏感菌株(n = 10)均保持活性(MIC,≤ 8 mg/L)。最常见的碳青霉烯酶是 KPC-2/3(占 CRE 的 57.1%)、OXA-48-like(16.3%)和 NDM(14.3%)。12.3% 的 CREs 中未发现碳青霉烯酶基因。头孢唑肟-阿维巴坦和美罗培南-伐硼巴坦对 100.0% 的 KPC 生产者具有活性,但头孢唑肟-阿维巴坦对 MBL 生产者的活性有限,美罗培南-伐硼巴坦对 OXA-48 样和 MBL 生产者的活性有限。对 CRE 最有效的非β-内酰胺类比较药物是庆大霉素(49.0% 易感)和阿米卡星(44.9% 易感):结论:氨曲南-阿维菌素对从美国医院 BSI 患者中分离出的大量肠杆菌,包括 CRE、MBL 生产者和对最近批准的 β-内酰胺酶抑制剂复方制剂耐药的分离菌具有强效活性。
{"title":"Antimicrobial susceptibility of enterobacterales causing bloodstream infection in United States medical centres: comparison of aztreonam-avibactam with beta-lactams active against carbapenem-resistant enterobacterales.","authors":"Helio S Sader, John H Kimbrough, Rodrigo E Mendes, Mariana Castanheira","doi":"10.1186/s12879-024-10133-5","DOIUrl":"10.1186/s12879-024-10133-5","url":null,"abstract":"<p><strong>Background: </strong>Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.</p><p><strong>Objectives: </strong>To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI.</p><p><strong>Methods: </strong>4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020-2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase-encoding genes using Next-generation sequencing.</p><p><strong>Results: </strong>Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48-like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48-like and MBL producers. The most active non-β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible).</p><p><strong>Conclusions: </strong>Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.</p>","PeriodicalId":8981,"journal":{"name":"BMC Infectious Diseases","volume":"24 1","pages":"1242"},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association between adherence to unhealthy plant-based diet and risk of COVID-19: a cross-sectional study. 坚持不健康植物性饮食与 COVID-19 风险之间的关系:一项横断面研究。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10115-7
Mina Darand, Sahar Golpour-Hamedani, Elham Karimi, Shirin Hassanizadeh, Masoud Mirzaei, Vahid Arabi, Azadeh Nadjarzadeh, Mahdieh Hosseinzadeh

Background: The fast spread of the coronavirus disease 2019 (COVID-19) epidemic and its high mortality were quickly considered by the health community. Dietary patterns play an important role in strengthening or weakening the immune system and thus incidence of diseases.

Aim: The present study can provide a comprehensive picture of the association between adherence to unhealthy plant-based diet (uPDI) and COVID-19 incidence.

Methods: This study was undertaken on 8157 adults' participants of the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study aged 20 to 70 years. Data on dietary intakes were obtained using a validated food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to assess the association between uPDI and COVID-19.

Results: We found a significant association between uPDI and the risk of COVID-19 (OR: 1.36; 95% CI: 1.05-1.75) in the crude model. After adjusting potential confounders, a significant increasing trend in the odds of COVID-19 across increasing quintiles of uPDI (OR: 1.58;95% CI: 1.05-2.37; P-value: 0.027) was observed. Stratified analysis based on sex indicated that uPDI significantly increased the risk of COVID-19 only in males (OR: 1.73;95% CI: 1.12-2.67; P-value: 0.012) and had no effect on females.

Conclusions: Participants in the highest quintiles of the uPDI had 58% higher odds of COVID-19 compared to subjects in the lowest quintile of uPDI. Although our study has promising results, stronger clinical studies are needed.

背景:2019年冠状病毒病(COVID-19)疫情的快速传播和高死亡率迅速引起了卫生界的关注。膳食模式在增强或削弱免疫系统、进而降低疾病发病率方面发挥着重要作用。目的:本研究可全面了解坚持不健康植物性膳食(uPDI)与 COVID-19 发病率之间的关联:本研究的对象是亚兹德健康研究(YaHS)和Taghzieh Mardom-e-Yazd(TAMIZ)研究的 8157 名成人参与者,年龄在 20 岁至 70 岁之间。膳食摄入量数据是通过有效的食物频率问卷(FFQ)获得的。采用多变量逻辑回归分析评估 uPDI 与 COVID-19 之间的关系:结果:我们发现,在粗略模型中,uPDI 与 COVID-19 风险之间存在明显关联(OR:1.36;95% CI:1.05-1.75)。在调整了潜在的混杂因素后,我们观察到 COVID-19 的几率在 uPDI 的五分位数增加时呈显著上升趋势(OR:1.58;95% CI:1.05-2.37;P 值:0.027)。基于性别的分层分析表明,uPDI 仅显著增加男性 COVID-19 的风险(OR:1.73;95% CI:1.12-2.67;P 值:0.012),对女性没有影响:结论:与uPDI最低五分位数的受试者相比,uPDI最高五分位数的受试者发生COVID-19的几率高出58%。虽然我们的研究结果很有希望,但还需要更有力的临床研究。
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引用次数: 0
Dynamic modelling of improved diagnostic testing for drug-resistant tuberculosis in high burden settings. 在高负担环境中改进耐药结核病诊断检测的动态模型。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10027-6
Marya Getchell, John Pastor Ansah, Dodge Lim, Ramon Basilio, Francis Tablizo, Surakameth Mahasirimongkol, Waritta Sawaengdee, David Matchar

Background: Limited diagnostic testing for drug-resistant TB (DR-TB) may lead to high rates of misdiagnosis and undertreatment. Current diagnostic tests focus only on detection of rifampicin-resistant TB (RR-TB). This study aims to determine the impact of improved diagnostic testing for a wider range of drug resistance on DR-TB outcomes in high-burden TB settings, using the Philippines and Thailand as case studies.

Methods: A dynamic compartmental model was designed to simulate population level TB transmission, accounting for acquired drug resistance from treatment failure of drug susceptible TB. Three scenarios were analyzed: (1) Use of GeneXpert MTB/RIF on all presumptive TB cases (Status Quo); (2) GeneXpert MTB/RIF + GeneXpert XDR, (3) GeneXpert MTB/RIF + targeted Next Generation Sequencing (tNGS). Scenarios were modelled over a 10-year period, from 2025 to 2034.

Results: Compared to the status quo, Scenario 2 results in a fourfold increase in annual DR-TB cases diagnosed in the Philippines and a fivefold increase in Thailand. DR-TB treatment failure decreases by 20% in the Philippines and 23% in Thailand. Scenario 3 further increases DR-TB case detection, reducing DR-TB treatment failure by 26% in the Philippines and 29% in Thailand. Reductions in DR-TB incidence and mortality ranged from 3 to 6%.

Conclusion: The use of GeneXpert XDR or tNGS as an additional diagnostic test for DR-TB significantly improves DR-TB case detection and reduces treatment failure, supporting their consideration for use in high burden settings. These findings highlight the importance of detecting a wider range of TB resistance in addition to RR-TB, the potential impact these improved diagnostic tests can have on DR-TB outcomes, and the need for additional research on cost-effectiveness of these interventions.

背景:耐药性结核病(DR-TB)诊断检测的局限性可能会导致高误诊率和治疗不足。目前的诊断检测仅侧重于检测耐利福平肺结核(RR-TB)。本研究旨在以菲律宾和泰国为案例,确定在结核病高负担地区,改进诊断检测以检测更广泛的耐药性对 DR-TB 治疗结果的影响:方法:设计了一个动态分区模型来模拟人群水平的结核病传播,并考虑到易感结核病治疗失败后获得的耐药性。分析了三种情况:(1) 对所有推定肺结核病例使用 GeneXpert MTB/RIF(现状);(2) GeneXpert MTB/RIF + GeneXpert XDR;(3) GeneXpert MTB/RIF + 目标下一代测序 (tNGS)。方案模拟期为 10 年,从 2025 年到 2034 年:结果:与现状相比,方案 2 导致菲律宾每年确诊的 DR-TB 病例增加四倍,泰国增加五倍。菲律宾的 DR-TB 治疗失败率下降了 20%,泰国下降了 23%。方案 3 进一步提高了 DR-TB 病例的发现率,使菲律宾的 DR-TB 治疗失败率降低了 26%,泰国降低了 29%。DR-TB 发病率和死亡率的降幅在 3% 到 6% 之间:结论:使用 GeneXpert XDR 或 tNGS 作为 DR-TB 的附加诊断检测可显著提高 DR-TB 病例的检出率并减少治疗失败,因此可考虑在高负担环境中使用。这些发现强调了除 RR-TB 外检测更广泛的结核病耐药性的重要性、这些改进的诊断检测对 DR-TB 治疗结果的潜在影响,以及对这些干预措施的成本效益进行更多研究的必要性。
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引用次数: 0
Association between toxin-antitoxin system mutations and global transmission of MDR-TB. 毒素-抗毒素系统突变与耐药结核病全球传播之间的关系。
IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1186/s12879-024-10142-4
Yameng Li, Yang Shao, Yifan Li, Xianglong Kong, Ningning Tao, Yawei Hou, Tingting Wang, Yingying Li, Yao Liu, Huaichen Li

Background: The emergence of Multidrug-Resistant Tuberculosis (MDR-TB) poses a significant threat to global tuberculosis control efforts. This study aimed to examine the influence of mutations in Toxin-Antitoxin system genes on the global transmission of MDR-TB caused by Mycobacterium tuberculosis (M. tuberculosis).

Methods: Whole-genome sequencing was conducted on 13,518 M. tuberculosis isolates. Genes of the Toxin-Antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Techniques such as Random Forest, Gradient Boosting Decision Tree, and Generalized Linear Mixed Models were employed to identify mutation sites in Toxin-Antitoxin system-related genes that facilitated the transmission of MDR-TB.

Results: 4,066 (30.08%) were identified as MDR-TB strains of all analyzed isolates. We found significant associations between specific gene mutations and MDR-TB transmission clusters including mutations in Rv0298 (G213A), Rv1959c (parE1, C88T), Rv1960c (parD1, C134T), Rv1991A (maze, G156A), Rv2547 (vapB, C54G), Rv2862A (vapB23, T2C), and Rv3385c (vapB46, G70A). Additionally, several gene mutations associated with MDR-TB transmission clades such as Rv1956 (higA, G445T), Rv1960c (parD1, C134T), and Rv1962A (vapB35, G99A) were noted. Certain gene mutations including vapB35 (G99A), higA (G445T), and parD1 (C134T) correlated with cross-regional transmission clades.

Conclusion: This study highlights the significant association between specific gene mutations in the Toxin-Antitoxin system and the global transmission of MDR-TB, providing valuable insights for developing targeted interventions to control MDR-TB.

背景:耐多药结核病(MDR-TB)的出现对全球结核病控制工作构成了重大威胁。本研究旨在探讨毒素-抗毒素系统基因突变对结核分枝杆菌(M. tuberculosis)引起的耐多药结核病全球传播的影响:方法:对 13,518 例结核分枝杆菌分离株进行了全基因组测序。毒素-抗毒素系统的基因来自美国国家生物技术信息中心(NCBI)基因数据库。采用随机森林、梯度提升决策树和广义线性混合模型等技术来确定毒素-抗毒素系统相关基因中促进 MDR-TB 传播的突变位点:在所有分析的分离株中,有 4,066 株(30.08%)被确定为 MDR-TB 菌株。我们发现了特定基因突变与 MDR-TB 传播集群之间的重要关联,包括 Rv0298 (G213A)、Rv1959c (parE1, C88T)、Rv1960c (parD1, C134T)、Rv1991A (maze, G156A)、Rv2547 (vapB, C54G)、Rv2862A (vapB23, T2C) 和 Rv3385c (vapB46, G70A) 的突变。此外,还发现了一些与 MDR-TB 传播支系相关的基因突变,如 Rv1956(higA,G445T)、Rv1960c(parD1,C134T)和 Rv1962A(vapB35,G99A)。某些基因突变包括 vapB35 (G99A)、higA (G445T) 和 parD1 (C134T) 与跨区域传播支系相关:本研究强调了毒素-抗毒素系统中特定基因突变与 MDR-TB 全球传播之间的重要关联,为制定有针对性的干预措施以控制 MDR-TB 提供了宝贵的见解。
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BMC Infectious Diseases
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