Mycobacterium abscessus complex

脓肿分枝杆菌复合体
  • 文章类型: Case Reports
    近几十年来,非结核分枝杆菌(NTM)感染的发病率大幅上升.然而,全球NTM的诊断和管理面临重大挑战,特别是在涉及脓肿分枝杆菌复合体(MABC)感染的病例中,有效的治疗选择有限。
    我们报道了一名38岁的女性患者,因美容院的“美容针”而感染了MABC的皮肤,双颊上有肿块,伴随着红肿,和痛苦,其中一些被切除了。从双侧脸颊肿块多次穿刺抽脓,用“甲硝唑”冲洗,口服“头孢菌素”治疗无效。因此,她来到我们医院。通过核酸质谱检测脓肿穿刺脓液中的MABC,并由脓液的培养结果证明。因此,患者被诊断为皮肤MABC感染,并采取抗NTM治疗。然而,不良反应,如耳鸣,在初始治疗期间发生肝毒性和神经毒性。在调整到含有康奈唑胺的方案后,这些不良反应有所改善。经过近6个月的治疗,面颊肿块逐渐减少,皮肤破裂逐渐愈合。随访10个月,患者面部症状明显改善,无药物相关不良反应发生。
    这是使用含有康奈唑胺的抗生素管理策略治疗的皮肤多重耐药性MABC感染的首例成功病例,在这种顽固性疾病中表现出显著的疗效和良好的安全性。
    UNASSIGNED: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited.
    UNASSIGNED: We reported a 38-year-old female patient who was infected with MABC of skin due to \"beauty needle\" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with \"metronidazole\", and oral \"cephalosporin\" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient\'s facial symptoms were significantly improved, and no drug-related adverse reactions happened.
    UNASSIGNED: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.
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  • 文章类型: Case Reports
    美容手术是非常受欢迎和魅力的主流媒体和名人。许多人认为某些身体特征对身体吸引力很有吸引力,并试图通过手术获得这些特征。然而,这些手术并非没有风险,如果不是由合格的医疗专业人员在无菌程序下进行,可能会产生重大后果。作者介绍了两名健康的年轻女性患者的新病例,这些患者在墨西哥的同一位整形外科医生相隔一周接受了巴西臀部提升(BBL)手术,并出现了继发于脓肿分枝杆菌的深色疼痛性病变(M.脓肿),多重耐药非结核分枝杆菌(NTM)。文献综述显示,通过此类外科手术进行NTM感染的数据很少。第一例是一名31岁的女性,她接受了BBL,并在几周后出现了双侧深色疼痛性臀部病变。病人回到整形外科医生那里,引流一些病变并开了口服抗生素。患者的临床状态继续恶化,并提交医院进行进一步评估。患者最初开始接受广谱抗生素治疗。发现该患者患有HIV感染,CD4淋巴细胞计数相对保留,并开始接受抗逆转录病毒治疗(ART)。术中切除组织样本培养物生长。患者开始服用经验性替加环素,头孢西丁,和利奈唑胺.初步培养物的敏感性显示对利奈唑胺具有抗性。利奈唑胺停药了,阿米卡星开始了,头孢西丁和替加环素继续使用。替加环素,头孢西丁,和阿米卡星继续进行,最终的敏感性显示出对当前治疗的敏感性。病人总共接受了四个月的替加环素治疗,头孢西丁,还有阿米卡星.第二例是一名28岁的妇女,该妇女在同一位外科医生的第一例患者一周后接受了BBL,并出现了多个臀部和身体脓肿。患者接受了双侧大腿和臀肌,右胸壁,在不同的医院设施进行乳腺外科清创术和术中培养,长了M.脓肿。在那里没有进行敏感性。患者被转移到我们的机构接受进一步治疗。术中文化保持阴性,患者接受了为期六个月的替加环素治疗,头孢西丁,还有阿米卡星.
    Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient\'s clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.
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  • 文章类型: Journal Article
    在快速增长的分枝杆菌(RGM)中,最相关和最致病的群体之一是脓肿分枝杆菌复合体(MABC),其中包括三个亚种:脓肿分枝杆菌亚种。脓肿,M.脓肿亚科。bolletii,和M.脓肿亚科。Massiliense.这项研究的目的是分析从波兰Malopolska地区患者中分离出的其他非结核分枝杆菌中MABC的患病率,在2018年至2021年之间,以及确定其亚种和对大环内酯类和氨基糖苷类耐药的分子机制。MABC发生率为5.4%(12/223)。八个菌株被分类为脓肿分枝杆菌亚种。脓肿,三个作为M.脓肿亚科。massiliense和一个M.脓肿亚种。bolletii.分子分析表明,八株脓肿分枝杆菌亚种对大环内酯类抗生素具有抗性。与erm(41)T28基因突变相关的脓肿。脓肿分枝杆菌亚种一株。脓肿对大环内酯类(同时有两个突变:erm(41)T28和rrl基因)和氨基糖苷类(rrs基因的点突变)具有抗性。一株脓肿分枝杆菌。bolletii对大环内酯类抗生素具有抗性(erm(41)T28突变),而氨基糖苷类无突变。M.脓肿亚科。Massiliense没有发现突变.脓肿分枝杆菌对克拉霉素的高耐药性,决定了基于易感性的治疗的迫切需要。对氨基糖苷类和大环内酯类的抗性机制的分子测定能够实现快速和准确的靶向治疗实施。
    One of the most relevant and pathogenic groups among the rapidly growing mycobacteria (RGM) is Mycobacterium abscessus complex (MABC) that includes three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. The aim of this study was the analysis of prevalence of MABC among other non-tuberculous mycobacteria isolated from patients in the Malopolska Region of Poland, between 2018 and 2021, as well as determination of their subspecies and molecular mechanisms of resistance to macrolides and aminoglycosides. The incidence of MABC was 5,4% (12/223). Eight strains were classified as M. abscessus subsp. abscessus, three as M. abscessus subsp. massiliense and one M. abscessus subsp. bolletii. Molecular analysis showed resistance to macrolides for eight strains of M. abscessus subsp. abscessus associated with erm(41)T28 gene mutations. One strain of M. abscessus subsp. abscessus showed resistance to macrolides (two mutations simultaneously: in erm(41)T28 and rrl genes) and aminoglycosides (point mutation in rrs gene). One strain of M. abscessus subs. bolletii was resistant to macrolides (erm(41)T28 mutation), whereas presented no mutations for aminoglycosides. M. abscessus subsp. massiliense reveal no mutations. High clarithromycin resistance of M. abscessus, determines the urgent need for susceptibility-based treatment. Molecular determination of resistance mechanisms to aminoglycosides and macrolides enables fast and accurate targeted treatment implementation.
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  • 文章类型: Case Reports
    非结核分枝杆菌(NTM)引起的感染发病率在世界范围内呈上升趋势,并且由于细菌对实践中常用的几种抗生素具有抗药性,因此它们变得越来越难以治疗。分枝杆菌脓肿复合体(MABC)是特别困难的治疗,因为它是最耐抗生素的物种之一,因此,有效清除感染的治疗选择有限。我们介绍了一名81岁的女性,她因类似的投诉在短时间内多次入院后被诊断出患有脓肿分枝杆菌,我们会讨论她的诊断和可能的治疗方案.这个案例探讨了医生在诊断NTM感染时面临的挑战,因为他们模仿了其他几种情况,并提出了高度临床怀疑的重要性。
    The incidence of infections caused by nontuberculous mycobacteria (NTM) is rising around the world, and they are becoming increasingly difficult to treat due to the bacteria being drug-resistant to several antibiotics commonly used in practice. Mycobacterium abscessus complex (MABC) is particularly difficult to treat as it is one of the most antibiotic-resistant species and, therefore, has limited treatment options that are effective at clearing the infection. We present the case of an 81-year-old female who was diagnosed with Mycobacterium abscessus after several hospital admissions in a short period of time for similar complaints, and we will discuss her diagnosis and possible treatment plan. This case explores the challenges that physicians face in diagnosing NTM infections due to them mimicking several other conditions and raises the importance of having a high clinical suspicion.
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  • 文章类型: Journal Article
    目的:本研究调查了流行病学和临床数据的差异,以及泰国一所医学院的脓肿分枝杆菌复合体(MABSC)临床分离株的不同亚种之间的抗菌敏感性。
    方法:对从74例患者中回收的143株MABSC临床分离株进行erm基因型分析(41株),rrl,和rrs突变,和抗菌敏感性是使用肉汤微量稀释法测定的。从病历中审查患者特征和临床结果。
    结果:74例患者感染了28/74(37.8%)脓肿亚种脓肿(MAB),43/74(58.1%)M.脓肿亚种。马西利(MMA),和3/74(4.1%)M.脓肿亚种。bolletii(MBO)。临床发现和结果通常在三个亚种之间没有区别。MABSC临床分离株的所有三个亚种对环丙沙星均表现出高耐药率,多西环素,莫西沙星,TMP/SMX,还有妥布霉素.MAB对克拉霉素的耐药率最高(27.8%,20/72)和阿米卡星(6.9%,5/72)与MBO和MMA相比,分别为p<0.001和p=0.004。此外,粗糙形态与阿米卡星耐药性显著相关(8.9%,5/56),克拉霉素(26.8%,15/56),和亚胺培南(76.8%,43/56)(p<0.001),而光滑形态对利奈唑胺具有抗性(57.1%,48/84)(p=0.002)。此外,ERM的T28(41),rrl(A2058C/G和A2059C/G),和rrs(A1408G)突变检测到87.4%(125/143),16.1%(23/143),和9.1%(13/143)的MABSC分离株,分别。
    结论:三种MABSC亚种在具有不同潜在合并症的患者中引起多种感染。泰国最近流行的MABSC菌株的药物敏感性模式在三个MABSC亚种和两个形态型中有所不同。
    OBJECTIVE: This study investigated the differences in epidemiological and clinical data, and antimicrobial susceptibilities among different subspecies of Mycobacterium abscessus complex (MABSC) clinical isolates at a medical school in Thailand.
    METHODS: A total of 143 MABSC clinical isolates recovered from 74 patients were genotypically analyzed for erm(41), rrl, and rrs mutations, and antimicrobial susceptibilities were determined using a broth microdilution method. Patient characteristics and clinical outcomes were reviewed from the medical records.
    RESULTS: Seventy-four patients were infected with 28/74 (37.8%) M. abscessus subspecies abscessus (MAB), 43/74 (58.1%) M. abscessus subsp. massiliense (MMA), and 3/74 (4.1%) M. abscessus subsp. bolletii (MBO). The clinical findings and outcomes were generally indistinguishable between the three subspecies. All three subspecies of MABSC clinical isolates exhibited high resistance rates to ciprofloxacin, doxycycline, moxifloxacin, TMP/SMX, and tobramycin. MAB had the highest resistance rates to clarithromycin (27.8%, 20/72) and amikacin (6.9%, 5/72) compared to MBO and MMA, with p < 0.001 and p = 0.004, respectively. In addition, the rough morphotype was significantly associated with resistance to amikacin (8.9%, 5/56), clarithromycin (26.8%, 15/56), and imipenem (76.8%, 43/56) (p < 0.001), whereas the smooth morphotype was resistant to linezolid (57.1%, 48/84) (p = 0.002). In addition, T28 of erm(41), rrl (A2058C/G and A2059C/G), and rrs (A1408G) mutations were detected in 87.4% (125/143), 16.1% (23/143), and 9.1% (13/143) of MABSC isolates, respectively.
    CONCLUSIONS: Three MABSC subspecies caused a variety of infections in patients with different underlying comorbidities. The drug susceptibility patterns of the recent circulating MABSC strains in Thailand were different among the three MABSC subspecies and two morphotypes.
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  • 文章类型: Journal Article
    目的:脓肿分枝杆菌复合物占所有非结核分枝杆菌肺部感染的2.6%-13.0%,由于需要复杂的治疗方案,这些疾病很难治疗。耐药性和不良反应。因此,噬菌体在临床实践中被认为是一种额外的治疗选择。这里,我们评估了脓肿分枝杆菌临床分离株的抗生素和噬菌体敏感性。全基因组测序(WGS)揭示了系统发育关系,显性循环克隆(DCC),患者间传播的可能性和存在的预言。
    方法:使用CLSI断点(n=95)进行抗生素敏感性测试,和斑块测定用于噬菌体敏感性测试(n=88,35粗糙和53光滑形态的子集)。WGS使用Illumina平台完成,并使用Snippy/snp-dists和DEPhT进行分析。
    结果:阿米卡星和替加环素是最活跃的药物(有两株对阿米卡星耐药,和一株替加环素MIC为4μg/ml)。大多数菌株对所有其他测试的药物都有抗药性,利奈唑胺和亚胺培南的耐药性最小,38%(36/95)和55%(52/95),分别。粗糙的菌落形态型菌株比光滑菌株对噬菌体更敏感(在斑块测定中,77%-27/35-与48%-25/53,但是在液体感染测定中,那些噬菌体不能有效地杀死光滑菌株)。我们还确定了100个居民先知,其中一些是抒情繁殖的。观察到DCC1(20%-18/90)和DCC4(22%-20/90)是主要的克隆,WGS鉴定了六个可能的患者间传播事件。
    结论:许多脓肿分枝杆菌复合体菌株对现有抗生素和噬菌体具有内在的耐药性,代表了一种替代治疗选择,但仅限于形态粗糙的菌株。需要进一步的研究来阐明医院传播的脓肿分枝杆菌的作用。
    OBJECTIVE: Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages.
    METHODS: Antibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT).
    RESULTS: Amikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 μg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%-27/35 versus 48%-25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%-18/90) and DCC4 (22%-20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission.
    CONCLUSIONS: Many strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission.
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  • 文章类型: Journal Article
    未经证实:目前推荐的抗脓肿分枝杆菌复合物(MABC)治疗方案的疗效不令人满意,导致了对抗MABC感染的新药的开发。在这项研究中,我们评估了bedaquiline(BDQ)和四种恶唑烷酮对MABC分离株的体外抗菌活性。
    UNASSIGNED:进行刃天青微板测定以确定BDQ和四种恶唑烷酮的最低抑制浓度(MIC),包括替迪唑胺(TZD),sutezolid(SZD),德帕唑啉(DZD),利奈唑胺(LZD),针对65个MABC分离株。使用棋盘法研究各种抗微生物药物组合的功效。
    未经鉴定:MABC分离株的BDQMIC范围为<0.031至1µg/mL,而MIC50和MIC90值分别为0.125µg/mL和0.25µg/mL,分别。MABC分离株的TZDMIC50和MIC90值分别为1µg/mL和4µg/mL,分别,比相应的LZD值低四倍(P<0.001)。MABC分离株的DZDMIC90值为8微克/毫升,比相应的LZD值低0.5倍(P<0.01)。BDQ的MIC,SZD,脓肿亚种分离株的LZD和LZD显着低于脓肿亚种分离株的相应MIC(P<0.05)。值得注意的是,使用恶唑烷酮(DZD,SZD,LZD,或TZD)与BDQ对MABC分离物的作用导致恶唑烷酮的中位MIC范围从4至0.125µg/mL降低至1-0.031µg/mL。
    UNASSIGNED:这些结果证明了对MABC分离株的优异BDQ抑制活性。与DZD的功效相比,TZD对MABC分离株表现出更强的抗微生物功效,SZD,还有LZD.重要的是,恶唑烷酮与BDQ联用时,其MIC显著降低,因此表明BDQ和恶唑烷酮的组合可能是MABC感染的有效治疗方法。
    UNASSIGNED: Unsatisfactory efficacies of currently recommended anti-Mycobacterium abscessus complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates.
    UNASSIGNED: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. A checkerboard method was used to investigate efficacies of various antimicrobial drug combinations.
    UNASSIGNED: BDQ MICs for MABC isolates ranged from <0.031 to 1 µg/mL, while MIC50 and MIC90 values were 0.125 µg/mL and 0.25 µg/mL, respectively. TZD MIC50 and MIC90 values for MABC isolates were 1 µg/mL and 4 µg/mL, respectively, which were fourfold lower than corresponding LZD values (P < 0.001). DZD MIC90 values for MABC isolates was 8 µg/mL, which were 0.5-fold lower than corresponding LZD values (P < 0.01). MICs of BDQ, SZD, and LZD for M. abscessus subspecies massiliense isolates were significantly lower than corresponding MICs for M. abscessus subspecies abscessus isolates (P < 0.05). Notably, use of oxazolidinones (DZD, SZD, LZD, or TZD) with BDQ against MABC isolates led to reduction of the oxazolidinone median MIC range from 4 to 0.125 µg/mL to 1-0.031 µg/mL.
    UNASSIGNED: These results demonstrated excellent BDQ inhibitory activity against MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections.
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  • 文章类型: Journal Article
    抗鸟分枝杆菌复合物(MAC)抗体测试可测量细菌细胞壁中针对糖肽脂(GPL)核心的IgA抗体水平,并且是非结核分枝杆菌肺病(NTM-PD)的有用临床指标。然而,目前尚不能单独使用抗MAC抗体来诊断该疾病.
    研究目的是评估抗MAC抗体和临床发现的组合对诊断潜在NTM-PD的功效。
    该横断面研究包括使用抗MAC抗体测试的938名患者。NTM-PD是通过痰样品中相同物种的多个阳性培养物诊断的。使用多因素logistic回归模型来确定与NTM-PD相关的临床因素。
    总的来说,19.6%(184/938)的参与者被诊断为NTM-PD。在多变量分析中,抗MAC抗体阳性,低体重指数,没有恶性肿瘤,在诊断时,空洞形成的肺部病变与NTM-PD显着相关。抗MAC抗体检测中,MAC阳性率为79.4%(135/170),脓肿分枝杆菌复合体阳性率为55.6%(5/9),分别。
    应该进行支气管镜检查,特别是在某些类型的无法获得痰样本的个体中。除携带MAC的患者外,抗MAC抗体也呈阳性,但由于GPL中的不同成分,该比率可能较低。
    The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone.
    The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD.
    This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD.
    Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively.
    Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.
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  • 文章类型: Journal Article
    脓肿分枝杆菌复合体(MABC)的成员是耐多药的非结核分枝杆菌,并且越来越多地引起机会性肺部感染。然而,在中国,MABC分离株的遗传分型仍不清楚。对2014年至2016年上海市肺科医院下呼吸道感染患者的69株MABC临床分离株进行基因组分析。收集了69个临床菌株的基因组草案,总长度为4.5至5.6Mb,%GC含量(GC%)范围从63.9%到68.1%,和4,492至5,404个基因每个基因组。药敏试验表明,大多数分离株对许多抗菌药物具有耐药性,包括克拉霉素,但对替加环素敏感.分析显示存在赋予抗生素抗性的基因,包括大环内酯类,氨基糖苷类,利福平,还有四环素.此外,每个基因组鉴定出80至114个毒力基因,包括那些与巨噬细胞入侵有关的,铁掺入,避免免疫清除。移动遗传元件,包括插入序列,转座子,和基因组岛,是在基因组中发现的。所有MABC分离株的系统发育分析与另外41个完整的MABC基因组确定了三个进化枝;46个分离株聚集在进化枝I中,对应于M.脓肿亚科。脓肿,25株属于现有的克隆复合物。总的来说,这是我国首次对MABC临床分离株进行比较基因组分析.这些结果显示了编码抗微生物药物抗性的遗传决定子的显著种内变异,毒力,以及使用当前标记基因组合的移动元素和有争议的亚种分类。这些信息将有助于理解进化,抗菌素耐药性,和MABC菌株的发病机理,并促进未来的疫苗开发和药物设计。重要性在过去的十年里,脓肿分枝杆菌复合体(MABC)分离株感染的报道越来越多。MABC菌株通常在囊性纤维化(CF)患者中显示出高发病率,而在亚洲,这些菌株通常从具有显著基因组多样性的非CF患者中回收.目前的工作涉及抗生素耐药性的分析,毒力,通过全基因组测序,对上海肺科医院非CF肺部患者的69株MABC分离株进行了系统发育分析;它代表了中国首次在基因组水平上对MABC菌株的全面调查。这些发现突出了该组非结核分枝杆菌的多样性,并提供了对进化和发病机理的机制理解。这对于在中国开发针对致命MABC感染的新型有效抗菌疗法具有重要意义。
    Members of the Mycobacterium abscessus complex (MABC) are multidrug-resistant nontuberculous mycobacteria and increasingly cause opportunistic pulmonary infections. However, the genetic typing of MABC isolates remains largely unclear in China. Genomic analyses were conducted for 69 MABC clinical isolates obtained from patients with lower respiratory tract infections in Shanghai Pulmonary Hospital between 2014 and 2016. The draft genomes of the 69 clinical strains were assembled, with a total length of 4.5 to 5.6 Mb, a percent GC content (GC%) ranging from 63.9 to 68.1%, and 4,492 to 5,404 genes per genome. Susceptibility test shows that most isolates are resistant to many antimicrobials, including clarithromycin, but susceptible to tigecycline. Analyses revealed the presence of genes conferring resistance to antibiotics, including macrolides, aminoglycosides, rifampicin, and tetracyclines. Furthermore, 80 to 114 virulence genes were identified per genome, including those related to the invasion of macrophages, iron incorporation, and avoidance of immune clearance. Mobile genetic elements, including insertion sequences, transposons, and genomic islands, were discovered in the genomes. Phylogenetic analyses of all MABC isolates with another 41 complete MABC genomes identified three clades; 46 isolates were clustered in clade I, corresponding to M. abscessus subsp. abscessus, and 25 strains belonged to existing clonal complexes. Overall, this is the first comparative genomic analysis of MABC clinical isolates in China. These results show significant intraspecies variations in genetic determinants encoding antimicrobial resistance, virulence, and mobile elements and controversial subspecies classification using current marker gene combinations. This information will be useful in understanding the evolution, antimicrobial resistance, and pathogenesis of MABC strains and facilitating future vaccine development and drug design. IMPORTANCE Over the past decade, infections by Mycobacterium abscessus complex (MABC) isolates have been increasingly reported worldwide. MABC strains often show a high incidence in cystic fibrosis (CF) patients, whereas in Asia, these strains are frequently recovered from non-CF patients with significant genomic diversity. The present work involves analyses of the antimicrobial resistance, virulence, and phylogeny of 69 selected MABC isolates from non-CF pulmonary patients in Shanghai Pulmonary Hospital by whole-genome sequencing; it represents the first comprehensive investigation of MABC strains in China at the genomic level. These findings highlight the diversity of this group of nontuberculous mycobacteria and provide a mechanistic understanding of evolution and pathogenesis, which is valuable for the development of novel and effective antimicrobial therapies for deadly MABC infections in China.
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  • 文章类型: Journal Article
    脓肿分枝杆菌越来越被认为是导致免疫功能低下患者的威胁生命的感染的人类病原体。在实体器官移植(SOT)接受者中,有关该主题的数据很少。
    这项工作是一项单中心回顾性队列研究,研究了2013年至2018年间所有患有M脓肿阳性培养的SOT接受者。
    共有20名患者(55%为女性)符合纳入标准,包括1名肾脏接受者(5.0%),2肝脏受体(10.0%),12个肺受体(60.0%),1名心脏接受者(5.0%),和4个联合器官接受者(20.0%)。从SOT到感染的中位时间为100天(范围,30-431天)。13例(65.0%)患者(1例肾脏,1心脏,7肺,1肝脏,1肠,和2个多内脏)治疗,中位持续时间为185天(范围,20-523天)。其中,从8例呼吸道样本和5例非呼吸道样本中分离出脓肿;13例患者中有4例(30.8%)治疗失败,13例中有3例(23.1%)在诊断后1年内无关死亡。7例患者(5例肺移植受者)从呼吸道样本中分离出的生物体未接受治疗,因为他们的培养物代表气道定植或污染;其中,随访1年后,2例(28.6%)死亡(与感染无关),5例(71.4%)无感染存活。
    脓肿分枝杆菌感染影响SOT受者,临床失败比例很高。然而,在肺接受者中,并非所有的阳性培养都与感染相关,一些患者在没有治疗的情况下取得了良好的临床结局.因此,区分定植和感染很重要,SOT受者需要预防感染的措施和新的治疗药物。
    UNASSIGNED: Mycobacterium abscessus is increasingly recognized as a human pathogen causing life-threatening infections in immunocompromised patients. There is a paucity of data around this topic in solid organ transplant (SOT) recipients.
    UNASSIGNED: This work was a single-center retrospective cohort study of all SOT recipients with a positive culture for M abscessus between 2013 and 2018.
    UNASSIGNED: A total of 20 patients (55% female) met inclusion criteria, including 1 kidney recipient (5.0%), 2 liver recipients (10.0%), 12 lung recipients (60.0%), 1 heart recipient (5.0%), and 4 combined organ recipients (20.0%). The median time from SOT to infection was 100 days (range, 30-431 days). Thirteen (65.0%) patients (1 kidney, 1 heart, 7 lung, 1 liver, 1 intestine, and 2 multivisceral) were treated with a median duration of 185 antibiotic days (range, 20-523 days). Among them, M abscessus was isolated from respiratory samples in 8 and nonrespiratory samples in 5; 4 of 13 (30.8%) patients had treatment failure and 3 of 13 (23.1%) had unrelated deaths within 1 year after diagnosis. Seven patients (5 lung transplant recipients) with the organism isolated from respiratory samples were not treated as their cultures represented airway colonization or contamination; of those, 2 (28.6%) died (unrelated to infection) and 5 (71.4%) were alive without the infection after 1 year of follow-up.
    UNASSIGNED: Mycobacterium abscessus infections affect SOT recipients with a high proportion of clinical failures. However, in lung recipients, not all positive cultures correlated with infection, and without treatment some patients had good clinical outcomes. Thus, differentiating colonization from infection is important, and infection prevention measures and novel therapeutic agents are needed for SOT recipients.
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