The problem of Mycobacterium abscessus complex: multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission.

The problem of Mycobacterium abscessus complex: multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission.
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DOI:
10.1016/j.cmi.2023.06.026
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发表时间:
2023-10
影响因子:
14.2
通讯作者:
Satta, Giovanni
Satta, Giovanni
中科院分区:
医学1区
文献类型:
--
作者:
Dedrick, Rebekah M.;Abad, Lawrence;Storey, Nathaniel;Kaganovsky, Ari M.;Smith, Bailey E.;Aull, Haley A.;Cristinziano, Madison;Morkowska, Anna;Murthy, Saraswathi;Loebinger, Michael R.;Hatfull, Graham F.;Satta, Giovanni

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脓肿分枝杆菌复合体占所有非结核分枝杆菌肺部感染的 2.6-13.0%,由于所需的治疗方案复杂、耐药性和不良反应,这些感染非常难以治疗。因此,噬菌体在临床实践中被认为是一种额外的治疗选择。在这里,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概况。全基因组测序(WGS)揭示了系统发育关系、显性循环克隆(DCC)、患者之间传播的可能性以及原噬菌体的存在。使用 CLSI 断点(n = 95)进行抗生素敏感性测试,并使用噬菌斑测定进行噬菌体敏感性测试(n = 88、35 个粗糙形态和 53 个光滑形态的子集)。使用 Illumina 平台完成 WGS,并使用 Snippy/snp-dists 和噬菌体发现和提取工具 (DEPhT) 进行分析。阿米卡星和替加环素是最活跃的药物(2 株对阿米卡星耐药,1 株替加环素 MIC 为 4 μg/mL)。大多数菌株对所有其他测试药物都具有耐药性,其中利奈唑胺和亚胺培南的耐药性最小,分别为 38% (36/95) 和 55% (52/95)。粗糙菌落形态型菌株比平滑菌株对噬菌体更敏感(噬菌斑测定中为 77%—27/35 对 48%—25/53,但在液体感染测定中平滑菌株不能被这些噬菌体有效杀死)。我们还鉴定了 100 种常驻原噬菌体,其中一些是通过裂解繁殖的。据观察,DCC1 (20%—18/90) 和 DCC4 (22%—20/90) 是主要克隆,WGS 确定了 6 个可能的患者间传播事件。脓肿分枝杆菌复合体的许多菌株本质上对可用的抗生素具有耐药性,噬菌体代表了一种替代治疗选择,但仅适用于形态粗糙的菌株。需要进一步的研究来阐明医院传播的脓肿分枝杆菌传播的作用。
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. 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). 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. 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.
DOI: 10.3390/v10040189
发表时间: 2018-04-12
期刊: Viruses
影响因子: --
作者:
Xie Y;Wahab L;Gill JJ
通讯作者: Gill JJ
DOI: 10.3201/eid2109.141634
发表时间: 2015-09-01
影响因子: 11.8
作者:
Lee, Meng-Rui;Sheng, Wang-Huei;Hsueh, Po-Ren
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发表时间: 2021-05-20
期刊: mBio
影响因子: 6.4
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Guerrero-Bustamante CA;Dedrick RM;Garlena RA;Russell DA;Hatfull GF
通讯作者: Hatfull GF
DOI: 10.1093/cid/ciac453
发表时间: 2023-01-06
期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子: --
作者:
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DOI: 10.1038/s41564-021-00963-3
发表时间: 2021-10
影响因子: 28.3
作者:
Ruis C;Bryant JM;Bell SC;Thomson R;Davidson RM;Hasan NA;van Ingen J;Strong M;Floto RA;Parkhill J
通讯作者: Parkhill J