Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections.
Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections.
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DOI：
10.1128/spectrum.04061-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
耐甲氧西林金黄色葡萄球菌（MRSA）在美国囊性纤维化（CF）患者中高度流行，并与CF的临床结局较差相关。这些感染往往成为慢性，尽管反复抗生素治疗。在这里，我们评估了细菌表型，包括抗生素耐受性，是否可以预测MRSA感染的临床结果。在事件中收集的MRSA分离株（n = 90）（即，对57名患者的急性）和早期感染状态进行了生长率、生物膜形成、溶血、色素沉着和万古霉素耐受性的表征。耐药性特征与既往研究一致。发现感染早期的分离株产生生物膜，70%的分离株表现出δ-溶血，这是agr活性的一个指标。24%的分离株存在较强的万古霉素耐受性，但与中等万古霉素敏感性无关。这些表型指标、抗生素耐药性和MRSA清除率之间没有关联。我们的研究表明，其他因素可能与预测MRSA的清除有关。重要性慢性MRSA感染仍然是囊性纤维化（CF）患者治疗的挑战。细菌种群在高浓度杀菌抗生素（包括万古霉素）中存活的能力，尽管缺乏耐药性，被认为是治疗失败的主要原因之一。抗生素耐受性和治疗结果之间的联系尚未探索，对于预后和根除方案的设计至关重要。在这项研究中，我们测量了90个从CF患者中分离的MRSA形成万古霉素耐受的持续细胞的能力，并评估了它们与临床结局的相关性。此外，系统地对可以反映这些MRSA分离株的代谢和/或毒力的各种性状进行表型分析，并纳入其预测能力。我们的研究强调，尽管抗生素耐受性很重要，但在预测MRSA清除率时还需要考虑其他因素。
Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in U.S. cystic fibrosis (CF) patients and is associated with worse clinical outcomes in CF. These infections often become chronic despite repeated antibiotic therapy. Here, we assessed whether bacterial phenotypes, including antibiotic tolerance, can predict the clinical outcomes of MRSA infections. MRSA isolates (n = 90) collected at the incident (i.e., acute) and early infection states from 57 patients were characterized for growth rates, biofilm formation, hemolysis, pigmentation, and vancomycin tolerance. The resistance profiles were consistent with those in prior studies. Isolates from the early stage of infection were found to produce biofilms, and 70% of the isolates exhibited delta-hemolysis, an indicator of agr activity. Strong vancomycin tolerance was present in 24% of the isolates but was not associated with intermediate vancomycin susceptibility. There were no associations between these phenotypic measures, antibiotic tolerance, and MRSA clearance. Our research suggests that additional factors may be relevant for predicting the clearance of MRSA. IMPORTANCE Chronic MRSA infections remain challenging to treat in patients with cystic fibrosis (CF). The ability of the bacterial population to survive high concentrations of bactericidal antibiotics, including vancomycin, despite lacking resistance is considered one of the main reasons for treatment failures. The connection between antibiotic tolerance and treatment outcomes remains unexplored and can be crucial for prognosis and regimen design toward eradication. In this study, we measured the capacity of 90 MRSA isolates from CF patients to form vancomycin-tolerant persister cells and evaluated their correlation with the clinical outcomes. Additionally, various traits that could reflect the metabolism and/or virulence of those MRSA isolates were systematically phenotyped and included for their predictive power. Our research highlights that despite the importance of antibiotic tolerance, additional factors need to be considered for predicting the clearance of MRSA.
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影响因子：
28.3
作者：
Rowe, Sarah E.;Wagner, Nikki J.;Conlon, Brian P.
通讯作者：
Conlon, Brian P.
影响因子：
5.2
作者：
Muhlebach, Marianne S.;Jiang, Xiaotong;Saiman, Lisa
通讯作者：
Saiman, Lisa
影响因子：
5.2
作者：
Jennings, Mark T.;Dasenbrook, Elliot C.;Merlo, Christian A.
通讯作者：
Merlo, Christian A.
通过巨噬细胞对沙门氏菌的内在化会导致形成非复制的持久性。
DOI：
10.1126/science.1244705
发表时间：
2014-01-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Helaine S;Cheverton AM;Watson KG;Faure LM;Matthews SA;Holden DW
通讯作者：
Holden DW
DOI：
10.1073/pnas.2014920118
发表时间：
2021-02-16
影响因子：
11.1
作者：
Huemer, Markus;Shambat, Srikanth Mairpady;Zinkernagel, Annelies S.
通讯作者：
Zinkernagel, Annelies S.