Biology and management of methicillin resistant Staphylococcus aureus in cystic fibrosis
Biology and management of methicillin resistant Staphylococcus aureus in cystic fibrosis
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DOI：
10.1002/ppul.24139
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发表时间：
2018-11-01
影响因子：
3.1
通讯作者：
Muhlebach, Marianne S.
中科院分区：
文献类型：
--
作者：
Akil, Nour;Muhlebach, Marianne S.
金黄色葡萄球菌是最早从囊性纤维化（CF）患者的呼吸道中分离出的细菌之一。它的甲氧西林耐药形式MRSA由于在过去几十年中的快速增加和慢性感染的更差结果而引起了人们的关注。在美国，MRSA在CF中的患病率约为27%，但在大多数其他国家要低得多（3-18%）。甲氧西林通常由mecA基因遗传编码，该基因编码替代青霉素结合蛋白（PRBa）。这种PRBa对β-内酰胺具有低亲和力，从而能够促进S的生长。金黄色葡萄球菌在青霉素酶抗性青霉素和大多数其他β-内酰胺存在下。MRSA的非mecA阳性菌株，即所谓的临界耐药（BORSA）也已被描述。除产生毒素外，S.金黄色葡萄球菌是由其适应性赋予的，其允许在面对抗生素治疗和宿主防御时的持久性。这些适应性生长机制包括小菌落变体、生物膜和厌氧条件下的生长。一些报告描述了成功根除MRSA，但只有两个随机试验根除早期感染。此处列出了与CF患者相关的MRSA特异性抗生素及其剂量。其中许多药物需要在CF患者中进行特殊剂量。新的抗生素正在用于皮肤和软组织感染的试验中，目前还不清楚这些抗生素是否以及何时可用于肺部感染。因此，MRSA的最佳策略是一级预防。
Staphylococcus aureus is one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3-18%) in most other countries. Methicillin is typically genetically encoded by the mecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to -lactams, thereby enabling growth of S. aureus in the presence of penicillinase resistant penicillins and most other -lactams. Non-mecA positive strains of MRSA, so-called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence of S. aureus is conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.