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菌血症治疗:耐甲氧西林金黄色葡萄球菌(MRSA)至万古霉素耐药金黄色葡萄球菌(VRSA)。

Treatment of bacteraemia: meticillin-resistant Staphylococcus aureus (MRSA) to vancomycin-resistant S. aureus (VRSA).

机构信息

Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK.

出版信息

Int J Antimicrob Agents. 2013 Jun;42 Suppl:S17-21. doi: 10.1016/j.ijantimicag.2013.04.006. Epub 2013 May 8.

Abstract

Around the world, Staphylococcus aureus remains a dominant cause of bacteraemia. Whilst meticillin resistance remains the major phenotype of concern, various levels of reduced glycopeptide susceptibility are emerging with increasing frequency. The most common MRSA phenotypes now have raised vancomycin MICs within the susceptible range (MICs of 1-2mg/L). This phenomenon, known as MIC creep, is hotly contested and often denied. Key to detecting MIC creep may be to examine isolates fresh, as freezing can allow reversion to wild-type MIC, presumably by loss of mutations. Treatment failure is common with vancomycin and it is uncertain whether higher doses are beneficial. At the other extreme, when enough mutations have accumulated, full VISA status is achieved, although this can also be unstable on storage. Heteroresistant and VISA strains can be considered the inevitable end result of continued MIC creep and are even more likely to fail glycopeptide treatment. Currently full vancomycin resistance is uncommon, with only approximately 20 strains described and confirmed worldwide. Empirical treatment for patients with undefined Gram-positive sepsis can undoubtedly be improved by knowledge of MRSA status, so this is a potential advantage of hospital admission screening. If a patient is risk-assessed or screen-positive for MRSA, and infection is not serious, then vancomycin or teicoplanin is appropriate empirical therapy, providing loading doses are given to achieve therapeutic concentrations immediately (trough 15 mg/L). For life-threatening infections, the glycopeptides are inadequate unless the isolate is likely to be fully susceptible (Etest<1.5mg/L). If not, daptomycin (8-10mg/L) can be used as monotherapy but the MIC should be measured as soon as possible.

摘要

在全球范围内,金黄色葡萄球菌仍然是导致菌血症的主要原因。虽然耐甲氧西林仍然是主要关注的表型,但各种程度的糖肽类药物敏感性降低的情况正越来越频繁地出现。目前最常见的耐甲氧西林金黄色葡萄球菌(MRSA)表型具有升高的万古霉素 MIC 值,处于敏感范围(MIC 值为 1-2mg/L)。这种现象被称为 MIC 爬行,目前存在争议,且经常被否认。检测 MIC 爬行的关键可能是新鲜检查分离株,因为冷冻可以使野生型 MIC 恢复,推测是通过突变丢失。万古霉素治疗失败很常见,目前尚不清楚是否更高的剂量有益。在另一个极端,当积累了足够的突变时,就会达到完全 VISA 状态,尽管在储存时也可能不稳定。异质性耐药和 VISA 菌株可以被认为是 MIC 爬行的不可避免的最终结果,并且甚至更有可能使糖肽类药物治疗失败。目前,完全的万古霉素耐药并不常见,全世界仅描述和确认了大约 20 株。通过了解耐甲氧西林金黄色葡萄球菌的状态,无疑可以改善对革兰氏阳性菌脓毒症患者的经验性治疗,因此这是住院筛选的潜在优势。如果患者的革兰氏阳性菌脓毒症情况不明,且存在耐甲氧西林金黄色葡萄球菌感染风险或筛查阳性,则如果感染不严重,则可以使用万古霉素或替考拉宁进行经验性治疗,需要给予负荷剂量以立即达到治疗浓度(谷浓度 15mg/L)。对于危及生命的感染,糖肽类药物是不够的,除非分离株可能完全敏感(Etest<1.5mg/L)。如果不是,则可以单独使用达托霉素(8-10mg/L),但应尽快测量 MIC 值。

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