Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein

Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein
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DOI:
10.1086/423145
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发表时间:
2004-09-15
影响因子:
6.4
通讯作者:
Bayer, AS
Bayer, AS
中科院分区:
医学2区
文献类型:
--
作者:
Fowler, VG;Sakoulas, G;Bayer, AS

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背景耐甲氧西林金黄色葡萄球菌(MRSA)引起持续性菌血症(PB)的原因知之甚少。本研究探讨了PB与关键临床特征和几种体外细菌基因型和表型特征之间的潜在相关性,分离自1个机构。脉冲场凝胶电泳(PFGE)相关性、凝血酶诱导的血小板杀微生物蛋白(tPMP)敏感性表型、辅助基因调节因子(agr)基因型和功能性(通过δ-溶素产生),从21例前瞻性确定的PB患者的血流中分离MRSA,(血培养阳性后大于或等于7天的治疗)和18例缓解菌血症(RB)的患者(无菌血培养在治疗的前2-4天内)。两组具有可比的基线特征,但其临床病程不同(例如,PB患者的心内膜炎发生率高于RB患者[分别为43% vs. 0%; p=.0016]); PB患者的分离株显示出较高的(1)暴露于tPMP后的体外存活率(分别为22.4+/-14.8% vs. 11.6+/-6.5%; P=.005);(2)δ-溶素产生缺陷(71.4% vs. 38.9%; P= 0.057);(3)非agr基因型II谱(100%对77.8%; P= 0.037);(4)特定PFGE基因型的过度表达(85.7%对44.4%; P= 0.015)。PB患者的分离株与RB患者的分离株在几个体外特征上不同。进一步的研究将是必要的,以确定这些因素可能如何影响临床结果。
Background. The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution.Methods. Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after greater than or equal to7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA.Results. The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; p=.0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4+/-14.8% vs. 11.6+/-6.5%, respectively; P=.005); (2) defective delta-lysin production (71.4% vs. 38.9%, respectively; P=.057); (3)non-agr genotype II profile (100% vs. 77.8%, respectively; P=.037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P=.015).Conclusions. Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.