Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant Staphylococcus aureus: Results of a Multinational Trial
Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant Staphylococcus aureus: Results of a Multinational Trial
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DOI：
10.1128/jcm.01643-09
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发表时间：
2009-12-01
影响因子：
9.4
通讯作者：
Fowler, Vance G., Jr.
中科院分区：
文献类型：
--
作者：
Bae, In-Gyu;Tonthat, Giang T.;Fowler, Vance G., Jr.
潘顿-瓦伦丁杀白细胞素 (PVL) 在确定由耐甲氧西林金黄色葡萄球菌 (MRSA) 引起的复杂皮肤和皮肤结构感染 (cSSSI) 的严重程度和结果方面的作用存在争议。我们通过使用来自两项大型跨国三期临床试验（评估特拉万星治疗 cSSSI）的患者的 MRSA 分离物来评估临床结果和 PVL 状态之间的潜在关联（ATLAS 计划）。通过脉冲场凝胶电泳 (PFGE) 和 PCR 对来自微生物学可评估患者的 MRSA 分离株进行 pvl 和 31 个其他假定毒力决定因素的基因分型。从 2,079 名随机患者中的 522 名微生物学可评估患者 (25.1%) 中分离出单一基线 MRSA 病原体。在这些 MRSA 分离株中，83.2% (432/519) 表现出 USA300 PFGE 基因型，89.1% (465/522) 呈 pvl 阳性。 pvl 阳性 MRSA 患者比 pvl 阴性 MRSA 患者更年轻、来自北美并且出现严重脓肿（均 P < 0.001）。感染 pvl 阳性 MRSA 的患者比感染 pvl 阴性 MRSA 的患者治愈的可能性明显更高（91.6% vs 80.7%；P = 0.015）。在调整脓肿、发烧或白细胞增多的存在后，这一观察结果仍然具有统计学意义；感染大小；糖尿病;患者年龄；并研究收到的药物。 fnbA、cna、sdrC、map-eap、sed、seg、sei、sej、SCCmec IV 型和 agr II 组基因也与临床反应相关（P < 0.05）。这项当代国际研究表明，pvl 并不是 MRSA cSSSI 患者预后的主要决定因素。
The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.