Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.
School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
Clin Infect Dis. 2024 Sep 26;79(3):626-634. doi: 10.1093/cid/ciae289.
The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question.
The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin-positive isolate.
金黄色葡萄球菌菌血症（SAB）中使用针对外毒素产生的辅助抗生素的做法非常普遍，许多指南都推荐这种做法，但这主要基于有限的证据。现有的指南基于抑制毒素的理论前提，因为许多金黄色葡萄球菌株会产生白细胞毒素（例如，潘顿-瓦伦丁白细胞毒素、中毒性休克综合征毒素 1、剥脱毒素和各种肠毒素）。因此，许多临床医生认为，限制金黄色葡萄球菌产生外毒素的释放可以降低其毒力并改善临床结局。克林霉素是一种抑制蛋白质合成的抗生素，常用于此目的。我们报告了特定领域的方案，该方案嵌入在一个大型适应性平台试验中，旨在明确回答这个问题。
金黄色葡萄球菌网络自适应平台（SNAP）试验是一项实用的、随机的、多中心适应性平台试验，旨在同时比较不同的 SAB 治疗方法，以 90 天死亡率为主要终点。辅助治疗领域旨在测试辅助抗生素的有效性，最初将克林霉素与无辅助抗生素进行比较，但未来的适应可能包括其他药物。将参与者随机分配接受 5 天的辅助克林霉素（或林可霉素）或无辅助抗生素治疗联合标准治疗抗生素。大多数 SAB 患者（在指数血培养后 72 小时内，且无禁忌症）将有资格参加该领域的研究。预设分析在核心方案的统计附录中定义，特定领域的次要分析将根据克林霉素耐药性、疾病表型（复杂或不复杂的 SAB）和潘顿-瓦伦丁白细胞毒素阳性分离株进行调整。
