Short and long term outcomes of doxycycline versus TMP-SMX for SSTI treatment

项目总结/摘要 社区相关性（CA）皮肤和软组织感染（SSTI）造成了巨大的健康负担 国际吧在过去十年中，美国的SSTI发病率增加了50%，导致超过1000万人次就诊 医疗保健提供者每年。这一增长是由社区相关的 耐甲氧西林金黄色葡萄球菌（MRSA）菌株，其现在引起大多数SSTI。没有其他 传染病的发病率急剧上升。非常令人担忧的是，SSTI因高利率而变得复杂 复发率（1年内>50%），以及住院、严重脓毒症，甚至死亡。 目前的指南没有充分解决旧的，廉价的抗生素在SSTI治疗中的作用。 SSTI的高发病率（超过肺炎和泌尿道感染） 感染，以及缺乏数据来指导处方医生是不合理的，只能通过以下措施来解决 高质量的临床试验。最近的研究表明，克林霉素和甲氧苄啶- 磺胺甲恶唑（TMP-SMX）对无并发症SSTI（uSSTI）具有相似的疗效和安全性。都有 与切开引流联合使用时，疗效超过安慰剂。然而，克林霉素 S.美国的金黄色葡萄球菌感染率正在增加，在世界某些地区超过90%。TMP-SMX 与克林霉素相比， S.金黄色葡萄球菌中TMP-SMX使用率高的人群。 强力霉素是uSSTI治疗研究的自然选择。它的耐受性，低成本， SSTI管理的初步数据表明，uSSTI治疗是有效和安全的。不幸的是， 目前缺乏高质量的多西环素SSTI治疗有效性比较数据。 我们将进行uSSTI的临床试验，目标是可能由CA-MRSA引起的感染， 以前在SSTI的其他试验中忽略的群体（例如，糖尿病患者、肥胖者）。我们将比较 多西环素与TMP-SMX治疗大龄儿童化脓性uSSTI的疗效和安全性 和成年人。我们还将比较在初始治疗后12个月内预防复发性uSSTI的疗效 并确定鼻腔和口咽定植与治疗成功之间的关系， 复发我们将量化和表征紧急殖民耐药S。金黄色葡萄球菌分离株。 最后，我们将使用结果期望性排名为SSTI开发新的临床试验结果 （DOOR）设计。这一结果将补充我们更传统的主要结果， 有意义的以患者为中心的结果。DOOR结果可以减少未来SSTI临床试验的样本量， 从而使未来的试验更便宜和更可行。我们的调查对确定 多西环素用于uSSTI治疗，并为循证治疗奠定基础， 这种极其常见但研究不足的感染的长期患者结局。

Project Summary / Abstract Community-associated (CA) skin and soft tissue infections (SSTIs) pose a substantial health burden worldwide. SSTI incidence in the U.S. has increased 50% in the past decade resulting in over 10 million visits to healthcare providers annually. This increase is driven by the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains, which now cause the majority of SSTIs. No other infectious disease has seen such a dramatic rise. Of great concern is that SSTIs are complicated by high rates of recurrence (>50% in 1 year), as well as hospitalization, severe sepsis, and even death. Current guidelines inadequately address the role of older, inexpensive antibiotics for SSTI treatment. The disconnect between the high incidence of SSTIs, which exceed that of pneumonia and urinary tract infections, and the lack of data to guide prescribing physicians is unjustifiable and can only be addressed by high quality clinical trials. Recent studies have demonstrated that clindamycin and trimethoprim- sulfamethoxazole (TMP-SMX) have similar efficacy and safety for uncomplicated SSTIs (uSSTIs). Both have efficacy, when combined with incision and drainage, that exceeds that of placebo. However, clindamycin resistance among S. aureus in the U.S. is increasing and exceeds 90% in some parts of the world. TMP-SMX is also limited by higher rates of recurrent SSTIs compared to clindamycin and by emergence of TMP-SMX resistance among S. aureus in populations where use of TMP-SMX is high. Doxycycline is the natural choice for study of uSSTI treatment. Its tolerability, low cost, and promising preliminary data for SSTI management suggest it is efficacious and safe for uSSTI treatment. Unfortunately, high quality comparative effectiveness data for SSTI treatment with doxycycline are lacking. We will perform a clinical trial of uSSTIs, targeting infections likely to be caused by CA-MRSA and populations previously ignored in other trials of SSTIs (e.g., diabetics, obese persons). We will compare the efficacy and safety of doxycycline versus TMP-SMX for the treatment of suppurative uSSTI in older children and adults. We will also compare efficacy of preventing recurrent uSSTIs up to 12 months after initial treatment and define the relationship between nasal and oropharyngeal colonization and treatment success and recurrence. We will quantify and characterize emergent colonizing antibiotic-resistant S. aureus isolates. Finally, we will develop a new clinical trial outcome for SSTIs using the Desirability Of Outcome Ranking (DOOR) design for this trial. This outcome will complement our more traditional primary outcome by capturing meaningful patient-centered outcomes. DOOR outcomes can reduce sample size of future SSTI clinical trials, thus making future trials less expensive and more feasible. Our investigation will be critical in defining the role of doxycycline for uSSTI treatment and lay the foundation for evidence-based therapies that improve short and long term patient outcomes in this extremely common yet understudied infection.