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

项目摘要/摘要 社区相关(CA)皮肤和软组织感染(SSTI)构成了巨大的健康负担 全世界。SSTI在美国的发病率在过去十年中增加了50%，导致超过1000万人次就诊 每年提供给医疗保健提供者。这一增长是由与社区相关的 耐甲氧西林金黄色葡萄球菌(MRSA)菌株，现在引起大多数SSTI。没有其他人了 传染病出现了如此戏剧性的上升。非常令人担忧的是，性传播感染因高比率而变得复杂。 复发(一年内50%)，住院，严重败血症，甚至死亡。 目前的指南不充分地解决了较老、廉价的抗生素在SSTI治疗中的作用。 SSTI高发超过肺炎与尿路脱节 感染，缺乏数据来指导医生开处方是不合理的，只能通过 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)对单纯SSTI(USSTI)的疗效和安全性相似。两个人都有 与切开和引流相结合的疗效超过了安慰剂。然而，克林霉素 美国金黄色葡萄球菌的耐药性正在增加，在世界一些地区超过90%。TMP-SMX 与克林霉素相比，SSTI的复发率更高，以及TMP-SMX的出现也限制了SSTI的复发 TMP-SMX使用率高的人群中金黄色葡萄球菌的耐药性。 强力霉素是研究uSSTI治疗的自然选择。它的耐受性、低成本和前景看好 SSTI管理的初步数据表明，USSTI治疗是有效和安全的。不幸的是， 缺乏用多西环素治疗SSTI的高质量比较有效性数据。 我们将进行uSSTI的临床试验，针对可能由CA-MRSA和 以前在其他性传播感染试验中被忽视的人群(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尿路感染的疗效和安全性比较 和成年人。我们还将比较首次治疗后12个月内预防尿路感染复发的效果。 并明确鼻腔和口咽定植与治疗成功的关系 复发。我们将量化和表征新出现的定植耐药金黄色葡萄球菌分离株。 最后，我们将使用结果排序的可取性来开发SSTI的新的临床试验结果 (门)这次审判的设计。这个结果将补充我们更传统的主要结果，通过捕获 以患者为中心的有意义的结果。DOOR结果可以减少未来SSTI临床试验的样本量， 从而使未来的试验成本更低，更可行。我们的调查将是确定角色的关键 多西环素用于uSSTI治疗，并为循证疗法奠定基础，以改善短期和 在这种极其常见但研究不足的感染中，患者的长期结局。

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.