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

强力霉素与 TMP-SMX 治疗 SSTI 的短期和长期结果

• 批准号: 10457315
• 负责人: LOREN G. MILLER
• 金额: $ 100.24万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457315
• 关键词: Accident and Emergency department; Accounting; Address; Adult; Affect; Aftercare; Allergic; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Cessation of life; Child; Clindamycin; Clinic; Clinical Trials; Communicable Diseases; Communities; Complement; Data; Disease Outbreaks; Doxycycline; Drug Industry; Epidemiology; Federal Government; Foundations; Future; Guidelines; Health; Health Personnel; Hospitalization; Household; Incidence; Incision and drainage; Infection; Infectious Skin Diseases; Investigation; Lead; Life; Methods; Monobactams; Nose; Oral; Oropharyngeal; Outcome; Outcome Measure; Patient-Focused Outcomes; Patients; Physicians; Placebos; Play; Pneumonia; Population; Prevention; Randomized Clinical Trials; Recurrence; Relapse; Resistance; Role; Safety; Sample Size; Sepsis; Skin Tissue; Soft Tissue Infections; Staphylococcus aureus; Treatment Efficacy; Trimethoprim-Sulfamethoxazole; United States; Urinary tract infection; Visit; beta-Lactams; comparative effectiveness; comparative efficacy; cost; diabetic; evidence base; improved; infection management; methicillin resistant Staphylococcus aureus; obese person; optimal treatments; prevent; primary outcome; recurrent infection; success; sulfa drug; transmission process; treatment comparison; treatment guidelines; treatment optimization; trial design; urgent care

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.

项目摘要 /摘要 社区相关（CA）皮肤和软组织感染（SSTIS）造成了重大的健康负担 全世界。在过去的十年中，美国的SSTI发病率增加了50％，导致访问超过1000万 每年致医疗保健提供者。这种增长是由社区相关的出现驱动的 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 传染病已经看到了如此巨大的崛起。非常关心的是，SSTIS因高率而变得复杂 复发（一年中> 50％），住院，严重的败血症甚至死亡。 当前的指南不足以解决较旧的廉价抗生素在SSTI治疗中的作用。 超过肺炎和尿路的SSTI高发病率之间的断开连接 感染以及缺乏指导处方医师的数据是不合理的，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）对于简单的SSTI（USSTIS）具有相似的功效和安全性。两者都有 当与切口和排水结合使用时，功效超过了安慰剂。但是，克林霉素 在美国，金黄色葡萄球菌之间的抵抗力增加，在世界某些地区超过90％。 TMP-SMX 与克林霉素相比，复发性SSTI的速率也更高，并且受到TMP-SMX的出现 在使用TMP-SMX的人群中，金黄色葡萄球菌之间的抵抗力很高。 强力霉素是研究USSTI治疗的自然选择。它的容忍度，低成本和有前途的 SSTI管理的初步数据表明它对USSTI治疗是有效且安全的。很遗憾， 缺乏用于强力霉素的SSTI治疗的高质量比较有效性数据。 我们将对USSTIS进行临床试验，以CA-MRSA和 以前在SSTI的其他试验中忽略了人群（例如糖尿病患者，肥胖者）。我们将比较 强力霉素与TMP-SMX的功效和安全性用于治疗大儿童的化脓性USSTI 和成人。我们还将比较防止在初次治疗后12个月内预防usstis的功效 并定义鼻腔和口咽定植与治疗成功之间的关系以及 复发。我们将量化和表征新兴的抗生素抗生素金黄色葡萄球菌分离株。 最后，我们将使用结果排名的可取性为SSTIS开发新的临床试验结果 （门）该试验的设计。这种结果将通过捕获来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。门结果可以减少未来SSTI临床试验的样本量， 从而使未来的试验更便宜，更可行。我们的调查对于定义角色至关重要 用于USSTI治疗的强力霉素，并为改善短暂的循证疗法奠定了基础 长期的患者结局在这种极为普遍但已研究的感染中。