Acne and group A strep: an unknown burden

痤疮和 A 组链球菌：未知的负担

• 批准号: 7280948
• 负责人: David Margolis
• 金额: $ 51.64万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-19 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7280948
• 关键词: Ache; Acne; Acne Vulgaris; Acute; Adolescent; Affect; Antibiotic Therapy; Antibiotics; Antimicrobial Effect; Bioterrorism; Caring; Characteristics; Chronic; Clindamycin; Condition; Cutaneous; Data; Disease; Dose; Doxycycline; Drug resistance; Economics; Environment; Erythromycin; Family; Human; Individual; Infection; Long-Term Effects; Medical; Minocycline; Modeling; Morbidity - disease rate; Numbers; Oral; Oral cavity; Organism; Oropharyngeal; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharyngeal structure; Pharyngitis; Physicians; Population; Prevalence; Prophylactic treatment; Public Health; Rate; Reporting; Resistance; Risk; Risk Factors; Series; Skin; Societies; Source; Standards of Weights and Measures; Streptococcus; Streptococcus pyogenes; Streptococcus salivarius; Surface; Systemic Therapy; Tetracycline; Tetracyclines; Time; Topical Antibiotic; Toxic effect; Upper Respiratory Infections; Viral; Week; bacterial resistance; cost; malignant breast neoplasm; microbial; pathogen; prescription document; prescription procedure; skin disorder; symposium; trend; young adult

DESCRIPTION (provided by applicant): Acne vulgaris is an illness that afflicts adolescents and young adults. About 20% of those with acne, who seek medical care, are severe enough to require systemic therapy. Those on antibiotics receive about 9.7 million prescriptions for oral antibiotics and about 8.2 million for the topical antibiotics. Therapy frequently continues for more than 6 months. Simply stated, very large quantities of antibiotics are used for an extended period of time by this sector of the population. The burden of both acne and acne therapies, as with all skin diseases, on society and the patient has not been well described as discussed at a recent NIAMS conference. We have recently demonstrated that antibiotic therapy for acne when given topical and/or orally to young adults may profoundly affect an individual's likelihood of being colonized with group A streptococcus (GAS), the main bacterial cause of pharyngitis. Upper respiratory tract infections, including pharyngitis, are extraordinarily common acute medical problems that are primarily of viral origin, are self-limited acute condition, and are generally mild but have huge public health implications due to the shear magnitude of numbers of individuals afflicted. In fact, the US economic cost is estimated to be more than 25 billion dollars per year. There are very few natural models of truly long-term human antibiotic use. Acne is a model of a disease for which long-term antibiotic use is standard and appropriate therapy. In this proposal, we will explore possible mechanisms that may be responsible for the increase in oro-pharyngeal colonization of GAS that we have noted in individuals who use antibiotics (oral and/or topical) for acne. We believe that the antimicrobial effect is through the elimination of competing normal bacterial flora. In fact, GAS in the oro-pharynx has been shown to be "regulated" by another organism, like S. Salivarius. Epidemiologically, very little is known about the association of changes in the normal flora of the throat and how this may impact the acquisition and chronic carriage of GAS, or whether these changes are associated with an infectious illness (i.e., pharyngitis). Persistent colonization, potentially does not only put the patient at risk but increases the risk of spread of GAS to close contacts. Persistent colonization of GAS also increases the likelihood of GAS acquiring resistance directly and horizontally from related species. Finally, with respect to bioterrorism post-exposure prophylaxis with antibiotics such as the tetracyclines, which are used to treat acne, will need to be maintained for prolonged periods of time (6 to 8 months). There is currently very limited data on the long-term consequences of tetracycline use. With respect to all of these issues, acne patients represent a great model to study regarding both the long-term toxicity of antibiotics and the risks of increasing resistance among bacterial pathogens exposed to drugs during treatment. We hypothesize that the use of long-term antibiotics for acne can result in oropharyngeal colonization with GAS and that this colonization can result in morbidity. To that end, we describe studies to help us understand who is at risk for colonization with GAS, the likelihood that these individuals will be persistently colonized, and the likelihood that individuals on antibiotics will develop pharyngitis.

描述（由申请人提供）：寻常痤疮是一种困扰青少年和年轻人的疾病。约 20% 寻求医疗护理的痤疮患者病情严重，需要全身治疗。服用抗生素的人收到约 970 万张口服抗生素处方和约 820 万张外用抗生素处方。治疗通常持续 6 个月以上。简而言之，这部分人群在很长一段时间内使用大量抗生素。与所有皮肤病一样，痤疮和痤疮治疗对社会和患者造成的负担尚未得到很好的描述，正如最近的 NIAMS 会议所讨论的那样。我们最近证明，当年轻人局部和/或口服抗生素治疗痤疮时，可能会极大地影响个体被 A 族链球菌 (GAS) 定植的可能性，而 A 族链球菌是咽炎的主要细菌原因。包括咽炎在内的上呼吸道感染是极其常见的急性医疗问题，主要由病毒引起，是自限性急性病症，通常症状较轻，但由于患病人数的巨大，对公共卫生产生巨大影响。事实上，美国每年的经济损失估计超过250亿美元。人类真正长期使用抗生素的自然模型非常少。痤疮是一种疾病的模型，长期使用抗生素是标准且适当的治疗方法。在本提案中，我们将探讨可能导致 GAS 口咽定植增加的可能机制，我们在使用抗生素（口服和/或局部）治疗痤疮的个体中注意到了这一点。我们相信抗菌作用是通过消除竞争性正常菌群来实现的。事实上，口咽部的 GAS 已被证明受到另一种生物体（如唾液链球菌）的“调节”。从流行病学角度来看，人们对喉咙正常菌群变化之间的关联以及这如何影响 GAS 的获得和长期携带，或者这些变化是否与传染病（即咽炎）有关知之甚少。持续定植不仅可能使患者面临风险，还会增加 GAS 传播给密切接触者的风险。 GAS 的持续定植也增加了 GAS 从相关物种直接横向获得抗性的可能性。最后，关于生物恐怖主义，使用抗生素（例如用于治疗痤疮的四环素）进行暴露后预防需要维持较长时间（6 至 8 个月）。目前关于使用四环素的长期后果的数据非常有限。就所有这些问题而言，痤疮患者代表了一个很好的模型，可以研究抗生素的长期毒性以及治疗期间接触药物的细菌病原体耐药性增加的风险。我们假设长期使用抗生素治疗痤疮会导致 GAS 在口咽部定植，并且这种定植会导致发病。为此，我们描述了一些研究，以帮助我们了解谁有 GAS 定植的风险，这些人持续定植的可能性，以及服用抗生素的人患咽炎的可能性。