Acne and group A strep: an unknown burden

痤疮和 A 组链球菌：未知的负担

• 批准号: 7125045
• 负责人: David Margolis
• 金额: $ 61.88万
• 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/7125045
• 关键词: Streptococcus infection; Streptococcus pyogenes; acne; antiinfective agents; clinical research; drug administration rate /duration; epidemiology; human subject; microorganism interaction; respiratory infections; therapy adverse effect; university student

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 ache 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)：寻常痤疮是一种折磨青少年和年轻人的疾病。在那些寻求医疗护理的痤疮患者中，约有20%的人病情严重，需要系统治疗。那些服用抗生素的人收到了大约970万张口服抗生素的处方和大约820万张局部抗生素的处方。治疗经常持续6个月以上。简单地说，这部分人口在很长一段时间内使用非常大量的抗生素。痤疮和痤疮疗法的负担，就像所有皮肤病一样，对社会和患者的负担并没有像最近在NIAMS会议上讨论的那样得到很好的描述。我们最近证明，当年轻人局部和/或口服疼痛的抗生素治疗时，可能会深刻影响个人感染A组链球菌(GAS)的可能性，A组链球菌(GAS)是咽炎的主要细菌原因。上呼吸道感染，包括咽炎，是非常常见的急性医疗问题，主要是由病毒引起的，是自限性的急性疾病，通常很轻微，但由于患病人数的巨大变化，对公共卫生造成了巨大的影响。事实上，据估计，美国每年的经济成本超过250亿美元。真正长期使用人类抗生素的自然模型很少。痤疮是一种疾病模型，长期使用抗生素是标准和适当的治疗方法。在这项提案中，我们将探索可能导致口咽部GAS定植增加的可能机制，我们注意到在使用抗生素(口服和/或局部)治疗痤疮的个人中。我们认为，抗菌作用是通过消除相互竞争的正常细菌菌群来实现的。事实上，口咽中的气体已经被证明是由另一种生物“调节”的，比如唾液链球菌。在流行病学方面，人们对咽喉正常菌群变化之间的联系以及这可能如何影响气体的获取和慢性运输，或者这些变化是否与感染性疾病(即咽炎)有关，知之甚少。持续的殖民，潜在地不仅会将患者置于危险之中，还会增加向密切接触者传播气体的风险。气体的持续定居也增加了气体直接和水平地从相关物种获得抗药性的可能性。最后，关于生物恐怖主义，暴露后预防需要长期(6至8个月)使用四环素等抗生素进行预防，这些抗生素用于治疗粉刺。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，痤疮患者是一个很好的模型，既可以研究抗生素的长期毒性，也可以研究在治疗期间接触药物的细菌病原体增加耐药性的风险。我们假设，长期使用抗生素治疗痤疮会导致口咽GAS定植，这种定植可能会导致发病率。为此，我们描述了一些研究，以帮助我们了解谁有被GAS殖民的风险，这些人被持续殖民的可能性，以及服用抗生素的人患咽炎的可能性。