Acne and group A strep: an unknown burden

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。在寻求医疗护理的痤疮患者中，约有20%的人严重到需要全身治疗。服用抗生素的患者收到约970万张口服抗生素处方，约820万张局部抗生素处方。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了大量抗生素。与所有皮肤病一样，痤疮和痤疮治疗对社会和患者的负担在最近的NIAMS会议上没有得到很好的描述。我们最近的研究表明，对年轻人局部和/或口服抗生素治疗痤疮可能会深刻影响个体被A群链球菌（GAS）定植的可能性，A群链球菌是导致咽炎的主要细菌。上呼吸道感染，包括咽炎，是非常常见的急性医学问题，主要是由病毒引起的，是一种自限性急性疾病，通常病情轻微，但由于患病人数众多，对公共卫生造成巨大影响。事实上，据估计，美国每年的经济成本超过250亿美元。人类真正长期使用抗生素的自然模型很少。痤疮是一种疾病的模型，长期使用抗生素是标准和适当的治疗方法。在本提案中，我们将探索可能的机制，可能负责在使用抗生素（口服和/或外用）治疗痤疮的个体中GAS的口咽定植增加。我们认为，抗菌作用是通过消除竞争正常菌群。事实上，口腔咽部的GAS已经被证明是由另一种生物“调节”的，比如唾液链球菌。在流行病学上，关于咽喉正常菌群变化的关联，以及这如何影响气体的获得和慢性携带，或者这些变化是否与传染病（即咽炎）有关，我们所知甚少。持续定植不仅可能使患者处于危险之中，而且会增加气体向密切接触者传播的风险。GAS的持续定植也增加了GAS直接和水平地从相关物种获得抗性的可能性。最后，关于生物恐怖主义，暴露后预防使用抗生素，如用于治疗痤疮的四环素，将需要维持较长时间（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来研究抗生素的长期毒性和在治疗期间暴露于药物的细菌病原体中增加耐药性的风险。我们假设，长期使用抗生素治疗痤疮可导致口咽定植与气体，这种定植可导致发病率。为此，我们描述了一些研究，以帮助我们了解哪些人有被GAS定植的风险，这些人被持续定植的可能性，以及使用抗生素的人患咽炎的可能性。

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.