This article reviews our evolving understanding of penicillin hypersensitivity at the 80th anniversary of penicillin’s clinical introduction. Penicillin breakdown products covalently bond to serum proteins, leading to classic drug hypersensitivity. Penicillin remains the most frequently reported drug “allergy.” Adverse reactions were presumed, in retrospect incorrectly, to implicate a risk for anaphylaxis, and therefore skin testing for IgE became the focus. Skin test positivity may wane over time. This insight has led to the radical conclusion that penicillin hypersensitivity may not be “forever.” Atopic background, other drug allergies, family history, gender, and race are apparently not risk factors for penicillin hypersensitivity. Confirmed penicillin hypersensitivity has declined since the 1960s, potentially due to “cleaner” penicillin products and lower dose oral, instead of parenteral, use. Avoiding penicillins, without evaluation, caused unanticipated problems that have been appreciated only recently including longer hospital stays, increased cost of care, suboptimal outcomes from serious infections, and greater toxicities and costs with alternative antibiotics. There are personal and public health advantages with broadly implemented penicillin allergy delabeling based on a reaction history–based risk assessment. Limited skin testing followed by an oral challenge, if negative, for higher-risk histories, and direct oral challenges in lower-risk individuals are currently the reference standard tests to confirm current tolerance.

在青霉素临床引入 80 周年之际，本文回顾了我们对青霉素超敏反应的不断发展的理解。青霉素分解产物与血清蛋白共价结合，导致典型的药物超敏反应。青霉素仍然是最常报告的药物“过敏”。回想起来，不良反应被错误地假定为存在过敏反应的风险，因此 IgE 的皮肤测试成为焦点。皮肤测试阳性可能会随着时间的推移而减弱。这种洞察力得出了一个激进的结论，即青霉素超敏反应可能不会“永远存在”。特应性背景、其他药物过敏、家族史、性别和种族显然不是青霉素超敏反应的危险因素。自 1960 年代以来，确认的青霉素超敏反应有所下降，这可能是由于“更清洁”的青霉素产品和较低剂量的口服而非肠胃外使用。在没有评估的情况下避免使用青霉素会导致意想不到的问题，这些问题最近才得到重视，包括住院时间延长、护理成本增加、严重感染导致的结果不理想，以及替代抗生素的毒性和成本更高。根据基于反应历史的风险评估，广泛实施青霉素过敏去标签对个人和公共健康都有好处。有限的皮肤测试后进行口腔挑战，如果为阴性，则针对高风险病史，以及针对低风险个体的直接口腔挑战目前是确认当前耐受性的参考标准测试。