Why Was There Ever a Warning Not to Use Cephalosporins in the Setting of a Penicillin "Allergy"?

It is now well-established that avoiding β-lactam antibiotics, when they are the drugs of choice, results in significantly worse long-term global outcomes for patients. Much of this avoidable morbidity has been caused by widespread warnings in electronic health care record systems not to use cephalosporins in the setting of penicillin allergy. High rates, up to 1000-fold higher than now seen, of immunologically mediated reactions were associated with early impure penicillin preparations. This instilled a rational fear of β-lactam-associated anaphylaxis in generations of physicians. In the late 1970s, several editorial comments regarding a potential increased risk to patients given cephalosporins who had a history of a penicillin allergy resulted in the warning that became imbedded in the culture of medicine. Over the past 40 years, compelling data have been developed that refute this warning and showed that the risks of avoiding cephalosporins outweighed the benefits. In late 2017, Kaiser Permanente Southern California completely removed all warnings not to use cephalosporins in the setting of a penicillin allergy. The results have recently been published in JAMA Network Open. This Rostrum article provides some of the backstory on the establishment and removal of this warning for physicians who trained over the past 30 years.