β-Lactam antibiotics are wide used for a reason – they are safe and effective antibiotics. Recent reports of issues with other drugs have served to emphasize this, for example the multiplicity of issues associated with flouroquinolones that has been prominent in recent medical literature. Self-reported allergies to penicillin and related drugs may limit their use, driving the use of less safe alternatives that also increase the risk for antimicrobial resistance. About 10% of the American population report penicillin allergy, with the rate even higher amongst older and hospitalized patients, but clinically significant IgE-mediated or T lymphocyte–mediated penicillin hypersensitivity is uncommon (<5%). It is known that IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Moreover, true cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than previously thought to be the case.
A moderate-risk history of symptoms that connote risk for more serious risk includes features such as urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. Direct amoxicillin challenge can be used ti determine the veracity of claimed penicillin allergy for patients with low-risk allergy histories, whereas moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Rejecting the option of treatment with penicillin or other β-lactam antibiotics can compromise important objectives of antimicrobial stewardship: more systematic assessment has been advocated to allow proper exploration of claimed penicillin allergy, with benefits including the preservation of a wider range of treatment options for the individual and avoidance of the development of multi-resistant microbes.