Background: Beta-lactam antibiotics are the most frequent drug family to cause allergic reactions. Herein, we examined the frequency of confirmed allergies to beta-lactam, as well as the sensitivity and negative predictive value (NPV) of skin testing in an adult population referred to a university allergy clinic in Switzerland. Methods: This is a retrospective analysis of the clinical records of patients who were investigated for a label of allergy to beta-lactam (penicillin, cephalosporin or carbapenem) between January 1 st 2011 and December 31 st 2018. Results: 582 patients were identified with a documented allergy to beta-lactam and 477 patients were systemically investigated by skin tests and/or drug challenge to confirm or rule out allergy. 262 patients reported a history of immediate reactions, 137 of delayed reactions, and 114 of unknown reactions. 88 (18.4%) patients had confirmed to any beta-lactam antibiotics; 64 (13.4%) with an immediate- and 24 (5%) with a delayed-type reaction. Most frequently identified allergy was penicillin (65 patients), followed by cephalosporin (21 patients) and carbapenem (2 patients). NPV of skin tests for all beta-lactam were 97.7% and 92.5% for immediate- and delayed-type reactions, respectively, and 96.3% and 92.1% when only penicillin was considered. Systemic allergic reaction occurred in 0.6% of skin tests and in 3.1% of drug challenges. Conclusions: Only 18% of patients with beta-lactam allergy label have a confirmed allergy and non-allergic patients can be safely delabelled through allergic workup based on skin tests and drug challenge. This approach supports the policy of saving second-line antibiotics through systemic allergy work-up.

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy, or with an allergic-like reaction after the first dose remains to be defined.  Methods: We studied two cohorts of individuals: one pre-vaccination, the second post-vaccination. Skin testing was performed with COVID-19 mRNA vaccines. Upon negative skin test, a two-step (10%-90%) vaccination protocol was performed. Positive skin tests were confirmed with basophil activation tests (BAT). Vaccine-sensitized patients were offered a five-step induction protocol. Results: We identified 187 patients with high-risk profiles for developing anaphylaxis. In parallel, among 385’926 doses of vaccine, 87 allergic-like reactions were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% in the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced acute asthma exacerbation during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Finally, 13 sensitized patients were successfully vaccinated with a five-step vaccination protocol. Conclusion: A two-step 10%-90%-vaccination protocol can be safely administered upon negative skin testing. Yet, it should be delayed in individuals with poorly controlled asthma. Importantly, mRNA vaccine sensitized individuals may receive a five-step vaccination protocol.