Management of Beta-Lactam Antibiotics Allergy: A Real-Life Study

Abstract

Beta-lactam allergy is a common problem in everyday medical practice and is recognized as a major public health issue. Carrying this label frequently leads to the avoidance of all beta-lactam antibiotics, favoring the use of other less preferred classes of antibiotics, that are more expensive and associated with more side effects and increased antimicrobial resistance. Therefore, delabeling a beta-lactam allergy is part of antimicrobial stewardship programs. Herein, we retrospectively examined the clinical records of 576 patients who were referred to our center for a label of allergy to beta-lactam antibiotics and were systematically investigated following a standardized algorithm. Our main aim was to evaluate the frequency of confirmed immediate- and delayed-type allergy to commonly prescribed subclasses of beta-lactam antibiotics (penicillin and cephalosporin), as well as the negative predictive value (NPV) and the sensitivity of skin tests. Our secondary aims were to examine the safety of beta-lactam skin testing and drug challenge. We identified that 260 patients reported a history of immediate reactions, 131 of delayed reactions, and 114 of unknown timing or mechanism of reactions. Following assessment and testing, 86 (18.3%) patients had a confirmed allergy to any beta-lactam antibiotics; 63 (13.4%) with an immediate- and 23 (4.9%) with a delayed-type reaction. Most frequently identified confirmed allergy was to penicillins (65 patients), followed by cephalosporins (21 patients). When immediate-type reactions were examined, NPV of skin tests were 96.3% and 100% for penicillins and cephalosporins, respectively. When delayed reactions were considered, NPV were 91.9 and 87.5% for penicillins and cephalosporins, respectively. Evaluation of the safety of skin tests according to the standardized procedure showed that systemic allergic reactions occurred in only 0.7% of skin tests and in 3.1% of drug challenges. Overall, our data indicate that only 18.3% of patients with a beta-lactam allergy label have a confirmed allergy and non-allergic patients can be safely delabeled through allergic workup based on skin tests and drug challenge. This approach supports the policy of saving second-line antibiotics through a standardized allergy workup.

Candent issues in pneumonia. Reflections from the Fifth Annual Meeting of Spanish Experts 2023

“…Although aztreonam has been classically considered secure in these patients, it shares the same lateral chain than ceftazidime and cefiderocol, so cross reactions are expected between them and its use in patients allergic to these specific cephalosporines is not recommended. In the case of carbapenems, a history of penicillin allergy contraindicates their use, but in practice it is important to know result of historical cutaneal allergy test against penicillin, which has a high negative predictive value [ 64 ]: in case it is negative, use of carbapenems is considered secure; in case it is positive or unknown, carbapenem should be administrated in a gradual way, with increasing concentration and with narrow surveillance of allergic reactions [ 70 – 73 ] .…”

“…Despite being a frequent problem among general population, different studies have demonstrated that only 18.3% to 28.6% of people who claim being allergic to beta-lactam are really allergic to them [62][63][64]. This false label limits possibilities of treatment and potentially causes worse outcomes as has been mentioned.…”

Drug-induced hypersensitivity reactions in a Lebanese outpatient population: A decade-long retrospective analysis (2012-2021)

“…Multiple studies showed that BL antibiotics are the most frequent elicitors of DHRs. 52 , 53 , 54 , 55 Doña et al recorded 25% to 35% of BL DHRs. 56 These percentages are lower than those recorded in our study (approximately 50%), which might be attributed to the high levels of misuse and over-the-counter delivery of antibiotics in Lebanon.…”

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“…In other words, antibodies are made preferentially towards the most accessible antigenic sites Ø and V, although antibodies against other sections of the protein are also formed [62]. However, antibody treatments such as nirsevimab and palivizumab are directed against specific epitopes (in the case of nirsevimab Ø and II in the case of palivizumab) [63], implying that we are dealing with monoclonal antibodies [64]. This results in significant discrepancies in active and passive immunization techniques, despite the fact that both paradigms examine different areas of protection and are, of course, complementary.…”

“…Despite being a frequent problem among general population, different studies have demonstrated that only 18.3% to 28.6% of people who claim being allergic to beta-lactam are really allergic to them [62][63][64]. This false label limits possibilities of treatment and potentially causes worse outcomes as has been mentioned.…”