Matthieu Picard1, Geneviève Robitaille2, Fatiha Karam2, Jean-Marc Daigle2, François Bédard3, Éric Biron3, Mélanie R Tardif2, Jonathan Lacombe-Barrios4, Philippe Bégin5. 1. Hôpital Maisonneuve-Rosemont (HMR), Department of Medicine, Division of Clinical Immunology and Allergy, Université de Montréal, Montréal, QC, Canada. Electronic address: matthieu.picard@umontreal.ca. 2. Institut National d'Excellence en Santé et Services Sociaux (INESSS), Montréal, QC, Canada. 3. Faculty of Pharmacy, Université Laval and Medicinal Chemistry Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada. 4. Centre Hospitalier Universitaire Sainte-Justine (CHU Sainte-Justine), Department of Pediatrics, Division of Clinical Immunology and Allergy, Université de Montréal, Montréal, QC, Canada. 5. Centre Hospitalier Universitaire Sainte-Justine (CHU Sainte-Justine), Department of Pediatrics, Division of Clinical Immunology and Allergy, Université de Montréal, Montréal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Department of Medicine, Division of Clinical Immunology and Allergy, Montréal, QC, Canada.
Abstract
BACKGROUND: There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillin allergy. OBJECTIVES: To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillin allergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity. METHODS: MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains. RESULTS: Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergic patients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillin allergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergic patients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32). CONCLUSIONS: Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillin allergy.
BACKGROUND: There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergicpatients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillinallergy. OBJECTIVES: To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillinallergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity. METHODS: MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains. RESULTS: Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergicpatients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillinallergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergicpatients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32). CONCLUSIONS: Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillinallergy.
Authors: Rebecca E Berger; Harjot K Singh; Angela S Loo; Victoria Cooley; Snezana Nena Osorio; Jennifer I Lee; Matthew S Simon Journal: Jt Comm J Qual Patient Saf Date: 2021-12-09
Authors: Jason A Trubiano; Kyra Y L Chua; Natasha E Holmes; Abby P Douglas; Effie Mouhtouris; Michelle Goh; Elizabeth J Phillips Journal: J Allergy Clin Immunol Pract Date: 2019-10-31
Authors: Michelle Maguire; Bryan D Hayes; Lanting Fuh; Ramy Elshaboury; Ronak G Gandhi; Sarah Bor; Erica S Shenoy; Anna R Wolfson; Christian M Mancini; Kimberly G Blumenthal Journal: World Allergy Organ J Date: 2020-01-07 Impact factor: 4.084