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J Allergy Clin Immunol Pract. 2019 Jun 4. pii: S2213-2198(19)30495-7. doi: 10.1016/j.jaip.2019.05.038. [Epub ahead of print]

Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses.

Author information

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.

KEYWORDS:

Beta-lactam; Carbapenem; Cephalosporin; Cross-reactivity; IgE-mediated; Meta-analysis; Penicillin; Systematic review; T-cell–mediated

PMID:
31170539
DOI:
10.1016/j.jaip.2019.05.038

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