In this episode, I’ll discuss the impact of giving a full-dose cephalosporin challenge to patients with a moderate, severe, or unknown beta-lactam allergy.
The label of “penicillin allergic” usually sticks to a patient’s medical record forever. The trouble is that many recorded allergies are actually intolerances, such as nausea, vomiting, and diarrhea. This occurs partly because there is no place in the medical record other than the allergy section to list a non-allergic but unpleasant side effect of a medication. Furthermore, even in the event of a true and serious allergy to penicillin, cross-allergenicity with cephalosporins is low and the reaction is mediated by B-cell memory which fades over time, often within 10 years.
Beta-lactams are often the first-line antibiotic for many infections, and unnecessarily choosing a second-line antibiotic to avoid a potential cross-reaction can lead to worse patient outcomes. However this argument may be overshadowed in the minds of many clinicians who prefer to be risk-averse in the setting of a recorded penicillin allergy.
To attempt to describe what happens if you simply give a full-dose challenge of a cephalosporin to a patient with a reported beta-lactam allergy that is either moderate, severe, or unknown, a group of authors conducted a retrospective study of adult ED patients challenged with a full dose of beta-lactam over a consecutive 24-month period at a single emergency department.
A total of 184 patients met the criteria of presenting to the ED and being admitted for bacterial infection, having a reported beta-lactam allergy history that was moderate, severe, or unknown in nature, and who did not have a documented history of beta-lactam tolerance.
90% of these patients reported an allergy to penicillin, and all but 2 were challenged with a full dose of a cephalosporin.
The documented allergy was severe in nature for 13% of patients, moderate for 43%, and unknown for 44%. Of the moderate and severe allergy histories, 100% of them were consistent with a possible IgE-mediated reaction, including anaphylaxis, swelling, difficulty breathing, hives, or urticaria. Given these attributes, this cohort accurately represents a group of patients that many clinicians consider at highest risk of a potential cross-reaction.
Only 5 patients from the cohort of 184 experienced an allergic reaction of any kind, and none of these were considered serious. The details of the patients who reacted are as follows:
1. A 50 y/o male with an SSTI had an unknown allergy to penicillin, received a single dose of ceftriaxone in the ED and was then switched to piperacillin-tazobactam as an inpatient. He experienced a rash to the piperacillin-tazobactam as an inpatient.
2. A 65 y/o female with pneumonia had an allergy history of hives from penicillins and cephaloprins, received piperacillin-tazobactam in the ED and was switched to nafcillin as an inpatient. She experienced a rash to the nafcillin as an inpatient.
3. An 80 y/o female with pneumonia had an unknown allergy to penicillin, received a single dose of ceftriaxone in the ED and no antibiotics as an inpatient. She experienced itching in the ED.
4. An 81 y/o male with an intra-abdominal infection had an allergy history of severe swelling from cephalosporins, was started on piperacillin-tazobactam in the ED and switched to minocycline as an inpatient. He experienced a rash to piperacillin-tazobactam as an inpatient.
5. A 96 y/o female with a urinary tract infection had an unknown allergy to penicillin, was started on ceftriaxone in the ED and switched to aztreonam as an inpatient. She experienced a rash to ceftriaxone as an inpatient.
The authors concluded:
This study suggests that full-dose challenge of moderate, severe, or unknown beta- lactam allergies can be safely accomplished in the ED. This approach avoids unnecessary penicillin allergy skin testing and reduces utilization of suboptimal alternative antibiotic regimens.
On the one hand, this study has limitations, including its single-center retrospective design, which analyzed under 200 patients. On the other hand, this cohort is essentially a perfect representation of challenging patients that we encounter in clinical practice — those with unknown or IgE-mediated reactions who ideally would receive treatment with a beta-lactam antibiotic. The low rate and non-serious nature of cross-reactivity in this cohort should give clinicians confidence that penicillin allergies can be challenged with cephalosporins in an ED setting, and hopefully give future researchers the clinical equipoise necessary to design larger and higher-quality investigations of antibiotic cross-allergenicity.
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