What is the likelihood of a penicillin allergy in a patient with a known cephalosporin (Cephalosporin) allergy?

From the Guidelines

If you have a cephalosporin allergy, the likelihood of also being allergic to penicillin is approximately 1-5%. This cross-reactivity is much lower than the reverse situation (where penicillin-allergic patients have about a 5-10% chance of reacting to cephalosporins) 1. The reason for this difference lies in the molecular structure of these antibiotics. While both belong to the beta-lactam family, they have different side chains that are typically responsible for allergic reactions. The cross-reactivity is primarily related to the beta-lactam ring they share, but most allergic reactions are triggered by the side chains, which differ between these drug classes.

Key Points to Consider

• The cross-reactivity between cephalosporins and penicillins is low, ranging from 2.0% to 4.8% 1.
• A study of 417 patients across 12 clinical studies conducted after 1980 found that only 8 (2%) had reactions to cephalosporins, representing cross-reactivity ranging between 2.0% and 4.8% 1.
• The reaction rate among patients with a confirmed penicillin allergy was recently determined to be just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic 1.
• If you have a confirmed cephalosporin allergy, your doctor might still prescribe penicillin with caution, possibly starting with a test dose or performing skin testing first 1. However, if you've had a severe, life-threatening reaction to cephalosporins (such as anaphylaxis), your doctor may avoid penicillins altogether as a precautionary measure.

Implications for Treatment

• It's essential to provide your healthcare provider with detailed information about your previous allergic reactions to ensure appropriate antibiotic selection 1.
• In patients with a history of penicillin or cephalosporin allergy, a carbapenem may be administered without testing or additional precautions, according to a consensus-based statement 1.
• The overall reported incidence of carbapenem allergy is 0.3%-3.7%, and clinical cross-reactivity between carbapenems and other beta-lactams is also low 1.

From the FDA Drug Label

THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS.

The likelihood of being allergic to other penicillins if you have a cephalosporin allergy is not directly stated in the provided drug label. However, it does mention that individuals with a history of penicillin hypersensitivity are more likely to experience severe reactions when treated with cephalosporins, implying a potential cross-reactivity.

• The label does not provide information on the reverse scenario, where a patient has a cephalosporin allergy and the potential risk of penicillin allergy.
• Therefore, no conclusion can be drawn regarding the likelihood of penicillin allergy in patients with a cephalosporin allergy based on the provided information 2.

From the Research

Cephalosporin Allergy and Cross-Reactivity with Penicillin

• The likelihood of a patient with a cephalosporin allergy being allergic to penicillin is not directly stated in the provided studies, but we can infer some information from the data on cross-reactivity between cephalosporins and penicillins 3, 4.
• Studies suggest that the cross-reactivity between penicillins and cephalosporins is lower than previously reported, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
• However, the cross-reactivity rate can be higher for specific cephalosporins, such as cefadroxil, with a reported prevalence of cross-reactivity as high as 27% 3.
• The cross-reactivity between cephalosporins and penicillins is mainly due to the similarity in their R1 side chains, and patients allergic to cephalosporins may tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains 4, 5.

Factors Influencing Cross-Reactivity

• The structure of the beta-lactam ring and the side chains of the antibiotics play a crucial role in determining cross-reactivity 4.
• Prior exposures to beta-lactam antibiotics may also contribute to coexisting sensitivities, and pre-treatment skin tests with related beta-lactams are recommended before administering them via graded challenges to beta-lactam-allergic patients 4.
• The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross-allergy 3.

Clinical Implications

• Avoiding beta-lactam antibiotics due to a reported penicillin or cephalosporin allergy can result in significantly worse long-term global outcomes for patients, and the risks of avoiding cephalosporins may outweigh the benefits 6.
• Inpatient allergy assessment may improve optimal antibiotic therapy for patients with a documented penicillin or cephalosporin allergy 7.
• Patients with a documented penicillin or cephalosporin allergy are less likely to receive recommended beta-lactams and more likely to receive alternative antibiotics, such as carbapenems and fluoroquinolones 7.