From the Guidelines
Patients with a penicillin allergy are at risk of cross-reacting with other beta-lactam antibiotics, including cephalosporins, with a risk of 5-10%, and carbapenems, with a risk of about 1%. The risk of cross-reactivity varies depending on the specific antibiotic and the individual patient's allergy. According to the most recent study 1, patients with a non-severe, delayed-type penicillin allergy can receive any monobactam or carbapenem without prior allergy testing. Key points to consider include:
- Cephalosporins with similar side chains to the suspected penicillin have a higher risk of cross-reactivity, ranging from 5-17% 1.
- Monobactams like aztreonam generally don't cross-react except in patients with specific ceftazidime allergies 1.
- Non-beta-lactam antibiotics that may occasionally cause reactions in penicillin-allergic patients include sulfonamides, fluoroquinolones, and rarely macrolides.
- For patients with severe penicillin allergies, alternative antibiotic classes should be considered first, or desensitization protocols may be necessary if a beta-lactam is absolutely required 1. It is essential to note that the cross-reactivity risk is lower for later-generation cephalosporins compared to first-generation cephalosporins, and carbapenems have a relatively low cross-reactivity risk 1. In clinical practice, it is crucial to carefully evaluate the patient's allergy history and consider alternative antibiotic options to minimize the risk of cross-reactivity and ensure the best possible outcome in terms of morbidity, mortality, and quality of life.
From the FDA Drug Label
WARNINGS Hypersensitivity Reactions to Cefepime, Cephalosporins, Penicillins, or Other Drugs Before therapy with cefepime for injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other drugs Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. WARNINGS BEFORE THERAPY WITH CEFAZOLIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.
Medications that can cause reactions in patients with a penicillin (PCN) allergy besides penicillin include:
- Cephalosporins, such as cefepime and cefazolin, due to cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2 3.
From the Research
Medications that can cause reactions in patients with a penicillin (PCN) allergy
- Cephalosporins, particularly first-generation cephalosporins, which have a cross allergy with penicillins (odds ratio 4.8; confidence interval 3.7-6.2) 4
- Cephalosporins with similar R1 side chains to the offending penicillin, which can cause cross-reactivity in penicillin-allergic patients 4, 5, 6
- Carbapenems, although the risk of cross-reactivity is lower than previously reported, with a risk of 0.87% (95% CI, 0.32-2.32) 6, 7
- Monobactams, such as aztreonam, which can cause cross-reactivity in some patients with a penicillin allergy, although the risk is low 5, 8
- Other beta-lactam antibiotics, such as oxacephems and beta-lactamase inhibitors, which may also cause cross-reactivity in patients with a penicillin allergy, although the risk is not well established 5
Factors that influence cross-reactivity
- Similarity in R1 side chains between penicillins and cephalosporins, which can increase the risk of cross-reactivity 4, 5, 6
- Type of penicillin allergy, with IgE-mediated and T-cell-mediated hypersensitivity having different risks of cross-reactivity to other beta-lactam antibiotics 5, 8, 6
- Specific cephalosporin or carbapenem used, with some having a higher risk of cross-reactivity than others 4, 5, 6