Q. What is the relationship between penicillin and cephalosporin allergy?
A. Penicillin and cephalosporins are both in the beta lactam class of antibiotics. Most of the allergic cross-reactivity is related to side chain similarity, as opposed to the beta lactam ring itself. The rate of true clinical cross reactivity varies based on the side chain but is overall two percent or less. Given that 95 percent of people who report a penicillin allergy are not truly allergic, avoiding cephalosporins in all patients who report a penicillin allergy likely results in suboptimal treatment for many people.
Q. I was taught that there is a 10 percent cross-reactivity rate between penicillin and cephalosporins, where did that come from?
A. I was taught that too! This has been debunked with a tremendous amount of evidence. There were early reports in the 1960’s and 1970’s, which reported a 10 percent cross-reactivity risk. This was related to earlier generation cephalosporin drugs, which had greater similarity in side chains to penicillins, and/or contamination of penicillin during the manufacturing process, which has since been refined. Despite this no longer being the case, this 10 percent rate of cross-reactivity continues to be taught and is oftentimes built into medication safety alerts in hospitals during the ordering and dispensing process, further perpetuating this myth.
Q. While the risk may be lower than 10 percent, it’s not zero and there are many other antibiotics. So, is it best to avoid cephalosporins in patients who report a penicillin allergy?
A. While there are certainly alternative classes of antibiotics (and in some cases those may be preferred due to the infection/condition itself), beta lactams are the treatment of choice for many routine pathogens and common syndromes. Patients who avoid these preferred first-line agents are more likely to have longer hospital stays, sequalae from second line agents (e.g., nephrotoxicity with vancomycin), and increased rates of MRSA, VRE, and surgical site infections. Thus, while avoiding a beta lactam may decrease an already exceedingly low allergy risk, it certainly increases other risks for the patient.
Q. How do I assess if my patient labeled penicillin allergic is low risk to receive a cephalosporin?
A. Recent recommendations from the American Academy of Allergy, Asthma and Immunology (AAAAI) have outlined guidance for assessing patients. In a patient with a non-anaphylactic history of reaction to a penicillin (with anaphylaxis being a true multisystem reaction, not a delayed rash), the recommended option is for any cephalosporin to be administered normally. Other options (which are less preferred based on evidence) are to consider penicillin skin testing or administer the cephalosporin in a graded challenge fashion.
If the patient DOES have a history of anaphylactic reaction to a penicillin, structurally dissimilar cephalosporins can be given normally. However, an allergy evaluation is needed for structurally similar cephalosporins prior to administration. A drug practice parameter from AAAAI provides cross-reactivity information about similar side chains. For example, amoxicillin shares an identical side chain with cefadroxil and cefprozil. Luckily the rate of true anaphylaxis to penicillin is 0.015-0.04 percent, so this scenario is uncommon. Therefore, the majority of routine patients who report non-anaphylactic symptoms with penicillin can receive any cephalosporin without additional monitoring or precautions.
The other clinical situation one would typically avoid a cephalosporin is a patient with a Severe Cutaneous Adverse Drug Reaction to a penicillin (i.e., Stevens-Johnson Syndrome/ Toxic Epidermal Necrolysis) as cross-reactivity has not been well characterized. Thankfully, these are also exceedingly rare and given the severity of their presentation, they would be difficult to miss in the medical history.
Using appropriate assessment of patients and their allergy history, allows antibiotic choice to be optimized, while avoiding suboptimal outcomes or adverse effects associated with alternative, less preferred options.
