Are Cephalosporins Safe if You're Allergic to Penicillin?

If you have ever had an allergic reaction to penicillin, you may have been told to also avoid cephalosporin antibiotics. That advice is outdated and no longer recommended.

Penicillins and cephalosporins are beta-lactam antibiotics used to treat a wide range of bacterial infections. The drugs are structurally similar to each other and have the potential to cause a cross-reaction.

However, recent research shows the likelihood of being allergic to both penicillins and cephalosporins is relatively small. What's more, studies show true penicillin allergies are rarer than once believed. These common misconceptions can affect care and treatment options.

This article discusses penicillin allergies and cephalosporins. It explains the signs of an allergic reaction, the different classes of antibiotics, and tests to confirm a true allergy.

What Is a Penicillin Allergy?

Penicillin allergies occur when the immune system misfires, mistaking the medication for a harmful invader. This can lead to a potentially fatal reaction known as anaphylaxis.

Signs of a penicillin allergy typically begin within two hours of taking the drug. Symptoms range from mild to severe and include:

• Hives
• Itchy skin
• Redness
• Swelling of the face, hands, or feet
• Throat tightness
• Wheezing, coughing, and chest tightness

A mild allergic reaction to penicillin can be treated with an antihistamine like Benedryl (diphenhydramine) and, in some cases, steroid medications.

Signs of a Severe Allergic Reaction

A seemingly minor reaction to an antibiotic can quickly progress to anaphylaxis. The following symptoms warrant emergency medical care:

• Difficulty breathing or swallowing
• Itching or tingling of the lips or tongue
• Fast heart rate
• Lightheadedness or dizziness
• Low blood pressure
• Loss of consciousness
• Seizures
• Swelling of the tongue or throat
• Vomiting, diarrhea, and abdominal cramps

True Penicillin Allergy vs. Other Reaction

About 10% of Americans have a history of allergic reactions to penicillin, but studies suggest only 1% have a true penicillin allergy.

A true allergic reaction to penicillin is an immunoglobulin E (IgE)-mediated, type 1 hypersensitivity response. When a person who is allergic to penicillin is exposed to it, they develop IgE antibodies that trigger a reaction.

A reaction after taking penicillin is not always an IgE-mediated response to the drug, though. The symptoms are often a reaction to something else. Side effects are also sometimes confused with a true allergy. Out of an abundance of caution, this is often documented in your medical chart as a penicillin allergy.

People with a potential penicillin allergy are often warned against taking beta-lactam antibiotics and given broad-spectrum antibiotics as an alternative. However, these medications may not be the best for treating specific infections and increase the risk of future antibiotic resistance.

What Are Beta-Lactam Antibiotics?

Beta-lactam antibiotics contain a particular structure (called the beta-lactam ring) within their molecular makeup. They fight bacterial infections by interrupting bacterial cell wall formation.

Penicillin, the first and perhaps most well-known beta-lactam antibiotic, was discovered in 1928. Since then, thousands of penicillin derivatives and related beta-lactam antibiotics have been discovered.

The beta-lactam class of antibiotics includes penicillin and penicillin derivatives, cephalosporins, and carbapenems.

Penicillin and Penicillin Derivaties

Penicillins and penicillin derivatives have generic names that end in -cillin. These include:

• First-generation penicillins: penicillin G, penicillin G benzathine, and penicillin V 
• Second-generation penicillins: dicloxacillin, oxacillin, and nafcillin
• Third-generation penicillins: ampicillin and amoxicillin
• Fourth-generation penicillin: piperacillin 

Cephalosporins

Cephalosporins have generic names that begin with the prefix ceph- or cef-. These include:

• First-generation cephalosporins: Keflex (cephalexin), Duricef (cefadroxil), and Velosef (cephradine)
• Second-generation cephalosporins: Ceclor (cefaclor), Ceftin (cefuroxime), and Cefzil (cefprozil)
• Third-generation cephalosporins: Suprax (cefixime), Cedax (ceftibuten), and Vantin (cefpodoxime)
• Fourth-generation cephalosporin: Maxipime (cefepime)
• Fifth-generation cephalosporin: Teflaro (ceftaroline)
  

Carbapenems

Carbapenem antibiotics have generic names that end in -penem. These drugs are not available in oral formulas and are only given through an IV.

Carbapenums used in the United States include Primaxin (imipenem), Merrem (meropenem), Invanz (ertapenem), and Doribax (doripenem).

Confirming a Penicillin Allergy

If you have a suspected penicillin allergy, your healthcare provider may refer you to an allergy specialist or immunologist for testing. Penicillin allergies can be confirmed by:

• Skin testing: This test involves pricking the skin with two different forms of penicillin and waiting to see if a reaction occurs. This is often followed by a second test where a small amount of penicillin is injected just under the skin (intradermal).
  
• Oral challenge: During this test, the person is given a small drug dose and monitored for symptoms over the next hour. If no reaction occurs, a larger dose is given, followed by a more extended monitoring period.

If skin testing is negative, the next step is an oral challenge. People with a history of a mild reaction to penicillin are sometimes given an oral challenge first without skin testing. If you do not react to the oral challenge, the allergy can be removed from your medical file.

Cephalosporins and Penicillin Allergies

Since the late 1970s, people with suspected penicillin allergies were also advised against cephalosporins. However, more recent research found the cross-reactivity rate is much lower than previously thought.

Studies show that between 1% and 4% of people with a true penicillin allergy are allergic to one or more cephalosporins.

Cross-reactions are more common with Keflex (cephalexin), cefadroxil, cefprozil, and cefaclor. These medications share an identical molecular side-chain structure with penicillins. One study found 16% of people with a true penicillin allergy also react to these medicines. 

Ancef (cefazolin), on the other hand, has a much lower cross-reactivity rate. A meta-analysis of 77 studies found less than 1% of those with a reported penicillin allergy and 3% of those with a confirmed penicillin allergy had an adverse reaction to cefazolin.

The real-world implications were tested in a large California health system that uses automated alerts in electronic health records. A warning against prescribing cephalosporins in people with penicillin allergies was removed from one region of the health system but left in place in another.

An analysis of more than 4 million patient records found a 47% increase in cephalosporin prescriptions when the warnings were removed. At the same time, rates of new allergies, severe allergic reactions, or anaphylaxis did not increase.

Summary

In the past, people allergic to penicillin were told to avoid cephalosporins. However, more recent studies show a relatively small risk of cross-reaction. 

The outdated advice to prescribe broad-spectrum antibiotics instead of penicillin or cephalosporins led to suboptimal treatment, higher healthcare costs, and increased rates of antibiotic resistance. 

True penicillin allergies are also less common than previously thought. While 10% of people report a reaction to penicillin, less than 1% have an IgE-mediated response to the drug. Additionally, some people are allergic to cephalosporins and not penicillins.

Research shows that most people outgrow a penicillin allergy within 10 years. If you’ve ever reacted to penicillin, cephalosporins, or other drugs, the CDC recommends skin tests and an oral challenge to confirm a true allergy.