Antibiotic Allergies: Be Prepared

If there is one thing that this global pandemic has taught all of us is to expect the unexpected. That type of thinking applies to so many areas of life. When it comes to an allergic reaction from a medication that we recommended or prescribed to one of our patients, we need to be prepared to assess the situation from the following angles:

• Did the patient forget to list his or her allergies on the intake papers, or did I just miss the fact that the patient was allergic to a certain medication or class of medications?
• Was there a cross-reaction between what I prescribed or recommended and an allergy to another medication or class of medications?
• What can I do to lessen the chance of this happening again?

New medications get approved and marketed frequently, and there have been quite a few that are now indicated for ocular diseases and conditions. Add that to the ever-expanding scopes of practice for optometric physicians, and you create the perfect opportunity for a quick refresher.

THE PROCESS OF THE REACTION

Many, if not most, allergic reactions to a drug will occur after more than one exposure. This is because the body sometimes needs to “see” the drug (or something with a similar structure) more than once before it decides that this harmless substance is a deadly invader.^1,2 First let’s go back to that “harmless substance” phrase I just used.

Let’s be clear: The body is never happy that a drug is swirling around in the bloodstream. The human body has a narcissistic and myopic view regarding itself. It has two t-shirts in its closet; one says “sexy beast” and the other says “fake it ‘til you make it,” because it lives under the short-sighted assumption that it has every antidote to every situation no matter the severity.

So every time a drug enters the bloodstream, the body hits the big red panic button and immediately begins the pharmacokinetic processes of trying to eliminate the drug as fast as possible. At minimum, a drug will cause the body to spend time and energy trying to metabolize and eliminate it as fast as possible. At maximum, a drug will permanently alter homeostasis and cause severe adverse effects and/or an allergic reaction. Imagine how this “sexy beast” feels when it has multiple medications to deal with on a daily basis.

TYPE I REACTION

Make no mistake: Each patient is unique. We are taught to look for “typical” reactions to drugs, but we have learned, sometimes the hard way, that many of our patients are anything but typical. Their genes, comorbidities, medications, bodies, and past experiences with drugs and allergies can differ widely, and this should affect how we approach the potential problem of a drug allergy.^1-4

Medical literature describes typical drug allergy reactions (Table 1) that may involve the gastrointestinal tract, the skin, the respiratory system, and even the vasculature in the case of anaphylactic shock.^1-6 These concerning antibody-mediated reactions result in an impressive list of problems, as they may bind to mast cells, basophils, histamine, leukotrienes, and prostaglandins. This may result in what is commonly known as the triple histamine response, which presents as edema, vasodilation, and inflammation.^1-4 These harbingers of doom typically occur quickly (within 1 hour) after exposure to the antigenic drug and are called immediate hypersensitivity reactions (type 1).^2,4,5

In general, any drug or drug class that has caused an immediate allergic reaction should be avoided.

CROSS-REACTIONS

Certain drugs are infamous in their potential to produce allergic reactions, and sometimes there are cross-reactions between drug classes. Some common and not-so-common allergenic drugs used in optometry include:

• Beta-lactams (eg, penicillins, cephalosporins)
• Sulfa/sulfonamide (eg, trimethoprim-sulfamethoxazole)
• Fluoroquinolones
• Nonsteroidal antiinflammatory drugs (NSAIDs)
• Opioids
• Biologics

The beta-lactam antibiotics are commonly used in optometry, as they are incredibly safe and can treat everything from acute dacryocystitis to preseptal cellulits. The penicillin relative amoxicillin and the cephalosporin cephalexin are the two most widely used in this class. Approximately 8% to 10% of the US population has a self-reported penicillin allergy; however, studies have found that upward of 90% of these patients are not actually allergic to penicillin when skin tested.^5-8 In the 10% of those patients who do react to a penicillin, the latest research indicates that the risk of a serious allergic reaction is less than 2%.^5,6,9-12

If a patient reports a serious penicillin (or any drug) allergy, that drug and drug class should generally be avoided, and it is reasonable to suggest that the patient get skin-tested, as this helps guide antibiotic choices for the patient in every medical setting. Suggesting that antibiotic-allergic patients seek additional testing with an allergist or immunologist has several benefits. Patients listed as “penicillin-allergic” will likely receive more broad-spectrum antibiotics to treat infections, which may result in antibiotic resistance, augmentation of the gut microbiome, and a higher likelihood of developing Clostridium difficile diarrhea.^9-12

What about another beta-lactam cephalosporin antibiotic, such as cephalexin? I have been told by more than one optometric physician that cephalexin is a favorite choice for susceptible infections because it is unlikely to cause an allergic reaction in a patient with a penicillin allergy.

As a fellow beta-lactam, cephalosporins, like penicillins, contain a beta-lactam ring that seems to play a role in the potential cross-allergy between the two classes.^9-12 A common myth is that more than 10% of patients with a penicillin allergy will also react to a cephalosporin.^11-14 This has largely been refuted by data from studies suggesting that the range is closer to 0.1% to 6%, with the higher end of the range seen particularly in patients with a positive skin test reaction to penicillin.^14-17

It has also been determined that the side chains attached to the beta-lactam ring likely increase or decrease the likelihood of a cross-reaction to a cephalosporin in a patient allergic to penicillin. In other words, the closer the chemistry of the cephalosporin side is to penicillin, the more likely the cross-reaction.^14-17

With this in mind, a first-generation cephalosporin is more likely to cause a reaction than a second- or third-generation agent. Some of you may think, “I have successfully used a first-generation cephalosporin (ie, cephalexin) in many patients with a mild or questionable penicillin allergy.” This is likely because that patient had a nonsevere, non–immunoglobulin-E (IgE)-mediated reaction to penicillin.^14-17

A reasonable way to approach the safe use of a cephalosporin in a patient listed as penicillin-allergic is summarized in Table 2.

THE TAKEAWAY

There will be further publications addressing allergies to other antibiotics, NSAIDs, pain medications, and biologics, as these are important drugs used in optometry. I could write a thousand articles and we would still not get through all of the potential drug allergens, as our finicky and sometimes feckless immune systems can mount a counterattack to literally anything (even itself)! Table 3 provides a short list of questions to ask patients who have a history of drug allergy.

In the end, all medical professionals should approach their patients with a macroscopic eye and always monitor for both efficacy and toxicity with drug therapy. It is good that the little voice in the back of our heads anticipates trouble when drugs are involved; it helps us remember to be proactive rather than reactive. That, my friends, is part of what makes for excellent practitioners.

The author thanks P. Scout McGowan, a premed student at Rider University in Lawrenceville, New Jersey, for her help in identifying references. Ms. McGowan has no financial disclosures.