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Penicillin is one of the most commonly used antibiotics. Penicillin encompasses a large group of chemically related drugs called beta-lactam antibiotics, which can be given by mouth or by injection.

Penicillin is the antibiotic of choice to treat common bacterial illnesses, including ear infection, strep throat, and pneumonia. Penicillin is also a go-to antibiotic in surgery to prevent surgical site infections, and in hospitalized patients to prevent severe illnesses. [1] Because of its widespread use, adverse reactions to penicillin are relatively common.

For every course of penicillin that’s prescribed, there’s a 1% to 2% chance of experiencing an adverse side effect. [2] But contrary to common belief, such side effects are rarely allergy-related.

Around 10% of the United States population reports that they are allergic to drugs containing penicillin, [1] but the majority of these individuals have not been tested to confirm their diagnosis.

A recent study has found that less than 2% of individuals that get tested for penicillin allergy test positive, [2] which means that the vast majority of these individuals who avoid penicillin can safely take it. With penicillin being the first-line option for many clinical scenarios, unverified penicillin allergy causes healthcare professionals to prescribe less appropriate antibiotics that have been shown to confer inferior outcomes and increased healthcare costs. [1]

Complications of Unverified Penicillin Allergy

It’s unclear why physicians are so hasty to assign a penicillin allergy diagnosis without testing to confirm, or why patients do not undergo the proper testing before making healthcare decisions related to penicillin use. In any case, the consequences of misdiagnosis are well-documented. Individuals with penicillin allergy are typically prescribed alternative antibiotics, such as vancomycin, quinolones, or carbapenems.

These alternative antibiotics are associated with longer hospital stays and increased rates of serious drug-resistant infections in hospitalized patients. Patients receiving non-beta-lactam antibiotics are more likely to contract gram-positive bacterial strains like enterococci and staphylococcus, as well as gram-negative strains like klebsiella. Of course, such bacterial infections are associated with increased costs, poorer outcomes, and even an increased risk of death. Another point of concern is that surgical patients see a higher rate of surgical site infections when penicillins are not used. [1]

In addition, avoidance of penicillin due to misdiagnosed allergy has been shown to confer poorer clinical outcomes in children with common bacterial illnesses, such as ear infection, strep throat, or pneumonia, avoidance of penicillin leads to poorer clinical outcomes. [1]

These observations favor penicillin use over penicillin avoidance when possible. With approximately 9 out 10 unverified penicillin allergy cases being mislabeled, most of these individuals receive suboptimal treatment in multiple clinical scenarios. All individuals with an unconfirmed penicillin allergy should have their penicillin allergy evaluated and, if appropriate, tested to confirm hypersensitivity or tolerance. [2]

Penicillin Allergy Testing

Penicillin allergy testing has been standardized to achieve a negative predictive value that exceeds 99%. [1] Testing protocol consists of a skin test followed by an oral challenge. Skin testing is reserved for high-risk patients – those with a recent penicillin-associated reaction or a history of shortness of breath or anaphylaxis associated with penicillin – but many physicians and patients choose to undergo skin testing first to confirm that the oral test will be safe even in the absence of high-risk clinical features.

Skin Testing

Skin testing begins by pricking the skin with a small amount of each form of a penicillin reagent. If the skin prick tests are negative, an intradermal test is performed in which a small amount of reagent is placed right underneath the skin using a small needle. If these skin tests are negative, penicillin allergy is unlikely, but an oral challenge is required to definitively confirm. [3] Individuals with positive skin test results should not undergo oral challenges.

Oral Amoxicillin Challenges

An oral amoxicillin challenge involves the patient taking a dose of penicillin by mouth under clinical observation. The reference standard test to confirm penicillin class antibiotic hypersensitivity or tolerance is an oral challenge with a therapeutic dose, typically 250 mg for adults, and 1 hour of observation to confirm acute tolerance, followed by 5 days of at home follow-up to confirm delayed tolerance. [2]

Economic Impact of Penicillin Allergy Testing

Evidence is beginning to emerge that more focus on de-labeling penicillin allergy, rather than avoiding penicillin use, has a positive effect on both patient and economic outcomes. One pediatric emergency department recently reported on 100 children 1 year after their conditions were delabeled as penicillin allergic. They calculated that delabeling saved over $1,300 in direct cost, and avoided an additional $1,800 per patient.

Extrapolating these findings to the patient volume of an average-sized emergency department, they estimated that an emergency department would save nearly $200,000 per year with up front penicillin allergy testing. [4] Additional cost savings are expected in the setting of surgery with reduced infections, and in primary care with improved antibiotic treatment outcomes.

References

[1] Lang, D. M., Castells, M. C., Khan, D. A., Macy, E. M., & Murphy, A. W. (2017). Penicillin Allergy Testing Should Be Performed Routinely in Patients with Self-Reported Penicillin Allergy. Journal of Allergy and Clinical Immunology: In Practice, 5(2), 333–334. https://doi.org/10.1016/j.jaip.2016.12.010

[2] Macy, E., & Vyles, D. (2018). Who needs penicillin allergy testing? Annals of Allergy, Asthma and Immunology, 121(5), 523–529. https://doi.org/10.1016/j.anai.2018.07.041

[3] Blumenthal, K. G., & Shenoy, E. S. (2019). Am I Allergic to Penicillin? JAMA, 321(2), 216. https://doi.org/10.1001/jama.2018.20470

[4] Cook, Q., & Burks, A. W. (2018). Antibiotic use after removal of penicillin allergy label. Pediatrics, 142(5), S224–S225. https://doi.org/10.1542/peds.2018-2420BB

Source: Uptown Allergy & Asthma, New Orleans, Louisiana