Stewardship in the pediatrician's office: De-labeling penicillin allergy - Healio
June 22, 2021
5 min read
Disclosures: Disclosures: Kothari, Noor and Schneider report no relevant financial disclosures.
Ulka Kothari
Amanda Schneider
Amoxicillin, an oral semisynthetic penicillin, is the most common antibiotic associated with childhood medication allergies.
An estimated 5 million children carry the label of penicillin allergy. According to Dyer and colleagues, among 13, 273 hospitalized children, 8.6% carried a penicillin allergy label. Cross-reactivity with cephalosporin in children labeled with penicillin allergy is another concern shared by pediatricians, although its estimated occurrence is only 2%.
Penicillin allergy labels modify pediatricians' prescribing patterns. They lead to the selection of a less effective antibiotic often associated with higher cost, more side effects and the risk of antibiotic resistance. These labels often persist through adulthood and pose a significant patient and public health burden. Penicillin de-labeling is an important component of antimicrobial stewardship. In the hospital setting, numerous screening and testing strategies exist. However, there is scarce information on the de-labeling approach in the pediatrician's office, mainly because of the limited availability of onsite resources. Pediatricians often rely on allergist referrals for allergy diagnostic evaluation. Pediatric allergists have the greatest familiarity with diagnostic evaluation and serve as the best resource for penicillin de-labeling. Additionally, most pediatricians lack formal training in penicillin skin testing and amoxicillin oral challenge tests.
In this article, we discuss a screening and referral strategy to de-label penicillin allergy in the office setting based on available resources.
Confronting the conundrum of appropriate antibiotic prescription
There are three common challenges pediatricians face when de-labeling patients, which are discussed in greater detail below. These include:
- differentiating allergic reaction from other adverse drug reactions;
- approaching parental report of penicillin allergy; and
- managing cephalosporin cross-reactivity in a child with penicillin allergy.
Differentiating hypersensitivity reaction from other adverse drug reactions (see Table):
How to approach penicillin allergy label in a child:
Most penicillin allergy labels are attributed to parental reports, rash being the most common symptom. Most of the reported penicillin allergy symptoms are low risk for true allergy. Low-risk symptoms are often adverse effects instead of bona fide type 1 to 4 hypersensitivity reactions. Symptoms like vomiting, diarrhea and maculopapular rash are commonly seen with viral infections and can be misinterpreted as allergies. Also, hives after 1 to 2 days of antibiotics are commonly due to the drug-viral interaction rather than type 1 hypersensitivity.
In the United States, the overall estimated incidence of self-reported penicillin allergies is approximately 15.3%. In an urban pediatric ED study, none of the children aged 4 to 18 years identified as having low risk by a penicillin allergy questionnaire had true penicillin allergy upon testing. Nonimmediate, delayed hypersensitivity reactions are the most common reasons children present with maculopapular rash, or urticaria, more than 1 hour after drug administration. In a prospective, 10-year study by Atanaskovic-Markovic and colleagues, 7.4% of children with nonimmediate hypersensitivity reactions to beta-lactam antibiotics were confirmed to have a delayed-type reaction by intradermal testing.
Diagnosis of penicillin allergy can be made by either penicillin skin testing or oral penicillin challenge. Skin testing is performed by administering increased amounts of drug over time — 1/10th of the full dose followed by a full dose after 30 minutes to an hour, or administration of the full dose followed by a 1-hour observation. The current negative predictive value is estimated at approximately 98%.
Penicillin skin testing is safe and effective in children with penicillin allergy labels. In a study involving 369 children with negative initial penicillin skin testing, on a subsequent oral penicillin challenge, only 3.8% of patients had a mild reaction. In addition, several studies have demonstrated the safety of direct oral penicillin challenge without initial skin testing. In a prospective multicenter study that included 732 children with a history of mild reaction to penicillin, researchers used a multistep challenge to oral penicillin and concluded that 0.8% of children had immediate reactions and 4% had delayed reactions.
Cephalosporin cross-reactivity:
Approximately 2% of patients with penicillin allergy will cross-react with a cephalosporin. Pediatricians are often faced with the dilemma of whether to use a cephalosporin in such a situation. The current belief is that the R1 and occasionally R2 side chain is responsible for cross-reactivity between penicillin and cephalosporins. Although skin testing with penicillin is recommended before the prescription of a cephalosporin in a child with penicillin allergy, this low risk of cross-reactivity can further be reduced by choosing a cephalosporin with a different R 1 gene as the culprit antibiotic. For example, oral second-generation (cefuroxime) or third-generation cephalosporins (cefdinir, cefixime) do not share R1 side chain with penicillin and can be safely prescribed. On the other hand, first-generation oral cephalosporins, such as cephalexin and cefadroxil, share the R1 side chain with amoxicillin, and penicillin testing should be performed before prescription.
Practice guidelines for outpatient settings
Most of the guidelines focus on screening questionnaires for penicillin allergy and differentiating children with a history of a hypersensitivity reaction vs. those with a low risk for adverse reactions. Also, most guidelines are extrapolated from adult data.
Operationalizing an ASP in your office through quality improvement and EHR
Operationalizing an antimicrobial stewardship program through quality improvement and electronic health records requires a multidisciplinary team with a physician lead, infectious disease specialist, allergist and, if available, a pharmacist. You will also need baseline data on number of patients with penicillin allergy and the level of severity (low, moderate and high).
Physicians should ensure that the association of symptoms with severity is appropriate in the EHR (eg, vomiting is low severity) and create an agreed-upon protocol for the management of patients based on the severity of their symptoms (see examples in this article). This includes:
- an allergy history with patient factors, medication factors and treatment details;
- risk-based stratification and a plan for patients with allergy labels (eg, remove label in patients with family history and further testing for patients with low risk); and
- education and shared decision-making with patients and families.
Consider the "train the trainer" approach in conjunction with the allergist for oral challenge and skin testing. A resourceful training video for pediatricians is available here.
Additionally, there are several steps to optimize EHR alerts:
- If patients have history of penicillin allergy and have subsequently tolerated penicillin, add this additional information to the allergy section. This can be done automatically or manually.
- Less than 2% of patients with penicillin allergy have cross-sensitivity to cephalosporins. Evaluate the EHR alert display for a cross-sensitivity allergy alert and its impact on clinical decision-making.
- For patients who have undergone skin testing and/or oral challenge and have been previously de-labeled, consider adding an electronic alert to prevent relabeling.
- Finally, team communication and patient education is vital, both for engaging them in the process of allergy testing and de-labeling.
References:
Atanaskovic-Markovic, M, et al. Pediatr Allergy Immunol. 2016;doi:10.1111/pai.12565.
Children's Hospital of Philadelphia. Clinical pathway for the assessment of children with a penicillin drug allergy. https://www.chop.edu/clinical-pathway/penicillin-drug-allergy-clinical-pathway. Accessed May 26, 2021.
Dyer K, et al. Impact of reported penicillin allergies on antibiotic prescribing practices in inpatient pediatrics. Presented at: Society of Hospital Medicine Converge Meeting; May 4-May 7, 2021 (virtual meeting).
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