Penicillin Allergy Delabeling Can Decrease Antibiotic Resistance, Reduce Costs, and Optimize Patient Outcomes
Background: Antibiotics are one of the most frequently prescribed medications. Among all classes of antibiotics, penicillins are prescribed due to their clinical efficacy, cost-effectiveness, and general safety. Unfortunately, penicillins also are the most common drug allergy listed in patient medical records. Increasing evidence shows that > 90% of patients labeled with a penicillin allergy are not allergic to penicillins and associated β -lactams. The health care consequences of penicillin allergy in the setting of military medicine and readiness are important to consider.
Observations: In the US, 8 to 10% of the population and up to 15% of hospitalized patients have a documented penicillin allergy, limiting the use of these effective antibiotics. When treating a patient with a penicillin allergy, many clinicians avoid prescribing all β -lactam antibiotics and stay away from cephalosporins due to the concern for potential cross-reactivity. The cost of treating those with a documented penicillin allergy is greater than the cost for those who can receive penicillin, as treatment with broad-spectrum antibiotics often results in longer hospitalizations with increased rates of adverse effects (AEs). Despite preventive programs such as vaccinations, hygiene measures, and prophylactic antibiotics, military personnel are at increased risk for infections due to the military’s mobile nature and crowded living situations.
Conclusions: Many patients report an allergy to penicillin, but only a small portion have a true immune-mediated allergy. Given the clinical, public health, and economic costs associated with a penicillin allergy label, evaluation and clearance of penicillin allergies improves clinical outcomes, decreases AEs from higher risk alternative broad-spectrum antibiotics, and prevents the spread of antibiotic resistance. In military personnel, penicillin delabeling improves readiness with optimal antibiotic options and avoidance of unnecessary risks, expediting return to full duty.
Military Relevance
Infectious diseases have always accompanied military activity.28-30 Despite preventive programs such as vaccinations, hygiene measures, and prophylactic antibiotics, military personnel are at increased risk for infections due to the military’s mobile nature and crowded living situations.28-30 This situation has operational relevance from basic training, deployments, and combat operations to peacetime activities.
Military recruits are treated routinely with penicillin G benzathine as standard prophylaxis against streptococcal infections.26,30 A recent study by the Marine Corps Recruiting Depot in San Diego, California showed that in a cohort of 402 young healthy male recruits, only 5 (1.5%) had a positive reaction to penicillin testing and challenge over a 21-month period.31 The delabeled other 397 (98.5%) marine recruits were able to receive benzathine penicillin prophylaxis successfully.31 Recruits with a penicillin allergy who had a positive test or were not tested received azithromycin (or erythromycin at some recruit training locations).26,31 Military members may need to operate in remote or austere locations; the ability to use penicillins is important for readiness.
Evaluation and Management of Reported Penicillin Allergy
Verifying penicillin allergies is an important first step in optimizing medical care and decreasing resistance and ADRs.3,4,32,33 Although allergists can provide specialized evaluation, due to the high prevalence of penicillin allergy in the US, all health care team members, including clinicians and pharmacists, should be educated about penicillin allergies and be able to implement evaluations in both inpatient and outpatient settings. Reactions to any of the penicillins should be considered, including the natural penicillins (penicillin V, etc), antistaphylococcal penicillins (dicloxacillin), aminopenicillins (amoxicillin and ampicillin), and extended-spectrum penicillins (piperacillin).3 A thorough history, including the prior reaction (age, type of reaction) and subsequent tolerance are helpful in stratifying patients.3,26
Patient Risk Levels
Based on the clinical history, patients would fall into 4 categories from low risk, medium risk, high risk, to do not test/use.3,32,33 Low-risk patients are those who report mild or nonallergic symptoms (ie, gastrointestinal symptoms, headache, yeast infection, etc), remote cutaneous reactions (> 10 years), or in those with a family history of penicillin allergy.3,32,33 Low-risk patients often can be safely tested with an oral challenge. Although there are different approaches to the oral challenge, a single amoxicillin dose of 250 mg followed by 1 hour of direct monitoring is usually sufficient.3,32,33
Medium-risk patients have a more recent (< 1 year) history of pruritic rashes, urticaria, and/or angioedema without a history of severe or systemic reactions. These patients benefit from negative skin testing prior to an oral challenge, which can be performed by trained clinicians or pharmacists or an allergist. However, due to limited availability of skin testing and the potential for false positive testing with skin tests, a single dose or graded challenge would be a reasonable approach as well.3,32,33
High-risk patients are those with severe symptoms (anaphylaxis), a history of reactions to other β-lactam antibiotics, and/or recurrent reactions to antibiotics. These patients benefit from a formal evaluation by an allergist and skin testing prior to challenge.3,32,33 Testing and/or challenge should not be performed in patients who report a history of severe cutaneous reactions (blistering rash, such as Stevens Johnson syndrome), hemolytic anemia, serum sickness, drug fever, and other organ dysfunction.3,4,31,32
The Figure describes a published questionnaire, personnel, resources, and procedures for penicillin delabeling.26 Although skin testing is reliable in revealing a immunoglobulin E-mediated penicillin allergy, there is potential for false positives.32,33 The oral amoxicillin challenge effectively clears the patient for future penicillin administration.3,32-34 In high-risk patients, desensitization should be considered if penicillins (or cephalosporins) are required as first-line treatment. A test dose (one-tenth dose, higher or lower depending on route of administration, historic reaction, clinical status, and level of certainty of prior reaction) may be considered in low- to moderate-risk patients, depending on the indication for the use of the antibiotics.32
Penicillin evaluation pathways can occur in both inpatient and outpatient settings where antibiotics will be prescribed.32-34 There are several proposed pathways, including a screening questionnaire to determine the penicillin allergy risk.26,32,33 Implementation of perioperative testing has been successful in decreasing the rates of vancomycin use and lessening the morbidity associated with use of second-line antibiotics.35 Many hospitals throughout the country have implemented standardized penicillin delabeling programs.3,32-34
