A Penicillin Allergy Questionnaire for Outpatient Clinics
Clinicians developed an algorithm and screening questionnaire for outpatient penicillin allergy evaluation, designed to stratify patients into high- and low-risk penicillin allergy groups. Here is the sample questionnaire to consider for use in clinics.
Approximately 20% of patients in medical settings report penicillin or β-lactam allergy, but less than 5% are confirmed when evaluated.
Image credit: pexels-ryutaro
In the United States, more than 200,000 cases of syphilis and 640,000 cases of gonorrhea were reported in 2022, and syphilis cases have increased by approximately 80% over 5 years. Additionally, more than 3700 congenital syphilis cases were reported by the Centers for Disease Control and Prevention (CDC), representing a 937% increase over the past 10 years.1
The CDC recommends penicillin and ceftriaxone as the preferred treatments for syphilis and gonorrhea, respectively.2 Penicillin allergy is commonly reported and may impact treatment options for sexually transmitted infections (STIs). Approximately 20% of patients in medical settings3,4 report penicillin or β-lactam allergy, but less than 5% are confirmed when evaluated.5,6 One strategy is penicillin skin testing (PST), which has been increasingly conducted by nonallergists, including pharmacists.7 PST requires well-trained personnel for test preparation and administration, which may be difficult to implement in a clinic with limited resources. An alternative strategy is oral challenge, such as with amoxicillin, either as a direct oral challenge with a single dose or as a graded oral challenge (GOC) with multiple escalating doses.
Lillis et al developed an algorithm and screening questionnaire for outpatient penicillin allergy evaluation, designed to stratify patients into high- and low-risk penicillin allergy groups, which takes approximately 5 to 7 minutes to administer (TABLE). A randomized trial was conducted at 4 STI clinics with the primary objective of validating this algorithm. Patients aged 18 years and older with a history of penicillin or other β-lactam allergy were included. Exclusion criteria were HIV with CD4 cell count less than 200 cells/mm3; recent antihistamine use; and rashes or tattoos, which may impact skin testing. Pregnant people could receive PST but were excluded from oral challenge.
Full questionnaire available in Supplemental Material Appendix 1 (Lillis RA, Barbee LA, McNeil CJ, et al. Randomized multicenter trial for the validation of an easy-to-administer algorithm to define penicillin allergy status in sexually transmitted infection clinic outpatients. Clin Infect Dis. 2024;78(5):1131-1139. doi:10.1093/cid/ciae064)
Participants with a low-risk allergy were randomly assigned to receive either PST (followed by oral challenge with amoxicillin 250 mg) or a 2-step GOC (of amoxicillin 25 mg followed by amoxicillin 250 mg). PST with both major determinants and minor determinants was conducted with pinprick testing followed by intradermal testing. The major determinant is commercially available, whereas the minor determinant was compounded on-site using penicillin G pharmaceutical powder. After a negative skin test result, participants proceeded with oral amoxicillin challenge and observation. Both groups received physical examination including vital signs and peak expiratory flow throughout the protocol.
Of the 325 patients screened between June 2021 and December 2022, 284 patients agreed to enroll in the study. A low-risk penicillin allergy was identified for 212 patients, and 206 completed the allergy assessment per protocol. The remaining 72 patients were determined to have a high-risk allergy and were excluded from further allergy evaluation. Of note, 6 patients with a high-risk allergy received a skin test in error, although all tolerated the amoxicillin challenge.
All 102 participants receiving PST had a negative pinprick test. After intradermal testing, 3 were excluded. Out of the remaining 99 participants who received oral challenge with amoxicillin 250 mg, 96 (97%) had a negative challenge and were identified as not penicillin-allergic and 3 (3.0%) had possible allergic reactions including nasal drainage and itching throat/eyes and conjunctival injection (n = 1); pruritic erythematous rash subsided with diphenhydramine (n = 1); and rash developed after 24 hours (n = 1), which was treated with prednisolone. Of 104 (50.5%) participants who received GOC, 4 (3.8%) experienced a possible allergic reaction such as upper body rash/itchiness. One withdrew due to anxiety. The remaining 99 (95.1%) participants received an amoxicillin 250-mg challenge and 4 (4.0%) experienced possible allergic reactions, which were similar to previous GOC patients. A total of 95 (91.4%) participants successfully completed the GOC and were determined to be penicillin nonallergic.
Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Out of 206 evaluated patients, 191 (92.7%) were not allergic and had their allergy label removed from the medical record. Additionally, 45 participants were subsequently safely treated with either penicillin or ceftriaxone at the STI clinics after delabeling. In survey responses, participants and clinicians favorably rated the protocol’s safety, effectiveness, helpfulness, and feasibility. Importantly, most participants responded they were “very confident” (70.2%) and “confident” (20.4%) that they could take penicillin after negative allergy testing results, although the PST group had a higher level of confidence than the GOC group.
After a screening questionnaire, both PST and GOC safely delabeled most reported penicillin allergies at STI clinics. Compared with PST, antibiotic challenge (both direct and graded) is easier to implement for most settings and has been validated in other randomized clinical trials.8 Additionally, for patients requiring cephalosporins for treatment of an infection, current literature and recommendations from the 2022 Drug Allergy Practice Parameter Update support direct challenge for patients depending on the severity of reaction (anaphylactic vs nonanaphylactic) and side chain similarities with the reported allergen.9 The protocol described in this publication optimized allergy assessments in the outpatient setting and can be adapted to other nonspecialty clinics, including those with limited pharmacy and allergist resources. The expansion of allergy delabeling interventions can increase accessibility to allergy assessment services and allow healthcare professionals to capture a greater proportion of the population through various points of contact with the healthcare system.
Highlighted study: Lillis RA, Barbee LA, McNeil CJ, et al. Randomized multicenter trial for the validation of an easy-to-administer algorithm to define penicillin allergy status in sexually transmitted infection clinic outpatients. Clin Infect Dis. 2024;78(5):1131-1139. doi:10.1093/cid/ciae064
