Reported penicillin allergy in Israel: Clinical outcomes and antibiotic costs in a nationwide population-based cohort study

Abstract

Background: Penicillin allergy (PA) is the most documented drug allergy and is overdiagnosed. Data on medical aspects and expenditure outcomes of PA in the outpatient setting are important for planning delabeling programs.

Objective: We sought to characterize the features of PA on a nationwide level and associated burden on the health care system.

Methods: This is a retrospective, matched cohort study conducted on members of a single health maintenance organization. Medical records of those with documented PA in 2022 were compared with those of matched subjects without allergy based on age group, sex, ethnicity, socioeconomic status, and comorbidities. Outcomes included physician encounters, hospitalizations, death events, antibiotic purchases, and costs.

Results: From a database of 2,602,110 individuals, 96,675 (3.7%) subjects with documented PA were included. Most were females (63.3%), mean age 47.3 ± 22 years, and had medium to high socioeconomic status (85.6%). PA was associated with more encounters with primary care physicians (odds ratio [OR], 1.42; 95% CI, 1.38-1.46; P < .001), pediatricians (OR, 1.1; 95% CI, 1.07-1.14; P < .001), and secondary care physicians (OR, 1.21; 95% CI, 1.19-1.24; P < .001), and increased hospitalizations (OR, 1.12; 95% CI, 1.07-1.17; P < .001). Death events were similar in both groups. PA was associated with increased antibiotic purchases per patient (average, 0.93 ± 1.79 vs 0.8 ± 1.58; P < .001) at higher costs (8.91 USD vs 6.03 USD, P < .01). It exhibited increased use of clindamycin (OR, 5.66; 95% CI, 5.38-5.95; P < .001), macrolides (OR, 4.20; 95% CI, 4.08-4.32; P < .001), and quinolones (OR, 1.50; 95% CI, 1.44-1.55; P < .001).

Conclusions: Reported PA is associated with an increased burden on health care resources but not increased mortality. PA delabeling strategies should improve antibiotic use and costs.

Keywords: Penicillin allergy; adverse drug reaction; drug hypersensitivity; health care utilization.

Fig 1

Study design.

Fig 2

Characteristics of penicillin-related antibiotic use. The total number of penicillin-related regimens that were administered to the PA group before the study period is represented by the relative proportion of each drug.

Fig 3

Hospitalization and mortality outcomes in subjects with reported PA. ∗ Analysis is based on logistic regression adjusted for continuous age and chronic illness. †Total admissions include the departments of internal medicine, geriatric medicine, gynecology, urology, ear nose and throat, pediatrics, dermatology, pulmonology, and critical care. ‡All-cause mortality events during 2022.

Fig 4

Annual antibiotic purchases and related costs. A, Average and SD of antibiotic purchases per patient comparing subjects with allergy and matched subjects without allergy. B, Average and SD of antiobiotic costs expressed in US dollars. ∗P < .001.

Fig 5

The use of alternative antibiotics in patients with PA. Analysis was based on logistic regression adjusted for continuous age and chronic illnesses.