Penicillin skin testing was performed on 3469 unique individuals between November 16, 1994, and January 21, 2008, including 3158 previously reported on.12,14–19
Study cohort demographics are reported in . Of 3469 study subjects tested, 255 had positive results on PenSTs. Of 411,543 Health Plan patients seen during 2007, 37,059 (9.0%) reported a history of penicillin allergy. More females, 11.0%, than males, 6.6%, reported a history of penicillin allergy (p < 0.0001). Males accounted for 33.2% of the Health Plan patients with a history of penicillin allergy in 2007 and 30.8% of the patients undergoing PenST over the course of the study (). The proportion of positive PenSTs, including the subgroup with positive results on penicillin puncture, was not significantly different between females and males (). TSR data was not available for 355 (10.2%) study subjects.
There were 36 adverse reactions, both subjective and objective, during testing, 13 (5.1%) in the group with positive PenST results and 23 (0.72%) in the group with negative PenST results (p < 0.001). In the former group, there were 21 (8.2%) who had positive results on penicillin puncture. There were 4 (19.0%) adverse reactions in the PenST group with positive findings on puncture and 9 (3.9%) in the PenST ID group with positive findings (p = 0.0024). None of the testing-associated reactions were severe. Fewer than half received any treatment. Seven were treated with epinephrine and antihistamines, five were treated with antihistamines only, two received ammonia inhalant, and the rest received no treatment.
The percentage of positive findings on PenSTs by year of test, along with mean age of tested study subject, TSR, and mean age of Health Plan patients, are shown in . There was a significant decrease in the rate of positive findings on PenSTs with time (R2 = 0.561; F = 14.069; p = 0.0032). Study subjects were progressively older at an average rate of 1.18 years per year over the 13 years studied (R2 = 0.556; F = 13.783; p = 0.0034). The average age of Health Plan patients increased by only 0.22 years per year. After 2001, a greater emphasis was placed on testing hospitalized individuals who were older than average Health Plan patients (data not shown).
Penicillin skin test results by year of test
The prevalence of positive findings on PenSTs was highest in younger patients and decreased significantly (p < 0.0001 χ2 for trend) with advancing age, as displayed in . Nearly 70% of patients with positive findings on PenSTs were ≤50 years old. Half of the study subjects with positive findings on PenSTs were ≤38 years old. If a patient reported an age of <38 years (median), the relative risk of a positive finding on a PenST was 2.1 (95% confidence interval [CI] = 1.6–2.7).
Relationship of subject age (by quartile) to the prevalence of positive findings on penicillin skin tests
The relationship between the TSR and the prevalence of positive findings on PenSTs is displayed in . Patients with positive findings on PenSTs had shorter TSRs (13.3 ± 15.4 years) than patients with negative PenSTs (21.7 ± 18.7 years; p = 0.0001). Half of the study subjects with positive findings on PenSTs had a TSR ≤6 years. One quarter of the study subjects with positive findings on PenSTs had a TSR ≤3 months. Ten percent of the study subjects with positive findings on PenSTs had a TSR ≥38.2 years. If a patient reported a TSR ≤13 years (mean) the relative risk of a positive finding on a PenST was 2.1 (95% CI = 1.6–2.8).
Relationship of time since reaction to the prevalence of positive findings on penicillin skin tests
Given that both study subject age and TSR correlated to PenST results and the overall population studied was older as the study progressed, a stepwise linear regression was performed to see if the year of testing had an independent effect on the proportion of patients with a positive finding on a PenST in a given year. The rate of positive findings could be accounted for by the year of testing (R2 = 0.56; p = 0.003) without any significant contribution from the patient's age or the TSR.
The prevalence of positive findings on PenSTs was highest in younger patients and decreased significantly … with advancing age …
The relationships among the type of index reaction to proportion of positive findings on PenSTs, patient age, and TSR are displayed in . Time to onset of the index adverse reaction to penicillin was not significantly associated with PenST outcome (n = 2279; χ2 = 4.05; p = 0.26). The index reaction type was related to a positive result for a PenST (Table 3; n = 3029; χ2 = 34.28; p < 0.0001). There was a significant relationship between age and the index reaction type (ANOVA; F = 40.85; p < 0.0001). The most pronounced difference was noted between individuals reporting hives (mean age, 40.7 years) compared with those reporting local swelling (mean age, 60.4 years). There was also a significant relationship noted between the TSR and the index reaction type (ANOVA; F = 35.72; p < 0.0001). Again, the most pronounced differences were seen between study subjects reporting hives (mean TSR, 15.5 years) and those reporting local swelling (mean TSR, 30.7 years). Subjects reporting anaphylaxis were intermediate (mean TSR, 21.6 years).
Relationship between the type of index reaction to the proportion of positive findings on penicillin skin tests, study subject age, and time since reaction
Patient recollection of the infection associated with the index reaction and the specific penicillin-class antibiotic used were too poor to produce a meaningful analysis.
Oral challenges with amoxicillin or penicillin were given to 311 individuals with negative results on PenSTs after July 16, 2006. Data on study subjects given oral challenges after testing before July 16, 2006, have been previously reported.12,15
There were six (1.9%) acute subjective reactions reported; five patients noted itching, but no visible rash was present; and one patient reported chest tightness but had completely normal spirometry results while symptomatic. There were also 5 (1.6%) delayed-onset reactions reported, all rashes starting from 5 to 30 hours after the oral challenge. Several were treated with oral antihistamines, and there were no severe reactions.