Eric Macy

Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper

Aspirin desensitization is indicated for patients who have aspirin-exacerbated respiratory disease and whose asthma and/or rhinosinusitis is suboptimally controlled with inhaled corticosteroids and leukotriene-modifying drugs. In this practice paper, the general requirements for aspirin desensitization are presented, the locations where desensitizations can be safely performed are outlined, prechallenge patient preparation is discussed, an oral aspirin challenge protocol is presented, treatment of adverse reactions is reviewed, and maintenance of aspirin desensitization is discussed.

Skin testing with penicilloate and penilloate prepared by an improved method: Amoxicillin oral challenge in patients with negative skin test responses to penicillin reagents

BACKGROUND Penicillin skin testing has been limited by the lack of commercially available penicilloate and penilloate reagents. OBJECTIVE This project was proposed to produce a stable, well-characterized supply of penicilloate and penilloate for intrastate use by our health maintenance organization and to document clinical safety and efficacy. METHODS An improved method of extraction for penicilloate and penilloate, which changed the solvents used during recrystallization, was developed. With these newly prepared reagents, penicillin skin testing was performed on 348 subjects. Skin testing was immediately followed by an oral challenge of 250 mg of amoxicillin in 215 of 288 (75%) subjects displaying a negative response to a battery of penicillin skin tests. RESULTS Nuclear magnetic resonance and mass spectrometry of the newly produced penicilloate and penilloate showed no evidence of organic contamination. Penicillin skin testing resulted in 17.2% (60 of 348) positive test results, with 20% of the subjects with positive results only responding to the newly produced minor determinants. The rate of mild adverse reactions to penicillin skin testing was 1.1% (4 of 348). The rate of mild acute adverse reactions was 5.1% (11 of 215), and the delayed reaction rate was 0.9% (2 of 215) with the amoxicillin challenge. CONCLUSIONS This improved penicillin minor determinant extraction method allows for the reproducible production of very pure preparations of penicilloate and penilloate. Large-scale penicillin skin testing, followed by amoxicillin challenge if results are negative is feasible in a large group model health maintenance organization operating within a single state with the use of internally produced penicilloate and penilloate and commercially available penicillin, amoxicillin, and penicilloyl polylysine.

Elective penicillin skin testing and amoxicillin challenge: Effect on outpatient antibiotic use, cost, and clinical outcomes

BACKGROUND Elective penicillin skin testing in advance of acute antibiotic need and amoxicillin challenge in patients with negative skin test responses have not been evaluated. METHODS I reviewed 236 patients previously entered in a study of new penicillin reagents who received at least 1 prescription drug over a 2-year period. Antibiotic use, outpatient visit rate, and adverse reactions to antibiotics during the year before and after skin testing were evaluated. RESULTS Forty (17%) of the 236 subjects had positive responses. Antibiotic courses dispensed to the 236 subjects fell 28% from 779 the year before testing to 558 the year after testing. The total cost for antibiotics dispensed fell 32% from

The falling rate of positive penicillin skin tests from 1995 to 2007.

17,211.88 to

Use of commercial anti–penicillin IgE fluorometric enzyme immunoassays to diagnose penicillin allergy

11,648.27, with a 5.5% reduction in the average cost per antibiotic. Outpatient visit rate did not change but shifted from primary to specialty departments in subjects with both positive and negative skin test responses. In 93 subjects with negative skin test responses, a total of 188 therapeutic courses of penicillin during the year after testing resulted in 3 (3.2%) unrechallenged mild adverse reactions. Optional amoxicillin challenge in 146 of the subjects with negative skin test responses resulted in complaints of an adverse reaction in 6 of these subjects. Four of these received a penicillin analogue in the next year without reaction. CONCLUSIONS Elective penicillin skin testing done by an allergist was associated with unexpected declines in the number and cost of antibiotics used the year after testing but only modestly lowered the average cost per antibiotic. Adverse reactions to penicillins in subjects with negative skin test responses were infrequent, and amoxicillin challenge did not affect outcomes.

Penicillin skin testing in pregnant women with a history of penicillin allergy and group B streptococcus colonization

BACKGROUND Data on the rate of positive penicillin skin test (PenST) results over time in large populations are rare. The factors that influence positive PenST results are incompletely understood. OBJECTIVES We sought to correlate demographic variables to the rate of positive PenST results over time in a large group of patients with a history of penicillin allergy. METHODS RESULTS from the first test for all patients tested for penicillin allergy in the Kaiser Permanente Health Care Program in San Diego County, CA, between 1995 and 2007 are reported. All patients were tested with penicillin, penicilloyl-poly-lysine, penilloate, penicilloate, and amoxicillin. RESULTS There were 255 positive PenST results in 3469 individuals. The rate of positive PenST results declined from >10% to <5% during the 13 years studied. The positive PenST result rate could be accounted for by the year of testing (R(2) = 0.56; p = 0.003) without any significant contribution from the patients age or the time since reaction (TSR). If the TSR was ≤13 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.8). If the study subjects age was ≤38 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.7). Females reported higher rates of penicillin allergy history than males did (11% compared with 6.6%; p < 0.0001), but there were no significant sex differences in the rate of positive PenST results. CONCLUSIONS There has been a steady decline in the proportion of positive PenST results between 1995 and 2007, independent of study subject age and TSR. Increasing age and increasing TSR were associated with a lower rate of positive PenST results.

The prevalence of reversible airflow obstruction and/or methacholine hyperreactivity in random adult asthma patients identified by administrative data.

BACKGROUND The intermittent unavailability of penicilloyl-polylysine since September 2000 has focused interest on commercial anti-penicillin IgE fluorometric enzyme immunoassay (FEIA) tests to evaluate penicillin allergy. There has been no published comparison of commercial anti-penicillin IgE FEIAs and penicillin skin testing performed in the United States. OBJECTIVE To determine whether the current commercial anti-penicillin IgE FEIAs can replace or augment penicillin skin testing and oral challenges when evaluating individuals with a history of penicillin allergy for future therapeutic penicillin tolerance. METHODS A prospective convenience sample of 150 individuals with a history of penicillin allergy were evaluated between January 23, 2007, and August 4, 2009, with both penicillin skin tests and commercial anti-penicillin IgE FEIAs to penicillin G, penicillin V, and amoxicillin. All individuals with a negative penicillin skin test result underwent oral penicillin class antibiotic challenges. All individuals with a positive anti-penicillin IgE FEIA result also underwent oral penicillin class antibiotic challenges. RESULTS Six individuals (4.0%; 95% confidence interval [CI], 0.9% to 7.1%) had positive penicillin skin test results, and none had positive FEIA results. Four individuals (2.7%; 95% CI, 0.1% to 5.3%) had positive FEIA results, and none had positive penicillin skin test results. Three individuals (2.0%; 95% CI, -0.2% to 4.2%) had positive oral challenge results, 1 with hives at 6 hours after challenge and 2 with delayed-onset (at >24 hours) nonurticarial rashes, and none had positive FEIA results. CONCLUSIONS The current commercial anti-penicillin IgE FEIAs are not useful in diagnosing penicillin allergy in patients with remote histories of penicillin allergy. Penicillin skin testing and, if the results are negative, an oral challenge remain the criterion standard tests to determine therapeutic penicillin tolerance.

Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases.

Background The safety and utility of penicillin skin testing (PST) in pregnant women with a history of penicillin allergy and group B streptococcus (GBS) colonization have not been studied. Objectives To document the safety and utility of PST in pregnant women with a history of penicillin allergy and GBS colonization. Methods Pregnant GBS culture–positive women with a history compatible with an IgE-mediated or unknown reaction to a penicillin-class antibiotic were recruited for PST. If PST results were negative, penicillin-class antibiotics were recommended for GBS prophylaxis. Adverse reactions associated with PST or antibiotic use from the time of PST through delivery and 6 months post partum were reported. Results In 56 enrolled patients, there were only 2 mild adverse reactions (4%) associated with PST and 3 positive PST results (5%). Of the 53 PST-negative patients, 47 (89%) received at least 1 course of penicillin. There were 2 delayed-onset rashes associated with the use of intrapartum penicillins and 1 immediate-onset rash with intrapartum vancomycin therapy in a PST-positive woman. There were 7 reactions (6%) associated with 122 antibiotic courses administered. Conclusions Penicillin skin testing can be performed safely in pregnant women and, if the results are negative, allows penicillins to be used safely at delivery for GBS prophylaxis.

Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America

Background. Asthma is a chronic inflammatory lung disease. It is commonly diagnosed and treated on the basis of clinical impression, although national guidelines recommend documenting reversible airflow obstruction. Objectives. Determine the frequency of reversible airflow obstruction, and/or methacholine hyperreactivity during 2003 in a well-characterized population with a low-risk asthma diagnosis during 2001. Methods. Of a total population of 7460 low-risk adult (18–64 years) asthma patients (no hospitalizations or emergency department visits; < 3 oral steroid courses; < 12 β-agonist canisters; and < 3 prescibers, all in prior 12 months) cared for by a large health care program, a random sample of 400 was recruited to undergo a diagnostic asthma evaluation. The evaluation included a physical examination, medical record review, questionnaires, allergy testing, spirometry for airflow obstruction and reversibility, and/or methacholine hyperreactivity. Results. Of the 400 randomly selected patients, 106 (26.5%) started and 82 (77.3%) completed the asthma evaluation. Evaluated subjects were predominately female (71%), middle-aged (mean 51.0 ± 11.0 years), diagnosed asthmatics for long duration (mean 22.1 ± 17.5 years), and nonsmokers (88.7%). Asthma was confirmed in 62.1% (51 of 82) based on a ΔFEV1 12% or greater after albuterol (n = 38), ΔFEV1 15% or greater after Advair® (n = 6), or a positive methacholine challenge (n = 7). Only 35 of 400 patients (8.7%) ever had reversibility measured in their medical record. Of these, only 12 (34.3%) had a ΔFEV1 12% or greater after albuterol. Reversibility was confirmed in all six who had asthma evaluations. Conclusions. More than one third of low-risk adult asthmatics cannot be confirmed to have asthma 2 years later. Spirometry that documented reversibility in the medical record accurately predicted asthma confirmation. Physicians should more widely perform spirometry with reversibility to establish the diagnosis of asthma as recommended by national asthma guidelines.

Penicillin Allergy Testing Should Be Performed Routinely in Patients with Self-Reported Penicillin Allergy

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD‐9 codes more specific for these conditions.