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Purpose of Review: An unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results., Recent Findings: Encouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative. Direct oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.

Penicillin is the most common beta-lactam antibiotic allergy and the most common drug class allergy, reported in about 8% of individuals using health care in the USA. Only about 1% of individuals using health care in the USA have a cephalosporin allergy noted in their medical record, and other specific non-penicillin, non-cephalosporin beta-lactam allergies are even rarer. Most reported penicillin allergy is not associated with clinically significant IgE-mediated reactions after penicillin rechallenge. Un-verified penicillin allergy is a significant and growing public health problem. Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and native penicillin G and, if skin test is negative, an oral amoxicillin challenge. Acute tolerance of an oral therapeutic dose of a penicillin class antibiotic is the current gold standard test for a lack of clinically significant IgE-mediated penicillin allergy. Cephalosporins and other non-penicillin beta-lactams are widely, safely, and appropriately used in individuals, even with confirmed penicillin allergy. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams. Routine cephalosporin skin testing should be restricted to research settings. It is rarely needed clinically to safely manage patients and has unclear predictive value at this time. The use of alternative cephalosporins, with different side chains, is acceptable in the setting of a specific cephalosporin allergy. Carbapenems and monobactams are also safely used in individuals with confirmed penicillin allergy. A certain predictable, but low, rate of adverse reactions will occur with all beta-lactam antibiotic use both pre- and post-beta-lactam allergy evaluations.

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., Objective: 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 safelyin pregnant women and, if the results are negative, allows penicillins to be used safely at delivery for GBS prophylaxis.

Background: There are few published data on adverse drug reactions and/or resensitization associated with oral penicillin use in penicillin allergy history-positive/penicillin skin test-negative individuals during routine clinical care with multiyear follow-up., Objectives: We sought to provide long-term follow-up data on the type, severity, and frequency of adverse reactions associated with oral penicillin use in individuals who have histories of penicillin "allergy" yet also have negative results on penicillin skin tests done in advance of need. We also aimed to repeat testing on individuals with penicillin-associated adverse reactions., Methods: Medical records were reviewed for penicillin use and associated adverse reactions in all 568 penicillin skin test-negative individuals who had received at least 1 course of oral penicillin after testing but before December 31, 2001, during routine care. These individuals were drawn from a group of 1246 penicillin skin test-negative individuals seen initially between November 16, 1994, and August 13, 2001., Results: The mean length of follow-up was 4.26 +/- 1.64 years (range, 0.39-7.12 years). The mean penicillin exposure was 3.94 +/- 3.91 courses (range, 1-22 courses). Only 65 (11.4%) of 568 subjects had any penicillin-associated reactions, and 6 subjects had 2 reactions each. A reaction occurred in 27 subjects (4.8%) with their first penicillin reexposure. There were 71 (3.2%) reactions with 2236 total penicillin courses. There were no serious reactions. Repeated testing was done in 33 subjects older than age 18 years. Only 1 subject was positive on repeated penicillin skin testing., Conclusion: Penicillin use after negative penicillin skin testing done in advance of need is safe, and resensitization is rare.

Background: Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare., Methods: Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures., Results: In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005)., Conclusions: Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

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 $17,211.88 to $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.

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.

Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated. [ABSTRACT FROM AUTHOR]