The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience

Arnold, Annabelle; Sommerfield, Aine; Ramgolam, Anoop; Rueter, Kristina; Muthusamy, Saravanan; Noble, Valerie; Ungern‐Sternberg, Britta S. von; Lucas, Michaela

doi:10.1111/jpc.14220

Cited by 20 publications

(22 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, most studies presented a low risk of bias regarding the other parameters evaluated. A similar frequency of severe reactions following DPTs was found in studies with three or more items classified as “high risk of bias” (0.11%, 95% CrI = 0.01%–0.26%; I 2 = 4.1%), 21,25,26,32,34,37,38,41,46,49,60,96,114,117,119,123,127,128 when compared with the remaining studies (0.06%, 95% CrI = 0.01%–0.14%; I 2 = 59.2%) 22–24,27–31,33,35,36,40,42–45,47,48,50–54,56–58,61–95,97–99,101–113,115,116,120–122,124–126,129–132 …”

Section: Resultssupporting

confidence: 70%

“…After excluding 2451 records in the screening phase, 351 articles were fully read, of which a total of 112 studies were included in the systematic review 21–50 ,51–100 ,101–132 Of these studies, 108 were included in all general analyses, 21–38 ,40–54 …”

Section: Resultsmentioning

confidence: 99%

“…Included studies were published between 1965 and 2019, and were mostly performed in North America ( n = 46, 41.1%) 21–23,25–27,31,32,34,36–38,40,41,44–46,53,58,69–71,74,75,84,85,88,90,96,99,102,104–107,110–112,114,116,122,123,125–127,131 and Europe ( n = 44, 39.3%) 24,28–30,33,35,39,42,43,47,50,52,55–57,59,61–66,68,73,76–80,82,83,86,91,92,94,97,100,109,118,121,124,128,129,132 . Thirty‐eight studies (34.9%) analyzed exclusively children 23,28,35,36,40,51,56,58–61,63,67,73,74,77,78,82,83,86,87,89,90,95,100,103,106‐110,113,115,118,120,121,130,132 and 28 (25.7%) only analyzed adult patients 21,31,32,37,38,41,49,52,53,62,68,71,76,79,88,94,101,102,104,105,114,117,123–125,127,128,131 . Most studies only included outpatients ( n = 69, 66.3%) …”

Section: Resultsmentioning

confidence: 99%

“…Most studies only included outpatients ( n = 69, 66.3%) 28–30,32–34,36,39,40,42–45,47–50 ,52–55,57,59–66,68,72 ,73,75,76,78–81,84–86,90–93,95,97–100 ,103,104,107,108,110,111,115,118 ,120–122,124‐126,128–130,132 From the 96 studies reporting information on the timing of the index reaction, 15 studies (15.6%) only evaluated patients reporting immediate allergic reactions, 24,30,33,38–40,42,54,60 ,67,80,91,102,103,130 and 12 studies (10.7%) exclusively evaluated patients reporting non‐immediate index reactions 50,55,56,76,78,79,86,95,98,100,119,121 …”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Cardoso-Fernandes

Blumenthal

Chiriac

et al. 2021

Clinical & Translational All

View full text Add to dashboard Cite

Background Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold‐standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. We aimed to assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other β‐lactams. Methods We performed a systematic review, searching MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta‐analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and metaregression analyses. Results We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% credible interval [95% CrI] = 0.01%–0.13%; I2 = 57.9%). Most severe reactions (80/93; 86.0%) consisted of anaphylaxis. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non‐immediate index reactions (OR = 0.05; 95% CrI = 0‐0.31). Patients reporting anaphylaxis as their index reaction were found to be at increased risk of developing severe reactions (OR = 13.5; 95% CrI = 7.7–21.5; I2 = 0.3%). Performance of direct DPTs in low‐risk patients or testing with the suspected culprit drug were not associated with clinically relevant increased risk of severe reactions. Conclusions In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. Therefore, except for patients with potentially life‐threatening index reactions or patients with positive skin tests—who were mostly not assessed in this analysis ‐, the safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.

show abstract

Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Cardoso-Fernandes

Blumenthal

Chiriac

et al. 2021

Clinical & Translational All

View full text Add to dashboard Cite

show abstract

“…To ensure that we could reproduce a delayed reaction, the drug provocation test has in our protocols included a prolonged/extended provocation for 3-10 days. The benefits and potential adverse effects of prolonged/extended provocation have been debated in the literature, and there is not yet consensus on the optimal DPT procedure [8][9][10][11][12][13][14][15][16]. Over the years, we have observed patients who developed moderate maculopapular rashes lasting up to several weeks after drug provocation.…”

Section: Introductionmentioning

confidence: 99%

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy

Fransson

Mosbech

Elberling

et al. 2021

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr. Methods: Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin. Results: In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr. Conclusion: Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions.

show abstract

Reaction Risk to Direct Penicillin Challenges

Blumenthal,

Smith,

Mann

et al. 2024

JAMA Intern Med

View full text Add to dashboard Cite

ImportanceWhile direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier.ObjectiveTo evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions.Data SourcesThree electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk.Study SelectionTwo reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy.Data Extraction and SynthesisTwo reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies.Main Outcomes and MeasuresThe primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions.ResultsA total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal.Conclusions and RelevanceThis systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.

show abstract

The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience

Cited by 20 publications

References 8 publications

Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta‐analysis

Intradermal Testing Identifies 1 in 4 Patients with Nonimmediate Penicillin Allergy

Reaction Risk to Direct Penicillin Challenges

Contact Info

Product

Resources

About