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However, allergy tests for drug allergies are often false\u2010negative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the components of a stepwise diagnostic algorithm for immediate BL hypersensitivity with regard to sensitivity (SENS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Consecutive patients with suspected allergy to BL antibiotics were retrospectively analyzed with regard to increasing sensitivity (plausible history of immediate BL hypersensitivity serving as external criterion) of (i) skin prick test (SPT) by adding a second reading (n = 746), (ii) BL\u2010specific IgE\u2010determination in vitro at two cut\u2010offs (n = 539), and (iii) adding in vivo testing of minor and major BL determinants (n = 288).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the history\u2010based population indicative of immediate BL hypersensitivity (n = 457), SPT with a sole 20\u2010minute reading identified 99 (SENS: 0.21) and SPT with 20\u2010 and 40\u2010minute\u2010reading identified 133 cases (SENS: 0.29). in vitro specific IgE\u2010examination identified 31 positives at a cut\u2010off \u22650.35 kUA\/L (5.8% of tested) and 99 at cut\u2010off \u22650.11 kUA\/L (18.4% of tested). In 203 SPT\u2010negative individuals, immediate BL hypersensitivity was identified by additional tests: in 79 by specific IgE (cut\u2010off \u22650.11 kUA\/L) (thereof 53 identified solely by this test) and in 150 by in vivo testing of BL determinants in combination with Penicillin and Ampicillin intradermally (thereof 124 solely by this test); in 26 individuals both additional tests were positive. The combination of the three outpatient\u2010based test modalities\u2014(i) optimized SPT, (ii) specific IgE at optimized cut\u2010off, and (iii) in vivo testing of BL determinants\/Penicillin\/Ampicillin\u2014identified altogether 336\/457 individuals with immediate BL\u2010hypersensitivity (SENS: 0.73), whereas the combination of the two (i)\u2009+\u2009(ii) identified 212\/457 (SENS: 0.46); (i)\u2009+\u2009(iii) 283\/457 (SENS: 0.61).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To overcome the low sensitivity of allergological tests, optimized reading times of the SPT of BL, a lower cut\u2010off for in vitro detection of BL\u2010specific IgE, and intradermal testing of Penicillin, Ampicillin, and BL\u2010determinants contribute to overall sensitivity under real life conditions to diagnose immediate BL\u2010hypersensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cod.13622","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T07:20:06Z","timestamp":1590650406000},"page":"361-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adding a second skin prick test reading and modifying the cut\u2010off for beta\u2010lactam\u2013specific<scp>IgE<\/scp>enhances the sensitivity in the routine diagnostic workup for immediate beta\u2010lactam hypersensitivity"],"prefix":"10.1111","volume":"83","author":[{"given":"Bernadette","family":"Rosti","sequence":"first","affiliation":[{"name":"Allergy\u2010Clinic of the Department of Dermatology University Hospital of Erlangen Erlangen Germany"},{"name":"Dental Practice Dr. Ludwig and Colleagues MVZ GmbH F\u00fcrth Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6471-1811","authenticated-orcid":false,"given":"Vera","family":"Mahler","sequence":"additional","affiliation":[{"name":"Allergy\u2010Clinic of the Department of Dermatology University Hospital of Erlangen Erlangen Germany"},{"name":"Division of Allergology Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1016\/S0140-6736(00)04972-2"},{"issue":"26","key":"e_1_2_7_3_1","first-page":"454","article-title":"Outpatient antibiotic prescription","volume":"113","author":"B\u00e4tzing\u2010Feigenbaum J","year":"2016","journal-title":"Dtsch Arztebl Int"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1136\/adc.55.11.857"},{"doi-asserted-by":"publisher","key":"e_1_2_7_5_1","DOI":"10.1086\/320752"},{"doi-asserted-by":"publisher","key":"e_1_2_7_6_1","DOI":"10.1016\/j.anai.2010.05.010"},{"issue":"4","key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"10S70","DOI":"10.1016\/S0761-8425(06)71661-8","article-title":"Allergie aux anti\u2010infectieux","volume":"23","author":"Hamzaoui A","year":"2006","journal-title":"Rev Mal Respir"},{"doi-asserted-by":"publisher","key":"e_1_2_7_8_1","DOI":"10.1046\/j.1365-2222.2003.01638.x"},{"doi-asserted-by":"publisher","key":"e_1_2_7_9_1","DOI":"10.1016\/j.aller.2009.01.001"},{"issue":"43","key":"e_1_2_7_10_1","first-page":"A2888","article-title":"Penicillintherapie trotz Penicillinallergie? 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