Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults.
Abstract
BACKGROUND: A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. METHODS: Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-ocytalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. RESULTS: Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. CONCLUSIONS: These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone.
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Penicillin skin testing with a major determinant analog (penicilloyl-polylysine) and minor determinants (benzylpenicilloate, benzylpenilloate, or benzylpenicillin isomers of penicillin) are used for skin test evaluation for IgE-dependent penicillin allergy and can reliably identify persons at high risk for IgE-mediated reactions to penicillin.
“Penicillin skin testing with a major determinant analog (penicilloyl-polylysine) and minor determinants (benzylpenicilloate, benzylpenilloate, or benzylpenicillin isomers of penicillin) are used for skin test evaluation for IgE-dependent penicillin allergy and can reliably identify persons at high risk for IgE-mediated reactions to penicillin (658,660,676).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [676]
Cites
Idsøe, O., GUTHE, T., Willcox, R. R., & WECK, A. L. D. (1968) · PubMed Central · Cited by 539 · see citing works
Immediate Hypersensitivity Reactions to Beta-Lactam Antibiotics
Saxon, A., BEALL, G. N., ROHR, A. S., & Adelman, D. C. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-2-204 · Cited by 410 · see citing works
Skin testing to detect penicillin allergy
Sullivan, T. J., Wedner, H. J., Shatz, G. S., Yecies, L. D., & Parker, C. W. (1981) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(81)90180-9 · Cited by 326 · see citing works
Penicillin allergy: clinical experience with a battery of skin-test reagents
Solley, G. O., Gleich, G. J., & Dellen, R. G. V. (1982) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(82)90105-1 · Cited by 230 · see citing works
Green, G. R., Rosenblum, A. H., & Sweet, L. C. (1977) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(77)90064-1 · Cited by 214 · see citing works
Prediction of penicillin allergy by immunological tests
Levine, B. B., & Zolov, D. M. (1969) · Journal of Allergy · doi:10.1016/0021-8707(69)90066-5 · Cited by 206 · see citing works
Routine elective penicillin allergy skin testing in children and adolescents: study of sensitization
Mendelson, L. M., Ressler, C., Rosen, J. P., & Selcow, J. E. (1984) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(84)90487-1 · Cited by 183 · see citing works
Penicillin allergy and the heterogenous immune responses of man to benzylpenicillin.
Levine, B. B., Redmond, A. P., FELLNER, M. J., Voss, H. E. V., & Levytska, V. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105494 · Cited by 150 · see citing works
Routine Use of Penicillin Skin Testing on an Inpatient Service
Adkinson, N. F., Thompson, W. L., Maddrey, W. C., & Lichtenstein, L. M. (1971) · New England Journal of Medicine · doi:10.1056/nejm197107012850104 · Cited by 125 · see citing works
Acute and chronic desensitization of penicillin-allergic patients using oral penicillin
Stark, B. J., Earl, H. S., Gross, G. N., et al. (1987) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(87)90371-x · Cited by 115 · see citing works
Diagnosis of penicillin allergy by skin testing: the Manitoba experience.
Warrington, R., Simons, F. E. R., Ho, H., & Gorski, B. A. (1978) · PubMed Central · Cited by 105 · see citing works
Penicilloyl-Polylysine as an Intradermal Test of Penicillin Sensitivity
Brown, B. C., Price, E. V., & Moore, M. B. (1964) · JAMA · doi:10.1001/jama.1964.03070080005001 · Cited by 92 · see citing works
Detection of Penicillin Hypersensitivity With Penicilloyl-Polylysine
Rytel, M. W., Klion, F. M., Arlander, T. R., & Miller, L. F. (1963) · JAMA · doi:10.1001/jama.1963.03710100032007 · Cited by 71 · see citing works
Report of the Penicillin Study Group—American Academy of Allergy
Green, G. R., & Rosenblum, A. H. (1971) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(71)90079-0 · Cited by 68 · see citing works
Differing patterns of wheal and flare skin reactivity in patients allergic to the penicillins
Dellen, R. G. V., Walsh, W. E., Peters, G. A., et al. (1971) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(71)80468-2 · Cited by 44 · see citing works
JUHLIN, L., Ahlstedt, S., Andal, L., et al. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000231804 · Cited by 36 · see citing works
The value of skin testing for penicillin allergy diagnosis.
VanArsdel, P. P., Martonick, G. J., Johnson, L. E., Sprenger, J. D., Altman, L. C., & Henderson, W. R. (1986) · PubMed · Cited by 21 · see citing works
Penicillin allergy: a practical approach to management.
Sussman, G., Davis, K., & Köhler, P. F. (1986) · PubMed · Cited by 17 · see citing works
Goldschmidt, B. M., & Levine, B. B. (1983) · The Journal of Antibiotics · doi:10.7164/antibiotics.36.709 · Cited by 4 · see citing works
[A study on the disc sensitivity test for cefatrizine].
KANAZAWA, Y., KURAMATA, T., & Matsumoto, K. (1983) · PubMed · Cited by 1 · see citing works
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Sexually Transmitted Infections Treatment Guidelines, 2021
Workowski, K. A., Bachmann, L. H., Chan, P. A., Johnston, C. M., Muzny, C. A., Park, I., Reno, H., Zenilman, J. M., & Bolan, G. A. (2021) · MMWR. Recommendations and Reports · doi:10.15585/mmwr.rr7004a1 · Cited by 2,759 · see citing works
Allergy Diagnostic Testing: An Updated Practice Parameter
Bernstein, I. L., Li, J. T., Bernstein, D. I., Hamilton, R., Spector, S. L., Tan, R., Sicherer, S., Golden, D. B. K., Khan, D. A., Nicklas, R. A., et al. (2008) · Annals of Allergy, Asthma & Immunology · doi:10.1016/s1081-1206(10)60305-5 · Cited by 723 · see citing works
Blumenthal, K. G., Peter, J. G., Trubiano, J. A., & Phillips, E. J. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32218-9 · Cited by 614 · see citing works
Clinical experience with penicillin skin testing in a large inner-city STD clinic.
Gadde, J. (1993) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1993.03510200062033 · Cited by 344 · see citing works
Macy, E., & Ngor, E. W. (2013) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2013.02.002 · Cited by 275 · see citing works
A proactive approach to penicillin allergy testing in hospitalized patients.
Chen, J. R., Tarver, S. A., Alvarez, K. S., Tran, T., & Khan, D. A. (2017) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2016.09.045 · Cited by 152 · see citing works
THE PENICILLINS: A REVIEW AND UPDATE
Miller, E. L. (2002) · Journal of Midwifery & Women's Health · doi:10.1016/s1526-9523(02)00330-6 · Cited by 147 · see citing works
Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy.
Goldberg, A., & Confino-Cohen, R. (2008) · Annals of Allergy, Asthma & Immunology · doi:10.1016/s1081-1206(10)60402-4 · Cited by 83 · see citing works
Solensky, R., Jacobs, J., Lester, M., Lieberman, P., McCafferty, F., Nilsson, T., Park, M., Schwarz, G., Soong, W., Wagelie-Steffen, A., et al. (2019) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2019.02.040 · Cited by 70 · see citing works
Implementation of an infectious disease fellow-managed penicillin allergy skin testing service.
Heil, E. L., Bork, J. T., Schmalzle, S. A., Kleinberg, M., Kewalramani, A., Gilliam, B. L., & Buchwald, U. K. (2016) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofw155 · Cited by 66 · see citing works
Leis, J. A., Palmay, L., Ho, G., Raybardhan, S., Gill, S., Kan, T., Campbell, J., Kiss, A., McCready, J. B., Das, P., et al. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix512 · Cited by 59 · see citing works
Dodek, P., & Phillips, P. (1999) · Clinical Infectious Diseases · doi:10.1086/313435 · Cited by 45 · see citing works
- Authors
- Sogn, D. D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Sogn, Dorothy D.
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 1992-05-01
- Volume
- 152
- Issue
- 5
- Pages
- 1025
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2120037190
- Cited by
- 337
- References
- 20
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 11 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 16 · 2018: 21 · 2017: 21 · 2016: 13 · 2015: 12 · 2014: 15 · 2013: 13 · 2012: 9
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (N01 AI-92631, N01 AI-92629, N01 AI-92630)
- Topics
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- penicillin allergy, skin testing, IgE-mediated hypersensitivity, predictive value, penicillin G, hospitalized adults, allergy history
- MeSH terms
- Adult, Drug Hypersensitivity, Female, Humans, Indicators and Reagents, Inpatients, Male, Penicillin G, Penicillins, Predictive Value of Tests, Skin Tests, Benzeneacetamides
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