Advertisement

Penicillin Allergy and Other Antibiotics

  • Thanai Pongdee
  • James T. Li
Living reference work entry

Abstract

Penicillin allergy is commonly diagnosed, reported in approximately 8% of the general population and 10–15% of hospitalized patients. Although penicillin allergy is widely reported, 80–90% of individuals with self-reported penicillin allergy are actually able to tolerate penicillins after undergoing evaluation for penicillin allergy. Since the majority of patients with self-reported penicillin allergy will have subsequent negative allergy testing and tolerate penicillins, they may be unnecessarily exposed to broader spectrum antibiotics. Use of such antibiotics leads to increased risks of developing antibiotic resistant microorganisms and incur greater health care utilization costs. Penicillin allergy evaluation and management should be a core component of antibiotic stewardship and can significantly improve health care quality and value for individual patients and health care systems as well as the public at large. Key knowledge points to effectively evaluate and manage patients with penicillin allergy discussed in this chapter include (1) clinical manifestations of penicillin allergy; (2) utility of clinical history; (3) methods for penicillin allergy testing; (4) management options based on testing results; and (5) penicillin allergy cross-reactivity with other beta-lactam antibiotics.

Keywords

Drug Allergy Penicillin Cephalosporin Carbapenem Monobactam Beta-Lactam 

References

  1. Ahmed KA, Fox SJ, Frigas E, et al. Clinical outcome in the use of cephalosporins in pediatric patients with a history of penicillin allergy. Int Arch Allergy Immunol. 2012;158:405–10.CrossRefPubMedGoogle Scholar
  2. Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1(134):1–7.Google Scholar
  3. Apter AJ, Schelleman H, Walker A, et al. Clinical and genetic risk factors of self-reported penicillin allergy. J Allergy Clin Immunol. 2008;122:152–8.CrossRefPubMedGoogle Scholar
  4. Assem ESK, Vickers MR. Tests for penicillin allergy in man – II. The immunological cross-reaction between penicillins and cephalosporins. Immunology. 1974;27:255–69.PubMedPubMedCentralGoogle Scholar
  5. Atanaskovic-Markovic M, Gaeta F, Medjo B, et al. Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins. Allergy. 2008;63:237–40.CrossRefPubMedGoogle Scholar
  6. Atanaskovic-Markovic M, Gaeta F, Gavrovic-Jankulovic M, et al. Tolerability of imipenem in children with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2009;124:167–9.CrossRefPubMedGoogle Scholar
  7. Audicana M, Bernaola G, Urrutia I, et al. Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin. Allergy. 1994;49:108–13.CrossRefPubMedGoogle Scholar
  8. Blanca M, Fernandez J, Miranda A, et al. Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies. J Allergy Clin Immunol. 1989;83:381–5.CrossRefPubMedGoogle Scholar
  9. Blanca M, Torres MJ, Garcia JJ, et al. Natural evolution of skin test sensitivity in patients with allergic to β-lactam antibiotics. J Allergy Clin Immunol. 1999;103:918–24.CrossRefPubMedGoogle Scholar
  10. Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64:183–93.CrossRefPubMedGoogle Scholar
  11. CDC. Core elements of hospital antibiotic stewardship programs. Atlanta: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.htmlGoogle Scholar
  12. Cernadas JR, Brockow K, Romano A, et al. General considerations on rapid desensitization for drug hypersensitivity – a consensus statement. Allergy. 2010;65:1357–66.CrossRefPubMedGoogle Scholar
  13. Confino-Cohen R, Rosman Y, Meir-Shafrir K, et al. Oral challenge without skin testing safely excludes clinically significant delayed-onset penicillin hypersensitivity. J Allergy Clin Immunol Pract. 2017;5:669–75.CrossRefPubMedGoogle Scholar
  14. Coombs RRA, Gell PGH. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: Gell PGH, Coombs RRA, Lachman PJ, editors. Clinical aspects of immunology. Oxford: Blackwell Scientific; 1975. p. 761–81.Google Scholar
  15. Corry DB, Kheradmand F. Induction and regulation of the IgE response. Nature. 1999;402(Suppl):B18–23.CrossRefPubMedGoogle Scholar
  16. Dash DH. Penicillin allergy and the cephalosporins. J Antimicrob Chemother. 1975;1(Suppl):107–18.CrossRefPubMedGoogle Scholar
  17. Demoly P, Adkinson NF, Brockow K, et al. International consensus on drug allergy. Allergy. 2014;69:420–37.CrossRefPubMedGoogle Scholar
  18. Dickson SD and Salazar KC. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins. Clinic Rev Allerg Immunol 2013;45:131–142.CrossRefGoogle Scholar
  19. Fox S, Park MA. Penicillin skin testing in the evaluation and management of penicillin allergy. Ann Allergy Asthma Immunol. 2011;106:1–7.CrossRefPubMedGoogle Scholar
  20. Gadde J, Spence M, Wheeler B, et al. Clinical experience with penicillin skin testing in a large inner-city STD clinic. JAMA. 1993;270:2456–63.CrossRefPubMedGoogle Scholar
  21. Gaeta F, Valluzzi RL, Alonzi C, et al. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2015;135:972–6.CrossRefPubMedGoogle Scholar
  22. Girard JP. Common antigenic determinants of penicillin G, ampicillin and the cephalosporins demonstrated in men. Int Arch Allergy. 1968;33:428–38.CrossRefPubMedGoogle Scholar
  23. Green GR, Rosenblum AH, Sweet LC. Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin G. J Allergy Clin Immunol. 1977;60:339–45.CrossRefPubMedGoogle Scholar
  24. Greenberger PA, Klemens JC. Utility of penicillin major and minor determinants for identification of allergic reactions to cephalosporins. J Allergy Clin Immunol. 2005;115:S182.CrossRefGoogle Scholar
  25. Gruchalla RS, Pirmohamed M. Antibiotic allergy. N Engl J Med. 2006;354:601–9.CrossRefPubMedGoogle Scholar
  26. Hershkovich J, Broides A, Kirjner L, et al. Beta lactam allergy and resensitization in children with suspected beta lactam allergy. Clin Exp Allergy. 2009;39:726–30.CrossRefPubMedGoogle Scholar
  27. Hicks LA, Taylor TH Jr. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368(15):1461–2.CrossRefPubMedGoogle Scholar
  28. Johansson SG, Adedoyin J, van Hage M, et al. False-positive penicillin immunoassay; an unnoticed common problem. J Allergy Clin Immunol. 2013;132:235–7.CrossRefPubMedGoogle Scholar
  29. Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125:S126–37.CrossRefPubMedGoogle Scholar
  30. Lee CE, Zembower TR, Fotis MA, et al. The incidence of antimicrobial allergies in hospitalized patients. Arch Intern Med. 2000;160:2819–22.CrossRefPubMedGoogle Scholar
  31. Levine BB, Ovary Z. Studies on the mechanism of the formation of the penicillin antigen: the N-(d-alpha-benzyl-penicilloyl) group as an antigenic determinant reponsible for hypersensitivity to penicillin G. J Exp Med. 1961;114:875–904.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Levine BB, Redmond AP. Minor haptenic determinant-specific reagins of penicillin hypersensitivity in man. Int Arch Allergy Appl Immunol. 1969;35:445–55.CrossRefPubMedGoogle Scholar
  33. Li M, Krishna MT, Razaq S, et al. A real time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of ‘penicillin allergy’ in a UK teaching hospital. J Clin Pathol. 2014;67:1088–92.CrossRefPubMedGoogle Scholar
  34. Macy E. Penicillin and beta-lactam allergy: epidemiology and diagnosis. Curr Allergy Asthma Rep. 2014;14:476.CrossRefPubMedGoogle Scholar
  35. Macy E, Burchette RJ. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy. 2002;57:1151–8.CrossRefPubMedGoogle Scholar
  36. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014;133:790–6.CrossRefPubMedGoogle Scholar
  37. Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol: In Pract. 2013;1:258–63.CrossRefGoogle Scholar
  38. Macy E, Shu YH. The effect of penicillin allergy testing on future health care utilization: a matched cohort study. J Allergy Clin Immunol Pract. 2017;5:705–10.CrossRefPubMedGoogle Scholar
  39. Macy E, Goldberg B, Poon K. Use of commercial anti-penicillin IgE fluorometric enzyme immunoassays to diagnose penicillin allergy. Ann Allergy Asthma Immunol. 2010;105:136–41.CrossRefPubMedGoogle Scholar
  40. Mendelson LM, Ressler C, Rosen JP, et al. Routine elective penicillin allergy skin testing in children and adolescents: study of sensitization. J Allergy Clin Immunol. 1984;73:76–81.CrossRefPubMedGoogle Scholar
  41. Mill C, Primeau MN, Medoff E, et al. Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children. JAMA Pediatr. 2016;170(6):e160033.CrossRefPubMedGoogle Scholar
  42. Miranda A, Blanca M, Vega JM, et al. Cross-reactivity between a penicillin and a cephalosporin with the same side chain. J Allergy Clin Immunol. 1996;98:671–7.CrossRefPubMedGoogle Scholar
  43. Moss RB. Sensitization to aztreonam and cross-reactivity with other beta-lactam antibiotics in high-risk patients with cystic fibrosis. J Allergy Clin Immunol. 1991;87:78–88.CrossRefPubMedGoogle Scholar
  44. Novalbos A, Sastre J, Cuesta J, et al. Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins. Clin Exp Allergy. 2001;31:438–43.CrossRefPubMedGoogle Scholar
  45. Park M, Matesic D, Markus PJ, et al. Female sex as a risk factor for penicillin allergy. Ann Allergy Asthma Immunol. 2007;99:54–8.CrossRefPubMedGoogle Scholar
  46. Park MA, Koch CA, Klemawesch P, et al. Increased adverse drug reactions to cephalosporins in penicillin allergy patients with positive penicillin skin test. Int Arch Allergy Immunol. 2010;153:268–73.CrossRefPubMedGoogle Scholar
  47. Parker CW, Shapiro J, Kern M, et al. Hypersensitivity to penicillenic acid derivatives in human beings with penicillin allergy. J Exp Med. 1962;115:821–38.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Parker PJ, Parrinello JT, Condemi JJ, et al. Penicillin resensitization among hospitalized patients. J Allergy Clin Immunol. 1991;88:213–7.CrossRefPubMedGoogle Scholar
  49. Petz LD. Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis. 1978;137(Suppl):S74–9.CrossRefPubMedGoogle Scholar
  50. Picard M, Bégin P, Bouchard H, et al. Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol: In Pract. 2013;1:252–7.CrossRefGoogle Scholar
  51. Pichichero ME, Pichichero DM. Diagnosis of penicillin, amoxicillin, and cephalosporin allergy: reliability of examination assessed by skin testing and oral challenge. J Pediatr. 1998;132:137–43.CrossRefPubMedGoogle Scholar
  52. Pichichero ME, Zagursky R. Penicillin and cephalosporin allergy. Ann Allergy Asthma Immunol. 2014;112:404–12.CrossRefPubMedGoogle Scholar
  53. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139:683–93.CrossRefPubMedGoogle Scholar
  54. Pumphrey RSH, Davis S. Under-reporting of antibiotic anaphylaxis may put patients at risk. Lancet. 1999;353:1157–8.CrossRefPubMedGoogle Scholar
  55. Romano A, Gueant-Rodriguez RM, Viola M, et al. Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med. 2004;141:16–22.CrossRefPubMedGoogle Scholar
  56. Romano A, Viola M, Gueant-Rodriquez R, et al. Imipenem in patients with immediate hypersensitivity to penicillins. N Engl J Med. 2006;354:2835–7.CrossRefPubMedGoogle Scholar
  57. Romano A, Viola M, Gueant-Rodriquez R, et al. Brief communication: tolerability of meropenem in patient with IgE-mediated hypersensitivity to penicillins. Ann Intern Med. 2007;146:266–9.CrossRefPubMedGoogle Scholar
  58. Sade K, Holtzer I, Levo Y, et al. The economic burden of antibiotic treatment of penicillin-allergic patients in internal medicine wards of a general tertiary care hospital. Clin Exp Allergy. 2003;33:501–6.CrossRefPubMedGoogle Scholar
  59. Sanz ML, Gamboa PM, Antepara I, et al. Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate-type reactions to betalactam antibiotics. Clin Exp Allergy. 2002;32:277–86.CrossRefPubMedGoogle Scholar
  60. Sastre J, Quijano LD, Novalbos A, et al. Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to amoxicillin and with good tolerance of penicillin. Allergy. 1996;51:383–6.CrossRefPubMedGoogle Scholar
  61. Saxon A, Beall GN, Rohr AS, et al. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med. 1987;107:204–15.CrossRefPubMedGoogle Scholar
  62. Shepherd GM, Burton DA. Administration of cephalosporin antibiotics to patients with a history of penicillin allergy. J Allergy Clin Immunol. 1993;91:262.Google Scholar
  63. Sogn DD, Evans R, Shepherd GM, et al. 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. Arch Intern Med. 1992;152:1025–32.CrossRefPubMedGoogle Scholar
  64. Solensky R, Khan DA, editors. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:273.e1–e78.Google Scholar
  65. Solensky R, Macy E. Minor determinants are essential for optimal penicillin allergy testing: a pro/con debate. J Allergy Clin Immunol Pract. 2015;3:883–7.CrossRefPubMedGoogle Scholar
  66. Solensky R, Earl HS, Gruchalla RS. Penicillin allergy: prevalence of vague history in skin test-positive patients. Ann Allergy Asthma Immunol. 2000;85:195–9.CrossRefPubMedGoogle Scholar
  67. Solensky R, Earl HS, Gruchalla RS. Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses. Arch Intern Med. 2002;162:822–6.CrossRefPubMedGoogle Scholar
  68. Solley GO, Gleich GJ, Van Dellen RG. Penicillin allergy: clinical experience with a battery of skin-test reagents. J Allergy Clin Immunol. 1982;69:238–44.CrossRefPubMedGoogle Scholar
  69. Spruill FG, Minette LJ, Sturner WQ. Two surgical deaths associated with cephalothin. JAMA. 1974;229:440–1.CrossRefPubMedGoogle Scholar
  70. Stember RH. Prevalence of skin test reactivity in patients with convincing, vague, and unacceptable histories of penicillin allergy. Allergy Asthma Proc. 2005;26:59–64.PubMedGoogle Scholar
  71. Sullivan TJ, Wedner HJ, Shatz GS, et al. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981;68:171–80.CrossRefPubMedGoogle Scholar
  72. Torres MJ, Padial A, Mayorga C, et al. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Clin Exp Allergy. 2004;34:1768–75.CrossRefPubMedGoogle Scholar
  73. Tucker MH, Lomas CM, Ramchandar N, et al. Amoxicillin challenge without penicillin skin testing in evaluation of penicillin allergy in a cohort of marine recruits. J Allergy Clin Immunol Pract. 2017;5:813–5.CrossRefPubMedGoogle Scholar
  74. Valyasevi MA, Van Dellen RG. Frequency of systemic reactions to penicillin skin tests. Ann Allergy Asthma Immunol. 2000;85:363–5.CrossRefPubMedGoogle Scholar
  75. Van Boeckel TP, Gandra S, Ashok A, et al. Global antibiotic consumption 2000–2010:an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–50.CrossRefPubMedGoogle Scholar
  76. Warrington RJ, Simons FER, Ho HW, et al. Diagnosis of penicillin allergy by skin testing: the Manitoba experience. Can Med Assoc J. 1978;118:787–91.PubMedPubMedCentralGoogle Scholar
  77. Wheatley LM, Plaut M, Schwaninger JM, et al. Report from the National Institute of Allergy and Infectious Diseases workshop on drug allergy. J Allergy Clin Immunol. 2015;136:262–71.CrossRefPubMedPubMedCentralGoogle Scholar
  78. World Health Organization. International drug monitoring: the role of the hospital, Technical report series, vol. 425. Geneva: World Health Organization; 1969.Google Scholar
  79. Wright AJ, Wilkowske CJ. The penicillins. Mayo Clin Proc. 1991;66:1047–63.CrossRefPubMedGoogle Scholar
  80. Zagursky RJ, Pichichero ME. Cross-reactivity in β-lactam allergy. J Allergy Clin Immunol Pract. 2018;6:72–81.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Allergic DiseasesMayo ClinicRochesterUSA

Section editors and affiliations

  • Tim Craig
    • 1
  • Massoud Mahmoudi
    • 2
  1. 1.Penn State UniversityHersheyUSA
  2. 2.Department of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations