Rapid Desensitizations for Antibiotic-Induced Hypersensitivity Reactions and Anaphylaxis



Drug-induced anaphylaxis prevents the utilization of antibiotic drugs to patients in need of first-line therapy, including those with cystic fibrosis. Avoidance of antibiotic therapy may be limited by the severity of the infection and the microbial sensitivity. Rapid desensitization for antibiotic-induced drug allergies is the induction of temporary clinical unresponsiveness to antibiotics by gradual reintroduction of small doses of antibiotic until the full antibiotic dose is delivered. Clinical unresponsiveness can be maintained until completion of the antibiotic course by regular administration of the antibiotic allowing safe administration of first-line medications to patients who have presented with hypersensitivity reactions to those medications, including anaphylaxis.

Principles, indications, targets and management of rapid desensitization procedures, including IgE- and non-IgE-dependent hypersensitivity reactions for the most relevant groups of antibiotics, antifungals and antivirals will be reviewed, and rapid desensitization protocols will be addressed for each group.


Anaphylaxis Desensitization Drug allergy Drug hypersensitivity Antibiotics Hypersensitivity reactions Penicillin Beta-lactams 


  1. 1.
    Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions inhospitalized patients. JAMA. 279;1998:1200–1205.PubMedCrossRefGoogle Scholar
  2. 2.
    Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122(3):574–580.PubMedCrossRefGoogle Scholar
  3. 3.
    Sullivan TJ, Yecies LD, Shatz GS, Parker CW, Wedner HJ. Desensitization of patients allergic to penicillin using orally administered beta-lactam antibiotics. J Allergy Clin Immunol. 1982;69(3):275–282.PubMedCrossRefGoogle Scholar
  4. 4.
    Hesterberg PE, Banerji A, Oren E, et al. Risk stratification for desensitization of patients with carboplatin hypersensitivity: clinical presentation and management. J Allergy Clin Immunol. 2009;123(6):1262–1267, e1.PubMedCrossRefGoogle Scholar
  5. 5.
    Legere HJ III, Palis RI, Bouza TR, Uluer AZ, Castells MC. A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros. 2009;8(6):418–424.PubMedCrossRefGoogle Scholar
  6. 6.
    Wendel GD Jr, Stark BJ, Jamison RB, Molina RD, Sullivan TJ. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med. 1985;312(19):1229–1232.PubMedCrossRefGoogle Scholar
  7. 7.
    Morales AR, Shah N, Castells M. Antigen-IgE desensitization in signal transducer and activator of transcription 6-deficient mast cells by suboptimal doses of antigen. Ann Allergy Asthma Immunol. 2005;94(5):575–580.PubMedCrossRefGoogle Scholar
  8. 8.
    Naclerio R, Mizrahi EA, Adkinson NF Jr. Immunologic observations during desensitization and maintenance of clinical tolerance to penicillin. J Allergy and Clin Immunol. 1983;71(3):294–301.CrossRefGoogle Scholar
  9. 9.
    Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371–376.CrossRefGoogle Scholar
  10. 10.
    Simons FE. Anaphylaxis. J Allergy and Clin Immunol. 2008;121(2 Suppl):S402-S407.CrossRefGoogle Scholar
  11. 11.
    Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987;316(26):1622–1626.PubMedCrossRefGoogle Scholar
  12. 12.
    Torres MJ, Blanca M, Fernandez J, et al. Selective allergic reaction to oral cloxacillin. Clin Exper Allergy. 1996;26(1):108–111.CrossRefGoogle Scholar
  13. 13.
    Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008;63(8):1061–1070.PubMedCrossRefGoogle Scholar
  14. 14.
    Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report. Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391–397.Google Scholar
  15. 15.
    Solensky R. Drug hypersensitivity. Med Clin NA. 2006;90(1):233–260.CrossRefGoogle Scholar
  16. 16.
    Zhao Y, Qiao H. Detection of specific IgE antibodies to major and minor antigenic determinants in sera of penicillin allergic patients. Chin Med J (Engl). 2003;116(12):1904–1910.Google Scholar
  17. 17.
    Castells M. Update on mast cells and mast cell precursors and hypersensitivity responses. Allergy Asthma Proc. 1997;18(5):287–292.CrossRefGoogle Scholar
  18. 18.
    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(1):137–143.PubMedCrossRefGoogle Scholar
  19. 19.
    Macy E, Burchette RJ. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy. 2002;57(12):1151–1158.PubMedCrossRefGoogle Scholar
  20. 20.
    Macy E, Mangat R, Burchette RJ. Penicillin skin testing in advance of need: multiyear follow-up in 568 test result-negative subjects exposed to oral penicillins. J Allergy Clin Immunol. 2003;111(5):1111–1115.PubMedCrossRefGoogle Scholar
  21. 21.
    Bousquet PJ, Pipet A, Bousquet-Rouanet L, Demoly P. Oral challenges are needed in the diagnosis of beta-lactam hypersensitivity. Clin Exp Allergy. 2008;38(1):185–190.PubMedGoogle Scholar
  22. 22.
    Weiss ME, Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy. 1988;18(6):515–540.PubMedCrossRefGoogle Scholar
  23. 23.
    Solley GO, Gleich GJ, Van Dellen RG. Penicillin allergy: clinical experience with a battery of skin-test reagents. J Allergy Clin Immunol. 1982;69(2):238–244.PubMedCrossRefGoogle Scholar
  24. 24.
    Sicherer SH. Risk of severe allergic reactions from the use of potassium iodide for radiation emergencies. J Allergy Clin Immunol. 2004;114(6):1395–1397.PubMedCrossRefGoogle Scholar
  25. 25.
    Luskin AT, Luskin SS. Anaphylaxis and anaphylactoid reactions: diagnosis and management. Am J Ther. 1996;3(7):515–520.PubMedCrossRefGoogle Scholar
  26. 26.
    DeSimone JA, Ojha A, Pathak R, Cohn J. Successful desensitization to enfuvirtide after a hypersensitivity reaction in an HIV-1-infected man. Clin Infect Dis. 2004;39(10):e110–112.PubMedCrossRefGoogle Scholar
  27. 27.
    Dutau H, Saadjian M, Bonneau V, Charpin D. Unsuccessful rapid intravenous desensitization to rifampicin. Allergy. 2000;55(8):778–779.PubMedCrossRefGoogle Scholar
  28. 28.
    Takahashi T, Hitani A, Yamada H, Nakamura T, Iwamoto A. Desenitization to fluconazole in an AIDS patient. Ann Pharmacother. 2001;35(5):642–643.PubMedCrossRefGoogle Scholar
  29. 29.
    Holland CL, Malasky C, Ogunkoya A, Bielory L. Rapid oral desensitization to isoniazid and rifampin. Chest. 1990;98(6):1518–1519.PubMedCrossRefGoogle Scholar
  30. 30.
    Buergin S, Scherer K, Hausermann P, Bircher AJ. Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance. Int Arch Allergy Immunol. 2006;140(1):20–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Pruzansky JJ, Patterson R. Desensitization of human basophils with suboptimal concentrations of agonist. Evidence for reversible and irreversible desensitization. Immunology. 1988;65(3):443–447.PubMedGoogle Scholar
  32. 32.
    Paolini R, Numerof R, Kinet JP. Phosphorylation/dephosphorylation of high-affinity IgE receptors: a mechanism for coupling/uncoupling a large signaling complex. Proc Natl Acad Sci USA. 1992;89(22):10733–10737.PubMedCrossRefGoogle Scholar
  33. 33.
    Rubinchik E, Shalit M, Levi-Schaffer F. Responsiveness of human skin mast cells to repeated activation: an in vitro study. Allergy. 1998;53(1):14–19.PubMedCrossRefGoogle Scholar
  34. 34.
    Pienkowski MM, Kazmier WJ, Adkinson NF Jr. Basophil histamine release remains unaffected by clinical desensitization to penicillin. J Allergy Clin Immunol. 1988;82(2):171–178.CrossRefGoogle Scholar
  35. 35.
    Macglashan D, Miura K. Loss of syk kinase during IgE-mediated stimulation of human basophils. J Allergy Clin Immunol. 2004;114(6):1317–1324.CrossRefGoogle Scholar
  36. 36.
    Odom S, Gomez G, Kovarova M, et al. Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase. J Exp Med. 2004;199(11):1491–1502.CrossRefGoogle Scholar
  37. 37.
    Kepley CL. Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels. Int Arch Allergy Immunol. 2005;138(1):29–39.PubMedCrossRefGoogle Scholar
  38. 38.
    Malaviya R, Uckun FM. Role of STAT6 in IgE receptor/FcepsilonRI-mediated late phase allergic responses of mast cells. J Immunol. 2002;168(1):421–426.PubMedGoogle Scholar
  39. 39.
    Shalit M, Levi-Schaffer F. Challenge of mast cells with increasing amounts of antigen induces desensitization. Clin Exp Allergy. 1995;25(9):896–902.CrossRefGoogle Scholar
  40. 40.
    Executive summary of disease management of drug hypersensitivity: a practice parameter. Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1999; 83(6Pt3):665–700.Google Scholar
  41. 41.
    Simpson AB, Murphy AW, Yousef E. The acceptability of a four-part protocol for penicillin allergy testing by practicing allergists. Allergy Asthma Proc. 2009;30(2):192–201.PubMedCrossRefGoogle Scholar
  42. 42.
    Fontaine C, Mayorga C, Bousquet PJ, et al. Relevance of the determination of serum-specific IgE antibodies in the diagnosis of immediate beta-lactam allergy. Allergy. 2007;62(1):47–52.PubMedCrossRefGoogle Scholar
  43. 43.
    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(2):277–286.PubMedCrossRefGoogle Scholar
  44. 44.
    Blanca M, Mayorga C, Torres MJ, et al. Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Allergy. 2001;56(9):862–870.PubMedCrossRefGoogle Scholar
  45. 45.
    Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64(2):183–193.PubMedCrossRefGoogle Scholar
  46. 46.
    Atanaskovic-Markovic M, Gaeta F, Gavrovic-Jankulovic M, Velickovic TC, Valluzzi RL, Romano A. Tolerability of imipenem in children with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2009;124(1):167–169.PubMedCrossRefGoogle Scholar
  47. 47.
    Solensky R. Bloomberg GR, Castells MC, et al. Cephalosporin Administration to Patients With a History of Penicillin Allergy. Immunology. AAoAA ed, 2009.Google Scholar
  48. 48.
    Solensky R. Drug desensitization. Immunol Allergy Clin North Am. 2004;24(3):425–443,vi.PubMedCrossRefGoogle Scholar
  49. 49.
    Madaan A, Li JT. Cephalosporin allergy. Immunol Allergy Clin NA. 2004;24(3):463–476, vi-vii.CrossRefGoogle Scholar
  50. 50.
    Ghosal S, Taylor CJ. Intravenous desensitization to ceftazidime in cystic fibrosis patients. J Antimicrobial Chemother. 1997;39(4):556–557.CrossRefGoogle Scholar
  51. 51.
    Papakonstantinou G, Bogner JR, Hofmeister F, Hehlmann R. Cefotaxime desensitization. Clin Invest. 1993;71(2):165–167.Google Scholar
  52. 52.
    Win PH, Brown H, Zankar A, Ballas ZK, Hussain I. Rapid intravenous cephalosporin desensitization. J Allergy Clin Immunol. 2005;116(1):225–228.PubMedCrossRefGoogle Scholar
  53. 53.
    Gorman SK, Zed PJ, Dhingra VK, Ronco JJ. Rapid imipenem/cilastatin desensitization for multidrug-resistant Acinetobacter pneumonia. Ann Pharmacother. 2003;37(4):513–516.Google Scholar
  54. 54.
    Burrows JA, Toon M, Bell SC. Antibiotic desensitization in adults with cystic fibrosis. Respirology. 2003;8(3):359–364.PubMedCrossRefGoogle Scholar
  55. 55.
    Turvey SE, Cronin B, Arnold AD, Dioun AF. Antibiotic desensitization for the allergic patient: 5 years of experience and practice. Ann Allergy Asthma Immunol. 2004;92(4):426–432.PubMedCrossRefGoogle Scholar
  56. 56.
    Lin RY. Desensitization in the management of vancomycin hypersensitivity. Arch Intern Med. 1990;150(10):2197–2198.CrossRefGoogle Scholar
  57. 57.
    Polk RE, Israel D, Wang J, Venitz J, Miller J, Stotka J. Vancomycin skin tests and prediction of “red man syndrome” in healthy volunteers. Antimicrob Agents Chemother. 1993;37(10):2139–2143.PubMedCrossRefGoogle Scholar
  58. 58.
    Wong JT, Ripple RE, Maclean JA, Marks DR, Bloch KJ. Vancomycin hypersensitivity: synergism with narcotics and “desensitization” by a rapid continuous intravenous protocol. J Allergy Clin Immunol. 1994;94(2Pt1):189–194.PubMedCrossRefGoogle Scholar
  59. 59.
    Kitazawa T, Ota Y, Kada N, et al. Successful vancomycin desensitization with a combination of rapid and slow infusion methods. Intern Med. 2006;45(5):317–321.PubMedCrossRefGoogle Scholar
  60. 60.
    Scherer K, Bircher AJ. Hypersensitivity reactions to fluoroquinolones. Curr Allergy Asthma Rep. 2005;5(1):15–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Venturini Diaz M, Lobera Labairu T, del Pozo Gil MD, Blasco Sarramian A, Gonzalez Mahave I. In vivo diagnostic tests in adverse reactions to quinolones. J Investig Allergol Clin Immunol. 2007;17(6):393–398.PubMedGoogle Scholar
  62. 62.
    Erdem G, Staat MA, Connelly BL, Assa’ad A. Anaphylactic reaction to ciprofloxacin in a toddler: successful desensitization. Pediatr Infect Dis J. 1999;18(6):563–564.PubMedCrossRefGoogle Scholar
  63. 63.
    Davila I, Diez ML, Quirce S, Fraj J, De La Hoz B, Lazaro M. Cross-reactivity between quinolones. Report of three cases. Allergy. 1993;48(5):388–390.PubMedCrossRefGoogle Scholar
  64. 64.
    Manfredi M, Severino M, Testi S, et al. Detection of specific IgE to quinolones. J Allergy Clin Immunol. 2004;113(1):155–160.PubMedCrossRefGoogle Scholar
  65. 65.
    Gea-Banacloche JC, Metcalfe DD. Ciprofloxacin desensitization. J Allergy Clin Immunol. 1996;97(6):1426–1427.CrossRefGoogle Scholar
  66. 66.
    Lantner RR. Ciprofloxacin desensitization in a patient with cystic fibrosis. J Allergy Clin Immunol. 1995;96(6Pt1):1001–1002.PubMedCrossRefGoogle Scholar
  67. 67.
    Schretlen-Doherty JS, Troutman WG. Tobramycin-induced hypersensitivity reaction. Ann Pharmacother. 1995;29(7–8):704–706.PubMedGoogle Scholar
  68. 68.
    Earl HS, Sullivan TJ. Acute desensitization of a patient with cystic fibrosis allergic to both beta-lactam and aminoglycoside antibiotics. J Allergy Clin Immunol. 1987;79(3):477–483.PubMedCrossRefGoogle Scholar
  69. 69.
    Araujo L, Demoly P. Macrolides allergy. Curr Pharm Des. 2008;14(27):2840–2862.PubMedCrossRefGoogle Scholar
  70. 70.
    Brown-Elliott BA, Wallace RJ Jr. Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev. 2002;15(4):716–746.PubMedCrossRefGoogle Scholar
  71. 71.
    Holmes NE, Hodgkinson M, Dendle C, Korman TM. Report of oral clarithromycin desensitization. Br J Clin Pharmacol. 2008; 66(2):323–324.PubMedCrossRefGoogle Scholar
  72. 72.
    Cawley MJ, Lipka O. Intravenous linezolid administered orally: a novel desensitization strategy. Pharmacotherapy. 2006;26(4):563–568.PubMedCrossRefGoogle Scholar
  73. 73.
    Shahar E, Moar C, Pollack S. Successful desensitization of enfuvirtide-induced skin hypersensitivity reaction. AIDS. 2005;19(4):451–452.PubMedCrossRefGoogle Scholar
  74. 74.
    Henry RE, Wegmann JA, Hartle JE, Christopher GW. Successful oral acyclovir desensitization. Ann Allergy. 1993;70(5):386–388.PubMedGoogle Scholar
  75. 75.
    Martinez E, Collazos J, Mayo J. Hypersensitivity reactions to rifampin. Pathogenetic mechanisms, clinical manifestations, management strategies, and review of the anaphylactic-like reactions. Medicine (Baltimore). 1999;78(6):361–369.CrossRefGoogle Scholar
  76. 76.
    Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328(23):1670–1674.PubMedCrossRefGoogle Scholar
  77. 77.
    Dibbern DA Jr, Montanaro A. Allergies to sulfonamide antibiotics and sulfur-containing drugs. Ann Allergy Asthma Immunol. 2008;100(2):91–100; quiz 3,11.PubMedCrossRefGoogle Scholar
  78. 78.
    Bonfanti P, Pusterla L, Parazzini F, et al. The effectiveness of desensitization versus rechallenge treatment in HIV-positive patients with previous hypersensitivity to TMP-SMX: a randomized multicentric study. C.I.S.A.I. Group. Biomed Pharmacother. 2000;54(1):45–49.PubMedCrossRefGoogle Scholar
  79. 79.
    Choquet-Kastylevsky G, Vial T, Descotes J. Allergic adverse reactions to sulfonamides. Curr Allergy Asthma Rep. 2002;2(1):16–25.PubMedCrossRefGoogle Scholar
  80. 80.
    Leoung GS, Stanford JF, Giordano MF, et al. Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ. J Infect Dis. 2001;184(8):992–997.PubMedCrossRefGoogle Scholar
  81. 81.
    Caumes E, Guermonprez G, Lecomte C, Katlama C, Bricaire F. Efficacy and safety of desensitization with sulfamethoxazole and trimethoprim in 48 previously hypersensitive patients infected with human immunodeficiency virus. Arch Dermatol. 1997;133(4):465–469.PubMedCrossRefGoogle Scholar
  82. 82.
    Carr A, Penny R, Cooper DA. Efficacy and safety of rechallenge with low-dose trimethoprim-sulphamethoxazole in previously hypersensitive HIV-infected patients. AIDS. 1993;7(1):65–71.PubMedCrossRefGoogle Scholar
  83. 83.
    Nguyen MT, Weiss PJ, Wallace MR. Two-day oral desensitization to trimethoprim-sulfamethoxazole in HIV-infected patients. AIDS. 1995;9(6):573–575.PubMedCrossRefGoogle Scholar
  84. 84.
    Solensky R. Drug desensitization. Immunol Allergy Clin NA. 2004;24(3):425–443,vi.CrossRefGoogle Scholar
  85. 85.
    Demoly P, Messaad D, Sahla H, et al. Six-hour trimethoprim-sulfamethoxazole-graded challenge in HIV-infected patients. J Allergy Clin Immunol. 1998;102(6Pt1):1033–1036.PubMedCrossRefGoogle Scholar
  86. 86.
    White MV, Haddad ZH, Brunner E, Sainz C. Desensitization to trimethoprim sulfamethoxazole in patients with acquired immune deficiency syndrome and Pneumocystis carinii pneumonia. Ann Allergy. 1989;62(3):177–179.PubMedGoogle Scholar
  87. 87.
    Craig TJ, Peralta F, Boggavarapu J. Desensitization for fluconazole hypersensitivity. J Allergy Clin Immunol. 1996;98(4):845–846.PubMedCrossRefGoogle Scholar
  88. 88.
    Douglas R, Spelman D, Czarny D, O’Hehir R. Desensitization to itraconazole. J Allergy Clin Immunol. 1997;99(2):269.PubMedGoogle Scholar
  89. 89.
    Bittleman DB, Stapleton J, Casale TB. Report of successful desensitization to itraconazole. J Allergy Clin Immunol. 1994;94(2Pt1):270–271.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA

Personalised recommendations