Antimicrobial Desensitization

Antimicrobial Desensitization

Considerations Before Desensitization

  • The drug of concern is deemed irreplaceable

    • e.g. penicillin for the treatment of syphilis
  • The drug of concern is more effective than available alternatives

  • The drug of concern is much safer than available alternatives

    • e.g. ampicillin + cefTRIAXone for Enterococcus faecalis endocarditis
  • Uncontrolled asthma or uncontrolled cardiac disease
  • Hemodynamic instability
  • Gravely ill patients in which effective alternatives are readily available
  • History of severe non-IgE mediated hypersensitivity reaction. For example:
    • Interstitial nephritis
    • Immune hepatitis
    • Hemolytic anemia
    • Serum sickness
    • Severe cutaneous reactions such as:
    • Stevens-Johnson syndrome (SJS)
    • Toxic epidermal necrolysis (TEN)
    • Drug rash with eosinophilia and systemic symptoms (DRESS)
    • etc.
  • Desensitization only temporarily induces drug tolerance; DO NOT remove the allergy label from the patient’s medical record. If the medication is not continued, tolerance will dissipate in as little as 24 hours, or approximately 4 half-lives of the medication
  • There is a potential that desensitization could induce an acute hypersensitivity reaction; carefully evaluate risks and benefits in patients with a history of severe anaphylaxis and/or anaphylactic shock
  • Beta-blockers may interfere with the treatment of anaphylaxis; if possible, hold beta-blockers prior to desensitization
  • Antihistamines and corticosteroids may mask early signs of a hypersensitivity reaction; if possible, hold prior to desensitization. DO NOT pre-treat with these agents to prevent reactions

Preparing for Desensitization

  • It is essential that the patient be observed continually, with one-to-one nursing care, for signs of a hypersensitivity reaction
  • Because desensitization exposes patients to drugs that have the potential to induce an acute hypersensitivity reaction, it should only be performed in a setting where anaphylaxis can be managed, preferably with staff comfortable and/or experienced with the management of anaphylaxis
  • Patient factors, such as severity of past reactions and comorbidities, may assist in determining the best location for the desensitization procedure
  • Desensitization has been shown to be safe, and does not always require to be performed in an intensive care unit. Many centres safely perform desensitization in a general ward or on an outpatient basis.
  • Written informed consent is mandatory prior to starting the procedure, since we are knowingly administering a medication that could provoke a hypersensitivity reaction
    • see local treatment consent forms
  • Benefits of the procedure should outweigh the risks
  • The physician should be available for immediate consultation, if required, throughout the procedure
  • All patients should have IV access BEFORE starting the procedure and any equipment or medications required to manage anaphylaxis should be readily available
  • Have all of the following medications readily available throughout the entire procedure:
    • EPINEPHrine 1 mg/mL ampule x 2
    • Salbutamol 100 mcg/inhalation MDI with aerochamber x1
    • DiphenhydrAMINE 50 mg IV x1
    • MethylPREDNISolone 125 mg IV x 1
    • Ranitidine 150 mg PO x1 (or famotidine 20 mg PO x1 if ranitidine unavailable)
    • Cetirizine 10 mg PO x 2

Desensitization Procedure

  • Many desensitization protocols are available for both oral and intravenous formulations of beta-lactams
  • The oral route may be easier, more cost-effective, and potentially safer than the intravenous route
  • Medications are typically started at diluted doses, usually 1/10,000th of the target dose, and, if no reaction, doses are doubled every 15-20 minutes until the target dose is achieved
  • If a more conservative approach is desired for patients with a history of severe anaphylactic reactions, a starting dose of 1/1,000,000th of the target dose could be considered

During the desensitization procedure, vital signs should be monitored closely and patients should be instructed to report symptoms of any potential hypersensitivity reaction

  • One-to-one nursing is MANDATORY during desensitization; may consider cardiac monitoring.
  • Monitor for signs of an immediate hypersensitivity reaction (e.g. anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, stridor, pruritis)
  • At baseline, and then at every dosing increment, monitor and record the following vital signs: T°, HR, RR, BP, and SaO₂
  • Upon completion of the procedure, monitor the vital signs listed above q30min x 4, then q6h x 4

Click here to access the NB-ASC Desensitization Guidelines for more details; such as sample densitization orders and protocols.

Additional Information

Guideline content derived from: NB Provincial Health Authorities Anti-Infective Stewardship Committee. Antimicrobial Desensitization. 05-2019

  1. Lagace-Wiens P, Rubinstein E. Adverse reactions to beta-lactam antimicrobials. Expert opinion on drug safety. 2012;11(3):381-399.

  2. Solensky R. Allergy to beta-lactam antibiotics. J Allergy Clin Immunol. 2012;130(6):1442-1442 e1445.

  3. Macy E, Schatz M, Lin C, Poon KY. The falling rate of positive penicillin skin tests from 1995 to 2007. The Permanente journal. 2009;13(2):12-18.

  4. Borch JE, Andersen KE, Bindslev-Jensen C. The prevalence of suspected and challenge-verified penicillin allergy in a university hospital population. Basic & clinical pharmacology & toxicology. 2006;98(4):357-362.

  5. Macy E, Ngor E. Recommendations for the management of beta-lactam intolerance. Clin Rev Allergy Immunol. 2014;47(1):46-55.

  6. Solensky R. Drug desensitization. Immunology and allergy clinics of North America. 2004;24(3):425-443, vi.

  7. Cernadas JR, Brockow K, Romano A, et al. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy. 2010;65(11):1357-1366.

  8. Legendre DP, Muzny CA, Marshall GD, Swiatlo E. Antibiotic hypersensitivity reactions and approaches to desensitization. Clin Infect Dis. 2014;58(8):1140-1148.

  9. Drug allergy: an updated practice parameter. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2010;105(4):259-273.

  10. Pham MN, Ho HE, Desai M. Penicillin desensitization: Treatment of syphilis in pregnancy in penicillin-allergic patients. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2017;118(5):537-541.

  11. The Scarborough Hospital. Desensitization Protocols; 2015. Adapted with permission.

  12. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunology and allergy clinics of North America. 2009;29(3):585-606.

  13. Mirakian R, Leech SC, Krishna MT, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. 2015;45(2):300-327.

  14. Yates AB. Management of patients with a history of allergy to beta-lactam antibiotics. Am J Med. 2008;121(7):572-576.

  15. Liu A, Fanning L, Chong H, et al. Desensitization regimens for drug allergy: state of the art in the 21st century. Clin Exp Allergy. 2011;41(12):1679-1689.

  16. Wendel GD, Jr., Stark BJ, Jamison RB, Molina RD, Sullivan TJ. Penicillin allergy and desensitization in serious infections during pregnancy. The New England journal of medicine. 1985;312(19):1229-1232.

  17. Saskatoon Health Region. IV Antibiotic Desensitization for Type 1 Reaction Protocol: Cloxacillin.

  18. Capital Health (NS). Antimicrobial Handbook - Beta-Lactam Desensitization Protocol. 2007.

  19. Drug allergy: an updated practice parameter. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2010;105(4):259-273.

  20. Blond-Hill E, Fryters S. Bugs and Drugs: An Antimicrobial/Infectious Disease. 2012:87-90.

  21. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199.