Introduction to antimicrobial desensitisation

Antimicrobial desensitisation (also known as induction of tolerance) is a specialised allergy management strategy. Although allergy assessment and allergy testing are all that is required for most patients who report an antimicrobial allergy, desensitisation may be appropriate for specific patients with IgE-mediated immediate hypersensitivity (see Patient appropriateness for antimicrobial desensitisation) to enable them to receive optimal treatment. Desensitisation can also be used in patients with other types of hypersensitivity reactions (eg nonsevere T-cell mediated reactions such as rash related to trimethoprim+sulfamethoxazole).

Drug desensitisation renders mast cells temporarily unresponsive so that a patient with a history of antimicrobial hypersensitivity can receive the drug. It establishes a temporary state of drug tolerance while the patient is exposed to the drug.

Antimicrobial desensitisation is a process of administering fractional doses of a drug, starting with very low doses and slowly increasing to the therapeutic dosage. It is usually performed with the antimicrobial needed for treatment. Once the therapeutic antimicrobial dosage has been attained, do not interrupt treatment – hypersensitivity returns soon after the drug is cleared from the body (typically after 5 drug half-lives)Legendre, 2014.

Note: Once the therapeutic antimicrobial dosage has been attained, do not interrupt treatment.
Figure 1. Patient appropriateness for antimicrobial desensitisation
Antimicrobial desensitisation is considered appropriate if all of the following apply:
  • the patient has a history of severe IgE-mediated immediate hypersensitivity (eg anaphylaxis) confirmed by allergy testing or strongly indicated by clinical history
  • there are no appropriate alternative antimicrobials, or a particular antimicrobial is the preferred drug (eg benzylpenicillin for streptococcal endocarditis).
Antimicrobial desensitisation is not appropriate in the following patients:
  • those with a history of delayed severe immune-mediated hypersensitivity [NB1], including:
    • drug rash with eosinophilia and systemic symptoms (DRESS)
    • Stevens–Johnson syndrome / toxic epidermal necrolysis (SJS/TEN)
    • acute generalised exanthematous pustulosis (AGEP)
    • acute interstitial nephritis (AIN)
    • drug-induced liver injury (DILI)
    • serum sickness
  • those with a history of immune-mediated cytopenias
  • those who meet criteria for direct delabeling (ie removal of the patient’s reported antibiotic allergy based on their clinical history only) or allergy testing.
Note:

NB1: Antimicrobial desensitisation is contraindicated in patients with a history of severe delayed immune-mediated hypersensitivity.

Desensitisation has been best validated for penicillins, but it has also been described for other antimicrobials. These guidelines include the following desensitisation protocols for adults:

Although protocols for other antimicrobials (eg quinolones, macrolides, vancomycin, clindamycin, pentamidine, antituberculosis drugs) have published, they have undergone limited clinical testingKhan 2022Zhu 2022. Consult a specialist in immunology or drug allergy to discuss any desensitisation protocol that has not been clinically validated.