Antimicrobial desensitization
From IDWiki
Background
- Goal of creating temporary tolerance to an antimicrobial to which the patient has a history of hypersensitivity reaction
- Best described for beta-lactam antibiotics with immediate IgE-mediated hypersensitivity reaction
- Must carefully evaluate risks and benefits
Procedure
- No well-defined universal procedure
- Most use a dilution of 0.1% or 1% of therapeutic dose as a continuous infusion (or oral, or subcut), with dose increased steadily over hours to days
Standardized IV Protocol
- As published in UpToDate
- Typically 12 steps with 3 concentrations
- Can extend to 16 steps with 4 concentrations for particularly severe past reactions
- Each step administered over 15 minutes with no waiting between doses
- Total time is typically 5 to 6 hours
- Calculator exists at https://globalrph.com/medcalcs/desensitization-protocol-12-step/
- Preparation:
- Hold beta blocks if possible
- Transfer to ICU for 1:1 care
- Have epinephrine, albuterol, diphenhydramine, and methylprednisolone available at bedside
- Managing reactions:
- Mild reactions: stop the infusion and given IV diphenhydramine; once the symptoms resolve resume the protocol by repeating the step at which the reaction occurred
- Severe reactions: stop the infusion and give epinephrine, diphenydramine, and methylprednisolone, as well as oxygen if needed, inhaled albuterol for bronchospasm, and IV normal saline; consider glucagon 1 to 2 mg IV bolus followed by 1 to 5 mg/hour infusion if patient was on beta-blockers
- For a 250 mL volume of 1 g of antimicrobial, the following is one example protocol:
| Solution | Total Volume in mL | Dose (mg) | Concentration (for 1 g dose) |
|---|---|---|---|
| 1 | 250 mL | 1% of target dose (e.g. 10 mg) | 0.04 mg/mL |
| 2 | 10% of target dose (e.g. 100 mg) | 0.4 mg /mL | |
| 3 | 100% of target dose (e.g. 1000 mg) | 4 mg/mL |
| Step | Solution | Rate (mL/hour) | Time (min) | Volume (mL) | Dose Administered (for 1 g dose) | Cumulative Dose (for 1 g dose) |
|---|---|---|---|---|---|---|
| 1 | 1 | 2 | 15 | 0.5 | 0.02 mg | 0.02 mg |
| 2 | 5 | 1.25 | 0.05 mg | 0.07 mg | ||
| 3 | 10 | 2.5 | 0.1 mg | 0.17 mg | ||
| 4 | 20 | 5 | 0.2 mg | 0.37 mg | ||
| 5 | 2 | 5 | 1.25 | 0.5 mg | 0.87 mg | |
| 6 | 10 | 2.5 | 1 mg | 1.87 mg | ||
| 7 | 20 | 5 | 2 mg | 3.87 mg | ||
| 8 | 40 | 10 | 4 mg | 7.87 mg | ||
| 9 | 3 | 10 | 2.5 | 10 mg | 18 mg | |
| 10 | 20 | 5 | 20 mg | 38 mg | ||
| 11 | 40 | 10 | 40 mg | 78 mg | ||
| 12 | 80 | 175 | 232 | 920 mg | 1000 mg |
Further Reading
- Antimicrobial Desensitization: A Review of Published Protocols. Pharmacy (Basel). 2019;7(3):112. doi: 10.3390/pharmacy7030112. PMID: 31405062; PMCID: PMC6789802.
- Evaluation of desensitization protocols to betalactam antibiotics. J Clin Pharm Ther. 2022;47(5):592-599. doi: 10.1111/jcpt.13578.
- Tested and published protocols for several antimicrobials, including meropenem, ceftriaxone, ceftazidime, ampicillin, ceftolozane-tazobactam, cloxacillin, piperacillin-tazobactam, amoxicillin-clavulanate, and penicillin G sodium
