Antimicrobial Desensitization: A Review of Published Protocols
Abstract
:1. Introduction
2. Results
2.1. Indications and Contraindications
2.1.1. Indications
2.1.2. Contraindications
2.2. Review of Antimicrobial Desensitization Protocols
2.2.1. β-Lactam Antimicrobials
Penicillins
Cephalosporins
Carbapenems
Monobactams
2.2.2. Non-β-Lactam Antimicrobials
Vancomycin
Daptomycin
Linezolid
Clindamycin
Macrolides
Aminoglycosides
Tetracyclines
Sulfonamides
Metronidazole
Fluoroquinolones
2.2.3. Antifungals
Polyene Antifungals
Triazole Antifungals
Echinocandins
2.2.4. Antivirals
3. Discussion
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Underlying Mechanism | Initial Dose | Protocol Duration | Potential Outcome | Duration of Induced Tolerance | Examples |
---|---|---|---|---|---|
Immunologic IgE (desensitization) | Micrograms | Hours | Blunting the mast cell response | Temporary | β-lactam antibiotics |
Immunologic non-IgE | Milligrams | Hours to days (e.g., 6 h to 10 days) | Unknown | Temporary | Delayed cutaneous reactions to SMX-TMP in HIV-infected patients |
Pharmacologic | Milligrams | Hours to days (e.g., 2 h to 5 days) | Inhibition of tyrosine kinases and STAT6 resulting in IL-4 suppression | Temporary | Aspirin-exacerbated respiratory disease (AERD) |
Undefined | Micrograms to milligrams | Prolonged; days to weeks | Unknown | Temporary | Allopurinol-induced pruritic maculopapular rash |
Indications | Relative Contraindications | Absolute Contraindications | |
---|---|---|---|
Immediate HSR | No safe and effective alternative is available Benefits > risks | Receiving β-blockers Previous severe anaphylactic reaction Chronic hepatic or renal disease | Severe asthma or COPD Hemodynamic instability Uncontrolled CVD |
Delayed HSR | No safe and effective alternative is available Previous delayed drug reaction was not severe Benefits > risks | AGEP Chronic hepatic or renal disease Chronic severe cardiac disease Uncontrolled autoimmune disorders | SJS TEN DRESS Cutaneous/systemic vasculitis Extensive mucosal ulcers Autoimmune drug reactions Internal organ involvement Cytopenias |
A | ||||
Dose Number | Penicillin Concentration (Units/mL) | Amount (mL) | Dose (Units) | Cumulative Dose (Units) |
1 | 1000 | 0.1 | 100 | 100 |
2 | 1000 | 0.2 | 200 | 300 |
3 | 1000 | 0.4 | 400 | 700 |
4 | 1000 | 0.8 | 800 | 1500 |
5 | 1000 | 1.6 | 1600 | 3100 |
6 | 1000 | 3.2 | 3200 | 6300 |
7 | 1000 | 6.4 | 6400 | 12,700 |
8 | 10,000 | 1.2 | 12,000 | 24,700 |
9 | 10,000 | 2.4 | 24,000 | 48,700 |
10 | 10,000 | 4.8 | 48,000 | 96,700 |
11 | 80,000 | 1.0 | 80,000 | 176,700 |
12 | 80,000 | 2.0 | 160,000 | 336,700 |
13 | 80,000 | 4.0 | 320,000 | 656,700 |
14 | 80,000 | 8.0 | 640,000 | 1,296,700 |
Interval between doses was 15–30 min, with a total time of 4–8 h. Observation before full parenteral therapeutic dose was 30 min. Each dose was diluted in 30 mL of water prior to oral administration. | ||||
B | ||||
Dose Number | Penicillin Concentration (mg/mL) | Amount (mL) | Dose (mg) | Cumulative Dose (mg) |
1 | 0.5 | 0.1 | 0.05 | 0.05 |
2 | 0.5 | 0.2 | 0.1 | 0.15 |
3 | 0.5 | 0.4 | 0.2 | 0.35 |
4 | 0.5 | 0.8 | 0.4 | 0.75 |
5 | 0.5 | 1.6 | 0.8 | 1.55 |
6 | 0.5 | 3.2 | 1.6 | 3.15 |
7 | 0.5 | 6.4 | 3.2 | 6.35 |
8 | 5.0 | 1.2 | 6.0 | 12.35 |
9 | 5.0 | 2.4 | 12.0 | 24.35 |
10 | 5.0 | 5.0 | 25.0 | 49.35 |
11 | 50 | 1.0 | 50.0 | 100.0 |
12 | 50 | 2.0 | 100.0 | 200.0 |
13 | 50 | 4.0 | 200.0 | 400.0 |
14 | 50 | 8.0 | 400.0 | 800.0 |
Dose Number | Penicillin Concentration (mg/mL) | Infusion Rate (mL/h) | Dose (mg) | Cumulative Dose (mg) |
---|---|---|---|---|
1 | 0.01 | 6 | 0.015 | 0.015 |
2 | 0.01 | 12 | 0.03 | 0.045 |
3 | 0.01 | 24 | 0.06 | 0.105 |
4 | 0.01 | 50 | 0.125 | 0.23 |
5 | 0.1 | 10 | 0.25 | 0.48 |
6 | 0.1 | 20 | 0.5 | 1.0 |
7 | 0.1 | 40 | 1.0 | 2.0 |
8 | 0.1 | 80 | 2.0 | 4.0 |
9 | 0.1 | 160 | 4.0 | 8.0 |
10 | 10.0 | 3 | 7.5 | 15.0 |
11 | 10.0 | 6 | 15.0 | 30.0 |
12 | 10.0 | 12 | 30.0 | 60.0 |
13 | 10.0 | 25 | 62.5 | 123.0 |
14 | 10.0 | 50 | 125.0 | 250.0 |
15 | 10.0 | 100 | 250.0 | 500.0 |
16 | 10.0 | 200 | 500.0 | 1000.0 |
A | ||||||
Solution: | Total Volume | Concentration | Dose | |||
Solution 1 | 100 mL | 0.100 mg/mL | 10 mg | |||
Solution 2 | 100 mL | 1.00 mg/mL | 100 mg | |||
Solution 3 | 100 mL | 10.00 mg/mL | 1000 mg | |||
B | ||||||
Step | Solution# | Rate (mL/hr) | Time (minutes) | Volume (mL) | Dose (mg) | Cumulative dose (mg) |
1 | 1 | 2 | 15 | 0.5 | 0.050 | 0.050 |
2 | 1 | 5 | 15 | 1.25 | 0.125 | 0.175 |
3 | 1 | 10 | 15 | 2.5 | 0.25 | 0.425 |
4 | 1 | 20 | 15 | 5 | 0.5 | 0.925 |
5 | 2 | 5 | 15 | 1.25 | 1.25 | 2.175 |
6 | 2 | 10 | 15 | 2.5 | 2.5 | 4.675 |
7 | 2 | 20 | 15 | 5 | 5 | 9.675 |
8 | 2 | 40 | 15 | 10 | 10 | 19.675 |
9 | 3 | 10 | 15 | 2.5 | 25 | 44.675 |
10 | 3 | 20 | 15 | 5 | 50 | 94.675 |
11 | 3 | 40 | 15 | 10 | 100 | 194.675 |
12 | 3 | 80 | 60.40 | 80.53 | 805.325 | 1000 |
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Chastain, D.B.; Hutzley, V.J.; Parekh, J.; Alegro, J.V.G. Antimicrobial Desensitization: A Review of Published Protocols. Pharmacy 2019, 7, 112. https://doi.org/10.3390/pharmacy7030112
Chastain DB, Hutzley VJ, Parekh J, Alegro JVG. Antimicrobial Desensitization: A Review of Published Protocols. Pharmacy. 2019; 7(3):112. https://doi.org/10.3390/pharmacy7030112
Chicago/Turabian StyleChastain, Daniel B., Vanessa Johanna Hutzley, Jay Parekh, and Jason Val G. Alegro. 2019. "Antimicrobial Desensitization: A Review of Published Protocols" Pharmacy 7, no. 3: 112. https://doi.org/10.3390/pharmacy7030112