DOM Morning Report: Antibiotic Allergies

1. DOM Morning Report:Antibiotic Allergies ? Week after Intern Retreat ? ? Week after Steelers� sixth Super Bowl victory ?

2. Objectives To know the most useful diagnostic tools To know the different types of reactions and examples of each To know the difference between observed and historical adverse drug reactions

3. Relatively Common 7% of Americans report penicillin allergy May not be true allergy Careful history Medication Reaction Results of skin testing or re-challenge

4. Classifications IgE-mediated Antibody-mediated Delayed hypersensitivity Idiopathic

5. Classification IgE-mediated Usually occurs within 15 min of exposure Common manifestations Pruritus Urticaria Angioedema Bronchospasm Hypotension

6. Classification Dangerous, but relatively uncommon Antibody-mediated Hemolysis Neutropenia 5-15% of pts on cephalosporins for > 10 days

7. Classifications Delayed hypersensitivity Nonurticarial rash with aminopenicillins ? with concomitant viral infections (EBV) Ampicillin Amoxicillin

8. Classifications Idiopathic Well known clinically Poorly understood mechanistically Reactions Erythema multiforme Stevens-Johnson syndrome Pulmonary hypersensitivity Drug fever

9. Classifications Erythema multiforme Acute, self-limited eruption Characteristics Target lesions Histology

10. Classifications Stevens-Johnson syndrome Prodrome of malaise and fever Erythematous or purpuric macules and plaques Progression to epidermal necrosis and sloughing Limited to < 10% of body surface area Pulmonary hypersensitivity Symptoms Development of new infiltrates on chest radiograph Exclusion of infection or other disease CT and lung pathology c/w drug reaction Clinical and radiologic improvement after withdrawal

11. Classification Drug fever Diagnosis of exclusion Only a few will have an obvious clue Rash Eosinophilia

12. Diagnosis History is usually the only useful tool Important to identify dangerous reactions IgE-mediated Stevens-Johnson syndrome

13. Diagnosis Skin testing Only standardized for penicillins Detects only IgE-mediated reactions Reagents available for �major determinant�

14. Diagnosis Protocol Administration Intracutaneous prick Intradermal administration + test ? = 5mm of induration after 15 minutes - test ? low prob on subsequent treatment

15. Cross-reactions Highly likely for structurally similar agents Ampicillin derivatives Semisynthetic agents Pipercillin derivatives Cephalosporins 8.1% for penicillin-allergic patients 4.5% for patients without penicillin allergies

16. Cross-reactions 10% for carbapenems Ertapenem Imipenem Meropenem

17. Desensitization Avoid �-lactams History of anaphylaxis Positive skin test Many antibiotic agents now available Macrolides Fluoroquinolones

18. Desensitization Rare circumstances Protocol Tiny doses of PO PCN increasing Q15min Monitored setting

19. Desensitization Hypotheses Due to neutralization of IgE Less compelling in case of sulfa antibiotics HIV patients have increased incidence of reactions ~ 75% success rate Slow degranulation of mast cells Reactions Urticarial rashes occur in ~ 1/3 of patients True anaphylaxis is rare

20. Documentation Adverse drug reactions (ADRs) Observed In clinic During hospitalization Within past three months Historical Greater than three months ago Danya Mitchell, PharmD

21. Objectives Revisited Diagnostic tools History Skin testing

22. Objectives Revisited Classifications IgE-mediated Antibody-mediated Delayed hypersensitivity Idiopathic

23. Objectives revisited IgE-mediated Pruritus Urticaria Angioedema Bronchospasm Hypotension

24. Objectives Revisited Antibody-mediated Hemolysis Neutropenia Delayed hypersensitivity Nonurticarial rash with aminopenicillins ? with concomitant viral infections (EBV)

25. Objectives Revisited Idiopathic Erythema multiforme Stevens-Johnson syndrome Pulmonary hypersensitivity Drug fever

26. Objectives Revisited Observed adverse drug reactions In clinic During hospitalization Within the last three months