Managing Penicillin Allergy

Transcription

1 Managing Penicillin Allergy Brian T. Kelly, MD MA April 12, 2019 Objectives Review penicillin allergy prevalence, morbidity, and management Describe the penicillin testing and oral challenge process Provide recommendations for clinicians on management of the penicillin allergic patient 1

2 Penicillin Chemical Structure Side chains make up different preparations e.g. amoxicillin Allergenic β lactam ring similar among other antibiotic classes Drug Allergies An immunologically mediated response to a pharmaceutical agent in a sensitized person Common In U.S., antibiotic associated adverse events have been implicated in 19.3% of all emergency department visits for drug related adverse events Penicillin is most likely medication Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: Legendre D. et al. Clin Infect Dis 2013:1 9 2

3 Penicillin Allergy Prevalence People in millions US Population Self Reported Allergy True Allergy Zhou L, et al.allergy. 2016;71(9): Macy E, Ho NJ. Ann Allergy Asthma Immunol. 2012;108(2):88 93 Trubiano JA, Adkinson NF, Phillips EJ. 2017;318(1): Penicillin Allergy Prevalence 90 98% of patients who self report PCN allergy really aren t! Rate of anaphylaxis 1 2/10,000 patients receiving IV penicillin UK study in 2007 revealed one death due to anaphylaxis in 100 million exposed to amoxicillin Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: Shenoy ES. et al. JAMA 2019;321(2): Lee P, Shanson D.J Antimicrob Chemother. 2007;60(5):

4 Why talk about this here? PANDAS is thought to be triggered by strep infection Gold standard therapy for strep is penicillin PANDAS patients tend to have frequent episodes associated with acute infection requiring antibiotics Some recommend penicillin prophylaxis Cooperstock, MS et al. J Child Adol Psycopharmacology 2017;27(7): Consequences of being Penicillin allergic Longer hospital stays (.59 day/person) $20 Million increase in healthcare cost/year Infectious complications 23% more infections with Clostridium difficile 14% more MRSA 30% more vancomycin resistant Enterococcus Macy E, Contreras R. JACI. 2014;133(3):

5 Consequences of being Penicillin allergic Treated with more fluoroquinolones, clindamycin, and vancomycin Breeds resistant organisms Increased cost compared to penicillins Increased rates of adverse reactions Infection Adverse reactions to those antibiotics (Redman s, DRESS, etc) Macy E, Contreras R. JACI. 2014;133(3):790 6 Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: What to do if PANDAS child is penicillin allergic? Refer to your friendly neighborhood allergist? Consider alternative agent? 1 st generation cephalosporins Macrolides Clindamycin Avoid antibiotics all together? Not ideal 5

6 Referral to Allergy History Goal is to identify whether reaction that occurred was IgE mediated or some other reaction type Often the history includes a cutaneous reaction Hives Maculopapular rash Severe cutaneous adverse reaction Steven s Johnson/TEN Shenoy ES. et al. JAMA 2019;321(2): IgE Mediated Reaction Onset Usually minutes to hour after drug exposure Requires prior exposure to drug or crossreacting drug (sensitization) Symptoms Urticaria, flushing, pruritus, angioedema, anaphylaxis Rash resolves without peeling or changes in pigmentation 6

7 Shenoy ES. et al. JAMA 2019;321(2): Risk Stratification Table 3. Risk Stratification for Penicillin Allergy Evaluation Low Risk Medium Risk High Risk History Isolated reactions that are unlikely allergic (e.g. gastrointestinal symptoms, headache) Pruritis without rash Remote (>10 years) unknown reaction without features of IgE Family history of penicillin allergy Urticaria or other pruritic rash Reactions with features of IgE but not anaphylaxis Anaphylacitic Symptoms Positive skin testing Recurrent reactions Reactions to multiple beta lactam antibiotics Action Prescribe amoxicillin course or perform direct oral amoxicillin challenge under observation Skin test followed by supervised amoxicillin challenge Desensitization Adapted from: Shenoy ES. et al. JAMA 2019;321(2):

8 Contraindications to testing Autoimmune Diseases Bullous pemphigoid, Pemphigus vulgaris, Linear IgA bullous disease, Drug induced lupus Neutrophilic Dermatosis Acute generalized exanthematous pustulosis (AGEP) Sweets syndrome Severe Cutaneous Drug Reactions Stevens Johnson Syndrome/TEN DRESS Exfoliative dermatitis Macy,E. JACI in practice 2013;1: Contraindications to testing Drug induced vasculitis Serum sickness like reaction Organ specific drug reactions Cytopenia Hemolytic anemia Hepatitis Nephritis Pneumonia Macy,E. JACI in practice 2013;1:

9 Testing Procedures PCN skin testing is done in a supervised allergy clinic Patients need to refrain from taking antihistamines for at least 72 hours before testing E.g. diphenhydramine, cetirizine, loratadine Skin Testing Most reliable method for evaluating IgE mediated penicillin allergy When performed by skilled personnel using proper technique, serious reactions are extremely rare Negative predictive value approaches 100% Positive predictive value between 40% and 100% Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105:

10 Penicillin Specific IgE (e.g. RAST) High specificity (97% 100%) but low sensitivity (29% 68%) Therefore, although a positive in vitro test result for penicillin specific IgE is highly predictive of penicillin allergy, a negative in vitro test result does not adequately exclude penicillin allergy Not routinely performed Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: Skin Testing Major Determinant (PrePen) Minor Determinant (Penicillin G) Stepwise approach Percutaneous Intradermal Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: Shenoy ES. et al. JAMA 2019;321(2):

11 Direct Provocation Testing Gold standard to establish a firm diagnosis in subjects with clear cut histories and negative allergy tests Done when penicillin skin testing is negative Patient is provided with provocative dose of amoxicillin Observation for 1 hour ACAAI Drug and Anaphylaxis Committee Expert Opinion 2015 Post Challenge Instructions Assure the patient that they are safe to take any penicillin antibiotic <5% chance with each future course of developing a new allergy to penicillin For select patients (e.g., very anxious or concern about a delayed reaction) consider a 5 day course of the antibiotic following the testing Send consultation letter to PCP indicating that patient is no longer considered to be allergic to penicillin Macy,E. JACI: In practice 2013;1:

12 INSERT CERTIFICATE HERE Positive testing Penicillin skin test positive patients should avoid penicillin Alternatives should always be tried If patients develop an absolute need for penicillin, rapid induction of drug tolerance is necessary AKA drug desensitization temporary induction of drug tolerance Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105:

13 Drug Desensitization Induction of immune drug tolerance by which effector cells are rendered less reactive or nonreactive to IgE mediated immune responses by rapid administration of incremental doses of an allergenic substance This can be used for penicillin allergy when there are no alternative agents Usually conducted in the ICU Solensky R. et al. Ann Allergy Asthma Immunol 2010; 105: Boys Town Experience Program started in June 2017 in conjunction with the Antibiotic Stewardship Committee Fliers created and given to patients through Boys Town Pediatrics offices Letters were sent to patients by their pediatrician if they were identified via EMR as penicillin allergic 13

14 Boys Town Experience Boys Town Allergy/Immunology Here to help!! 5 Providers Jill Hanson, MD Brian Kelly, MD Kevin Murphy, MD Nicki Nair, MD Jen Banfield, NP 3 offices 72 nd & Center (402) West Hospital (144 th & Pacific) (531) Lakeside Clinic (16929 Frances St) (402)

15 Questions?? Thanks! 15

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