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8/30/2012 Penicillin Allergy Neeti Bhardwaj, MD, MS Fellow, Allergy and Immunology Penn State Milton S. Hershey Medical Center Financial Disclosures • None Case 1 • 67 year-old female with history of right knee arthroplasty • Post-operative course was complicated by infection of prosthesis accompanied by bacteremia • Removal of prosthesis 1 8/30/2012 Case 1 (Contd…) • Tissue and blood cultures cultures grew penicillin sensitive MSSA • Infectious disease specialists recommended cefazolin based on culture sensitivity results • However,………. Case 1 (Contd…) • ….The patient had penicillin listed as a drug allergy • History: urticarial rash and passing out within an hour after taking penicillin when she was “very young”. Was treated in the emergency room. • Could not provide further specifics about the “reaction” • Had avoided penicillins and cephalosporins all her life. maxarmstrong.wikispaces.com 2 8/30/2012 • Is the reaction consistent with a drug allergy? • What are the options for diagnosis? • What drugs are safe to use? • How can we manage the patient? Immediate Hypersensitivity Reactions • Caused by rapid IgE-mediated release of vasoactive mediators from mast cells and basophils • Characterized by hives, pruritis, flushing, respiratory compromise, hypotension • Can be detected by skin testing Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 The Problem • Approximately 10 % of patients report a history of reacting to a penicillin class antibiotic. • When evaluated for penicillin allergy, up to 90 % of these individuals are able to tolerate penicillins Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 3 8/30/2012 Why this discrepancy? • Penicillin specific IgE antibodies rapidly wane over time. • Some reactions are the result of an underlying bacterial or viral infection or an interaction between the infectious agent and the antibiotic. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Why this discrepancy? (Cont…) • Some patients may mislabel the antibiotic they were treated with as penicillin • Or may attribute predictable reactions (such as diarrhea) as allergic Why is this so important? Treatment of patients assumed to be penicillin allergic with alternate broadspectrum antibiotics may lead to: • Multiple drug-resistant organisms • Higher costs • Increased toxic side-effects Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 4 8/30/2012 Why is this so important? Evaluation of patients with reported penicillin allergy by skin testing leads to: • Reduction in the use of broad spectrum antibiotics • Decrease in treatment costs Diagnostic Options • Graded challenge: only when pre-test probability is low. • Skin testing • In vitro tests: not reliable, limited to experimental studies only Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Penicillin Skin Testing • Detects the presence or absence of penicillin specific IgE antibodies • Major determinant: penicilloylpolylysine (PLL) • Native drug : Penicillin G (10,000 U/mL). Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 5 8/30/2012 Application of Penicillin G (1:10,000 U/mL) and PPL by prick technique Negative Intradermal testing Negative Oral challenge with amoxicillin with one hour observation in the office Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Penicillin Skin Testing • Negative predictive value: approaches 100% • Positive predictive value: 40-100% Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Back to our patient… 6 8/30/2012 Case 1 Penicillin skin testing followed by oral amoxicillin challenge Testing negative Patient treated with cefazolin per ID recommendations What if the skin test is positive? • Non-bactam antibiotic • Induction of tolerance to the drug • Graded challenge (recommended only if the history of last reaction is remote and benign) • And what about cephalosporins?........ Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 7 8/30/2012 Cephalosporin Administration to Patients with a History of Penicillin Allergy Approximately, 2% of penicillin skin testpositive patients react with cephalosporins (older literature suggests 10%) Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Skin test results for penicillin major and minor determinants: negative Safe to give cephalosporins, regardless of severity of reaction to penicillin Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Penicillin Skin Test Positive non-β-lactam antibiotic Desensitization to cephalosporin Graded challenge to cephalosporin Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 8 8/30/2012 Aztreonam • Penicillin and cephalosporin allergic patients may receive aztreonam , with the exception of those allergic to ceftazidime (theoretical risk of cross-reactivity due to similar side chain) Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Carbapenems • Penicillin allergic patients may receive carbapenems (imipenem, meropenem) via graded challenge Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 What if there is no alternative to penicillin or cephalosporin? 9 8/30/2012 Drug Desensitization • In patients with convincing history of IgEmediated reaction, particularly if recent. • Informed consent must be obtained for skin testing, graded challenge as well as desensitization Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Drug Desensitization • Temporary induction of drug tolerance • Involves rapid administration of incremental doses of the drug until the target dose is reached • Effector cells are rendered less reactive or non-reactive • Does not indicate a permanent state of tolerance Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Graded Challenge • May be indicated in patients with distant or questionable reaction histories • Administration of progressively increasing doses of the medication until the full dose is reached Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 10 8/30/2012 Graded Challenge • Involves fewer doses than desensitization and do not induce tolerance • Intended to verify that the patient does not have immediate hypersensitivity Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273 Case 2 • A 5-year-old boy referred to Allergy and Immunology clinic by his PCP for evaluations of “antibiotic allergy” • Had history of recurrent ear infections. • Had a reaction to amoxicillin. Case 2 (Contd…) • Had previously tolerated amoxicillin multiple times • Developed a generalized “rash” with no accompanying symptoms on the 7th day of the last amoxicillin course. • No other symptoms • Parents were advised by the pediatrician that the child should not receive penicillins again 11 8/30/2012 bestpractice.bmj.com • • • • Is this a dangerous drug allergy? What diagnostic tests are available? Can this patient have penicillins again? What about other beta lactams? Benign T cell Mediated Reactions • Delayed cutaneous eruptions, such as maculopapular exanthems • The exanthem may be a manifestation of the underlying infection process • Usually not reproducible upon readministration 12 8/30/2012 Diagnostic options • Give medication again • Perform oral challenge (graded or full) • Skin test to rule out IgE-mediated mechanism if history is unclear Case 2 History was not consistent with true type 1 IgE mediated reaction to the implicated drugs Child was too young to tolerate penicillin skin testing Passed graded oral challenge in to amoxicillin in the clinic Cleared of penicillin and cephalosporin allergy Take Home Messages… • Ninety per cent of patients with reported penicillin allergy are able to tolerate penicillin • Treatment of patients assumed to be penicillin allergic may compromise optimal medical care • Evaluation of patients with penicillin allergy by skin testing leads to reduction in the use of broad-spectrum antibiotics and may decrease costs 13 8/30/2012 Take Home Messages… • Patients with negative skin test results may receive penicillin with minimal risk of an IgE-mediated reaction • Penicillin skin-test positive patients should avoid penicillin. If there is an absolute need, rapid induction of tolerance may be performed 14