Breaking the myth: Cephalosporin use in patients with Penicillin

allergy Sheikh M. Zakaria

Pharm.D Candidate, Class of 2017University of Saint Joseph School of Pharmacy

Objectives Introduce what Penicillin allergy is and its underlying causes.

Discuss Penicillin chemistry and its congruency with Cephalosporins.

Understand cross allergenicity and the protocol of using cephalosporin in patients with penicillin allergy.

Given a certain cohort of patients, decide which generation of Cephalosporin to use for suspected penicillin allergy.

Penicillin Allergy: the culprit of the Hypersensitivity continuum1,2,3

Penicillin allergy is the most widely reported drug allergy ADR 5-10% report some type of allergic reactions Classified as immediate vs delayed type reactions IgE mediated type 1 reaction accounts for the more life

threatening manifestations Typical risk factors for penicillin allergy include route of

administration, multiple drug allergy syndrome, hereditary factors, work environment

Your regular dairy milk may contain traces of penicillin commonly used for livestock infections.

Erythema from Type I Hypersensitivity Rx4

Penicillin Pharmacochemistry5

Penicilloyl and penicillanic acid—byproducts formed when the beta-lactam ring is opened—are considered the major determinants of penicillin allergy.

Benzylpenicillin and sodium benzylpenicilloate, called the minor determinants, are produced by drug degradation in the gastrointestinal tract and metabolism.

Penicillin & Cephalosporins: Finding the cross allerginicity moieties6

R group side chains shared by both classes exhibit cross allergenicity

Figure: A matrix of penicillin and cephalosporins with side chain similarities.5

Algorithm to treat PCNA with CPN6

Major confounders: Much ado about Allergy!5,7

The 10% range we have is from clinical history analysis, which is an overestimate with respect to true penicillin allergy!

Actual incidence rate confounded by nonallergic ADRs reported as drug allergy

The percentage comes from studies done in mid 70s with 1st generation CPN with similar side chains to PCNs

Early manufacturers extracted penicillin from cephalosporin moulds. Estimate is based upon retrospective studies in which patients with a

history of penicillin allergy were treated with cephalosporins WITHOUT preceding penicillin allergy testing (skin testing or in vitro testing) Such studies are the source of warnings in the package inserts of first and second generation cephalosporins

Cross reactivity studies performed WITH confirmatory PCN allergy test performed after 1980 reveals only 2% propensity.

Clinical Literature & PCN/CPN cross allergenicity.8,9

Buonomo A et al. studied 97 patients with PHx of PCN rx and +ve skin patch test were tried with 13 beta lactams

129 reactions recorded; concluded that cross rx is as high as 10.9% for 1st generation and 1.1% for 3rd generation.

Campagna JD et a. performed MEDLINE searches of articles since 1950 till 2012 using search terms "penicillin$," "cephalosporin$," "allerg$," "hypersensitivity," and "cross-react$”

Searches revealed overall cross rx is approx. 1% with CPNs with similar side chain.

Conclusion Generally, Cephalosporins can be safely used to treat infections for

patients with penicillin allergy Past studies overestimated the prevalence of cross reactivity

MDAS a major confounder Risk assessment/patch skin test should be carried out for patients

with confirmed PCN allergy before cephalosporin therapy is chosen Please refer to the chart below

Assessment question

Which antibody is involved in mediating the life threatening allergic reaction caused by Penicillin?

IgA IgD IgE IgG

References1. Macy E, Contreras R. Health care use and serious infection prevalence associated with

penicillin "allergy" in hospitalized patients: A cohort study ;J Allergy Clin Immunol. 2014 Mar;133(3):790-6. Epub 2013 Nov 1

2. Mirakian R, Leech SC, Krishna MT, Richter AG, Huber PA, Farooque S, Khan N, Pirmohamed M, Clark AT, Nasser SM. Management of allergy to penicillins and other beta-lactams ;Clin Exp Allergy. 2015 Feb;45(2):300-27

3. Idsoe O, Guthe T, Willcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock; Bull World Health Organ. 1968;38(2):159

4. Non drowsy Antihistamine [Internet]. Wordpress: Handla Online; Accessed: 2015 Aug 30. Available from: http://www.nondrowsyantihistamine.org/amoxicillin-allergy-symptoms/

5. Daryl D. DePestel, PharmD; Michael S. Benninger, MD; Larry Danziger, PharmD et al. Cephalosporin Use in Treatment of Patients With Penicillin Allergies; J Am Pharm Assoc. 2008;48(4):530-540

6. UpToDate [Internet]. Netherlands: Wolters Kluwer. 2015 May 12 - [cited 2015 Aug 30]. Available from: http://ezproxy.usj.edu:4385/contents/penicillin-allergic-patients-use-of-cephalosporins-carbapenems-and-monobactams?source=search_result&search=penicillin+allergy&selectedTitle=1%7E150#H12

7. Lee QU. Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited ; Hong Kong Med J 2014 Oct;20(5):428-36. doi: 10.12809/hkmj144327.

8. Buonomo A, Nucera E, Pecora V et al. Cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins; J Investig Allergol Clin Immunol. 2014;24(5):331-7.

9. Campagna JD, Bond MC, Schabelman E et al. The use of cephalosporins in penicillin-allergic patients: a literature review; J Emerg Med. 2012 May;42(5):612-20. doi: 10.1016/j.jemermed.2011.05.035. Epub 2011 Jul 13.