IgE is involved in mediating the life threatening allergic reactions caused by penicillin. Penicillin allergy is commonly reported and affects 5-10% of patients. Immediate IgE-mediated reactions are responsible for more severe manifestations. While penicillin allergy was thought to affect 10% based on early studies, more recent studies using skin testing and in vitro testing have found the true incidence and rate of cross-reactivity between penicillins and cephalosporins to be lower, around 1-2%. Risk assessment including skin testing should be performed before using cephalosporins in patients with a history of penicillin allergy.

1. Breaking the myth: Cephalosporin use in
patients with Penicillin allergy
Sheikh M. Zakaria
Pharm.D Candidate, Class of 2017
University of Saint Joseph School of Pharmacy

2. 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.

3. 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.

4. Erythema from Type I Hypersensitivity
Rx4

5. 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.

6. Penicillin & Cephalosporins: Finding the
cross allerginicity moieties6
 R group side chains shared by both classes exhibit cross allergenicity

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

8. Algorithm to treat PCNA with CPN6

9. 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.

10. 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.

11. 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

12. Assessment question
 Which antibody is involved in mediating the life threatening allergic reaction
caused by Penicillin?
 IgA
 IgD
 IgE
 IgG

13. References
1. 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.