/clinical/,/clinical/cckm-tools/,/clinical/cckm-tools/content/,/clinical/cckm-tools/content/cpg/,/clinical/cckm-tools/content/cpg/infection-and-isolation/,

/clinical/cckm-tools/content/cpg/infection-and-isolation/name-97535-en.cckm

201710284

page

100

UWHC,UWMF,

Tools,

Clinical Hub,UW Health Clinical Tool Search,UW Health Clinical Tool Search,Clinical Practice Guidelines,Infection and Isolation

Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics - Adult - Inpatient

Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics - Adult - Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Infection and Isolation


1
Treatment of Patients with Reported Allergies
to Beta-Lactam Antibiotics – Adult – Inpatient
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ...................................................................................................................... 3
SCOPE ................................................................................................................................................. 3
METHODOLOGY ................................................................................................................................. 3
DEFINITIONS ....................................................................................................................................... 4
TABLE 1. FDA-APPROVED BETA-LACTAM ANTIBIOTICS WITH SIMILAR SIDE CHAINS ............ 5
INTRODUCTION .................................................................................................................................. 5
RECOMMENDATIONS ........................................................................................................................ 7
ANTIBIOTIC ORDERING .................................................................................................................. 7
PENICILLIN SKIN TESTING ............................................................................................................ 9
GRADED CHALLENGES ................................................................................................................. 9
UW HEALTH IMPLEMENTATION ..................................................................................................... 10
FIGURE 1. BETA-LACTAM ALLERGY PRACTICE PARAMETER ALGORITHM ........................... 12
APPENDIX A. EVIDENCE GRADING SCHEME ................................................................................ 13
REFERENCES ................................................................................................................................... 14
Contact for Content: Contact for Changes:
Name: Lucas Schulz, PharmD, BCPS AQ-ID Name: Philip Trapskin, PharmD, BCPS
Phone Number: 608-890-8617 Phone Number: 608-263-1328
Email Address: lschulz2@uwhealth.org Email Address: ptrapskin@uwhealth.org
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

2

Guideline Authors:
Jeff Fish, PharmD
Joshua Vanderloo, PharmD

Coordinating Team Members:
Joshua Vanderloo, PharmD, Drug Policy Program

Review Individuals/Bodies:
Barry Fox, MD ± Division of Infectious Disease
Lucas Schulz, PharmD ± Department of Pharmacy
Margaret Jorgenson, PharmD ± Department of Pharmacy
James Gern, MD; Mark Biagtan, MD; Sameer Mathur, MD ± Division of Allergy and Immunology
Shelly VanDenbergh, RN, CNS D4/4

Committee Approvals
Nursing Practice Council April 2014
Antimicrobial Use Subcommittee August 2016
Pharmacy and Therapeutics Committee (Last Periodic Review: September 2016)

Release Date: September 2016

Next Review Date: September 2018


Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

3


Executive Summary
Guideline Overview
This guideline provides information on evaluating patient-reported beta lactam allergies to facilitate optimized antibiotic
selection to improve outcomes, to reduce risk of multiple-drug resistant pathogens, to reduce length of stay, and to reduce
cost.

Key Revisions (2016 Periodic Review)
Addition of new clinical evidence supporting extremely low rates of cross-reactivity between penicillins, cephalosporins,
and carbapenems in patients reporting an allergy to a beta lactam outside that class.

Key Practice Recommendations
1. Reported beta lactam allergies should be extensively investigated including an evaluation of beta lactam antibiotics
that the patient has received and tolerated (or not tolerated).
2. Antibiotic selection should be based on allergy evaluation and possibility of cross reactivity.
3. Penicillin skin testing and graded challenges may be considered in patients with specific characteristics for whom beta
lactam antibiotics are needed.

Companion Documents
None

Scope
Disease Condition: This clinical practice guideline is designed to lease prescribers through the evaluation, ordering,
processing, and administering of beta-lactam antibiotics in patients with reported beta-lactam allergies.

Clinical Specialty: All medical specialties

Intended Users: Physicians, Advanced Practice Providers, Nurses, and Pharmacists

Objective
The clinical practice guideline is intended to provide a standardized process for the evaluation of beta lactam antibiotic
allergies or intolerances and the subsequent selection of antibiotics with respect to the evaluation.

Target Population
Adult patients with reported beta-lactam allergies for whom the use of beta-lactam antibiotics may be desired.

Interventions and Practices Considered
The clinical interventions and practices recommended in this guideline are intended for patients with reported beta lactam
allergies receiving antibiotic therapy. Practices include evaluation of reported allergies, prescribing of beta lactam
antibiotics in patients with a reported allergy, utilization of oral and intravenous graded challenges, and penicillin skin
testing.

Major Outcomes Considered
ξ Utilization of oral and intravenous graded challenges
ξ Utilization of penicillin skin testing

Methodology
Methods Used to Collect/Select the Evidence
Electronic database searches (i.e. PUBMED) were conducted and workgroup members to collect evidence for review; for
the 2016 revision, clinical evidence dating back to January 2014 was reviewed. Additionally, hand searches were
performed within selected evidence for other relevant resources. Expert opinion, clinical experience, and regard for
patient safety/experience were also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations
All recommendations endorsed or developed by the guideline workgroup were reviewed and approved by other
stakeholders or committees.



Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

4

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations, or those adopted from external sources without an assigned evidence grade,
were evaluated by the guideline workgroup a modified Grading of Recommendations Assessment, Development and
Evaluation (GRADE) methodology.1

Rating Scheme for the Strength of the Evidence/Strength of the Recommendations:
See Appendix A for the rating scheme used within this document.

Recognition of Potential Health Care Disparities
No potential disparities identified.

Definitions
1. Gell and Coombs classification allergic drug reactions2-9
1.1. Type 1: IgE-mediated ± most common Type 1 reaction
1.1.1. Immediate reactions (onset less than one hour after drug administration): systemic manifestations of
anaphylaxis
1.1.1.1. Urticaria (hives), pruritus, bronchospasm, laryngeal edema, hypotension, and/or cardiac
arrhythmias
1.1.1.2. Life-threatening
1.1.1.3. Tested by minor determinant of penicillin skin test
1.1.1.4. Immediate reactions occurring greater than one hour after infusion, or during sustained
therapy, even in the presence of urticaria, are rare
1.1.2. Accelerated reactions (onset one to 72 hours after drug administration) ± less common Type 1
reaction
1.1.2.1. Urticaria, angioedema, laryngeal edema, wheezing
1.1.2.2. Rarely life-threatening
1.1.2.3. Determined by penicillin skin test
1.1.3. Usually associated with beta-lactam antibiotics
1.2. Type 2: Cytotoxic/antibody-mediated (IgG-,IgM-complement mediated)
1.2.1. Hemolysis, thrombocytopenia, neutropenia, or interstitial nephritis
1.2.2. Usually associated with quinidine, methyldopa, and penicillins
1.2.3. IgG and IgM antibodies do not induce allergic reactions
1.2.3.1. Only IgE binds to mast cells and basophils to produce allergic reactions
1.3. Type 3: Immune complex (IgG, IgM immune complexes)
1.3.1. Serum sickness or vasculitis
1.3.2. Fever, rash, urticaria, lymphadenopathy, and arthralgias
1.3.3. Usually associated with antisera, penicillin, sulfonamides, and phenytoin
1.4. Type 4: Cellular immune-mediated/delayed hypersensitivity reaction
1.4.1. Contact dermatitis
1.4.1.1. Example: health care workers involved in the manufacturing and dispensing of offending
agents
1.4.2. Delayed non-urticarial rashes caused by aminopenicillins and drug reaction with eosinophilia and
systemic symptoms syndrome (DRESS)
1.5. Unknown mechanism: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed
drug reaction, pulmonary infiltrates (nitrofurantoin), autoimmune disease (vasculitis, rheumatoid arthritis,
lupus), drug fever, drug-induced hypersensitivity syndrome (antiepileptics)
1.5.1. Penicillin skin testing will not detect these type of reactions
1.5.2. Desensitization or reexposure should not be performed due to the risk of reactivation of the reaction
2. Rashes
2.1. Urticaria (IgE-mediated) rashes are an intensely pruritic, circumscribed, raised, and erythematous eruption
with central pallor.
2.1.1. Usually occur within minutes to hours of receiving offending agent, but may occur up to 72 hours after
administering.10
2.2. Macular papular or morbilliform rashes (non-IgE-mediated) begin in dependent areas and generalize, often
with associated mucous membrane erythema, and are pruritic.
2.2.1. Usually occur more than 72 hours after receiving offending agent.
3. Graded Challenge: A graded challenge is cautiously administering a medication to a patient who is unlikely to be
allergic to it. It does not entail modification of the immune response (unlike desensitization).6,9
4. Desensitization: Induction of a temporary state of unresponsiveness to a drug that initially caused an IgE-mediated
hypersensitivity reaction; the tolerant state is lost 24 to 36 hours after discontinuation of the drug.11
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

5

5. Beta-lactams may share common side chains (Table 1).6,9,12,13
5.1. Cefazolin does not share a common side chain with any other beta-lactams

Table 1. FDA-approved Beta-lactam Antibiotics with Similar Side Chainsa
Agent Agents with Similar Side Chains
Amoxicillin Ampicillin Cefaclor Cefadroxilc Cefprozilc Cephalexin
Ampicillin Amoxicillin Cefaclorc Cefadroxil Cefprozil Cephalexinc
Aztreonamb Ceftazidimec Ceftolozane
Cefaclor Amoxicillin Ampicillinc Cefadroxil Cefprozil Cephalexinc
Cefadroxil Amoxicillinc Ampicillin Cefaclor Cefprozilc Cephalexin
Cefdinir Cefiximed
Cefditoren Cefepimec Cefotaximec Cefpodoximec Ceftriaxonec
Cefepime Cefditorenc Cefotaximec Cefpodoximec Ceftriaxonec Ceftaroline
Cefixime Cefdinird
Cefotaxime Cefditorenc Cefepimec Cefpodoximec Ceftriaxonec Ceftaroline
Cefoxitin Cefuroximed Penicillin G
Cefpodoxime Cefditorenc Cefepimec Cefotaximec Ceftriaxonec Ceftaroline
Cefprozil Amoxicillinc Ampicillin Cefaclor Cefadroxilc Cephalexin
Ceftaroline Cefepime Cefotaxime Cefpodoxime Ceftriaxone Ceftazidime
Ceftazidime Aztreonamc Ceftolozane
Ceftolozane Aztreonam Ceftazidime
Ceftriaxone Cefditorenc Cefepimec Cefotaximec Cefpodoximec Ceftaroline
Cefuroxime Cefoxitind
Cephalexin Amoxicillin Ampicillinc Cefaclorc Cefadroxil Cefprozil
Penicillin G Cefoxitin
aAgents not listed are either not approved for use in the United States (ceftizoxime, ceftibiprole) or do not share common side chains (e.g.
piperacillin, ticarcillin, nafcillin, dicloxacillin)
bAztreonam cross-reacts with ceftazidime and ceftolozane, with which it shares an identical side-chain
c
Identical R1 side chain
d
Identical R2 side chain

Introduction
The reported penicillin allergy rate for inpatients and outpatients is 10%.2-4,14,15 Of these patients, 80% to 90% will not
have positive penicillin skin testing, which test for IgE-mediated reactions only.5,6 The patient may state they are allergic
to a medication, but the reaction could be an adverse drug reaction (e.g. GI intolerance) or attributed to the disease being
treated (e.g. rash caused by viral infection while on amoxicillin).5 The positive penicillin skin test also decreases 10%
annually after a penicillin allergic reaction and 78% of penicillin allergic patients have negative skin tests after ten years of
avoidance.16

Since beta-lactam antibiotics share a common beta ring, there is a risk of cross-reactivity.2-10,12,14-31 Indeed,
patients with a history of penicillin allergy are three times more likely to have an adverse reaction to any additional
antibiotics (including cephalosporins and sulfa).17,32 An explanation for not having higher cross-reactivity is that
the alpha rings between the different classes vary. Penicillins have a thiazolidine ring, cephalosporins have a
dihydrothiazine ring, carbapenems have a modified thiazolidine ring, and monobactams are missing the alpha
ring.3,4,8,15 Common side chains also contribute to cross-reactivity.4,6,9,10,12,20 The degree of cross-reactivity
appears to be greater among the same class of antibiotics than between classes.9,20 The greatest risk of cross-
reactivity is among penicillins.9,12,20,21 The penicillins and monobactams have an R1 side chain while the
cephalosporins and carbapenems have both an R1 and R2 side chain.3,5,19,20 For the majority of cephalosporins,
the R1 side chain is more clinically relevant for cross-reactivity than the R2 side chain as the R2 side chain acts
as a leaving group during carrier protein conjugation and therefore it cannot contribute to the epitope for IgE
binding.25

Prior to 1980, the cross-reactivity between penicillins and cephalosporins was reported to be 10% to 20%. This
was probably due to the fact that the cephalosporins used at the time, cephalothin and cephaloridine, share a
similar side chain with benzyl penicillin (Table 1).6 Also during this time, some cephalosporins were contaminated
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

6

with trace amounts of penicillin.6,26 Since 1980, reaction rates in penicillin-history positive and skin-test positive
patients who received cephalosporins decreased to between 1% and 4%.3,6,12,21 A review of cross-reactivity and
postmarketing studies of second- and third-generation cephalosporins revealed no increase in allergic reactions in
those patients with a history of penicillin allergy.17 If a patient is penicillin-history positive, but skin-test negative
they are at no increased risk of cephalosporin cross-reactivity.15,21 If patients with a history of penicillin allergies
are not skin tested, the risk of a reaction when given a second- or third-generation cephalosporin is less than 1%,
but some of these reactions may be anaphylaxis.9 Generally, cross reactivity between penicillins and
cephalosporins is higher among penicillins and first generation cephalosporins.33 A meta-analysis found that
penicillin-allergic patients have increased cross reactivity to first-generation cephalosporins (excluding cefazolin)
but no increased cross reactivity to second- or third-generation cephalosporins.34 However, as cefazolin has a
unique side chain, cross reactivity potential with other beta-lactams is low.11

Cephalosporins cause immune-mediated reactions in 1% to 3% of patients without a history of a penicillin
allergy.4 Cross reactivity of cephalosporins is mediated by cephalosporin side chains and not the beta-lactam
ring.35

The estimated cross-reactivity between carbapenems and other beta-lactams is variable. None of the currently
available carbapenems have a similar side chain to any penicillin or cephalosporin antibiotic. Retrospective
studies show a cross-reactivity rate of about 9% to 11%.23,24,36 These retrospective studies are limited as penicillin
allergies were not verified with skin testing, allergic reactions were not limited to IgE-mediated reactions, and
clinical data was taken from chart documentation.23,25,30 Additionally, a systematic review reveals a very low
incidence of proven penicillin IgE-mediated cross reactivity with cephalosporins and carbapenems at 0.5% (1/221
patients).37

Prospective studies demonstrate a cross-reactivity rate of 1% to 47%.38-41 The study showing a 47% cross-
reactivity rate was a positive skin test to imipenem or its metabolites performed in nineteen penicillin skin-test
positive patients; none of the patients received systemic imipenem.38 Three other prospective studies showed
cross-reactivity rates of 0.9% to 1%. These studies included penicillin skin-test positive patients who received a
carbapenem skin test, but not any carbapenem metabolites. Patients who were carbapenem skin test negative
then received a systemic carbapenem via a graded challenge. None of the patients had an allergic reaction to the
systemic carbapenem.39-41

Newer prospective clinical data demonstrate that in patients with a positive penicillin skin test there was no cross
reactivity to aztreonam or carbapenem challenges.42 Additionally, a large retrospective review found that patients
with a claimed penicillin allergy versus those with no claimed penicillin allergy had no increased rate of
carbapenem hypersensitivity.43

Aztreonam cross-reactivity with other beta-lactams does not exist, excepting ceftazidime, and it may be used
safely in beta-lactam allergic patients.8-10,15,30 Despite side-chain homology between aztreonam and ceftazidime,
aztreonam is generally tolerated in patients with beta-lactam sensitivity and cross sensitivity with ceftazidime is
rare.11,35


Penicillin is the only drug class with a valid skin test. Degradation products of other antibiotics are not known or
not commercially available. Under physiologic conditions, penicillin degrades to reactive intermediates that act as
haptens. These haptens bind to self-proteins and elicit an immune response. Approximately 95% of penicillin
degrades to the penicilloyl moiety which is the major determinant. The rest degrades to penicilloate and
penicillanyl moieties which are the minor determinants.9,10,28,44

A graded challenge is used when there is an indication for the antibiotic and based on the patiHQW¶V�UHDFWLRQ�
history, there is a low pretest probability of an immediate drug allergy (e.g. reaction happened in the distant past,
delayed onset cutaneous reaction, vague allergy history without IgE-mediated symptoms).9 A graded challenge
does not desensitize the patient to the antibiotic, but verifies that a patient will not experience an immediate
adverse reaction to the antibiotic.9 A graded challenge involves progressively increasing the dose of the antibiotic
until a full dose is reached. Graded challenges involve fewer doses and are of shorter duration than
desensitization protocols.9 Smaller doses are used so if an allergic reaction is provoked, it should be minor and
easily treated.9,44 If an allergic reaction develops during the graded challenge, the antibiotic should only be
administered via desensitization.9 Graded challenges may be performed in an outpatient setting without
intravenous access as long as severe allergic reactions can be treated.9 Patients who tolerate the graded
challenge are considered not to be allergic to the antibiotic and the SDWLHQW¶V�DOOHUJLHV�should be updated to reflect
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

7

this. These patients are not at an increased risk for future reactions compared with the general population.9
Graded challenges should not be performed in patients who have a history consistent with a severe non-IgE-
mediated reaction (e.g. hemolysis, Stevens-Johnson syndrome, toxic epidermal necrolysis).2,9

Switching to another class of antibiotics due to a reported patient allergy may adversely affect patient care.5,18,19
Alternative agents may be less effective, cause more adverse effects (e.g. C. difficile infection), treat too broadly
(contributing to increased resistance), and be more expensive.45,46 Patients with a OLVWHG�SHQLFLOOLQ�³DOOHUJ\´�RQ�
admission to a hospital have increased length of stay, increased occurrence of C. difficile infection, and increased
incidence of MRSA and VRE.47 The use of a clinical guideline increases utilization of beta-lactam antibiotics in
patients with reported penicillin or cephalosporin allergy.48

Recommendations

Antibiotic Ordering (refer to Figure 2)
1. When a beta-lactam antibiotic is indicated, it should be determined if the patient has any medication allergies. (UW
Health Strong Recommendation, High Quality of Evidence)
2. The beta-lactam antibiotic may be ordered, processed, and administered if the patient does not have an allergy to
beta-lactam antibiotics. (UW Health Strong Recommendation, Moderate Quality of Evidence)
3. In the case of a reported allergy:
3.1. A health care professional should investigate and determine the type and severity of the reaction.9 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
3.2. Additional information to investigate a medication allergy includes:9,15
ξ 3DWLHQW¶V�DJH�DW�WKH�WLPH�RI�WKH�UHDFWLRQ as concomitant viral rash at time of beta-lactam administration
is more common in childhood
ξ 3DWLHQW¶V�UHFDOO�RI�WKH�UHDFWLRQ�RU�ZKR�LQIRUPHG�WKHP�RI�LW
ξ Time of onset of the reaction after beginning the penicillin (e.g. after one dose or several days of
repeated dosing)
o Nearly all Type I (IgE-mediated) reactions occur within 72 hours of drug administration.10,49
ξ Signs/symptoms of the reaction
o Was an antidote or treatment given?
o Did it require a visit to emergency room?
o Was there a loss of consciousness?
ξ Route of administration (oral or IV)
ξ Indication for medication
ξ Concurrent medications
ξ Did the reaction abate after the medication was discontinued?
ξ Had the patient taken other medications in the same or related class before or after the reaction?
o If yes, was there any sort of reaction?
3.3. Documentation of a reported allergy or intolerance should be as specific as to which drug led to the reported
reaction (e.g. amoxicilliQ��FHSKDOH[LQ��FHID]ROLQ��HWF���DV�LW�FDQ�EH�GHWHUPLQHG�DQG�DYRLG�HQWHULQJ�³SHQLFLOOLQ´�DV�D�
class reaction. (UW Health Strong Recommendation, Very Low Quality of Evidence)
3.4. A beta-lactam antibiotic may be utilized if the patient has received that class of beta-lactam in the past without a
reaction.9 (UW Health Strong Recommendation, Moderate Quality of Evidence)
3.4.1. Physicians and/or pharmacists should review the medical record and potentially FDOO�WKH�SDWLHQW¶V�KRPH�
pharmacy to investigate previous antibiotic use.
3.5. If the patient has NOT received an antibiotic in the same class in the past, the type of reaction should be
ascertained. (UW Health Strong Recommendation, Very Low Quality of Evidence)
3.5.1. If it is determined that the reaction was actually a side effect (e.g. GI intolerance including nausea or
diarrhea), the original beta-lactam antibiotic may be ordered, processed, and administered. (UW Health
Weak/conditional Recommendation, Very Low Quality of Evidence)
3.5.2. If the type of reaction is unable to be ascertained from the patient, family or medical record:
3.5.2.1. Prescribe beta-lactam antibiotic from different class based on class of beta-lactam allergy.9
(UW Health Weak/conditional Recommendation, Very Low Quality of Evidence)
3.5.2.1.1. The prescribed beta-lactam antibiotic should also have a different side chain (see
Table 1) than antibiotic the patient is allergic to due to increased
reactivity.3,9,12,19,20 (UW Health Weak/conditional Recommendation, Very Low
Quality of Evidence)
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

8

3.5.2.1.1.1. A graded challenge (see Graded Challenges) may be used if the
reaction happened recently.9 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
3.5.2.1.2. Penicillin-allergic patients may be prescribed a cephalosporin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.2.1.3. Cephalosporin-allergic patients may be prescribed a penicillin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.2.1.4. Carbapenem-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.2.1.5. Aztreonam-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line) or a carbapenem (second line).9 (UW Health
Strong Recommendation, Very Low Quality of Evidence)
3.5.2.2. If use of beta-lactam from same class is desired, consult Allergy for recommendations. (UW
Health Strong Recommendation, Very Low Quality of Evidence)
3.5.3. If the reaction is determined to have been a non-severe, non-IgE mediated reaction that
occurred AFTER 72 hours:
3.5.3.1. Prescribe beta-lactam antibiotic from different class based on class of beta-lactam allergy.9
(UW Health Weak/conditional Recommendation, Very Low Quality of Evidence )
3.5.3.1.1. Prescribed beta-lactam antibiotic should also have a different side chain (see
Table 1) than antibiotic the patient is allergic to due to increased
reactivity.3,9,12,19,20 (UW Health Weak/conditional Recommendation, Very Low
Quality of Evidence)
3.5.3.1.1.1. A graded challenge (see Graded Challenges) may be used if the
reaction happened recently.9 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
3.5.3.1.2. Penicillin-allergic patients may be prescribed a cephalosporin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.3.1.3. Cephalosporin-allergic patients may be prescribed a penicillin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.3.1.4. Carbapenem-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.3.1.5. Aztreonam-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line) or a carbapenem (second line).9 (UW Health
Strong Recommendation, Very Low Quality of Evidence)
3.5.3.2. If use of beta-lactam from same class is desired, consult Allergy for recommendations. (UW
Health Weak/conditional Recommendation, Very Low Quality of Evidence)
3.5.4. If the reaction is determined to have been a possible IgE-mediated reaction occurring WITHIN 72
hours (i.e. rash + hives) :
3.5.4.1. Prescribe beta-lactam antibiotic from different class via graded challenge (see Graded
Challenges) based on class of beta-lactam allergy.9 (UW Health Strong Recommendation,
Very Low Quality of Evidence)
3.5.4.1.1. Prescribed beta-lactam antibiotic should also have a different side chain (see
Table 1) than antibiotic the patient is allergic to due to increased
reactivity.3,9,12,19,20 (UW Health Weak/conditional Recommendation, Very Low
Quality of Evidence)
3.5.4.1.2. Penicillin-allergic patients may be prescribed a cephalosporin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.4.1.3. Cephalosporin-allergic patients may be prescribed a penicillin (first line) or a
carbapenem (second line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3.5.4.1.4. Carbapenem-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line).9 (UW Health Strong Recommendation, Very Low
Quality of Evidence)
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

9

3.5.4.1.5. Aztreonam-allergic patients may be prescribed either a penicillin or a
cephalosporin (either first line) or a carbapenem (second line).9 (UW Health
Strong Recommendation, Very Low Quality of Evidence)
3.5.4.2. If use of beta-lactam from same class is desired, consult Allergy for recommendations. (UW
Health Weak/conditional Recommendation, Very Low Quality of Evidence)
3.5.5. If the reaction is determined to have been an IgE-mediated reaction occurring WITHIN 24 hours
(i.e. immediate urticarial, angioedema, anaphylaxis):
3.5.5.1. First Line: use non-beta lactam antibiotic.9 (UW Health Strong Recommendation, High Quality
of Evidence)
3.5.5.1.1. If no alternatives are available, aztreonam may be considered for Gram-negative
infections.9 (UW Health Strong Recommendation, Moderate Quality of Evidence)
3.5.5.1.2. Do not use aztreonam in ceftazidime-allergic patients.9 (UW Health Strong
Recommendation, Moderate Quality of Evidence)
3.5.5.2. Second Line (and therapy requires beta-lactam)
3.5.5.2.1. If use of penicillin antibiotic planned, consult Allergy for penicillin skin testing
(see Penicillin Skin Testing) and/or desensitization.9 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
3.5.5.2.2. If use of cephalosporin or carbapenem antibiotic planned, consult Allergy for
desensitization.9 (UW Health Strong Recommendation, Very Low Quality of
Evidence)
3.5.6. If the reaction is determined to have been a severe, non-IgE mediated reaction (e.g. hemolysis,
Stevens Johnson Syndrome, toxic epidermal necrolysis):
3.5.6.1. Use non-beta-lactam antibiotic.9 (UW Health Strong Recommendation, High Quality of
Evidence)
3.5.6.1.1. If no alternatives are available, aztreonam may be considered for Gram-negative
infections.9 (UW Health Strong Recommendation, Moderate Quality of Evidence)
3.5.6.1.2. Do not use aztreonam in ceftazidime-allergic patients.9 (UW Health Strong
Recommendation, Moderate Quality of Evidence)

Penicillin Skin Testing
1. Penicillin skin testing is an option for patients with a possible IgE-mediated reactions to penicillin.9
1.1. There is no commercially available skin test for cephalosporins, carbapenems, or monobactams.9
1.2. For patients with multiple non-beta-lactam allergies, and an unknown or vague history of penicillin allergy,
penicillin skin testing by the Allergy department should be encouraged. (UW Health Weak/conditional
Recommendation, Very Low Quality of Evidence)
2. The risk of having an adverse reaction to a penicillin skin test is less than 1% and the reaction is usually only
urticaria.9
3. Patients with a history of severe, non-IgE mediated reactions should not be skin tested.9 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
4. Perform penicillin skin testing with both major and minor determinants when possible.9 (UW Health Strong
Recommendation, Moderate Quality of Evidence)
4.1. An oral challenge should be included, when feasible, to increase sensitivity.49 (UW Health Weak/conditional
Recommendation, Very Low Quality of Evidence)
5. Prior to conducting skin testing, patients should be instructed to hold antihistamines, beta-blockers, and tricyclic
antidepressants. (UW Health Strong Recommendation, Very Low Quality of Evidence)
6. Patients with negative penicillin skin test results are at a small risk of IgE-mediated reaction and can receive penicillin
via a graded challenge (see Graded Challenges) if the risk of reaction is felt to be low.9 (UW Health Strong
Recommendation, Moderate Quality of Evidence)
7. Patients with negative penicillin skin test results can safely receive cephalosporin and carbapenem antibiotics. 9 (UW
Health Strong Recommendation, Moderate Quality of Evidence)
8. If the penicillin skin test is positive, the patient should not receive penicillins or a beta-lactam antibiotic with a similar
side chain.9 (UW Health Strong Recommendation, Moderate Quality of Evidence )
8.1. These patients should be desensitized when an alternative class of antibiotics may not be substituted (e.g.
treatment of syphilis during pregnancy).2-5,9,12,14,16 (UW Health Strong Recommendation, Very Low Quality of
Evidence )

Graded Challenges
1. Performed in patients who have a low pretest probability of an immediate allergic reaction.11 (UW Health
Weak/conditional Recommendation, Moderate Quality of Evidence)
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

10

2. Prescribers should be contacted prior to initiating graded challenge. (UW Health Strong Recommendation, Very Low
Quality of Evidence)
3. Patients do not need to increase their level of care during the graded challenge.9 (UW Health Weak/conditional
Recommendation, Very Low Quality of Evidence)
3.1. Patients must be able to report symptoms and use their call light. .
3.2. Providers should be contacted if the patient develops any sign of an allergic reaction (examples: hives, clearing
of throat, coughing, dyspnea, abdominal pain, uneasiness) for up to 60 minutes after the full dose is
administered. (UW Health Strong Recommendation, Very Low Quality of Evidence)
3.2.1. Medications used to treat allergic reactions will be ordered prior to the graded challenge and are
available in the unit crash cart or Acudose cabinet.
4. Oral graded challenge9 (UW Health Weak/conditional Recommendation, Very Low Quality of Evidence)
4.1. Used if oral therapy is desired
4.2. Procedure: give 10% of dose, then in 60 minutes give full dose.
5. Intravenous graded challenge9 (UW Health Weak/conditional Recommendation, Very Low Quality of Evidence)
5.1. Used if intravenous therapy is desired
5.2. Procedure: give 1% of dose, then in 30 to 60 minutes give 10% of dose, then in 30 to 60 minutes give full dose.
6. If the patient has no signs of an allergic reaction, they should be monitored for adverse reactions for up to 60 minutes
after the full dose has been administered.9,31 (UW Health Weak/conditional Recommendation, Very Low Quality of
Evidence)
6.1. Further monitoring is patient-specific and at the discretion of the provider, as delayed non-immune mediated
reactions can occur days after administration.9
7. If the patient has signs and/or symptoms of an allergic reaction, do not give additional doses before discussing with
provider next steps in the graded challenge and further monitoring.
8. If a severe reaction develops during the graded challenge and it is determined the patient needs the antibiotic, Allergy
should be consulted for desensitization.9 (UW Health Weak/conditional Recommendation, Very Low Quality of
Evidence)
8.1. Graded challenges and desensitization should not be performed if there is a history of a severe non-IgE
mediated reaction (e.g. hemolysis, Stevens Johnson Syndrome, toxic epidermal necrolysis), due to the risk of
reactivation.9 (UW Health Weak/conditional Recommendation, Very Low Quality of Evidence)
9. The results of the graded challenge should be documented in the SDWLHQW¶V allergy record. (UW Health Strong
Recommendation, Very Low Quality of Evidence)
9.1. 7KH�DOOHUJ\�VKRXOG�QRW�EH�GHOHWHG�IURP�WKH�SDWLHQW¶V�PHGLFDO�UHFRUG�IRU�HDVH�LQ�WUDFNLQJ�WKH�UHVXOWV�RI�WKH�JUDGHG�
challenge. (UW Health Weak/conditional Recommendation, Very Low Quality of Evidence)
9.2. Updates to the allergy records should include the specific drug used in the graded challenge (e.g. amoxicillin,
cephalexin, cefazolin). (UW Health Strong Recommendation, Very Low Quality of Evidence)
10. Patients should have beta blockers discontinued prior to the graded challenge, if possible, to prevent resistance to
treatment if a severe adverse reaction occurs.5,14,16 (UW Health Weak/conditional Recommendation, Very Low Quality
of Evidence)
11. Do not pretreat patients with glucocorticoids or antihistamines as these can mask the signs of allergic reactions.9,50
(UW Health Weak/conditional Recommendation, Moderate Quality of Evidence)


UW Health Implementation
Potential Benefits and Harms of Implementation
ξ Standardizing the treatment of patients with beta-lactam allergies lessens complications associated with inadequate
or inappropriate therapy.
ξ Standardizing the ordering of antibiotics for beta-lactam allergic patients, will lead to more consistent patient care.
ξ $FFXUDWHO\�GHWHUPLQLQJ�SDWLHQW¶V�DQWLELRWLF�DOOHUJLHV�WKURXJK�LQWHUYLHZV��SHQLFLOOLQ�VNLQ�WHVWV��DQG�JUDGHG�FKDOOHQJHV��
make future care more efficient.
ξ Avoiding switching to another antibiotic unnecessarily decreases adverse events, increases efficiency, lowers
antimicrobial resistance, and saves money.
ξ Potential of allergic reactions when performing penicillin skin tests, graded challenges, or switching antibiotics within
the same class.

Pertinent UW Health Policies and Procedures
ξ UWHC Clinical Policy 7.60 Medication Reconciliation

Patient Resources
None
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

11

Guideline Metrics
ξ Utilization of graded challenge order sets

Implementation Plan/Clinical Tools
1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the guideline recommendations will
be reviewed for consistency and modified as appropriate.

Order Set
IP ± Beta-lactam Graded Challenge ± Adult ± Supplemental [5987]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This
JXLGHOLQH�RXWOLQHV�WKH�SUHIHUUHG�DSSURDFK�IRU�PRVW�SDWLHQWV��,W�LV�QRW�LQWHQGHG�WR�UHSODFH�D�FOLQLFLDQ¶V�MXGJPHQW�RU�WR
establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a
guideline and that a guideline will rarely establish the only appropriate approach to a problem.

Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

12

Figure 1. Beta-Lactam Allergy Practice Parameter Algorithm
Indication for beta lactam antibiotic
and history of beta lactam allergy
or adverse reaction?
No
Has the patient received
antibiotic in the same class in
the past without reaction?
Yes
Type of reaction?
Adverse reaction or
side effect
(examples: GI
intolerance or
headache)
Order, process, and/or
administer beta-lactam antibiotic
No
Unable to ascertain
type of reaction from
patient, family, or
medical record
Non-severe, Non-IgE
mediated reaction
occurring AFTER 72
hours (delayed
macular papular
rash)
Possible IgE
mediated reaction
occurring WITHIN 72
hours (rash ± hives)
IgE mediated
reaction
occurring WITHIN 24
hours (immediate
urticaria,
angioedema,
anaphylaxis)
Severe, Non-IgE
mediated reaction
(hemolysis, Stevens-
Johnson Syndrome,
toxic epidermal
nerolysis, etc.)
Use non-beta lactam antibiotic
C,D
First Line: Use non-beta lactam antibiotic
C,D
Second Line and beta lactam needed:
ξ If penicillin antibiotic planned: consult Allergy for
penicillin skin testing and/or desensitization
ξ If cephalosporin or carbapenem planned: consult
Allergy for desensitization
Penicillin Allergy
- First Line: Cephalosporin
- Second Line: Carbapenem
Cephalosporin Allergy
- First Line: Penicillin
- Second Line: Carbapenem
Carbapenem Allergy
- First Line: Penicillin or Cephalosporin
Aztreonam Allergy
- First Line: Penicillin or Cephalosporin
- Second Line: Carbapenem
** Use beta lactam with different side chain (See Table 1)
** If use of beta lactam from same class is desired, consult Allergy
Prescribe beta
lactam antibiotic
from different class
based on class of
beta lactam allergy
A
Prescribe beta
lactam antibiotic
from different class
via GRADED
CHALLENGE
B
based
on class of beta
lactam allergy
Yes
Footnotes
A
May give via graded challenge if reaction history was recent
B
Graded challenge: use oral challenge if oral therapy is desired; use IV challenge if IV therapy is desired
ξ Graded challenges are intended for patients with low probability of an immediate allergic reaction.
Patients must be able to report symptoms and use a call light
ξ Patients do not need to increase their level of care during a graded challenge
ξ Use Acudose cabinet and Crash Cart stock, if needed, for anaphylaxis medications (epinephrine,
diphenhydramine, albuterol nebs) during graded challenges
ξ Patients should be monitored for immediate hypersensitivity reactions (hives, clearing of throat,
coughing, dyspnea, abdominal pain, uneasiness) for up to 60 minutes after the full dose is
administered
C
Do not use aztreonam in ceftazidime-allergic or ceftolozane-allergic patients
D
If no alternatives are available, aztreonam may be considered for Gram-negative infections

From: Treatment of Patients with Reported Allergies to
Beta-Lactam Antibiotics; Revision Date 9/2016; Guideline
Contact Philip Trapskin, PharmD, 608-263-1328,
PTrapskin@uwhealth.org
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

13

Appendix A. Evidence Grading Scheme
Figure 1. GRADE Methodology adapted by UW Health1







GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it is also
possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances are
unlikely to affect the decision.
Weak/conditional Recommendation may be conditional upon patient values and preferences, the
resources available, or the setting in which the intervention will be implemented.
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

14

References
1. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical practice guideline methodology summit report: a report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll
Cardiol. Jan 15 2013;61(2):213-265.
2. Solensky R. Drug desensitization. Immunol Allergy Clin North Am. Aug 2004;24(3):425-443, vi.
3. Park MA, Li JT. Diagnosis and management of penicillin allergy. Mayo Clin Proc. Mar 2005;80(3):405-410.
4. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing
cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. Apr 2005;115(4):1048-1057.
5. Salkind AR, Cuddy PG, Foxworth JW. The rational clinical examination. Is this patient allergic to penicillin? An evidence-based
analysis of the likelihood of penicillin allergy. JAMA. May 16 2001;285(19):2498-2505.
6. Executive summary of disease management of drug hypersensitivity: a practice parameter. Joint Task Force on Practice
Parameters, the American Academy of Allergy, Asthma and Immunology, the American Academy of Allergy, Asthma and
Immunology, and the Joint Council of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. Dec 1999;83(6 Pt
3):665-700.
7. Gallelli J, Calis K. Penicillin allergy and cephalosporin cross-reactivity. Hosp Pharm 1992;27:540-541
8. Robinson JL, Hameed T, Carr S. Practical aspects of choosing an antibiotic for patients with a reported allergy to an antibiotic.
Clin Infect Dis. Jul 1 2002;35(1):26-31.
9. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. Oct 2010;105(4):259-273.
10. Lagace-Wiens P, Rubinstein E. Adverse reactions to beta-lactam antimicrobials. Expert Opin Drug Saf. May 2012;11(3):381-
399.
11. Mirakian R, Leech SC, Krishna MT, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. Feb
2015;45(2):300-327.
12. DePestel DD, Benninger MS, Danziger L, et al. Cephalosporin use in treatment of patients with penicillin allergies. J Am
Pharm Assoc (2003). Jul-Aug 2008;48(4):530-540.
13. Skalweit MJ. Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections.
Drug Des Devel Ther. 2015;9:2919-2925.
14. Solensky R, Earl HS, Gruchalla RS. Clinical approach to penicillin-allergic patients: a survey. Ann Allergy Asthma Immunol.
Mar 2000;84(3):329-333.
15. Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. Feb 9 2006;354(6):601-609.
16. Grabenstein J. PredictinJ�DOOHUJ\�WR�SHQLFLOOLQ��D�GHFLVLRQ�PDNHU¶V�GLOHPPD��Hosp Pharm. 1993;28:1020-1025.
17. Puchner TC, Jr., Zacharisen MC. A survey of antibiotic prescribing and knowledge of penicillin allergy. Ann Allergy Asthma
Immunol. Jan 2002;88(1):24-29.
18. MacLaughlin EJ, Saseen JJ, Malone DC. Costs of beta-lactam allergies: selection and costs of antibiotics for patients with a
reported beta-lactam allergy. Arch Fam Med. Aug 2000;9(8):722-726.
19. Sade K, Holtzer I, Levo Y, Kivity S. The economic burden of antibiotic treatment of penicillin-allergic patients in internal
medicine wards of a general tertiary care hospital. Clin Exp Allergy. Apr 2003;33(4):501-506.
20. Pichichero ME. Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagn Microbiol Infect Dis. Mar
2007;57(3 Suppl):13S-18S.
21. Kelkar PS, Li JT. Cephalosporin allergy. N Engl J Med. Sep 13 2001;345(11):804-809.
22. Prescott WA, Jr., DePestel DD, Ellis JJ, Regal RE. Incidence of carbapenem-associated allergic-type reactions among
patients with versus patients without a reported penicillin allergy. Clin Infect Dis. Apr 15 2004;38(8):1102-1107.
23. Prescott WA, Jr., Kusmierski KA. Clinical importance of carbapenem hypersensitivity in patients with self-reported and
documented penicillin allergy. Pharmacotherapy. Jan 2007;27(1):137-142.
24. Sodhi M, Axtell SS, Callahan J, Shekar R. Is it safe to use carbapenems in patients with a history of allergy to penicillin? J
Antimicrob Chemother. Dec 2004;54(6):1155-1157.
25. Leviton I. Separating fact from fiction: the data behind allergies and side effects caused by penicillins, cephalosporins, and
carbapenem antibiotics. Curr Pharm Des. 2003;9(12):983-988.
26. Perez-Inestrosa E, Suau R, Montanez MI, et al. Cephalosporin chemical reactivity and its immunological implications. Curr
Opin Allergy Clin Immunol. Aug 2005;5(4):323-330.
27. Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: a literature
review. J Emerg Med. May 2012;42(5):612-620.
28. Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. Feb
2009;64(2):183-193.
29. Sastre J, Quijano LD, Novalbos A, et al. Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to
amoxicillin and with good tolerance of penicillin. Allergy. Jun 1996;51(6):383-386.
30. Frumin J, Gallagher JC. Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: what are the
chances? Ann Pharmacother. Feb 2009;43(2):304-315.
31. Demoly P, Romano A, Botelho C, et al. Determining the negative predictive value of provocation tests with beta-lactams.
Allergy. Mar 2010;65(3):327-332.
32. Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide
nonantibiotics. N Engl J Med. Oct 23 2003;349(17):1628-1635.
33. 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):331-337.
34. Pichichero ME, Casey JR. Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis. Otolaryngol
Head Neck Surg. Mar 2007;136(3):340-347.
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org

15

35. Romano A, Gaeta F, Valluzzi RL, Caruso C, Rumi G, Bousquet PJ. IgE-mediated hypersensitivity to cephalosporins: cross-
reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol. Nov 2010;126(5):994-999.
36. McConnell SA, Penzak SR, Warmack TS, Anaissie EJ, Gubbins PO. Incidence of imipenem hypersensitivity reactions in
febrile neutropenic bone marrow transplant patients with a history of penicillin allergy. Clin Infect Dis. Dec 2000;31(6):1512-
1514.
37. Kula B, Djordjevic G, Robinson JL. A systematic review: can one prescribe carbapenems to patients with IgE-mediated allergy
to penicillins or cephalosporins? Clin Infect Dis. Oct 15 2014;59(8):1113-1122.
38. Saxon A, Adelman DC, Patel A, Hajdu R, Calandra GB. Imipenem cross-reactivity with penicillin in humans. J Allergy Clin
Immunol. Aug 1988;82(2):213-217.
39. Atanaskovic-Markovic M, Gaeta F, Medjo B, Viola M, Nestorovic B, Romano A. Tolerability of meropenem in children with IgE-
mediated hypersensitivity to penicillins. Allergy. Feb 2008;63(2):237-240.
40. Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Pettinato R, Gueant JL. Imipenem in patients with immediate
hypersensitivity to penicillins. N Engl J Med. Jun 29 2006;354(26):2835-2837.
41. Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Valluzzi R, Gueant JL. Brief communication: tolerability of meropenem in
patients with IgE-mediated hypersensitivity to penicillins. Ann Intern Med. Feb 20 2007;146(4):266-269.
42. Gaeta F, Valluzzi RL, Alonzi C, Maggioletti M, Caruso C, Romano A. Tolerability of aztreonam and carbapenems in patients
with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. Apr 2015;135(4):972-976.
43. Wall GC, Nayima VA, Neumeister KM. Assessment of hypersensitivity reactions in patients receiving carbapenem antibiotics
who report a history of penicillin allergy. J Chemother. Jun 2014;26(3):150-153.
44. Legendre DP, Muzny CA, Marshall GD, Swiatlo E. Antibiotic hypersensitivity reactions and approaches to desensitization. Clin
Infect Dis. Apr 2014;58(8):1140-1148.
45. Li M, Krishna MT, Razaq S, Pillay D. A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic
label of 'penicillin allergy' in a UK teaching hospital. J Clin Pathol. Dec 2014;67(12):1088-1092.
46. Picard M, Begin P, Bouchard H, et al. Treatment of patients with a history of penicillin allergy in a large tertiary-care academic
hospital. J Allergy Clin Immunol Pract. May-Jun 2013;1(3):252-257.
47. 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. Mar 2014;133(3):790-796.
48. Blumenthal KG, Shenoy ES, Varughese CA, Hurwitz S, Hooper DC, Banerji A. Impact of a clinical guideline for prescribing
antibiotics to inpatients reporting penicillin or cephalosporin allergy. Ann Allergy Asthma Immunol. Oct 2015;115(4):294-300
e292.
49. Rive CM, Bourke J, Phillips EJ. Testing for drug hypersensitivity syndromes. Clin Biochem Rev. Feb 2013;34(1):15-38.
50. Samant SA, Campbell RL, Li JT. Anaphylaxis: diagnostic criteria and epidemiology. Allergy Asthma Proc. Mar-Apr
2013;34(2):115-119.


Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org