Background: Most children diagnosed with β-lactam allergy based only on history are not truly allergic, and mislabeling leads to use of less effective and more costly alternative broader-spectrum antibiotics, significantly increasing drug resistance. Objective: To determine the frequency and risk factors of confirmed allergy in patients with β-lactam allergy reported by parents or their doctors and evaluate cross-reactivity between β-lactams in children with confirmed allergy. Method: Sixty-seven children with suspected β-lactam allergy were evaluated via history, sIgE measurements, skin tests, and drug provocation tests over a period of 5 years. Results: β-Lactam allergy was confirmed in 10 (14.9%) patients. Six patients had a positive intradermal test result to one or more of the penicillin skin test materials or ceftriaxone, 4 patients with negative skin test results had positive test results with suspected drugs. Age, gender, time interval between evaluation and the initial reaction, personal history of atopy, parental history of drug allergy, reaction type, and multiple drug allergy history were not significantly different between allergic and tolerant patients. For culprit drugs, there was a significant different between the 2 groups; the rate of confirmed diagnosis was significantly higher for cephalosporins such as ceftriaxone, cefuroxime, and cefprozil (p = 0.03). Three patients with allergy to penicillin tolerated cefuroxime; in 4 patients with selective allergy to ceftriaxone tolerated cephalosporins with a dissimilar side chain (cefadroxil, cefuroxime, cefaclor, and cefdinir). Conclusion: Our study indicates that most patients with a suspected β-lactam allergy tolerated this drug. An appropriate diagnostic allergy workup may prevent the use of less effective and more expensive alternatives.

1.
Cars
O
,
Mölstad
S
,
Melander
A
.
Variation in antibiotic use in the European Union
.
Lancet
.
2001
Jun
;
357
(
9271
):
1851
3
.
[PubMed]
0140-6736
2.
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
.
[PubMed]
0091-6749
3.
Solensky
R
,
Earl
HS
,
Gruchalla
RS
.
Clinical approach to penicillin-allergic patients: a survey
.
Ann Allergy Asthma Immunol
.
2000
Mar
;
84
(
3
):
329
33
.
[PubMed]
1081-1206
4.
Goossens
H
,
Ferech
M
,
Vander Stichele
R
,
Elseviers
M
;
ESAC Project Group
.
Outpatient antibiotic use in Europe and association with resistance: a cross-national database study
.
Lancet
.
2005
Feb
;
365
(
9459
):
579
87
.
[PubMed]
0140-6736
5.
Atanasković-Marković
M
,
Velicković
TC
,
Gavrović-Jankulović
M
,
Vucković
O
,
Nestorović
B
.
Immediate allergic reactions to cephalosporins and penicillins and their cross-reactivity in children
.
Pediatr Allergy Immunol
.
2005
Jun
;
16
(
4
):
341
7
.
[PubMed]
0905-6157
6.
Pichichero
ME
,
Pichichero
DM
.
Diagnosis of penicillin, amoxicillin, and cephalosporin allergy: reliability of examination assessed by skin testing and oral challenge
.
J Pediatr
.
1998
Jan
;
132
(
1
):
137
43
.
[PubMed]
0022-3476
7.
Ponvert
C
,
Le Clainche
L
,
de Blic
J
,
Le Bourgeois
M
,
Scheinmann
P
,
Paupe
J
.
Allergy to beta-lactam antibiotics in children
.
Pediatrics
.
1999
Oct
;
104
(
4
):
e45
54
.
[PubMed]
0031-4005
8.
Romano
A
,
Gaeta
F
,
Valluzzi
RL
,
Alonzi
C
,
Viola
M
,
Bousquet
PJ
.
Diagnosing hypersensitivity reactions to cephalosporins in children
.
Pediatrics
.
2008
Sep
;
122
(
3
):
521
7
.
[PubMed]
0031-4005
9.
Al-Ahmad
M
,
Rodriguez Bouza
T
,
Arifhodzic
N
.
Penicillin allergy evaluation: experience from a drug allergy clinic in an Arabian Gulf Country, Kuwait
.
Asia Pac Allergy
.
2014
Apr
;
4
(
2
):
106
12
.
[PubMed]
2233-8276
10.
Antúnez
C
,
Martín
E
,
Cornejo-García
JA
,
Blanca-Lopez
N
,
R-Pena
R
,
Mayorga
C
, et al
Immediate hypersensitivity reactions to penicillins and other betalactams
.
Curr Pharm Des
.
2006
;
12
(
26
):
3327
33
.
[PubMed]
1381-6128
11.
Torres
MJ
,
Blanca
M
,
Fernandez
J
,
Romano
A
,
Weck
A
,
Aberer
W
, et al;
ENDA
;
EAACI Interest Group on Drug Hypersensitivity
.
Diagnosis of immediate allergic reactions to beta-lactam antibiotics
.
Allergy
.
2003
Oct
;
58
(
10
):
961
72
.
[PubMed]
0105-4538
12.
Sogn
DD
,
Evans
R
 3rd
,
Shepherd
GM
,
Casale
TB
,
Condemi
J
,
Greenberger
PA
, et al
Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults
.
Arch Intern Med
.
1992
May
;
152
(
5
):
1025
32
.
[PubMed]
0003-9926
13.
Aberer
W
,
Bircher
A
,
Romano
A
,
Blanca
M
,
Campi
P
,
Fernandez
J
, et al;
European Network for Drug Allergy (ENDA)
;
EAACI interest group on drug hypersensitivity
.
Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations
.
Allergy
.
2003
Sep
;
58
(
9
):
854
63
.
[PubMed]
0105-4538
14.
Petz
LD
.
Immunologic reactions of humans to cephalosporins
.
Postgrad Med J
.
1971
Feb
;
47
suppl
:
64
9
.
[PubMed]
0032-5473
15.
Dash
CH
.
Penicillin allergy and the cephalosporins
.
J Antimicrob Chemother
.
1975
;
1
(
3
Suppl
):
107
18
.
[PubMed]
0305-7453
16.
Al-Ahmad
M
,
Rodriguez-Bouza
T
.
Drug allergy evaluation for betalactam hypersensitivity: cross-reactivity with cephalosporines, carbapenems and negative predictive value
.
Asian Pac J Allergy Immunol
.
2018
Mar
;
36
(
1
):
27
31
.
[PubMed]
0125-877X
17.
Blanca
M
,
Romano
A
,
Torres
MJ
,
Férnandez
J
,
Mayorga
C
,
Rodriguez
J
, et al
Update on the evaluation of hypersensitivity reactions to betalactams
.
Allergy
.
2009
Feb
;
64
(
2
):
183
93
.
[PubMed]
0105-4538
18.
Daulat
S
,
Solensky
R
,
Earl
HS
,
Casey
W
,
Gruchalla
RS
.
Safety of cephalosporin administration to patients with histories of penicillin allergy
.
J Allergy Clin Immunol
.
2004
Jun
;
113
(
6
):
1220
2
.
[PubMed]
0091-6749
19.
Lee
QU
.
Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited
.
Hong Kong Med J
.
2014
Oct
;
20
(
5
):
428
36
.
[PubMed]
1024-2708
20.
Romano
A
,
Gaeta
F
,
Arribas Poves
MF
,
Valluzzi
RL
.
Cross-Reactivity among Beta-Lactams
.
Curr Allergy Asthma Rep
.
2016
Mar
;
16
(
3
):
24
.
[PubMed]
1529-7322
21.
Misirlioglu
ED
,
Guvenir
H
,
Toyran
M
,
Vezir
E
,
Capanoglu
M
,
Civelek
E
, et al
Frequency of selective immediate responders to aminopenicillins and cephalosporins in Turkish children
.
Allergy Asthma Proc
.
2017
Sep
;
38
(
5
):
376
82
.
[PubMed]
1088-5412
22.
Perez-Inestrosa
E
,
Suau
R
,
Montañez
MI
,
Rodriguez
R
,
Mayorga
C
,
Torres
MJ
, et al
Cephalosporin chemical reactivity and its immunological implications
.
Curr Opin Allergy Clin Immunol
.
2005
Aug
;
5
(
4
):
323
30
.
[PubMed]
1528-4050
23.
Miranda
A
,
Blanca
M
,
Vega
JM
,
Moreno
F
,
Carmona
MJ
,
García
JJ
, et al
Cross-reactivity between a penicillin and a cephalosporin with the same side chain
.
J Allergy Clin Immunol
.
1996
Sep
;
98
(
3
):
671
7
.
[PubMed]
0091-6749
24.
Torres
MJ
,
Mayorga
C
,
Blanca
M
. Urticaria and anaphylaxis due to beta lactams (penicillins and cephalosporins). In:
Pichler
WJ
, editor
.
Drug Hypersensitivity
.
Basel
:
Karger
;
2007
. pp.
190
203
.
25.
Ponvert
C
,
Perrin
Y
,
Bados-Albiero
A
,
Le Bourgeois
M
,
Karila
C
,
Delacourt
C
, et al
Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests
.
Pediatr Allergy Immunol
.
2011
Jun
;
22
(
4
):
411
8
.
[PubMed]
0905-6157
26.
Caubet
JC
,
Kaiser
L
,
Lemaître
B
,
Fellay
B
,
Gervaix
A
,
Eigenmann
PA
.
The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge
.
J Allergy Clin Immunol
.
2011
Jan
;
127
(
1
):
218
22
.
[PubMed]
0091-6749
27.
Fox
S
,
Park
MA
.
Penicillin skin testing in the evaluation and management of penicillin allergy
.
Ann Allergy Asthma Immunol
.
2011
Jan
;
106
(
1
):
1
7
.
[PubMed]
1081-1206
28.
Goldberg
A
,
Confino-Cohen
R
.
Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy
.
Ann Allergy Asthma Immunol
.
2008
Jan
;
100
(
1
):
37
43
.
[PubMed]
1081-1206
29.
Torres
MJ
,
Romano
A
,
Mayorga
C
,
Moya
MC
,
Guzman
AE
,
Reche
M
, et al
Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing
.
Allergy
.
2001
Sep
;
56
(
9
):
850
6
.
[PubMed]
0105-4538
30.
Co Minh
HB
,
Bousquet
PJ
,
Fontaine
C
,
Kvedariene
V
,
Demoly
P
.
Systemic reactions during skin tests with beta-lactams: a risk factor analysis
.
J Allergy Clin Immunol
.
2006
Feb
;
117
(
2
):
466
8
.
[PubMed]
0091-6749
31.
Valyasevi
MA
,
Van Dellen
RG
.
Frequency of systematic reactions to penicillin skin tests
.
Ann Allergy Asthma Immunol
.
2000
Nov
;
85
(
5
):
363
5
.
[PubMed]
1081-1206
32.
Kanny
G
,
Guenard
L
,
Demoly
P
,
Ponvert
C
,
Grand
J
,
Gallen
C
, et al
Severe drug allergy: the first 100 cases declared to Allergy Vigilance Network
.
J Allergy Clin Immunol
.
2005
;
115
(
2
):
S183
. 0091-6749
33.
Versporten
A
,
Bolokhovets
G
,
Ghazaryan
L
,
Abilova
V
,
Pyshnik
G
,
Spasojevic
T
, et al;
WHO/Europe-ESAC Project Group
.
Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe
.
Lancet Infect Dis
.
2014
May
;
14
(
5
):
381
7
.
[PubMed]
1473-3099
34.
Madaan
A
,
Li
JT
.
Cephalosporin allergy
.
[vi–vii.]
.
Immunol Allergy Clin North Am
.
2004
Aug
;
24
(
3
):
463
76
.
[PubMed]
0889-8561
35.
Annè
S
,
Reisman
RE
.
Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy
.
Ann Allergy Asthma Immunol
.
1995
Feb
;
74
(
2
):
167
70
.
[PubMed]
1081-1206
36.
Tadokoro
K
,
Niimi
N
,
Ohtoshi
T
,
Nakajima
K
,
Takafuji
S
,
Onodera
K
, et al
Cefotiam-induced IgE-mediated occupational contact anaphylaxis of nurses; case reports, RAST analysis, and a review of the literature
.
Clin Exp Allergy
.
1994
Feb
;
24
(
2
):
127
33
.
[PubMed]
0954-7894
37.
Volz
MA
,
Nelson
HS
.
Drug allergy. Best diagnostic and treatment approaches
.
Postgrad Med
.
1990
Apr
;
87
(
5
):
137
42
.
[PubMed]
0032-5481
38.
Macy
E
,
Ho
NJ
.
Adverse reactions associated with therapeutic antibiotic use after penicillin skin testing
.
Perm J
.
2011
;
15
(
2
):
31
7
.
[PubMed]
1552-5767
39.
Pichichero
ME
,
Casey
JR
.
Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis
.
Otolaryngol Head Neck Surg
.
2007
Mar
;
136
(
3
):
340
7
.
[PubMed]
0194-5998
40.
Romano
A
,
Di Fonso
M
,
Papa
G
,
Pietrantonio
F
,
Federico
F
,
Fabrizi
G
, et al
Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes
.
Allergy
.
1995
Feb
;
50
(
2
):
113
8
.
[PubMed]
0105-4538
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.