Abstract
Introduction: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. Methods: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1–6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. Results: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. Conclusion: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.
Journal Section:
Clinical Allergy – Research Article
References
1.
Gómez
E
, Blanca-Lopez
N
, Salas
M
, Canto
G
, Campo
P
, Torres
MJ
, et al. Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms
. Ann Allergy Asthma Immunol
. 2013
;110
(4
):267
–73
. 2.
Romano
A
, Atanaskovic-Markovic
M
, Barbaud
A
, Bircher
AJ
, Brockow
K
, Caubet
JC
, et al. Towards a more precise diagnosis of hypersensitivity to beta-lactams: an EAACI position paper
. Allergy
. 2020
;75
(6
):1300
–15
. 3.
Terrados
S
, Blanca
M
, Garcia
J
, Vega
J
, Torres
M
, Carmona
M
, et al. Nonimmediate reactions to betalactams: prevalence and role of the different penicillins
. Allergy
. 1995
;50
(7
):563
–7
. 4.
Demoly
P
, Adkinson
NF
, Brockow
K
, Castells
M
, Chiriac
AM
, Greenberger
PA
, et al. International Consensus on drug allergy
. Allergy
. 2014
;69
(4
):420
–37
. 5.
Gomes
E
, Brockow
K
, Kuyucu
S
, Saretta
F
, Mori
F
, Blanca-Lopez
N
, et al. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group
. Allergy
. 2016
;71
(2
):149
–61
. 6.
Blanca
M
, Vega
J
, Garcia
J
, Carmona
MJ
, Terados
S
, Avila
MJ
, et al. Allergy to penicillin with good tolerance to other penicillins; study of the incidence in subjects allergic to beta-lactams
. Clin Exp Allergy
. 1990
;20
(5
):475
–81
. 7.
Brockow
K
, Romano
A
, Blanca
M
, Ring
J
, Pichler
W
, Demoly
P
. General considerations for skin test procedures in the diagnosis of drug hypersensitivity
. Allergy
. 2002
;57
(1
):45
–51
. 8.
Graham
F
, Caubet
J-C
. Diagnosis of drug causality in non-immediate drug hypersensitivity in children
. Expert Rev Clin Pharmacol
. 2018
;11
(7
):655
–8
. 9.
Demoly
P
, Kropf
R
, Bircher
A
, Pichler
WJ
. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity
. Allergy
. 1999
;54
(9
):999
–1003
. 10.
Muraro
A
, Lemanske
R
Jr, Castells
M
, Torres
MJ
, Khan
D
, Simon
HU
, et al. Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European academy of allergy and clinical Immunology and the American academy of allergy, asthma and Immunology
. Asthma Immunol Allergy
. 2017
;72
(7
):1006
–21
. 11.
Aberer
W
, Bircher
A
, Romano
A
, Blanca
M
, Campi
P
, Fernandez
J
, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations
. Allergy
. 2003
;58
(9
):854
–63
. 12.
Tortajada Girbés
M
, Ferrer Franco
A
, Gracia Antequera
M
, Clement Paredes
A
, García Muñoz
E
, Tallón Guerola
M
. Hypersensitivity to clavulanic acid in children
. Allergologia et immunopathologia
. 2008
;36
(5
):308
–10
. 13.
Chiriac
AM
, Rerkpattanapipat
T
, Bousquet
PJ
, Molinari
N
, Demoly
P
. Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity
. Allergy
. 2017
;72
(4
):552
–61
. 14.
Labrosse
R
, Paradis
L
, Lacombe-Barrios
J
, Samaan
K
, Graham
F
, Paradis
J
, et al. Efficacy and safety of 5-day challenge for the evaluation of nonsevere amoxicillin allergy in children
. J Allergy Clin Immunol Pract
. 2018
;6
(5
):1673
–80
. 15.
Vezir
E
, Dibek Misirlioglu
E
, Civelek
E
, Capanoglu
M
, Guvenir
H
, Ginis
T
, et al. Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics
. Pediatr Allergy Immunol
. 2016
;27
(1
):50
–4
. 16.
Ratzon
R
, Reshef
A
, Efrati
O
, Deutch
M
, Forschmidt
R
, Cukierman-Yaffe
T
, et al. Impact of an extended challenge on the effectiveness of β-lactam hypersensitivity investigation
. Ann Allergy Asthma Immunol
. 2016
;116
(4
):329
–33
. 17.
Barbaud
A
, Garvey
LH
, Torres
M
, Laguna
JJ
, Arcolaci
A
, Bonadonna
P
, et al. EAACI/ENDA position paper on drug provocation testing
. Allergy
. 2023
;79
(3
):565
–79
. 18.
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
;22
(4
):411
–8
. 19.
Kulalert
P
, Phinyo
P
, Chiriac
AM
, Demoly
P
, Saokaew
S
, Kanchanaphoomi
K
, et al. Is a prolonged drug provocation test better than a single-day drug provocation test? a systematic review and meta-analysis
. J Allergy Clin Immunol Pract
. 2024
;12
(2
):431
–48
. 20.
García Rodríguez
R
, Moreno Lozano
L
, Extremera Ortega
A
, Borja Segade
J
, Galindo Bonilla
P
, Gómez Torrijos
E
. Provocation tests in nonimmediate hypersensitivity reactions to β-lactam antibiotics in children: are extended challenges needed
. J Allergy Clin Immunol Pract
. 2019
;7
(1
):265
–9
. 21.
Kulhas Celik
I
, Guvenir
H
, Hurmuzlu
S
, Toyran
M
, Civelek
E
, Kocabas
CN
, et al. The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children
. Ann Allergy Asthma Immunol
. 2020
;124
(5
):494
–9
. 22.
Caubet
J-C
, 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
;127
(1
):218
–22
. 23.
Mori
F
, Cianferoni
A
, Barni
S
, Pucci
N
, Rossi
ME
, Novembre
E
. Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions
. J Allergy Clin Immunol Pract
. 2015
;3
(3
):375
–80.e1
. 24.
Lezmi
G
, Alrowaishdi
F
, Bados‐Albiero
A
, Scheinmann
P
, de Blic
J
, Ponvert
C
. Non-immediate-reading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children
. Pediatr Allergy Immunol
. 2018
;29
(1
):84
–9
. 25.
Tonson la Tour
A
, Michelet
M
, Eigenmann
PA
, Caubet
J-C
. Natural history of benign nonimmediate allergy to beta-lactams in children: a prospective study in retreated patients after a positive and a negative provocation test
. J Allergy Clin Immunol Pract
. 2018
;6
(4
):1321
–6
. 26.
Demoly
P
, Romano
A
, Botelho
C
, Bousquet-Rouanet
L
, Gaeta
F
, Silva
R
, et al. Determining the negative predictive value of provocation tests with beta-lactams
. Allergy
. 2010
;65
(3
):327
–32
. 27.
Gibson
MK
, Crofts
TS
, Dantas
G
. Antibiotics and the developing infant gut microbiota and resistome
. Curr Opin Microbiol
. 2015
;27
:51
–6
. 28.
Brunser
O
, Gotteland
M
, Cruchet
S
, Figueroa
G
, Garrido
D
, Steenhout
P
. Effect of a milk formula with prebiotics on the intestinal microbiota of infants after an antibiotic treatment
. Pediatr Res
. 2006
;59
(3
):451
–6
. © 2024 S. Karger AG, Basel
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.
2024
You do not currently have access to this content.
