Journal Information
Vol. 96. Issue 2.
Pages 157-158 (1 February 2022)
Vol. 96. Issue 2.
Pages 157-158 (1 February 2022)
Scientific Letter
Open Access
New antibiotic susceptibility testing definitions: «I» no longer means intermediate susceptibility
Novedades en el antibiograma: «I» ya no significa sensibilidad intermedia
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David Aguilera-Alonsoa,e,
Corresponding author
david.aguilera@salud.madrid.org

Corresponding author.
, Leticia Martínez Camposb, Cecilia M. Fernández Llamazaresc, Cristina Calvod,e, Fernando Baquero-Artigaod,e, en representación del Grupo de Trabajo PROA-SEIP 1
a Sección de Enfermedades Infecciosas, Servicio de Pediatría, Instituto de Investigación Sanitaria, Hospital General Universitario Gregorio Marañón, Sociedad Española de Infectología Pediátrica (SEIP), Red de Investigación Traslacional en Infectología Pediátrica (RITIP), Madrid, Spain
b Servicio de Pediatría, Hospital Torrecárdenas, Sociedad Española de Infectología Pediátrica (SEIP), Almería, Spain
c Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Sociedad Española de Farmacia Hospitalaria (SEFH), Madrid, Spain
d Servicio de Pediatría, Enfermedades Infecciosas y Patología Tropical, Hospital La Paz, Sociedad Española de Infectología Pediátrica (SEIP), Red de Investigación Traslacional en Infectología Pediátrica (RITIP), Madrid, Spain
e CIBER de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
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Dear Editor:

Antibiotic susceptibility testing is an essential tool for adjusting antibiotherapy to the isolated bacteria. The minimum inhibitory concentration (MIC), defined as the lowest concentration of an antimicrobial that can inhibit the growth of a microorganism, was traditionally used to classify the isolate as susceptible (“S”), resistant (“R”) or with intermediate susceptibility to the antimicrobial (“I”). The latter category encompassed bacteria with MICs for which antimicrobial activity was uncertain based on the available evidence.1

Every year, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) publishes a document reviewing the evidence and updating the breakpoints that define each of these categories. A growing number of microbiology laboratories in Spain have been applying these standards in adherence with the recommendations of the Spanish Committee on Antibiotic Susceptibility Testing (Comité Español del Antibiograma, COESANT).

In 2019, the EUCAST published an important update, changing the definition of “I”. Since then, both “S” and “I” refer to susceptible isolates. The difference is that isolates classified as susceptible could be treated with a standard dosing regimen, while those classified as intermediate would require an enhanced dosage. Thus, isolates classified as “I” are defined as susceptible to the antimicrobial as long as exposure is increased. Increased exposure may be achieved by changing the route of administration, dose, interval between doses or rate of infusion or by using agents with a distribution, metabolism and elimination that are favourable based on the location and severity of infection. Thus, “I” would stand for increased exposure as opposed to intermediate susceptibility.2

This change is based on mounting evidence that there is a MIC range that corresponds to a high probability of therapeutic success using an increased dose of the antimicrobial. Exposure to each antimicrobial is optimised based on its pharmacokinetics and pharmacodynamics, establishing different objectives for different antibiotic classes.3,4

On behalf of the Working Group on antimicrobial stewardship of the Sociedad Española de Infectología Pediátrica (Spanish Society of Paediatric Infectious Diseases, SEIP), we want to promote awareness and understanding of this change, as its incorrect interpretation may result in an increase in the inappropriate use of restricted antimicrobials.5 For example, a Pseudomonas aeruginosa isolate with a MIC of 8 mg/L or less of ceftazidime used to be considered susceptible, but it would now be classified as “I” based on recent updates. The rational is the recommendation of using a dose higher than the standard dose for some β-lactam antibiotics (ceftazidime, cefepime or piperacillin-tazobactam) for treatment of P. aeruginosa infections.6 Thus, with the new classification system, the EUCAST aims to avoid the use of the standard dose and promote the use of the optimised dose.7 Consequently, the “I” classification does not indicate a need to use broader-spectrum antibiotics, such as carbapenems, but to increase the dosage of the antimicrobial, administering higher doses and possibly even using extended or continuous infusion.

We ought to highlight that the EUCAST has developed a table that includes the standard and the increased doses for different antibiotics.8 However, this table did not address the dosage for the paediatric population. For this reason, the Working Group on antimicrobial stewardship for the SEIP, with the collaboration of the Sociedad Española de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacy, SEFH), has taken the initiative to make a paediatric adaptation of the table (https://www.seipweb.es/dosisantibioticos/), to be updated periodically based on the current evidence. We hope that it will contribute to improving antimicrobial use, reducing associated risks, the development of microbial drug resistance and the incidence of adverse events. We also encourage readers to consult and check with the laboratory of microbiology of each facility about the integration of the new guidelines in everyday clinical practice.

Funding

The authors did not receive any funding specifically for this work. David Aguilera-Alonso receives funding from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) through a Río Hortega grant (CM18/00100).

Conflicts of interest

The authors have no conflicts of interest to declare in relation to this article.

Appendix A
Working Group on Antimicrobial Stewardship-SEIP

Coordinator: Fernando Baquero Artigao (JD SEIP, Hospital La Paz, Madrid)

Secretary: Leticia Martínez Campos (JD SEIP- GT IA SEIP, H. Torrecárdenas, Almería)

Members: Carlos Rodrigo Gonzalo de Liria (GT-IB SEIP, H. Germans Trias i Pujol, Barcelona) José Tomás Ramos Amador (GT-IF-SEIP, H. Clínico San Carlos, Madrid) Cristian Launes Montaña (GT-IR-SEIP, H. Sant Joan de Deu, Barcelona) María Carmen Suarez Arrabal (GT IyF-SEIP, C.S. Sardinero, Santander) Luis Escosa García (GT IRAS, H. La Paz, Madrid) Susana Melendo Pérez (H. Vall d’Hebron, Barcelona) David Aguilera-Alonso (H. Gregorio Marañón, Madrid) Walter Goycoechea Valdivia (H. Virgen del Rocío, Seville) Eneritz Velasco Arnaiz (H. Sant Joan de Déu, Barcelona) Cristina Epalza Ibarrondo (H. 12 de Octubre, Madrid) Marta García Ascaso (H. Niño Jesús, Madrid).

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E. Cercenado, J. Saavedra-Lozano.
El antibiograma. Interpretación del antibiograma: conceptos generales (I).
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[2]
G. Kahlmeter, EUCAST Steering Committee.
EUCAST proposes to change the definition and usefulness of the susceptibility category ‘Intermediate’.
Clin Microbiol Infect, 23 (2017), pp. 894-895
[3]
J. Le, J.S. Bradley.
Optimizing antibiotic drug therapy in pediatrics: current state and future needs.
J Clin Pharmacol, 58 (2018), pp. S108-22
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In the name of common sense: EUCAST breakpoints and potential pitfalls.
Clin Microbiol Infect, 26 (2020), pp. 1593-1594
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G. Kahlmeter, R. Cantón, C.G. Giske, J. Turnidge, C.G. Giske, J. Turnidge, et al.
Re: In the name of common sense: EUCAST breakpoints and potential pitfalls. National dissemination of EUCAST guidelines is a shared responsibility.
Clin Microbiol Infect, 26 (2020), pp. 1692-1693
[8]
Clinical breakpoints and dosing of antibiotics [Internet]. EUCAST Available from: https://www.eucast.org/clinical_breakpoints/. [Accessed February 2021].

Please cite this article as: Aguilera-Alonso D, Martínez Campos L, Fernández Llamazares CM, Calvo C, Baquero-Artigao F, en representación del Grupo de Trabajo PROA-SEIP. Novedades en el antibiograma: «I» ya no significa sensibilidad intermedia. An Pediatr (Barc). 2022;96:157–158.

Appendix A Lists the members of the PROA-SEIP working group.

Copyright © 2021. Asociación Española de Pediatría
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