Scientific Letter
New antibiotic susceptibility testing definitions: «I» no longer means intermediate susceptibility
Novedades en el antibiograma: «I» ya no significa sensibilidad intermedia
David Aguilera-Alonsoa,e,
, Leticia Martínez Camposb, Cecilia M. Fernández Llamazaresc, Cristina Calvod,e, Fernando Baquero-Artigaod,e, en representación del Grupo de Trabajo PROA-SEIP 1
Corresponding author
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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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 <span class="elsevierStyleItalic">susceptible</span> (“S”), <span class="elsevierStyleItalic">resistant</span> (“R”) or with <span class="elsevierStyleItalic">intermediate susceptibility</span> to the antimicrobial (“I”). The latter category encompassed bacteria with MICs for which antimicrobial activity was uncertain based on the available evidence.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">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).</p><p id="par0015" class="elsevierStylePara elsevierViewall">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 <span class="elsevierStyleItalic">increased exposure</span> as opposed to <span class="elsevierStyleItalic">intermediate susceptibility.</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">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.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">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.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> For example, a <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> 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 <span class="elsevierStyleItalic">P. aeruginosa</span> infections.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> 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.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> 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.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We ought to highlight that the EUCAST has developed a table that includes the standard and the increased doses for different antibiotics.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> 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 (<a href="https://www.seipweb.es/dosisantibioticos/">https://www.seipweb.es/dosisantibioticos/</a>), 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.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors did not receive any funding specifically for this work. David Aguilera-Alonso receives funding from the <span class="elsevierStyleGrantSponsor" id="gs0005">Fondo de Investigaciones Sanitarias</span>, Instituto de Salud Carlos III (<span class="elsevierStyleGrantSponsor" id="gs0010">ISCIII</span>) and the European Regional Development Fund (<span class="elsevierStyleGrantSponsor" id="gs0015">ERDF</span>) through a Río Hortega grant (<span class="elsevierStyleGrantNumber" refid="gs0015">CM18/00100</span>).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare in relation to this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-16" "fechaAceptado" => "2021-04-23" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">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.</p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Appendix A Lists the members of the PROA-SEIP working group.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0045" class="elsevierStylePara elsevierViewall">Coordinator: Fernando Baquero Artigao (JD SEIP, Hospital La Paz, Madrid)</p> <p id="par0050" class="elsevierStylePara elsevierViewall">Secretary: Leticia Martínez Campos (JD SEIP- GT IA SEIP, H. Torrecárdenas, Almería)</p> <p id="par0055" class="elsevierStylePara elsevierViewall">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).</p>" "etiqueta" => "Appendix A" "titulo" => "Working Group on Antimicrobial Stewardship-SEIP" "identificador" => "sec0015" ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "El antibiograma. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 102 | 45 | 147 |
| 2024 September | 120 | 39 | 159 |
| 2024 August | 121 | 68 | 189 |
| 2024 July | 113 | 40 | 153 |
| 2024 June | 95 | 28 | 123 |
| 2024 May | 105 | 42 | 147 |
| 2024 April | 89 | 29 | 118 |
| 2024 March | 61 | 21 | 82 |
| 2024 February | 80 | 28 | 108 |
| 2024 January | 91 | 29 | 120 |
| 2023 December | 110 | 35 | 145 |
| 2023 November | 81 | 51 | 132 |
| 2023 October | 89 | 23 | 112 |
| 2023 September | 65 | 37 | 102 |
| 2023 August | 58 | 20 | 78 |
| 2023 July | 63 | 24 | 87 |
| 2023 June | 56 | 23 | 79 |
| 2023 May | 76 | 30 | 106 |
| 2023 April | 45 | 19 | 64 |
| 2023 March | 88 | 32 | 120 |
| 2023 February | 90 | 16 | 106 |
| 2023 January | 62 | 19 | 81 |
| 2022 December | 82 | 36 | 118 |
| 2022 November | 77 | 34 | 111 |
| 2022 October | 79 | 52 | 131 |
| 2022 September | 84 | 26 | 110 |
| 2022 August | 69 | 47 | 116 |
| 2022 July | 95 | 53 | 148 |
| 2022 June | 74 | 45 | 119 |
| 2022 May | 72 | 39 | 111 |
| 2022 April | 54 | 40 | 94 |
| 2022 March | 85 | 62 | 147 |
| 2022 February | 96 | 76 | 172 |
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