Imipenem heteroresistance but not tolerance in Haemophilus influenzae during chronic lung infection associated with chronic obstructive pulmonary disease

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dc.contributor.authorGil Campillo, Celia
dc.contributor.authorGonzález-Díaz, Aida
dc.contributor.authorRapún Araiz, Beatriz
dc.contributor.authorIriarte-Elizaintzin, Oihane
dc.contributor.authorElizalde Gutiérrez, Iris
dc.contributor.authorFernández Calvet, Ariadna
dc.contributor.authorLázaro-Díez, María
dc.contributor.authorMartí, Sara
dc.contributor.authorGarmendia García, Juncal
dc.contributor.departmentCienciases_ES
dc.contributor.departmentZientziakeu
dc.contributor.departmentInstitute for Multidisciplinary Research in Applied Biology - IMABen
dc.date.accessioned2024-05-28T17:33:26Z
dc.date.available2024-05-28T17:33:26Z
dc.date.issued2023
dc.date.updated2024-05-28T17:01:50Z
dc.description.abstractAntibiotic resistance is a major Public Health challenge worldwide. Mechanisms other than resistance are described as contributors to therapeutic failure. These include heteroresistance and tolerance, which escape the standardized procedures used for antibiotic treatment decision-making as they do not involve changes in minimal inhibitory concentration (MIC). Haemophilus influenzae causes chronic respiratory infection and is associated with exacerbations suffered by chronic obstructive pulmonary disease (COPD) patients. Although resistance to imipenem is rare in this bacterial species, heteroresistance has been reported, and antibiotic tolerance cannot be excluded. Moreover, development of antibiotic heteroresistance or tolerance during within-host H. influenzae pathoadaptive evolution is currently unknown. In this study, we assessed imipenem resistance, heteroresistance and tolerance in a previously sequenced longitudinal collection of H. influenzae COPD respiratory isolates. The use of Etest, disc diffusion, population analysis profiling, tolerance disc (TD)-test methods, and susceptibility breakpoint criteria when available, showed a significant proportion of imipenem heteroresistance with differences in terms of degree among strains, absence of imipenem tolerance, and no specific trends among serial and clonally related strains could be established. Analysis of allelic variation in the ftsI, acrA, acrB, and acrR genes rendered a panel of polymorphisms only found in heteroresistant strains, but gene expression and genome-wide analyses did not show clear genetic traits linked to heteroresistance. In summary, a significant proportion of imipenem heteroresistance was observed among H. influenzae strains isolated from COPD respiratory samples over time. These data should be useful for making more accurate clinical recommendations to COPD patients.en
dc.description.sponsorshipCG-C is funded by a PhD studentship from AEI, PRE2019-088382. SM is supported by Miguel Servet contract (CP19/00096) (ISCIII). This work has been funded by grants from MICIU RTI2018-096369-B-I00 and PID2021-125947OB-I00, 875/2019 from SEPAR, PC150 and PC136 from Gobierno de Navarra, to JG; by grant from Fondo de Investigaciones Sanitarias PI22/00257, to SM. CIBER is an initiative from Instituto de Salud Carlos III (ISCIII), Madrid, Spain.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGil-Campillo, C., González-Díaz, A., Rapún-Araiz, B., Iriarte-Elizaintzin, O., Elizalde-Gutiérrez, I., Fernández-Calvet, A., Lázaro-Díez, M., Martí, S., Garmendia, J. (2023) Imipenem heteroresistance but not tolerance in Haemophilus influenzae during chronic lung infection associated with chronic obstructive pulmonary disease. Frontiers in Microbiology, 14, 1-19. https://doi.org/10.3389/fmicb.2023.1253623.en
dc.identifier.doi10.3389/fmicb.2023.1253623
dc.identifier.issn1664-302X
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48204
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Microbiology 14, 2023, 1-19en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096369-B-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-125947OB-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00257/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//PC150/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//PC136/
dc.relation.publisherversionhttps://doi.org/10.3389/fmicb.2023.1253623
dc.rights© 2023 Gil-Campillo, González-Díaz, Rapún- Araiz, Iriarte-Elizaintzin, Elizalde-Gutiérrez, Fernández-Calvet, Lázaro-Díez, Martí and Garmendia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAntibiotic heteroresistanceen
dc.subjectAntibiotic resistanceen
dc.subjectAntibiotic toleranceen
dc.subjectHaemophilus influenzaeen
dc.subjectImipenemen
dc.subjectTherapeutic failureen
dc.titleImipenem heteroresistance but not tolerance in Haemophilus influenzae during chronic lung infection associated with chronic obstructive pulmonary diseaseen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication45523631-0bc0-4010-b999-22ab4f7ef380
relation.isAuthorOfPublicationeab5adde-437b-46f6-9496-2fa2b16b308f
relation.isAuthorOfPublication.latestForDiscovery45523631-0bc0-4010-b999-22ab4f7ef380

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