{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T21:34:28Z","timestamp":1776202468440,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>A collection of 177 Francisella tularensis subsp. holarctica clinical isolates (29 from humans and 148 from animals, mainly hares and voles) was gathered from diverse tularemia outbreaks in the Castilla y Le\u00f3n region (northwestern Spain) that occurred from the end of the 20th century to the 2020s. Along with four F. tularensis subsp. holarctica reference strains, all of these clinical isolates were tested using a broth microdilution method to determine their susceptibility to 22 antimicrobial agents, including \u03b2-lactams, aminoglycosides and one member each of the tetracycline, glycylcycline, quinolone and sulphonamide classes. Many multi-resistance profiles were found among the tested isolates, but especially among those of human origin (all but two isolates showed resistance to at least 13 of 18 antimicrobial agents). Even so, all human isolates were susceptible to gentamicin and tobramycin, while more than 96% of animal isolates were susceptible to these two aminoglycosides. Ciprofloxacin showed activity against more than 92% of animal and human isolates. However, almost 21% of human isolates were resistant to tetracycline, and more than 65% were resistant to tigecycline. Finally, a quite similar activity to other F. tularensis subsp. holarctica isolates collected 20 years earlier in Spain was observed.<\/jats:p>","DOI":"10.3390\/antibiotics10080938","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T02:16:07Z","timestamp":1628043367000},"page":"938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Vitro Antimicrobial Susceptibilities of Francisella tularensis subsp. holarctica Isolates from Tularemia Outbreaks That Occurred from the End of the 20th Century to the 2020s in Spain"],"prefix":"10.3390","volume":"10","author":[{"given":"Sonia","family":"Mart\u00ednez-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Departmento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24007 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u00edas-Fernando","family":"Rodr\u00edguez-Ferri","sequence":"additional","affiliation":[{"name":"Departmento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24007 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-854X","authenticated-orcid":false,"given":"David","family":"Rodr\u00edguez-L\u00e1zaro","sequence":"additional","affiliation":[{"name":"Unidad de Microbiolog\u00eda, Departamento de Biotecnolog\u00eda y Ciencia de los Alimentos, Facultad de Ciencias, and Research Centre for Emerging Pathogens and Global Health, University of Burgos, 09001 Burgos, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-9987","authenticated-orcid":false,"given":"Marta","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular y Microbiolog\u00eda, Instituto Tecnol\u00f3gico Agrario de Castilla y Le\u00f3n (ITACyL), 47071 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9-Ignacio","family":"G\u00f3mez-Campillo","sequence":"additional","affiliation":[{"name":"Laboratorio Regional de Sanidad Animal, Villaquilambre, 24193 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda del Carmen","family":"Mart\u00ednez-Nistal","sequence":"additional","affiliation":[{"name":"Laboratorio Regional de Sanidad Animal, Villaquilambre, 24193 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda-Isabel","family":"Fern\u00e1ndez-Natal","sequence":"additional","affiliation":[{"name":"Jefe de Servicio de An\u00e1lisis Cl\u00ednicos\/Coordinadora del Laboratorio de Diagn\u00f3stico Cl\u00ednico del Complejo Asistencial Universitario, Hospital Universitario de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-6561","authenticated-orcid":false,"given":"Mar\u00eda-Jos\u00e9","family":"Garc\u00eda-Iglesias","sequence":"additional","affiliation":[{"name":"Departmento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24007 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"M\u00ednguez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Jefe de Servicio de Sanidad Animal, Consejer\u00eda de Agricultura, Ganader\u00eda y Desarrollo Rural, Direcci\u00f3n General de Producci\u00f3n Agropecuaria, Junta de Castilla y Le\u00f3n, 47014 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9sar-Bernardo","family":"Guti\u00e9rrez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Departmento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24007 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1086\/313586","article-title":"Detection of selected fastidious bacteria","volume":"30","author":"Doern","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","unstructured":"Murray, P.A., Baron, E.J., Pfaller, M.A., Tenover, F.C., and Yoken, R.H. (1995). Francisella. Manual of Clinical Microbiology, American Society for Microbiology. [6th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Challacombe, J.F., Petersen, J.M., Gallegos-Graves, L.V., Hodge, D., Pillai, S., and Kuske, C.R. (2017). Whole-genome relationships among Francisella bacteria of diverse origins define new species and provide specific regions for detection. Appl. Environ. Microbiol., 83.","DOI":"10.1128\/AEM.00174-17"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3201\/eid2005.130654","article-title":"Molecular investigation of tularemia outbreaks, Spain, 1997\u20132008","volume":"20","author":"Johansson","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1409.009","article-title":"Tularemia: History, epidemiology, pathogen physiology, and clinical manifestations","volume":"1105","year":"2007","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/BF01964409","article-title":"In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacina and ciprofloxacin","volume":"10","author":"Schildt","year":"1991","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/jac\/46.2.287","article-title":"In vitro antibiotic susceptibility of Francisella tularensis isolated from humans and animals","volume":"46","author":"Karhukorpi","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.rvsc.2003.12.002","article-title":"In vitro susceptibility of field isolates of Francisella tularensis subsp. holarctica recovered in Spain to several antimicrobial agents","volume":"76","year":"2004","journal-title":"Res. Vet. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/jac\/dkx460","article-title":"Antibiotic susceptibility of Francisella tularensis subsp. holartica strains isolated from tularemia patients in France between 2006 and 2016","volume":"73","author":"Caspar","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"O353","DOI":"10.1111\/1469-0691.12414","article-title":"Validation of EUCAST zone diameter breakpoints against reference broth microdilution","volume":"20","author":"Bengtsson","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_11","unstructured":"Clinical and Laboratory Standards Institute (2018). Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated from Animals, Wayne. [4th ed.]. CLSI Supplement VET08."},{"key":"ref_12","unstructured":"Clinical and Laboratory Standards Institute (2018). Performance Standards for Antimicrobial Susceptibility Testing, Wayne. [28th ed.]. CLSI Supplement M100."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3389\/fcimb.2017.00122","article-title":"Francisella tularensis susceptibility to antibiotics: A comprehensive review of the data obtained in vitro and in animal models","volume":"7","author":"Caspar","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/jac\/dks399","article-title":"Antimicrobial susceptibility of Francisella tularensis subsp. holartica strains from Hungary, Central Europe","volume":"68","author":"Kreizinger","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0732-8893(93)90115-N","article-title":"Qualitative susceptibility tests versus quantitative MIC tests","volume":"16","author":"Craig","year":"1993","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fcimb.2014.00040","article-title":"New therapeutic approaches for treatment of tularemia: A review","volume":"4","author":"Boisset","year":"2014","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/jac\/dkx182","article-title":"Antibiotic susceptibility in vitro of Francisella tularensis subsp. holarctica isolates from Germany","volume":"72","author":"Tomaso","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/jac\/dkr338","article-title":"Antimicrobial susceptibilities of Francisella tularensis subsp. holarctica strains isolated from humans in the Central Anatolia region of Turkey","volume":"66","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_19","first-page":"7","article-title":"In vitro antimicrobial susceptibility of Francisella tularensis isolated in Bulgaria","volume":"39","author":"Velinov","year":"2011","journal-title":"Probl. Infect. Parasit. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.7883\/yoken.66.534","article-title":"In vitro antibiotic susceptibility of Francisella tularensis isolates from Japan","volume":"66","author":"Hotta","year":"2013","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Heine, H.S., Miller, L., Halsohoris, S., and Purcell, B. (2017). In vitro antibiotic susceptibilities of Francisella tularensis determined by broth microdilution following CLSI methods. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00612-17"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/00365548.2012.751125","article-title":"In vitro susceptibility of isolates of Francisella tularensis from Turkey","volume":"45","author":"Celebi","year":"2013","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_23","first-page":"189","article-title":"In vitro activity of tigecycline against Francisella tularensis subsp. holarctica in comparison with doxycycline, ciprofloxacin and aminoglycosides","volume":"47","author":"Celebi","year":"2013","journal-title":"Mikrobiyol. Bol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1128\/AAC.01584-07","article-title":"In vitro susceptibility of isolates of Francisella tularensis types A and B from North America","volume":"52","author":"Urich","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1128\/AAC.44.12.3428-3431.2000","article-title":"Bactericidal activities of antibiotics against intracellular Francisella tularensis","volume":"44","author":"Maurin","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/jac\/dki248","article-title":"Tigecycline","volume":"56","author":"Pankey","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"593542","DOI":"10.3389\/fmicb.2020.593542","article-title":"Evolution of antibiotic resistance in surrogates of Francisella tularensis (LVS and Francisella novicida): Effects on biofilm formation and fitness","volume":"11","author":"Biot","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1128\/JCM.41.7.2924-2931.2003","article-title":"Genome-wide DNA microarray analysis of Francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent F. tularensis subsp. tularensis","volume":"41","author":"Broekhuijsen","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.7883\/yoken.JJID.2006.46","article-title":"Development of a real-time PCR assay for detection and quantification of Francisella tularensis","volume":"59","author":"Fujita","year":"2006","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_30","unstructured":"World Health Organization (2019, March 07). Guidelines on Tularaemia. Geneva: The Organization. Epidemic and Pandemic Alert and Response, 2007. Available online: http:\/\/www.who.int\/crs\/\/resources\/publications\/WHOCDSEPR20077.pdf."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/8\/938\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:39:58Z","timestamp":1760164798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/8\/938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,3]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["antibiotics10080938"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10080938","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,3]]}}}