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Therefore, determining the antibiotic concentration in tissues, the physiopathological parameters, and the R\/TF after treatment is relevant. After exploring different antibiotic quantities, we found that a combined dose of 100 \u00b5g\/g of doxycycline (for 45 days) and 7.5 \u00b5g\/g of streptomycin (for 14 days), respectively, achieved therapeutic levels of more than fourfold minimum inhibitory concentrations (MICs) against\n              <jats:italic>Brucella abortus<\/jats:italic>\n              in the spleen, liver, bone marrow, and plasma of mice, causing minimal pathophysiological effects. After 30 days of infection, mice received antibiotics, and hematological, histopathological, biochemical, and immunological analyses were performed. After antibiotic therapy, the pathological, hematological, immunological, and physiological profiles paralleled those described in human brucellosis. Treatment lowered antibody titers, reduced proinflammatory cytokines, and reduced inflammation in the target organs for a protracted period. No bacteria were detected in tissues 8 weeks after treatment, suggesting complete recovery. However, despite high doxycycline and streptomycin concentrations in tissues, relapses appeared in 100% of the animals after 182 days post-infection, estimated by the bacterial counts and PCR from organs. This proportion contrasts with the 15% R\/TF observed in humans after antibiotic treatments. None of the\n              <jats:italic>B. abortus<\/jats:italic>\n              isolated from relapses showed augmented MICs or mutations coding for antibiotic resistance in chromosomal-relevant regions. We discuss whether our findings constitute a general phenomenon or differences in the exhaustive screening method for bacteria detection related to the murine model. Along these lines, we envision likely mechanisms of bacterial persistence in tissues after antibiotic treatment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01302-24","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:00:46Z","timestamp":1735650046000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Reactivation of hidden-latent\n            <i>Brucella<\/i>\n            infection after doxycycline and streptomycin treatment in mice"],"prefix":"10.1128","volume":"69","author":[{"given":"Eugenia","family":"Sancho-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Garc\u00eda-Arteaga","sequence":"additional","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Granados-Chinchilla","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Enfermedades Tropicales, Facultad de Microbiolog\u00eda, Universidad de Costa Rica","place":["San Jos\u00e9, Costa Rica"]},{"name":"Escuela de Qu\u00edmica, Universidad de Costa Rica, Sede Rodrigo Facio, San Pedro Montes de Oca","place":["San Jos\u00e9, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graciela","family":"Artavia","sequence":"additional","affiliation":[{"name":"Centro Nacional de Ciencia y Tecnolog\u00eda de Alimentos, Universidad de Costa Rica","place":["San Jos\u00e9, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Alfaro-Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]},{"name":"Berlin Institute of Health, Institute of Virology, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s","family":"Villalobos-Villalobos","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lisis Cl\u00ednicos, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bouza-Mora","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lisis Cl\u00ednicos, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Su\u00e1rez-Esquivel","sequence":"additional","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0865-0772","authenticated-orcid":true,"given":"Carlos","family":"Chac\u00f3n-D\u00edaz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Enfermedades Tropicales, Facultad de Microbiolog\u00eda, Universidad de Costa Rica","place":["San Jos\u00e9, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Guzm\u00e1n-Verri","sequence":"additional","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-3959","authenticated-orcid":true,"given":"Edgardo","family":"Moreno","sequence":"additional","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-3340","authenticated-orcid":true,"given":"El\u00edas","family":"Barquero-Calvo","sequence":"additional","affiliation":[{"name":"Programa de Investigaci\u00f3n en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional","place":["Heredia, Costa Rica"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040317"},{"key":"e_1_3_3_3_2","volume-title":"Brucelosis","author":"Ruiz-Casta\u00f1eda M","year":"1986","unstructured":"Ruiz-Casta\u00f1eda M. 1986. 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