{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:49:15Z","timestamp":1790232555736,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00115"],"award-info":[{"award-number":["PI17\/00115"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0016\/0011"],"award-info":[{"award-number":["RD16\/0016\/0011"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CM19\/00069"],"award-info":[{"award-number":["CM19\/00069"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["PEJD-2018-PRE\/BMD-8237"],"award-info":[{"award-number":["PEJD-2018-PRE\/BMD-8237"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.<\/jats:p>","DOI":"10.3390\/genes12010041","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T09:35:23Z","timestamp":1609320923000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Long-Term Impact of Suppressive Antibiotic Therapy on Intestinal Microbiota"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5736-8111","authenticated-orcid":false,"given":"Rosa","family":"Escudero-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Servicio de Enfermedades Infecciosas, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-9373","authenticated-orcid":false,"given":"Manuel","family":"Ponce-Alonso","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Barrag\u00e1n-Prada","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Morosini","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-3173","authenticated-orcid":false,"given":"Rafael","family":"Cant\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-7421","authenticated-orcid":false,"given":"Javier","family":"Cobo","sequence":"additional","affiliation":[{"name":"Servicio de Enfermedades Infecciosas, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7923","authenticated-orcid":false,"given":"Rosa","family":"del Campo","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), and Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,30]]},"reference":[{"key":"ref_1","unstructured":"Ministerio de Sanidad, Consumo y Bienestar Social (2020, June 21). Subdirecci\u00f3n General de Informaci\u00f3n Sanitaria e Innovaci\u00f3n. Registro de Atenci\u00f3n Especializada\/Conjunto M\u00ednimo B\u00e1sico de Datos (RAE-CMBD) de los hospitales del Sistema Nacional de Salud. Available online: http:\/\/icmbd.es."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0140-6736(14)61798-0","article-title":"Periprosthetic joint infection","volume":"387","author":"Kapadia","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.cmi.2019.09.007","article-title":"Suppressive antibiotic therapy in prosthetic joint infections: A multicentre cohort study","volume":"26","author":"Senneville","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7150\/jbji.37262","article-title":"Clinical outcome of antibiotic suppressive therapy in patients with a prosthetic joint infection after hip replacement","volume":"4","author":"Leijtens","year":"2019","journal-title":"J. Bone Jt. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s10096-017-2971-2","article-title":"Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: A national multicentre cohort study","volume":"36","author":"Prendki","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7150\/jbji.17353","article-title":"Efficacy of antibiotic suppressive therapy in patients with a prosthetic joint infection","volume":"2","author":"Nijman","year":"2017","journal-title":"J. Bone Jt. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ismej.2007.3","article-title":"Long-term ecological impacts of antibiotic administration on the human intestinal microbiota","volume":"1","author":"Jernberg","year":"2007","journal-title":"ISME J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jakobsson, H.E., Jernberg, C., Andersson, A.F., Sj\u00f6lund-Karlsson, M., Jansson, J.K., and Engstrand, L. (2010). Short-term antibiotic treatment has differing long- term impacts on the human throat and gut microbiome. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009836"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00820-19","DOI":"10.1128\/AAC.00820-19","article-title":"Impact of antibiotic gut exposure on the temporal changes in microbiome diversity","volume":"63","author":"Burdet","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.molmed.2016.04.003","article-title":"Antibiotic-induced changes in the intestinal microbiota and disease","volume":"22","author":"Becattini","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000443360","article-title":"Effects of antibiotics on gut microbiota","volume":"34","author":"Lange","year":"2016","journal-title":"Dig. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucl. Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2307\/1942268","article-title":"An ordination of the upland forest communities of Southern Wisconsin","volume":"27","author":"Bray","year":"1957","journal-title":"Ecol. Monogr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2047-217X-2-16","article-title":"EMPeror: A tool for visualizing high-throughput microbial community data","volume":"2","author":"Pirrung","year":"2013","journal-title":"Gigascience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1099\/mic.0.040618-0","article-title":"Long-term impacts of antibiotic exposure on the human intestinal microbiota","volume":"156","author":"Jernberg","year":"2010","journal-title":"Microbiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/s41564-018-0257-9","article-title":"Recovery of gut microbiota of healthy adults following antibiotic exposure","volume":"3","author":"Palleja","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1128\/AAC.00789-12","article-title":"High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin","volume":"56","author":"Fouhy","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1073\/pnas.1000087107","article-title":"Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation","volume":"108","author":"Dethlefsen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1136\/gutjnl-2012-303184","article-title":"Gut microbiota disturbance during antibiotic therapy: A multi-omic approach","volume":"62","author":"Gosalbes","year":"2013","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Panda, S., El khader, I., Casellas, F., L\u00f3pez Vivancos, J., Garc\u00eda Cors, M., Santiago, A., Cuenca, S., Guarner, F., and Manichanh, C. (2014). Short-term effect of antibiotics on human gut microbiota. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095476"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/ismej.2015.148","article-title":"The initial state of the human gut microbiome determines its reshaping by antibiotics","volume":"10","author":"Raymond","year":"2016","journal-title":"ISME J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00974","DOI":"10.1128\/mBio.00974-15","article-title":"Antibiotic-induced alterations of the murine gut microbiota and subsequent effects on colonization resistance against Clostridium difficile","volume":"6","author":"Schubert","year":"2015","journal-title":"mBio"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, R., Wang, H., Shi, Q., Wang, N., Zhang, Z., Xiong, C., Liu, J., Chen, Y., Jiang, L., and Jiang, Q. (2017). Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181690"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Thuny, F., Richet, H., Casalta, J.P., Angelakis, E., Habib, G., and Raoult, D. (2010). Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009074"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1128\/AAC.02437-14","article-title":"Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquin","volume":"58","author":"Angelakis","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1136\/gutjnl-2016-312297","article-title":"Antibiotics as deep modulators of gut microbiota: Between good and evil","volume":"65","author":"Ianiro","year":"2016","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fcimb.2019.00099","article-title":"Antibiotic-Induced disruption of gut microbiota alters local metabolomes and immune responses","volume":"9","author":"Sun","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9277","DOI":"10.1007\/s00253-019-10165-x","article-title":"Antibiotic effects on gut microbiota, metabolism, and beyond","volume":"103","author":"Mu","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nature25979","article-title":"Extensive impact of non-antibiotic drugs on human gut bacteria","volume":"555","author":"Maier","year":"2018","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.chom.2019.10.011","article-title":"Recovery of the gut microbiota after antibiotics depends on host diet, community context, and environmental reservoirs","volume":"26","author":"Ng","year":"2019","journal-title":"Cell Host Microbe."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00206-19","DOI":"10.1128\/IAI.00206-19","article-title":"Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation","volume":"87","author":"Morjaria","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00543-17","DOI":"10.1128\/AAC.00543-17","article-title":"Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with dav131a in a model of moxifloxacin-induced Clostridium difficile colitis","volume":"61","author":"Burdet","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/cen.13495","article-title":"Antibiotics, gut microbiome and obesity","volume":"88","author":"Leong","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.tim.2018.06.003","article-title":"Antibiotic scars left on the gut microbiota from the stringent response","volume":"26","author":"Yi","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ebiom.2018.11.035","article-title":"Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial","volume":"38","author":"Wei","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/imr.12563","article-title":"The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens","volume":"279","author":"Kim","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1172\/JCI86674","article-title":"Antibiotic effects on gut microbiota and metabolism are host dependent","volume":"126","author":"Fujisaka","year":"2016","journal-title":"J. Clin. Investig."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/1\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:56Z","timestamp":1760179676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/1\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,30]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["genes12010041"],"URL":"https:\/\/doi.org\/10.3390\/genes12010041","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,30]]}}}