{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:07Z","timestamp":1787027467068,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>An 8-year-old girl diagnosed with cardiofaciocutaneous syndrome presented to our department with gingival pain, inflammation, and bleeding. Her medical history included hypoplasia of the corpus callosum, intellectual disability, trichothiodystrophy, global developmental delay, myopia, laryngomalacia, hypothyroidism, and osteoporosis. A diagnosis was reached of \u201cperiodontitis as a direct manifestation of systemic diseases\u201d. During 9 years of follow-up, there were exacerbation episodes with spontaneous gum bleeding, ulcers in the interdental papilla, tooth mobility, and progressive tooth loss. Some of these exacerbation episodes resolved clinically with the administration of amoxicillin and metronidazole. We therefore proposed an oral microbiome study (subgingival and saliva samples) before and after antibiotic therapy. The most abundant genera at the subgingival level before administering antibiotics were Prevotella, Streptococcus, Fusobacterium, Leptotrichia, and Aggregatibacter. Of the 94 genera sequenced, 57 were less abundant in the post-treatment state than at baseline, particularly certain Gram-negative periodontal pathogens such as Porphyromonas, Treponema, Aggregatibacter, Fusobacterium, and Campylobacter. In contrast, other genera related to oral health, such as Haemophilus, Granulicatella, and Abiotrophia, showed an increase after administering the antibiotic. In conclusion, periodontitis exacerbations as a direct manifestation of systemic disease can occasionally be controlled exclusively with systemic antibiotics, without the need for performing mechanical periodontal therapy. This clinical recovery is correlated to substantial changes in the oral microbiome, which lead to the recovery of eubiosis of the microbiota.<\/jats:p>","DOI":"10.3390\/antibiotics11121754","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:56:26Z","timestamp":1670208986000},"page":"1754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analysis of the Oral Microbiome in a Patient with Cardiofaciocutaneous Syndrome and Severe Periodontal Disease: Impact of Systemic Antibiotic Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Carolina","family":"Mu\u00f1oz Navarro","sequence":"first","affiliation":[{"name":"Special Care Dentistry Postgraduate Training Program, School of Medicine and Dentistry, University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-533X","authenticated-orcid":false,"given":"Mar\u00eda","family":"del Carmen S\u00e1nchez Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"GINTRAMIS Research Group (Translational Research Group on Microbiota and Health), Department of Medicine, Faculty of Medicine, University Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-1598","authenticated-orcid":false,"given":"Carolina","family":"Arriagada Vargas","sequence":"additional","affiliation":[{"name":"Special Care Dentistry Postgraduate Training Program, School of Medicine and Dentistry, University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Batalla V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-1091","authenticated-orcid":false,"given":"M\u00e1rcio","family":"Diniz Freitas","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-1993","authenticated-orcid":false,"given":"Jacobo","family":"Limeres Posse","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1483-401X","authenticated-orcid":false,"given":"Pedro","family":"Diz Dios","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Garc\u00eda Mato","sequence":"additional","affiliation":[{"name":"Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global burden of severe periodontitis in 1990\u20132010: A systematic review and meta-regression","volume":"93","author":"Kassebaum","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/prd.12323","article-title":"Recent epidemiologic trends in periodontitis in the USA","volume":"82","author":"Eke","year":"2020","journal-title":"Periodontol. 2000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/jre.12821","article-title":"Adjunctive systemic antimicrobials in the treatment of chronic periodontitis: A systematic review and network meta-analysis","volume":"56","author":"Sgolastra","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/sj.ebd.6401197","article-title":"Antibiotics in aggressive periodontitis, is there a clinical benefit?","volume":"17","author":"Rajendra","year":"2016","journal-title":"Evid. Based Dent."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000510188","article-title":"Antibiotics against Periodontal Biofilms","volume":"29","author":"Guentsch","year":"2021","journal-title":"Monogr. Oral Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S237","DOI":"10.1002\/JPER.17-0733","article-title":"Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Jepsen","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_9","unstructured":"Kavamura, M.I. (2022, September 10). Cardiofaciocutaneous Syndrome. Available online: https:\/\/www.orpha.net\/consor\/cgi-bin\/Disease_Search.php?lng=ES&data_id=1559&MISSING%20CONTENT=S-ndrome-cardio-facio-cut-neo&search=Disease_Search_Simple&title=S%EDndrome%20cardio-facio-cut%E1neo."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ocr.12144","article-title":"A review of craniofacial and dental findings of the RASopathies","volume":"20","author":"Cao","year":"2017","journal-title":"Orthod. Craniofac. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ejogrb.2019.06.035","article-title":"Antenatal diagnosis of cardio-facio-cutaneous syndrome: Prenatal characteristics and contribution of fetal facial dysmorphic signs in utero. About a case and review of literature","volume":"240","author":"Biard","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1177\/00220345820610100901","article-title":"A comparison of whole mouth resting and stimulated salivary measurement procedures","volume":"61","author":"Navazesh","year":"1982","journal-title":"J. Dent. Res."},{"key":"ref_13","first-page":"308","article-title":"Black-pigmenting gram-negative bacteria in periodontal disease","volume":"26","author":"Mombelli","year":"1991","journal-title":"II. Screening strategies for detection of P. gingivalis. J. Periodontal Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies","volume":"41","author":"Klindworth","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","article-title":"Quality control and preprocessing of metagenomic datasets","volume":"27","author":"Schmieder","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_16","unstructured":"R Core Team (2012). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.R-project.org\/."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ondov, B.D., Bergman, N.H., and Phillippy, A.M. (2011). Interactive metagenomic visualization in a Web browser. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-385"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/SCS.0000000000000616","article-title":"LEOPARD syndrome: Maxillofacial care","volume":"25","author":"Aboh","year":"2014","journal-title":"J. Craniofac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1097\/SCS.0000000000000668","article-title":"Langerhans cell histiocytosis: Treatment strategies","volume":"2","author":"Giovannetti","year":"2014","journal-title":"J. Craniofac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1097\/00001665-199605000-00010","article-title":"Study and planning of the surgical procedure for the orbital district in patients affected by craniofacial malformations","volume":"7","author":"Fadda","year":"1999","journal-title":"J. Craniofac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/ajmg.a.36951","article-title":"A de novo proximal 3q29 chromosomemicroduplication in a patientwithoculo auriculo vertebral spectrum","volume":"167A","author":"Guida","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_24","first-page":"563","article-title":"Cardiofaciocutaneoussyndrome\u2014A longitudinal study of a case over 33 years: Case report and review of the literature","volume":"62","author":"Iuhas","year":"2021","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.gim.2022.04.004","article-title":"Neurologic and neurodevelopmental complications in cardiofaciocutaneous syndrome are associated with genotype: A multinational cohort study","volume":"24","author":"Pierpont","year":"2022","journal-title":"Genet. Med."},{"key":"ref_26","first-page":"271","article-title":"Periodontal disease in Noonan\u2019ssyndrome","volume":"48","year":"1991","journal-title":"Bol. Med. Hosp. Infant. Mex."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"703613","DOI":"10.3389\/fped.2021.703613","article-title":"Clinical and Cytometric Study of Immune Involvement in a Heterogeneous Cohort of Subjects WithRASopathies and mTORopathies","volume":"9","author":"Valencic","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1186\/s13023-021-02050-6","article-title":"Risk of autoimmune diseases in patients with RASopathies: Systematic study of humoral and cellular immunity","volume":"16","author":"Siano","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/ajmg.a.62588","article-title":"Characterization of bone homeostasis in individuals affected by cardio-facio-cutaneous syndrome","volume":"188","author":"Leoni","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/0022034516682017","article-title":"Bone density and clinical periodontal attachment in postmenopausal women: A systematic review and meta-analysis","volume":"96","author":"Penoni","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/cre2.247","article-title":"Relationship between hypothyroidism and periodontitis: A scoping review","volume":"6","author":"Aldulaijan","year":"2020","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.5037\/jomr.2022.13102","article-title":"Amoxicillin\/Metronidazole Dose Impact as an Adjunctive Therapy for Stage II\u2013III Grade C Periodontitis (Aggressive Periodontitis) at 3- And 6-Month Follow-Ups: A Systematic Review and Meta-Analysis","volume":"13","author":"Karrabi","year":"2022","journal-title":"J. Oral Maxillofac. Res."},{"key":"ref_33","first-page":"E54","article-title":"Treatment of periodontitis as a manifestation of neutropenia with or without systemic antibiotics: A systematic review","volume":"35","author":"Schmidt","year":"2013","journal-title":"Pediatr. Dent."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/j.1600-051X.2006.00957.x","article-title":"Effects of metronidazole plus amoxicillin as the only therapy on the microbiological and clinical parameters of untreated chronic periodontitis","volume":"33","author":"Socransky","year":"2006","journal-title":"J. Clin. Periodontol."},{"key":"ref_35","first-page":"196","article-title":"Amoxicillin\/metronidazole or scaling and root planing in the treatment of chronic periodontitis","volume":"23","author":"Bono","year":"2010","journal-title":"Acta Odontol. Latinoam."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Faveri, M., Retamal-Valdes, B., Mestnik, M.J., de Figueiredo, L.C., Bar\u00e3o, V.A.R., Souza, J.G.S., Duarte, P.M., and Feres, M. (J. Periodontol., 2022). Microbiological effects of amoxicillin plus metronidazole in the treatment of young patients with stages III and IV periodontitis: A secondary analysis from a 1-year double-blinded placebo-controlled randomized clinical trial, J. Periodontol., ahead of print.","DOI":"10.1002\/JPER.21-0171"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Di Stefano, M., Polizzi, A., Santonocito, S., Romano, A., Lombardi, T., and Isola, G. (2022). Impact of Oral Microbiome in Periodontal Health and Periodontitis: A Critical Review on Prevention and Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095142"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.2041-1014.2012.00663.x","article-title":"Beyond the red complex and into more complexity: The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology","volume":"27","author":"Hajishengallis","year":"2012","journal-title":"Mol. Oral Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/ismej.2011.191","article-title":"Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing","volume":"6","author":"Griffen","year":"2012","journal-title":"ISME J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ismej.2012.174","article-title":"The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation","volume":"7","author":"Abusleme","year":"2013","journal-title":"ISME J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.archoralbio.2019.02.012","article-title":"Subgingival microbiome in Chinese patients with generalized aggressive periodontitis compared to healthy controls","volume":"101","author":"Cui","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"N\u00f3voa, L., S\u00e1nchez, M.D.C., Blanco, J., Limeres, J., Cuenca, M., Mar\u00edn, M.J., Sanz, M., Herrera, D., and Diz, P. (2020). The Subgingival Microbiome in Patients with Down Syndrome and Periodontitis. J.Clin. Med., 9.","DOI":"10.3390\/jcm9082482"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hagenfeld, D., Koch, R., J\u00fcnemann, S., Prior, K., Harks, I., Eickholz, P., Hoffmann, T., Kim, T.-S., Kocher, T., and Meyle, J. (2018). Do we treat our patients or rather periodontal microbes with adjunctive antibiotics in periodontal therapy? A 16S rDNA microbial community analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195534"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/JPER.20-0128","article-title":"Microbiome changes in young periodontitis patients treated with adjunctive metronidazole and amoxicillin","volume":"92","author":"Feres","year":"2021","journal-title":"J. Periodontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/odi.13405","article-title":"Using next-generation sequencing to detect oral microbiome change following periodontal interventions: A systematic review","volume":"27","author":"Zhang","year":"2021","journal-title":"Oral Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/JPER.20-0764","article-title":"Effect of adjunctive systemic antibiotics on microbial populations compared with scaling and root planing alone for the treatment of periodontitis: A pilot randomized clinical trial","volume":"93","author":"Lu","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Laugisch, O., Auschill, T.M., Tumbrink, A., Sculean, A., and Arweiler, N.B. (2022). Influence of Anti-Infective Periodontal Therapy on Subgingival Microbiota Evaluated by Chair-Side Test Compared to qPCR-A Clinical Follow-Up Study. Antibiotics, 11.","DOI":"10.3390\/antibiotics11050577"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Retamal-Valdes, B., Tavares, A.P.L., Monique, S., da Silva, H.D.P., Mestnik, M.J., Duarte, P.M., Miranda, T.S., Borges, I., Soares, G.M.S., and Faveri, M. (J. Clin. Periodontol., 2022). Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials, J. Clin. Periodontol., ahead of print.","DOI":"10.1111\/jcpe.13704"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ardila, C.M., Bedoya-Garc\u00eda, J.A., and Arrubla-Escobar, D.E. (Oral Dis., 2022). Antibiotic resistance in periodontitis patients: A systematic scoping review of randomized clinical trials, Oral Dis., ahead of print.","DOI":"10.1111\/odi.14288"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1034\/j.1600-0757.2002.2801123.x","article-title":"Effective, safe, practical and affordable periodontal antimicrobial therapy: Where are we going, and are we there yet?","volume":"28","author":"Slots","year":"2002","journal-title":"Periodontol. 2000"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/12\/1754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:33:51Z","timestamp":1760146431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/12\/1754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,4]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["antibiotics11121754"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11121754","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,4]]}}}