{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:46:10Z","timestamp":1788918370634,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Recently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18\u00a0years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with \u201cgeneral disorders and administration site conditions\u201d and \u201cgastrointestinal disorders,\u201d while minocycline was more frequently linked to \u201cskin and subcutaneous tissue disorders\u201d and \u201cgastrointestinal disorders.\u201d Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48\u201342.67), although it remained unclear whether the discoloration was permanent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1413944","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:59:22Z","timestamp":1721969962000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety profiles of doxycycline, minocycline, and tigecycline in pediatric patients: a real-world pharmacovigilance analysis based on the FAERS database"],"prefix":"10.3389","volume":"15","author":[{"given":"Yanli","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","first-page":"905","volume-title":"Red Book: 2018 report of the committee on infectious diseases","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"bcr2013200723","DOI":"10.1136\/bcr-2013-200723","article-title":"Doxycycline and suicidality","volume":"2013","author":"Atigari","year":"2013","journal-title":"BMJ Case Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1111\/j.1525-1470.2007.00395.x","article-title":"Hyperthyroidism and lupus-like syndrome in an adolescent treated with minocycline for acne vulgaris","volume":"24","author":"Benjamin","year":"2007","journal-title":"Pediatr. Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1001\/archdermatol.2008.521","article-title":"Minocycline-induced drug hypersensitivity syndrome followed by multiple autoimmune sequelae","volume":"145","author":"Brown","year":"2009","journal-title":"Arch. Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1001\/jama.1948.02900020013004","article-title":"Aureomycin; experimental and clinical investigations","volume":"138","author":"Bryer","year":"1948","journal-title":"J. Am. Med. Assoc."},{"key":"B6","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40264-015-0289-5","article-title":"Comparison of statistical signal detection methods within and across spontaneous reporting databases","volume":"38","author":"Candore","year":"2015","journal-title":"Drug Saf."},{"key":"B7","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance","volume":"65","author":"Chopra","year":"2001","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.jmii.2018.11.004","article-title":"Recommendations and guidelines for the treatment of pneumonia in Taiwan","volume":"52","author":"Chou","year":"2019","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B9","doi-asserted-by":"publisher","first-page":"m4102","DOI":"10.1136\/bmj.m4102","article-title":"Doxycycline: coroner calls for MHRA to review side effects after student jumped from plane","volume":"371","author":"Dyer","year":"2020","journal-title":"BMJ"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1001\/jama.2021.17633","article-title":"Management of acne vulgaris: a review","volume":"326","author":"Eichenfield","year":"2021","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.jpeds.2008.03.013","article-title":"Chronic minocycline-induced autoimmunity in children","volume":"153","author":"El-Hallak","year":"2008","journal-title":"J. Pediatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/jac\/dkg208","article-title":"The quinolones: decades of development and use","volume":"51","author":"Emmerson","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1176\/appi.ajp.2021.20091347","article-title":"Lyme borreliosis and associations with mental disorders and suicidal behavior: a nationwide Danish cohort study","volume":"178","author":"Fallon","year":"2021","journal-title":"Am. J. Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1093\/qjmed\/hcac113","article-title":"Minocycline and black thyroid","volume":"115","author":"Goto","year":"2022","journal-title":"QJM"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3776","DOI":"10.1007\/s00415-020-10090-4","article-title":"Emerging themes in idiopathic intracranial hypertension","volume":"267","author":"Grech","year":"2020","journal-title":"J. Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e369","DOI":"10.1097\/INF.0000000000004041","article-title":"Guidelines for the management of respiratory infectious diseases in children in Japan 2022","volume":"42","author":"Ishiwada","year":"2023","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"54","DOI":"10.4103\/jpgm.JPGM_454_19","article-title":"Doxycycline-induced staining of teeth and malar rash in a child","volume":"66","author":"Joshi","year":"2020","journal-title":"J. Postgrad. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.joen.2010.03.031","article-title":"Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: a case report","volume":"36","author":"Kim","year":"2010","journal-title":"J. Endod."},{"key":"B20","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.anai.2015.12.010","article-title":"A severe case of minocycline-induced DRESS resulting in liver transplantation and autoimmune sequelae","volume":"116","author":"Lan","year":"2016","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/ciaa1215","article-title":"Clinical practice guidelines by the infectious diseases society of America (IDSA), American Academy of neurology (AAN), and American college of rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease","volume":"72","author":"Lantos","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1080\/07853890.2022.2085881","article-title":"Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance","volume":"54","author":"LaPlante","year":"2022","journal-title":"Ann. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1111\/j.1365-2133.2012.10845.x","article-title":"Comparative analysis of adverse drug reactions to tetracyclines: results of a French national survey and review of the literature","volume":"166","author":"Lebrun-Vignes","year":"2012","journal-title":"Br. J. Dermatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1108345","DOI":"10.3389\/fmed.2023.1108345","article-title":"Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in childhood: a narrative review","volume":"10","author":"Manieri","year":"2023","journal-title":"Front. Med. (Lausanne)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"757","DOI":"10.3390\/antibiotics10070757","article-title":"A review of systemic minocycline side effects and topical minocycline as a safer alternative for treating acne and rosacea","volume":"10","author":"Martins","year":"2021","journal-title":"Antibiot. (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1159\/000112926","article-title":"Minocycline-induced DRESS: evidence for accumulation of the culprit drug","volume":"216","author":"Maubec","year":"2008","journal-title":"Dermatology"},{"key":"B27","unstructured":"Prescribing information of DORYX\u00ae2022"},{"key":"B28","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.ijantimicag.2013.01.020","article-title":"All-cause mortality imbalance in the tigecycline phase 3 and 4 clinical trials","volume":"41","author":"McGovern","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B29","unstructured":"Prescribing information of DOXINE\u00ae2023"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e2021054980","DOI":"10.1542\/peds.2021-054980","article-title":"Management of pediatric Lyme disease: updates from 2020 Lyme guidelines","volume":"149","author":"Meissner","year":"2022","journal-title":"Pediatrics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1159\/000502843","article-title":"Case series: minocycline-associated thyroiditis","volume":"92","author":"Millington","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3760\/cma.j.cn331340-20230217-00023","article-title":"Guidelines for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children(2023 edition)","volume":"50","year":"2023","journal-title":"Inter J. Epidemiol. Infect. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"7246","DOI":"10.3390\/ijerph19127246","article-title":"Tetracyclines-an important therapeutic tool for dermatologists","volume":"19","author":"Orylska-Ratynska","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B59","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.eimc.2019.12.018","article-title":"Tigecycline therapy in pediatric patients with multidrug resistant bacteremia","volume":"38","author":"Ozkaya-Parlakay","year":"2020","journal-title":"Enferm. Infecc. Microbiol. Clin. (Engl Ed)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e252731","DOI":"10.1136\/bcr-2022-252731","article-title":"Optic atrophy secondary to minocycline-induced idiopathic intracranial hypertension","volume":"16","author":"Paramo","year":"2023","journal-title":"BMJ Case Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/WNO.0000000000001536","article-title":"Increased incidence of pseudotumor cerebri syndrome among users of tetracycline antibiotics","volume":"42","author":"Passi","year":"2022","journal-title":"J. Neuroophthalmol."},{"key":"B61","unstructured":"Prescribing information of NUZYRA\u00ae2021"},{"key":"B36","unstructured":"Prescribing information of MINOCIN\u00ae2017"},{"key":"B38","unstructured":"Prescribing information of TYGACIL\u00ae2020"},{"key":"B39","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.jpeds.2016.03.034","article-title":"Severe and persistent thyroid dysfunction associated with tetracycline-antibiotic treatment in youth","volume":"173","author":"Pollock","year":"2016","journal-title":"J. Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/pds.615","article-title":"The role of databases in drug postmarketing surveillance","volume":"10","author":"Rodriguez","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"B41","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ijid.2015.08.009","article-title":"Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs","volume":"39","author":"Shen","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"727","DOI":"10.4065\/74.7.727","article-title":"The tetracyclines","volume":"74","author":"Smilack","year":"1999","journal-title":"Mayo Clin. Proc."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/j.clinthera.2005.09.005","article-title":"Safety of doxycycline and minocycline: a systematic review","volume":"27","author":"Smith","year":"2005","journal-title":"Clin. Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1046\/j.1525-1470.1999.00106.x","article-title":"Complications of minocycline therapy for acne vulgaris: case reports and review of the literature","volume":"16","author":"Somech","year":"1999","journal-title":"Pediatr. Dermatol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ijid.2018.08.007","article-title":"Tigecycline salvage therapy for critically ill children with multidrug-resistant\/extensively drug-resistant infections after surgery","volume":"75","author":"Song","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1177\/1060028019863796","article-title":"Doxycycline and tooth discoloration in children: changing of recommendations based on evidence of safety","volume":"53","author":"Stultz","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"B47","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1089\/thy.2008.0048","article-title":"Drug-induced thyroiditis and papillary carcinoma in a minocycline-pigmented black thyroid gland","volume":"18","author":"Tacon","year":"2008","journal-title":"Thyroid"},{"key":"B48","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/S1473-3099(11)70177-3","article-title":"Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis","volume":"11","author":"Tasina","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"B62","unstructured":"Prescribing information of XERAVA\u00ae2018"},{"key":"B50","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1093\/cid\/ciz242","article-title":"Omadacycline: a novel tetracycline derivative with oral and intravenous formulations","volume":"69","author":"Watkins","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.jaad.2023.02.072","article-title":"Drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis","volume":"90","author":"Wei","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s11096-022-01397-5","article-title":"A pharmacovigilance study of the association between tetracyclines and hepatotoxicity based on Food and Drug Administration adverse event reporting system data","volume":"44","author":"Wei","year":"2022","journal-title":"Int. J. Clin. Pharm."},{"key":"B53","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/nrd1857","article-title":"Tigecycline","volume":"4","author":"Wenzel","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"B55","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.jaad.2015.12.037","article-title":"Guidelines of care for the management of acne vulgaris","volume":"74","author":"Zaenglein","year":"2016","journal-title":"J. Am. Acad. Dermatol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ijid.2017.05.013","article-title":"Tigecycline treatment in an infant with extensively drug-resistant Acinetobacter baumannii bacteremia","volume":"61","author":"Zeng","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"B56","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s40265-016-0545-8","article-title":"Review of eravacycline, a novel fluorocycline antibacterial agent","volume":"76","author":"Zhanel","year":"2016","journal-title":"Drugs"},{"key":"B57","doi-asserted-by":"publisher","first-page":"101967","DOI":"10.1016\/j.eclinm.2023.101967","article-title":"Psychiatric disorders associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database","volume":"59","author":"Zhou","year":"2023","journal-title":"EClinicalMedicine"},{"key":"B58","doi-asserted-by":"publisher","first-page":"e0085421","DOI":"10.1128\/AAC.00854-21","article-title":"Tigecycline-induced tooth discoloration in children younger than eight years","volume":"65","author":"Zhu","year":"2021","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1413944\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T08:51:04Z","timestamp":1722243064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1413944\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":58,"alternative-id":["10.3389\/fphar.2024.1413944"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1413944","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1413944"}}