{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:55:37Z","timestamp":1791312937131,"version":"4.3.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP\/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012405","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T17:40:04Z","timestamp":1724348404000},"page":"e0012405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Updated therapeutic options for human brucellosis: A systematic review and network meta-analysis of randomized controlled trials"],"prefix":"10.1371","volume":"18","author":[{"given":"Shanjun","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-4539","authenticated-orcid":true,"given":"Qing","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Shui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"pntd.0012405.ref001","unstructured":"Brucellosis: Endemic and re-emerging zoonosis. Available from: https:\/\/www.healio.com\/news\/infectious-disease\/20130917\/10_3928_1081_597x_20130101_00_1309029."},{"issue":"1","key":"pntd.0012405.ref002","article-title":"The impact of the COVID-19 pandemic on the incidence and mortality of zoonotic diseases in China","volume":"7","author":"C Ma","year":"2022","journal-title":"BMJ Glob Health"},{"issue":"5","key":"pntd.0012405.ref003","first-page":"823","article-title":"The current therapeutical strategies in human brucellosis Infection.","volume":"49","author":"M Bosilkovski","year":"2021"},{"issue":"4","key":"pntd.0012405.ref004","first-page":"333","article-title":"Doxycycline Plus Trimethoprim-Sulfamethoxazole versus Doxycycline plus Rifampicin in Treatment of Brucellosis: A Randomized Controlled Trial Al-Azhar.","volume":"20","author":"WA Hassan","year":"2022","journal-title":"Assiut Medical Journal"},{"key":"pntd.0012405.ref005","doi-asserted-by":"crossref","first-page":"1136674","DOI":"10.3389\/fcimb.2023.1136674","article-title":"Research progress on complications of Brucellosis","volume":"13","author":"M Jin","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"issue":"22","key":"pntd.0012405.ref006","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1056\/NEJMra050570","article-title":"Brucellosis.","volume":"352","author":"G Pappas","year":"2005","journal-title":"N Engl J Med"},{"issue":"12","key":"pntd.0012405.ref007","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S1473-3099(07)70286-4","article-title":"Human brucellosis","volume":"7","author":"MP Franco","year":"2007","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"pntd.0012405.ref008","first-page":"327","article-title":"Human brucellosis in Macedonia\u201410 years of clinical experience in endemic region Croat","volume":"51","author":"M Bosilkovski","year":"2010","journal-title":"Med J."},{"key":"pntd.0012405.ref009","first-page":"1","article-title":"Joint FAO-WHO Expert Committee on Brucellosis.","volume":"464","year":"1971","journal-title":"Fifth report World Health Organ Tech Rep Ser."},{"issue":"8","key":"pntd.0012405.ref010","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1001\/jama.1951.02920260021006","article-title":"Terramycin, chloramphenicol and aureomycin in acute brucellosis; a preliminary report","volume":"145","author":"JH Killough","year":"1951","journal-title":"JAMA"},{"key":"pntd.0012405.ref011","first-page":"1","article-title":"Joint FAO\/WHO expert committee on brucellosis","volume":"740","year":"1986","journal-title":"World Health Organ Tech Rep Ser"},{"issue":"2","key":"pntd.0012405.ref012","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000238662","article-title":"Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis","volume":"35","author":"JD Colmenero Castillo","year":"1989","journal-title":"Chemotherapy"},{"issue":"4","key":"pntd.0012405.ref013","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1128\/AAC.28.4.548","article-title":"Comparative trial of rifampin-doxycycline versus tetracycline-streptomycin in the therapy of human brucellosis","volume":"28","author":"J Ariza","year":"1985","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pntd.0012405.ref014","doi-asserted-by":"crossref","first-page":"e0262551","DOI":"10.1371\/journal.pone.0262551","article-title":"Proteomics-based screening and antibiotic resistance assessment of clinical and sub-clinical Brucella species: An evolution of brucellosis infection control","volume":"17","author":"A Elbehiry","year":"2022","journal-title":"PLoS ONE"},{"issue":"12","key":"pntd.0012405.ref015","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1371\/journal.pmed.0040317","article-title":"Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations.","volume":"4","author":"J Ariza","year":"2007","journal-title":"PLoS Med."},{"issue":"1","key":"pntd.0012405.ref016","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ijantimicag.2012.03.018","article-title":"Long-term triple-antibiotic treatment against brucellar vertebral osteomyelitis","volume":"40","author":"E Giannitsioti","year":"2012","journal-title":"Int J Antimicrob Agents."},{"issue":"6","key":"pntd.0012405.ref017","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00406-016-0715-4","article-title":"Network meta-analyses should be the highest level of evidence in treatment guidelines","volume":"266","author":"S Leucht","year":"2016","journal-title":"Eur Arch Psychiatry Clin Neurosci."},{"issue":"11","key":"pntd.0012405.ref018","doi-asserted-by":"crossref","first-page":"777","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations","volume":"162","author":"B Hutton","year":"2015","journal-title":"Ann Intern Med"},{"key":"pntd.0012405.ref019","author":"JPT Higgins","journal-title":"Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023)."},{"issue":"2","key":"pntd.0012405.ref020","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/jrsm.1037","article-title":"Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool","volume":"3","author":"G Salanti","year":"2012","journal-title":"Res Synth Methods"},{"issue":"7646","key":"pntd.0012405.ref021","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1136\/bmj.39497.500903.25","article-title":"Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials","volume":"336","author":"K Skalsky","year":"2008","journal-title":"BMJ"},{"issue":"9","key":"pntd.0012405.ref022","doi-asserted-by":"crossref","first-page":"e0011590","DOI":"10.1371\/journal.pntd.0011590","article-title":"Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis.","volume":"17","author":"S Huang","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012405.ref023","doi-asserted-by":"crossref","first-page":"m3907","DOI":"10.1136\/bmj.m3907","article-title":"GRADE approach to drawing conclusions from a network meta-analysis using a partially contextualised framework","volume":"371","author":"R Brignardello-Petersen","year":"2020","journal-title":"BMJ"},{"key":"pntd.0012405.ref024","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"JAC Sterne","year":"2019","journal-title":"BMJ"},{"issue":"10","key":"pntd.0012405.ref025","doi-asserted-by":"crossref","first-page":"e76654","DOI":"10.1371\/journal.pone.0076654","article-title":"Graphical tools for network meta-analysis in STATA.","volume":"8","author":"A Chaimani","year":"2013","journal-title":"PLoS ONE."},{"issue":"5","key":"pntd.0012405.ref026","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/clind\/16.5.671","article-title":"Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis","volume":"16","author":"JM Montejo","year":"1993","journal-title":"Clin Infect Dis"},{"key":"pntd.0012405.ref027","first-page":"209","article-title":"Comparison Between Efficacy of Cipofoxacin Doxycycline and Rifampin\u2014Doxycycline Regimens in Treatment and Relapse of Brucellosis","volume":"14","author":"H Sarmadian","year":"2009","journal-title":"Trop Med Int Health"},{"key":"pntd.0012405.ref028","article-title":"Efficacy of cotrimoxasol plus rifampin for six and eight weeks of therapy in childhood brucellosis","author":"M Hasanjani Roushan","year":"2005","journal-title":"European Congress of Clinical Microbiology and Infectious Diseases"},{"issue":"10","key":"pntd.0012405.ref029","first-page":"Cd007179","article-title":"Antibiotics for treating human brucellosis.","volume":"10","author":"R Yousefi-Nooraie","year":"2012","journal-title":"Cochrane Database Syst Rev."},{"issue":"4 Suppl","key":"pntd.0012405.ref030","first-page":"221","article-title":"Treatment of brucellosis with rifampicin+tetracycline vs TMP\/SMZ: A prospective and randomized study.","volume":"1","author":"L Buzon","year":"1982","journal-title":"Chemioterapia"},{"issue":"2","key":"pntd.0012405.ref031","doi-asserted-by":"crossref","first-page":"e32090","DOI":"10.1371\/journal.pone.0032090","article-title":"Systematic review and meta-analysis of randomized clinical trials in the treatment of human brucellosis.","volume":"7","author":"J Sol\u00eds Garc\u00eda del Pozo","year":"2012","journal-title":"PLoS ONE."},{"issue":"2","key":"pntd.0012405.ref032","doi-asserted-by":"crossref","first-page":"e0191993","DOI":"10.1371\/journal.pone.0191993","article-title":"Rifampicin versus streptomycin for brucellosis treatment in humans: A meta-analysis of randomized controlled trials.","volume":"13","author":"F Meng","year":"2018","journal-title":"PLoS ONE."},{"issue":"5","key":"pntd.0012405.ref033","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1179\/joc.2003.15.5.466","article-title":"Comparison of five antimicrobial regimens for the treatment of brucellar spondylitis: a prospective, randomized study.","volume":"15","author":"Y Bayindir","year":"2003","journal-title":"J Chemother."},{"issue":"8","key":"pntd.0012405.ref034","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1128\/AAC.33.8.1409","article-title":"Comparative in vitro activities of ofloxacin, difloxacin, ciprofloxacin, and other selected antimicrobial agents against Brucella melitensis","volume":"33","author":"MY Khan","year":"1989","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"pntd.0012405.ref035","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1046\/j.1469-0691.2002.00416.x","article-title":"In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey","volume":"8","author":"S Kocag\u00f6z","year":"2002","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"pntd.0012405.ref036","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jinf.2006.09.015","article-title":"Doxycycline-rifampicin: physicians\u2019 inferior choice in brucellosis or how convenience reigns over science","volume":"54","author":"G Pappas","year":"2007","journal-title":"J Infect"},{"key":"pntd.0012405.ref037","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijid.2015.12.012","article-title":"Health literacy: a concept with potential to greatly impact the infectious diseases field","volume":"43","author":"RH Osborne","year":"2016","journal-title":"Int J Infect Dis"},{"issue":"6","key":"pntd.0012405.ref038","first-page":"889","article-title":"Comparison of two chemotherapy regimen: Doxycycline-rifampicin and doxycycline cotrimoxazol in the brucellosis patients Ahwaz, Iran, 2004\u20132006.","volume":"23","author":"S Alavi","year":"2007","journal-title":"Pak J Med Sci"},{"issue":"2","key":"pntd.0012405.ref039","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.idc.2009.01.009","article-title":"Meta-analyses on the optimization of the duration of antimicrobial treatment for various infections.","volume":"23","author":"PI Rafailidis","year":"2009","journal-title":"Infect Dis Clin North Am."},{"issue":"2","key":"pntd.0012405.ref040","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijantimicag.2005.06.001","article-title":"New approaches to the antibiotic treatment of brucellosis","volume":"26","author":"G Pappas","year":"2005","journal-title":"Int J Antimicrob Agents."},{"issue":"1","key":"pntd.0012405.ref041","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1080\/21655979.2021.1962683","article-title":"Short- and long-term follow-up outcomes of patients with Brucella endocarditis: a systematic review of 207 Brucella endocarditis Cases.","volume":"12","author":"X Li","year":"2021","journal-title":"Bioengineered"},{"issue":"6","key":"pntd.0012405.ref042","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.athoracsur.2012.07.006","article-title":"Medical versus medical and surgical treatment for brucella endocarditis","volume":"201294","author":"M Keshtkar-Jahromi","journal-title":"Ann Thorac Surg."}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T17:40:30Z","timestamp":1724348430000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012405"}},"subtitle":[],"editor":[{"given":"David Joseph","family":"Diemert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012405","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]}}}