{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:02:46Z","timestamp":1789531366381,"version":"build-2803163510"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"ROK National Institute of Health","award":["022-ER-210400 and 2022-NI-036"],"award-info":[{"award-number":["022-ER-210400 and 2022-NI-036"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trop Med Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Doxycycline is the standard treatment for scrub typhus, but evidence regarding parenteral alternatives remains limited in hospitalized patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>\n                      We conducted a multicenter, prospective, randomized, open-label trial in Korea. Participants were enrolled and randomized from November 2022 through December 6, 2024. Adults aged 19\u00a0years or older hospitalized with clinically suspected scrub typhus were randomized to intravenous tigecycline or oral doxycycline; all randomized participants were subsequently laboratory-confirmed by PCR and\/or seroconversion on paired serologic testing. Tigecycline was given as a 100\u00a0mg loading dose followed by 50\u00a0mg every 12\u00a0h for 5\u00a0days; doxycycline was given as 100\u00a0mg every 12\u00a0h for 7\u00a0days. The primary outcome was time from first dose to body temperature &lt;37.3\u00a0\u00b0C sustained for at least 48 consecutive hours without antipyretics. Of 27 randomized patients, 24 were included in the per-protocol efficacy analysis. Median time to defervescence was shorter with tigecycline than with doxycycline (16.6\u00a0h [interquartile range, 11.0\u201332.0] vs. 55.0\u00a0h [24.0\u201364.3];\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0079). No recurrence requiring additional antirickettsial therapy occurred within 30\u00a0days. One patient in each group reported nausea.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this preliminary randomized trial, intravenous tigecycline was associated with faster defervescence than oral doxycycline in clinically stable hospitalized adults with scrub typhus. These findings support further evaluation of tigecycline as an intravenous option in selected patients.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      ClinicalTrials.gov, NCT07513103.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41182-026-01073-8","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:06:56Z","timestamp":1789528016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tigecycline versus doxycycline for scrub typhus: a preliminary randomized trial"],"prefix":"10.1186","volume":"54","clinical-trial-number":[{"clinical-trial-number":"nct07513103","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jae Hyoung","family":"Im","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukbin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ju","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DaeHyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Jun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonghyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyeon","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kyoung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EunJi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Myoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Hyun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Wook","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Gyu","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Soo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"2","key":"1073_CR1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3947\/ic.2023.0055","volume":"55","author":"MH Chung","year":"2023","unstructured":"Chung MH, Lee JS, Im JH. Antibiotic combination therapy for severe scrub typhus: is it necessary? Infect Chemother. 2023;55(2):179\u201384. https:\/\/doi.org\/10.3947\/ic.2023.0055.","journal-title":"Infect Chemother"},{"key":"1073_CR2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002150.pub2","volume":"9","author":"I El Sayed","year":"2018","unstructured":"El Sayed I, Liu Q, Wee I, Hine P. Antibiotics for treating scrub typhus. Cochrane Database Syst Rev. 2018;9:CD002150. https:\/\/doi.org\/10.1002\/14651858.CD002150.pub2.","journal-title":"Cochrane Database Syst Rev"},{"issue":"9","key":"1073_CR3","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1128\/AAC.00508-07","volume":"51","author":"K Phimda","year":"2007","unstructured":"Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S, et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother. 2007;51(9):3259\u201363. https:\/\/doi.org\/10.1128\/AAC.00508-07.","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"1073_CR4","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1056\/NEJMoa2208449","volume":"388","author":"GM Varghese","year":"2023","unstructured":"Varghese GM, Dayanand D, Gunasekaran K, Kundu D, Wyawahare M, Sharma N, et al. Intravenous doxycycline, azithromycin, or both for severe scrub typhus. N Engl J Med. 2023;388(9):792\u2013803. https:\/\/doi.org\/10.1056\/NEJMoa2208449.","journal-title":"N Engl J Med"},{"issue":"4","key":"1073_CR5","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.3349\/ymj.2016.57.4.1034","volume":"57","author":"SM Lee","year":"2016","unstructured":"Lee SM, Kwon HY, Im JH, Baek JH, Hwang SS, Kang JS, et al. In vitro activity of tigecycline against Orientia tsutsugamushi. Yonsei Med J. 2016;57(4):1034\u20137. https:\/\/doi.org\/10.3349\/ymj.2016.57.4.1034.","journal-title":"Yonsei Med J"},{"issue":"3","key":"1073_CR6","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1093\/jac\/dki260","volume":"56","author":"CT Ong","year":"2005","unstructured":"Ong CT, Babalola CP, Nightingale CH, Nicolau DP. Penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs). J Antimicrob Chemother. 2005;56(3):498\u2013501. https:\/\/doi.org\/10.1093\/jac\/dki260.","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"1073_CR7","doi-asserted-by":"publisher","first-page":"368","DOI":"10.4269\/ajtmh.2010.09-0233","volume":"82","author":"GCKW Koh","year":"2010","unstructured":"Koh GCKW, Maude RJ, Paris DH, Newton PN, Blacksell SD. Diagnosis of scrub typhus. Am J Trop Med Hyg. 2010;82(3):368\u201370. https:\/\/doi.org\/10.4269\/ajtmh.2010.09-0233.","journal-title":"Am J Trop Med Hyg"},{"issue":"2","key":"1073_CR8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1517\/14740338.2015.997206","volume":"14","author":"Q Kaewpoowat","year":"2015","unstructured":"Kaewpoowat Q, Ostrosky-Zeichner L. Tigecycline: a critical safety review. Expert Opin Drug Saf. 2015;14(2):335\u201342. https:\/\/doi.org\/10.1517\/14740338.2015.997206.","journal-title":"Expert Opin Drug Saf"},{"issue":"9","key":"1073_CR9","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1086\/425008","volume":"39","author":"YS Kim","year":"2004","unstructured":"Kim YS, Yun HJ, Shim SK, Koo SH, Kim SY, Kim S. A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus. Clin Infect Dis. 2004;39(9):1329\u201335. https:\/\/doi.org\/10.1086\/425008.","journal-title":"Clin Infect Dis"},{"issue":"6","key":"1073_CR10","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1128\/AAC.01460-06","volume":"51","author":"DM Kim","year":"2007","unstructured":"Kim DM, Yu KD, Lee JH, Kim HK, Lee SH. Controlled trial of a 5-day course of telithromycin versus doxycycline for treatment of mild to moderate scrub typhus. Antimicrob Agents Chemother. 2007;51(6):2011\u20135. https:\/\/doi.org\/10.1128\/AAC.01460-06.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Tropical Medicine and Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41182-026-01073-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41182-026-01073-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41182-026-01073-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:07:00Z","timestamp":1789528020000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41182-026-01073-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1073"],"URL":"https:\/\/doi.org\/10.1186\/s41182-026-01073-8","relation":{},"ISSN":["1349-4147"],"issn-type":[{"value":"1349-4147","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"19 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Institutional Review Boards of Inha University Hospital (IRB no. 2022\u201304-017), Dankook University Hospital (IRB no. 2022\u201311-018), and Gyeongsang National University Hospital (IRB no. 2022\u201311-007). Written informed consent was obtained from all participants before enrollment. The study was conducted in accordance with the Declaration of Helsinki and applicable national and institutional regulations.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"200"}}