{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:12:48Z","timestamp":1788952368338,"version":"build-2803163510"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222983\/Z\/21\/Z"],"award-info":[{"award-number":["222983\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.ebiom.2026.106447","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:10:29Z","timestamp":1787379029000},"page":"106447","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Determining intracellular and extracellular activities of azithromycin against azithromycin-resistant Salmonella Typhi and their association with clinical treatment responses"],"prefix":"10.1016","volume":"131","author":[{"given":"Ngo Ngoc Phuong","family":"Thuy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voong Vinh","family":"Phat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Dongol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-3281","authenticated-orcid":false,"given":"Nguyen Hoang Thu","family":"Trang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Bista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5975-3600","authenticated-orcid":false,"given":"Quynh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-7267","authenticated-orcid":false,"given":"Chau","family":"Vinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy E.","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buddha","family":"Basnyat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-7282","authenticated-orcid":false,"given":"Christopher M.","family":"Parry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia A.","family":"Rabaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay C.D.","family":"Hinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhilasha","family":"Karkey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7029-9210","authenticated-orcid":false,"given":"Pham Thanh","family":"Duy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2026.106447_bib1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0377-1237(03)80060-6","article-title":"Current trends in the management of typhoid fever","volume":"59","author":"Kalra","year":"2003","journal-title":"Med J Armed Forces India"},{"key":"10.1016\/j.ebiom.2026.106447_bib2","series-title":"The Lancet","first-page":"1136","article-title":"Typhoid fever","author":"Wain","year":"2015"},{"key":"10.1016\/j.ebiom.2026.106447_bib3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1128\/CMR.00002-15","article-title":"Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive salmonella infections","volume":"28","author":"Crump","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"10.1016\/j.ebiom.2026.106447_bib4","series-title":"World Health Organization Model List of Essential Medicines \u2013 23rd List, 2023","year":"2023"},{"key":"10.1016\/j.ebiom.2026.106447_bib5","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00105-18","article-title":"Emergence of an Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins","volume":"9","author":"Klemm","year":"2018","journal-title":"mBio"},{"key":"10.1016\/j.ebiom.2026.106447_bib6","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/cid\/ciz1204","article-title":"A novel lineage of ceftriaxone-resistant Salmonella Typhi from India that is closely related to XDR S. Typhi found in Pakistan","volume":"71","author":"Sah","year":"2020","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib7","doi-asserted-by":"crossref","DOI":"10.1093\/jacamr\/dlaa109","article-title":"The emergence of azithromycin-resistant Salmonella Typhi in Nepal","volume":"2","author":"Duy","year":"2020","journal-title":"JAC Antimicrob Resist"},{"key":"10.1016\/j.ebiom.2026.106447_bib8","doi-asserted-by":"crossref","first-page":"624","DOI":"10.3201\/eid2702.203874","article-title":"Azithromycin-resistant Salmonella enterica serovar typhi AcrB-R717Q\/L, Singapore","volume":"27","author":"Octavia","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib9","doi-asserted-by":"crossref","first-page":"e120","DOI":"10.1093\/cid\/ciaa1773","article-title":"Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India","volume":"72","author":"Carey","year":"2021","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib10","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00215-20","article-title":"A race against time: reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan","volume":"5","author":"Iqbal","year":"2020","journal-title":"mSphere"},{"key":"10.1016\/j.ebiom.2026.106447_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007868","article-title":"Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance","volume":"13","author":"Hooda","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib13","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1128\/AAC.04729-14","article-title":"Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A","volume":"59","author":"Parry","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s10787-012-0165-1","article-title":"Antibacterial and immunomodulatory properties of azithromycin treatment implications for periodontitis","volume":"21","author":"Bartold","year":"2013","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.ebiom.2026.106447_bib15","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1128\/AAC.02011-12","article-title":"Blood, tissue, and intracellular concentrations of azithromycin during and after end of therapy","volume":"57","author":"Matzneller","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1128\/AAC.40.1.75","article-title":"Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions","volume":"40","author":"Wildfeuer","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S1473-3099(15)00530-7","article-title":"Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial","volume":"16","author":"Arjyal","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.12688\/wellcomeopenres.16801.1","article-title":"Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol","volume":"6","author":"Giri","year":"2021","journal-title":"Wellcome Open Res"},{"key":"10.1016\/j.ebiom.2026.106447_bib19","author":"Andrews"},{"key":"10.1016\/j.ebiom.2026.106447_bib20","doi-asserted-by":"crossref","first-page":"e85867","DOI":"10.7554\/eLife.85867","article-title":"Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from a meta-analysis of 13,000 Salmonella Typhi genomes","volume":"12","author":"Carey","year":"2023","journal-title":"Elife"},{"key":"10.1016\/j.ebiom.2026.106447_bib21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ijc.2910260208","article-title":"Establishment and characterization of a human acute monocytic leukemia cell line (THP-1)","volume":"26","author":"Tsuchiya","year":"1980","journal-title":"Int J Cancer"},{"key":"10.1016\/j.ebiom.2026.106447_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0193601","article-title":"The phorbol 12-myristate-13-acetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium","volume":"13","author":"Starr","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.ebiom.2026.106447_bib23","article-title":"Salmonella enterica serovar typhi induces host metabolic reprogramming to increase glucose availability for intracellular replication","volume":"22","author":"Wang","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ebiom.2026.106447_bib24","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1099\/mic.0.041624-0","article-title":"Intracellular survival of Salmonella enterica serovar Typhi in human macrophages is independent of Salmonella pathogenicity island (SPI)-2","volume":"156","author":"Forest","year":"2010","journal-title":"Microbiology (Reading)"},{"key":"10.1016\/j.ebiom.2026.106447_bib25","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1002\/cpmc.56","article-title":"Salmonella Typhimurium Infection of Human Monocyte-Derived Macrophages","volume":"50","author":"Lathrop","year":"2018","journal-title":"Curr Protoc Microbiol"},{"key":"10.1016\/j.ebiom.2026.106447_bib26","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1128\/AAC.01146-08","article-title":"Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: study of antibiotic combinations","volume":"53","author":"Nguyen","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib27","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1038\/psp.2013.80","article-title":"Population pharmacokinetics of azithromycin in whole blood, peripheral blood mononuclear cells, and polymorphonuclear cells in healthy adults","volume":"3","author":"Sampson","year":"2014","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"Suppl 5","key":"10.1016\/j.ebiom.2026.106447_bib28","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1289\/ehp.97105s51261","article-title":"Cell size of alveolar macrophages: an interspecies comparison","volume":"105","author":"Krombach","year":"1997","journal-title":"Environ Health Perspect"},{"key":"10.1016\/j.ebiom.2026.106447_bib29","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jac\/dks442","article-title":"Activity of ceftaroline against extracellular (broth) and intracellular (THP-1 monocytes) forms of methicillin-resistant Staphylococcus aureus: Comparison with vancomycin, linezolid and daptomycin","volume":"68","author":"M\u00e9lard","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1128\/AAC.00852-06","article-title":"Comparative pharmacokinetics of azithromycin in serum and white blood cells of healthy subjects receiving a single-dose extended-release regimen versus a 3-day immediate-release regimen","volume":"51","author":"Liu","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib31","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vaccine.2018.04.022","article-title":"Typhoid vaccines: WHO position paper, March 2018\u2014recommendations","volume":"37","year":"2019","journal-title":"Vaccine"},{"key":"10.1016\/j.ebiom.2026.106447_bib32","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.3201\/eid2911.230499","article-title":"Case of carbapenem-resistant Salmonella Typhi infection, Pakistan, 2022","volume":"29","author":"Nizamuddin","year":"2023","journal-title":"Emerg Infect Dis"},{"key":"10.1016\/j.ebiom.2026.106447_bib33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ijid.2016.11.409","article-title":"A case of clinical and microbiological failure of azithromycin therapy in Salmonella enterica serotype Typhi despite low azithromycin MIC","volume":"54","author":"Manesh","year":"2017","journal-title":"Int J Infect Dis"},{"issue":"9","key":"10.1016\/j.ebiom.2026.106447_bib34","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1128\/AAC.38.9.1915","article-title":"Intracellular activity of azithromycin against bacterial enteric pathogens","volume":"38","author":"Rakita","year":"1994","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.ebiom.2026.106447_bib35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007955","article-title":"Treatment responses to azithromycin and ciprofloxacin in uncomplicated Salmonella Typhi infection: a comparison of clinical and microbiological data from a controlled human infection model","volume":"13","author":"Jin","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"10.1016\/j.ebiom.2026.106447_bib36","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1128\/iai.64.7.2765-2773.1996","article-title":"Acidification of phagosomes containing Salmonella typhimurium in murine macrophages","volume":"64","author":"Rathman","year":"1996","journal-title":"Infect Immun"},{"key":"10.1016\/j.ebiom.2026.106447_bib37","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/jac\/47.4.455","article-title":"In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula","volume":"47","author":"Butler","year":"2001","journal-title":"J Antimicrob Chemother"},{"issue":"10","key":"10.1016\/j.ebiom.2026.106447_bib38","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/BF01975836","article-title":"Effects of environmental factors on the in vitro potency of azithromycin","volume":"10","author":"Retsema","year":"1991","journal-title":"Eur J Clin Microbiol Infect Dis"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396426003312?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396426003312?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:27:05Z","timestamp":1788949625000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396426003312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":37,"alternative-id":["S2352396426003312"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2026.106447","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Determining intracellular and extracellular activities of azithromycin against azithromycin-resistant Salmonella Typhi and their association with clinical treatment responses","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2026.106447","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"106447"}}