{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:24:21Z","timestamp":1768454661445,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Erasmus MC2"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Mycobacterium abscessus can cause severe infections in at-risk patients. Treatment efficacy for M. abscessus infections remains low, and better treatment options are needed. Factors hampering antibiotic potency may include the ability of M. abscessus to form biofilms and to endure in nutrient-deprived environments. These factors are underrepresented in current preclinical drug activity assays. Diversifying preclinical models by incorporating characteristics of these harsh environments may be important to better predict drug efficacy in patients. We aimed to develop a novel tool for studying drug activity against biofilm-embedded M. abscessus. In addition, drug activity was assessed against actively multiplying and nutrient-starved M. abscessus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An in-house 3D-printed platform-disc\u2013based biofilm model was developed to study M. abscessus pellicle biofilms. In vitro activity of 16\u00d7 the MICs of amikacin, bedaquiline, clofazimine, imipenem, rifabutin and tigecycline was assessed using time\u2013kill kinetics assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The platform-disc\u2013based model established reliable and reproducible quantification of M. abscessus biofilms. Drug activity against biofilm-embedded and nutrient-starved M. abscessus seemed less pronounced than against actively multiplying mycobacteria. For biofilm-embedded M. abscessus, drug activity was dependent on the developmental stage of the biofilm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The varying levels of drug activity observed across the different M. abscessus populations highlight their distinct physiological relevance. As such, the platform-disc\u2013based biofilm model could serve as a valuable asset in preclinical drug activity assays for M. abscessus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf468","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:37:26Z","timestamp":1765197446000},"source":"Crossref","is-referenced-by-count":0,"title":["Towards enhanced translational value: preclinical drug activity testing against actively multiplying, nutrient-starved and pellicle biofilm-embedded\n                    <i>Mycobacterium abscessus<\/i>"],"prefix":"10.1093","volume":"81","author":[{"given":"Henri\u00ebtte M","family":"Meliefste","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9910-156X","authenticated-orcid":false,"given":"Saskia E","family":"Mudde","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole C","family":"Ammerman","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel L","family":"Bexkens","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corn\u00e9 P","family":"de Vogel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem J B","family":"van Wamel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurriaan E M","family":"de Steenwinkel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannelore I","family":"Bax","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"2026011413253065900_dkaf468-B1","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1093\/jac\/dkr578","article-title":"Mycobacterium abscessus: a new antibiotic nightmare","volume":"67","author":"Nessar","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2026011413253065900_dkaf468-B2","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1586\/14787210.2013.830413","article-title":"Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative patients: the evidence","volume":"11","author":"van Ingen","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2026011413253065900_dkaf468-B3","doi-asserted-by":"publisher","first-page":"511","DOI":"10.3201\/eid2203.150828","article-title":"Treatment of Mycobacterium abscessus infection","volume":"22","author":"Novosad","year":"2016","journal-title":"Emerg Infect Dis"},{"key":"2026011413253065900_dkaf468-B4","doi-asserted-by":"publisher","first-page":"2000535","DOI":"10.1183\/13993003.00535-2020","article-title":"Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS\/ERS\/ESCMID\/IDSA clinical practice guideline","volume":"56","author":"Daley","year":"2020","journal-title":"Eur Respir J"},{"key":"2026011413253065900_dkaf468-B5","doi-asserted-by":"publisher","first-page":"e02179-20","DOI":"10.1128\/AAC.02179-20","article-title":"Differential in vitro activities of individual drugs and bedaquiline-rifabutin combinations against actively multiplying and nutrient-starved Mycobacterium abscessus","volume":"65","author":"Lee","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B6","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.3389\/fmicb.2018.02417","article-title":"Novel screen to assess bactericidal activity of compounds against non-replicating Mycobacterium abscessus","volume":"9","author":"Berube","year":"2018","journal-title":"Front Microbiol"},{"key":"2026011413253065900_dkaf468-B7","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3389\/fmicb.2020.00359","article-title":"Extreme drug tolerance of Mycobacterium abscessus \u201cpersisters\u201d","volume":"11","author":"Yam","year":"2020","journal-title":"Front Microbiol"},{"key":"2026011413253065900_dkaf468-B8","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1183\/13993003.01102-2015","article-title":"Chronic pulmonary disease with Mycobacterium abscessus complex is a biofilm infection","volume":"46","author":"Qvist","year":"2015","journal-title":"Eur Respir J"},{"key":"2026011413253065900_dkaf468-B9","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1164\/rccm.201508-1586IM","article-title":"Biofilm formation by Mycobacterium abscessus in a lung cavity","volume":"193","author":"Fennelly","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026011413253065900_dkaf468-B10","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S1473-3099(12)70316-X","article-title":"Rapidly growing mycobacterial bloodstream infections","volume":"13","author":"El Helou","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"2026011413253065900_dkaf468-B11","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1093\/jac\/dkz267","article-title":"Omadacycline as a promising new agent for the treatment of infections with Mycobacterium abscessus","volume":"74","author":"Bax","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2026011413253065900_dkaf468-B12","doi-asserted-by":"publisher","first-page":"3169","DOI":"10.1093\/jac\/dkae336","article-title":"Mycobacterium abscessus strain variability in preclinical drug development: does it really matter?","volume":"79","author":"Mudde","year":"2024","journal-title":"J Antimicrob Chemother"},{"key":"2026011413253065900_dkaf468-B13","author":"CLSI"},{"key":"2026011413253065900_dkaf468-B14","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaf413","article-title":"Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies","author":"Mudde","year":"2025; 413","journal-title":"J Antimicrob Chemother"},{"key":"2026011413253065900_dkaf468-B15","doi-asserted-by":"publisher","first-page":"5485","DOI":"10.1128\/AAC.05293-11","article-title":"Sterilizing activity of novel TMC207- and PA-824-containing regimens in a murine model of tuberculosis","volume":"55","author":"Tasneen","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B16","doi-asserted-by":"publisher","first-page":"e00388-19","DOI":"10.1128\/AAC.00388-19","article-title":"Treatment-shortening effect of a novel regimen combining clofazimine and high-dose rifapentine in pathologically distinct mouse models of tuberculosis","volume":"63","author":"Saini","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B17","doi-asserted-by":"publisher","first-page":"2988","DOI":"10.3389\/fmicb.2018.02988","article-title":"A closer look at the genomic variation of geographically diverse Mycobacterium abscessus clones that cause human infection and disease","volume":"9","author":"Davidson","year":"2018","journal-title":"Front Microbiol"},{"key":"2026011413253065900_dkaf468-B18","doi-asserted-by":"publisher","first-page":"e02623-18","DOI":"10.1128\/AAC.02623-18","article-title":"In vitro activity of the new \u03b2-lactamase inhibitors relebactam and vaborbactam in combination with \u03b2-lactams against Mycobacterium abscessus complex clinical isolates","volume":"63","author":"Kaushik","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B19","doi-asserted-by":"publisher","first-page":"e00470-19","DOI":"10.1128\/AAC.00470-19","article-title":"In vitro activity of new tetracycline analogs omadacycline and eravacycline against drug-resistant clinical isolates of Mycobacterium abscessus","volume":"63","author":"Kaushik","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B20","doi-asserted-by":"publisher","first-page":"e1004697","DOI":"10.1371\/journal.ppat.1004697","article-title":"Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili","volume":"11","author":"Floyd","year":"2015","journal-title":"PLoS Pathog"},{"key":"2026011413253065900_dkaf468-B21","doi-asserted-by":"publisher","first-page":"e0154521","DOI":"10.1128\/AAC.01545-21","article-title":"In vitro activity of bedaquiline and imipenem against actively growing, nutrient-starved, and intracellular Mycobacterium abscessus","volume":"65","author":"Martins","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B22","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jgar.2022.10.015","article-title":"Unraveling antibiotic resistance mechanisms in Mycobacterium abscessus: the potential role of efflux pumps","volume":"31","author":"Mudde","year":"2022","journal-title":"J Glob Antimicrob Resist"},{"key":"2026011413253065900_dkaf468-B23","doi-asserted-by":"publisher","first-page":"554","DOI":"10.5588\/ijtld.24.0139","article-title":"Omadacycline enhances the in vitro activity of clofazimine against Mycobacterium abscessus","volume":"28","author":"Mudde","year":"2024","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026011413253065900_dkaf468-B24","doi-asserted-by":"publisher","first-page":"e0038123","DOI":"10.1128\/aac.00381-23","article-title":"ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant M. abscessus in caseum surrogate","volume":"67","author":"Xie","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B25","doi-asserted-by":"publisher","first-page":"e2423842122","DOI":"10.1073\/pnas.2423842122","article-title":"Next-generation rifamycins for the treatment of mycobacterial infections","volume":"122","author":"Dartois","year":"2025","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026011413253065900_dkaf468-B26","doi-asserted-by":"publisher","first-page":"e00827-19","DOI":"10.1128\/AAC.00827-19","article-title":"Bedaquiline eliminates bactericidal activity of \u03b2-lactams against Mycobacterium abscessus","volume":"63","author":"Lindman","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B27","doi-asserted-by":"publisher","first-page":"5020","DOI":"10.1038\/s41598-021-84525-x","article-title":"Mycobacterium abscessus biofilms have viscoelastic properties which may contribute to their recalcitrance in chronic pulmonary infections","volume":"11","author":"Gloag","year":"2021","journal-title":"Sci Rep"},{"key":"2026011413253065900_dkaf468-B28","doi-asserted-by":"publisher","first-page":"e01782-17","DOI":"10.1128\/AAC.01782-17","article-title":"Mycobacterium abscessus smooth and rough morphotypes form antimicrobial-tolerant biofilm phenotypes but are killed by acetic acid","volume":"62","author":"Clary","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B29","doi-asserted-by":"publisher","first-page":"001402","DOI":"10.1099\/mic.0.001402","article-title":"Population heterogeneity in Mycobacterium smegmatis and Mycobacterium abscessus","volume":"169","author":"Born","year":"2023","journal-title":"Microbiology (Reading)"},{"key":"2026011413253065900_dkaf468-B30","doi-asserted-by":"publisher","first-page":"1392606","DOI":"10.3389\/fmicb.2024.1392606","article-title":"A laboratory perspective on Mycobacterium abscessus biofilm culture, characterization and drug activity testing","volume":"15","author":"Meliefste","year":"2024","journal-title":"Front Microbiol"},{"key":"2026011413253065900_dkaf468-B31","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1002\/ptr.5994","article-title":"Curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of Mycobacterium abscessus","volume":"32","author":"Marini","year":"2018","journal-title":"Phytother Res"},{"key":"2026011413253065900_dkaf468-B32","doi-asserted-by":"publisher","first-page":"e02488-18","DOI":"10.1128\/AAC.02488-18","article-title":"Mycobacterium abscessus cells have altered antibiotic tolerance and surface glycolipids in artificial cystic fibrosis sputum medium","volume":"63","author":"Hunt-Serracin","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026011413253065900_dkaf468-B33","doi-asserted-by":"publisher","first-page":"743126","DOI":"10.3389\/fmicb.2021.743126","article-title":"Unique features of Mycobacterium abscessus biofilms formed in synthetic cystic fibrosis medium","volume":"12","author":"Belardinelli","year":"2021","journal-title":"Front Microbiol"},{"key":"2026011413253065900_dkaf468-B34","doi-asserted-by":"publisher","first-page":"100051","DOI":"10.1016\/j.tcsw.2021.100051","article-title":"Mycobacterium abscessus biofilms produce an extracellular matrix and have a distinct mycolic acid profile","volume":"7","author":"Dokic","year":"2021","journal-title":"Cell Surf"},{"key":"2026011413253065900_dkaf468-B35","doi-asserted-by":"publisher","first-page":"147644","DOI":"10.1016\/j.gene.2023.147644","article-title":"Delineation of transcriptional regulators involved in biofilm formation cycle of Mycobacterium abscessus","volume":"882","author":"Veigyabati Devi","year":"2023","journal-title":"Gene"},{"key":"2026011413253065900_dkaf468-B36","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.eimc.2010.08.016","article-title":"Importance of antibiotic penetration in the antimicrobial resistance of biofilm formed by non-pigmented rapidly growing mycobacteria against amikacin, ciprofloxacin and clarithromycin","volume":"29","author":"Ort\u00edz-P\u00e9rez","year":"2011","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"2026011413253065900_dkaf468-B37","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s44259-024-00046-3","article-title":"Mechanisms of antimicrobial resistance in biofilms","volume":"2","author":"Liu","year":"2024","journal-title":"NPJ Antimicrob Resist"},{"key":"2026011413253065900_dkaf468-B38","doi-asserted-by":"publisher","first-page":"e0128772","DOI":"10.1371\/journal.pone.0128772","article-title":"Mycobacterium avium possesses extracellular DNA that contributes to biofilm formation, structural integrity, and tolerance to antibiotics","volume":"10","author":"Rose","year":"2015","journal-title":"PLoS One"},{"key":"2026011413253065900_dkaf468-B39","doi-asserted-by":"publisher","first-page":"100166","DOI":"10.1016\/j.bioflm.2023.100166","article-title":"Disruption of nontuberculous mycobacteria biofilms induces a highly vulnerable to antibiotic killing phenotype","volume":"6","author":"Kurbatfinski","year":"2023","journal-title":"Biofilm"},{"key":"2026011413253065900_dkaf468-B40","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1038\/s41467-021-21748-6","article-title":"Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis","volume":"12","author":"Chakraborty","year":"2021","journal-title":"Nat Commun"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/1\/dkaf468\/66123363\/dkaf468.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/1\/dkaf468\/66123363\/dkaf468.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:25:39Z","timestamp":1768415139000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkaf468\/8404116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,24]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf468","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,12,24]]},"article-number":"dkaf468"}}