{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:18:08Z","timestamp":1772691488034,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020171","name":"the Foreign, Commonwealth & Development Office","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"the Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Global Health Trials","award":["MR\/S004998\/1"],"award-info":[{"award-number":["MR\/S004998\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Bacterial vaginosis (BV) is associated with significant reproductive health risks and high recurrence rates after standard antibiotic treatment. Sulfadoxine\/pyrimethamine, an antimalarial drug, demonstrated unexpected clearance of BV in clinical trials, suggesting potential antimicrobial effects. Drug repurposing, which leverages existing drugs for new therapeutic applications, offers a promising approach to address the challenges of antimicrobial resistance and high recurrence rates in BV.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the in vitro activity of sulfadoxine\/pyrimethamine and its components, sulfadoxine and pyrimethamine, on key species associated with BV.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined for sulfadoxine\/pyrimethamine (20:1 ratio), sulfadoxine, pyrimethamine, and standard-of-care antibiotics, metronidazole and clindamycin, against BV-associated species (Gardnerella spp., Fannyhessea vaginae, Prevotella bivia) and Lactobacillus crispatus (vaginal health marker). Gardnerella biofilms were also exposed to sulfadoxine\/pyrimethamine, pyrimethamine, or metronidazole, and biofilm biomass and biofilm cells culturability were assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Sulfadoxine had no effect, while pyrimethamine inhibited all Gardnerella strains with MIC values ranging from 0.125 to 4\u2005mg\/L, lower than MICs observed for metronidazole (2\u2013128\u2005mg\/L). Pyrimethamine also outperformed metronidazole in inhibiting biofilm mass accumulation and reducing biofilm culturable cells in 3\/4 Gardnerella strains. Sulfadoxine\/pyrimethamine presented lower MICs than metronidazole for 5\/8 Gardnerella strains. Sulfadoxine, pyrimethamine, and sulfadoxine\/pyrimethamine showed no activity against other BV-associated species or L. crispatus.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings suggest that pyrimethamine (and sulfadoxine\/pyrimethamine) could be promising alternative or adjuvant therapies for BV, warranting further clinical trials.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jac\/dkaf157","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:34:16Z","timestamp":1747740856000},"page":"1972-1979","source":"Crossref","is-referenced-by-count":3,"title":["Repurposing antimalarials: pyrimethamine exhibits superior in vitro<\/i> activity to metronidazole against Gardnerella<\/i> while sparing Lactobacillus<\/i>"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-4732","authenticated-orcid":false,"given":"Aliona S","family":"Rosca","sequence":"first","affiliation":[{"name":"Department of Diagnostic Sciences, Laboratory Bacteriology Research, Ghent University , C. Heymanslaan 10, Ghent 9000 ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enesia Banda","family":"Chaponda","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Zambia , Lusaka ,","place":["Zambia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thalia","family":"Beckers","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Laboratory Bacteriology Research, Ghent University , C. Heymanslaan 10, Ghent 9000 ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry P","family":"De Koning","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow , 120 University Place, Glasgow G12 8TA ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R Matthew","family":"Chico","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Laboratory Bacteriology Research, Ghent University , C. Heymanslaan 10, Ghent 9000 ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"2025070104564141500_dkaf157-B1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/OLQ.0000000000000972","article-title":"High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis","volume":"46","author":"Peebles","year":"2019","journal-title":"Sex Transm Dis"},{"key":"2025070104564141500_dkaf157-B2","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41598-018-36964-2","article-title":"Association between preterm delivery and bacterial vaginosis with or without treatment","volume":"9","author":"Shimaoka","year":"2019","journal-title":"Sci Rep"},{"key":"2025070104564141500_dkaf157-B3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1136\/sextrans-2019-054191","article-title":"Novel bacterial vaginosis-associated organisms mediate the relationship between vaginal douching and pelvic inflammatory disease","volume":"96","author":"Gondwe","year":"2020","journal-title":"Sex Transm Infect"},{"key":"2025070104564141500_dkaf157-B4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1471-2334-11-10","article-title":"Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis","volume":"11","author":"Gillet","year":"2011","journal-title":"BMC Infect Dis"},{"key":"2025070104564141500_dkaf157-B5","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1097\/QAD.0000000000001741","article-title":"Bacterial vaginosis modifies the association between hormonal contraception and HIV acquisition","volume":"32","author":"Haddad","year":"2018","journal-title":"AIDS"},{"key":"2025070104564141500_dkaf157-B6","doi-asserted-by":"publisher","first-page":"9913878","DOI":"10.1155\/2021\/9913878","article-title":"Characterizations of bacterial vaginosis among HIV-positive and HIV-negative women in rural Eastern Cape Province, South Africa","volume":"2021","author":"Apalata","year":"2021","journal-title":"Int J Microbiol"},{"key":"2025070104564141500_dkaf157-B7","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1097\/01.AOG.0000183594.45524.d2","article-title":"Adherent biofilms in bacterial vaginosis","volume":"106","author":"Swidsinski","year":"2005","journal-title":"Obstet Gynecol"},{"key":"2025070104564141500_dkaf157-B8","doi-asserted-by":"publisher","first-page":"e105998","DOI":"10.1371\/journal.pone.0105998","article-title":"The vaginal microbiota: what have we learned after a decade of molecular characterization?","volume":"9","author":"van de Wijgert","year":"2014","journal-title":"PLoS One"},{"key":"2025070104564141500_dkaf157-B9","doi-asserted-by":"publisher","first-page":"e53997","DOI":"10.1371\/journal.pone.0053997","article-title":"Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis","volume":"8","author":"Swidsinski","year":"2013","journal-title":"PLoS One"},{"key":"2025070104564141500_dkaf157-B10","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1093\/infdis\/jiz342","article-title":"An updated conceptual model on the pathogenesis of bacterial vaginosis","volume":"220","author":"Muzny","year":"2019","journal-title":"J Infect Dis"},{"key":"2025070104564141500_dkaf157-B11","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1093\/infdis\/jiv338","article-title":"Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis","volume":"212","author":"Machado","year":"2015","journal-title":"J Infect Dis"},{"key":"2025070104564141500_dkaf157-B12","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1093\/infdis\/jiu131","article-title":"Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model","volume":"210","author":"Alves","year":"2014","journal-title":"J Infect Dis"},{"key":"2025070104564141500_dkaf157-B13","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1086\/503780","article-title":"High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence","volume":"193","author":"Bradshaw","year":"2006","journal-title":"J Infect Dis"},{"key":"2025070104564141500_dkaf157-B14","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3390\/antibiotics11040500","article-title":"The role of antimicrobial resistance in refractory and recurrent bacterial vaginosis and current recommendations for treatment","volume":"11","author":"Muzny","year":"2022","journal-title":"Antibiotics (Basel)"},{"key":"2025070104564141500_dkaf157-B15","doi-asserted-by":"publisher","first-page":"1100029","DOI":"10.3389\/frph.2023.1100029","article-title":"Bacterial vaginosis: a review of approaches to treatment and prevention","volume":"5","author":"Abbe","year":"2023","journal-title":"Front Reprod Health"},{"key":"2025070104564141500_dkaf157-B16","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12978-022-01449-z","article-title":"Probiotics are a good choice for the treatment of bacterial vaginosis: a meta-analysis of randomized controlled trial","volume":"19","author":"Chen","year":"2022","journal-title":"Reprod Health"},{"key":"2025070104564141500_dkaf157-B17","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1038\/s41591-019-0600-6","article-title":"Vaginal microbiome transplantation in women with intractable bacterial vaginosis","volume":"25","author":"Lev-Sagie","year":"2019","journal-title":"Nat Med"},{"key":"2025070104564141500_dkaf157-B18","doi-asserted-by":"publisher","first-page":"fnz025","DOI":"10.1093\/femsle\/fnz025","article-title":"Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis","volume":"366","author":"Ma","year":"2019","journal-title":"FEMS Microbiol Lett"},{"key":"2025070104564141500_dkaf157-B19","doi-asserted-by":"publisher","first-page":"824860","DOI":"10.3389\/fcimb.2022.824860","article-title":"Six bacterial vaginosis-associated species can form an in vitro and ex vivo polymicrobial biofilm that is susceptible to Thymbra capitata essential oil","volume":"12","author":"Rosca","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2025070104564141500_dkaf157-B20","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1055\/s-0031-1296346","article-title":"Inhibitory activity of thymol on native and mature Gardnerella vaginalis biofilms: in vitro study","volume":"60","author":"Braga","year":"2010","journal-title":"Arzneimittelforschung"},{"key":"2025070104564141500_dkaf157-B21","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1097\/OLQ.0b013e3181b08456","article-title":"Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis","volume":"36","author":"Reichman","year":"2009","journal-title":"Sex Transm Dis"},{"key":"2025070104564141500_dkaf157-B22","doi-asserted-by":"publisher","first-page":"750","DOI":"10.25259\/IJDVL_1322_2023","article-title":"Bacterial vaginosis and biofilms: therapeutic challenges and innovations\u2014a narrative review","volume":"90","author":"Lachyan","year":"2024","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"2025070104564141500_dkaf157-B23","doi-asserted-by":"publisher","first-page":"116833","DOI":"10.1016\/j.ejmech.2024.116833","article-title":"Drug repurposing against antibiotic resistant bacterial pathogens","volume":"279","author":"Aggarwal","year":"2024","journal-title":"Eur J Med Chem"},{"key":"2025070104564141500_dkaf157-B24","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"2025070104564141500_dkaf157-B25","author":"WHO\/HTM\/GMP\/2014.4 2014"},{"key":"2025070104564141500_dkaf157-B26","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1093\/cid\/cix026","article-title":"Sulfadoxine-pyrimethamine exhibits dose-response protection against adverse birth outcomes related to malaria and sexually transmitted and reproductive tract infections","volume":"64","author":"Chico","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2025070104564141500_dkaf157-B27","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/S0140-6736(22)02535-1","article-title":"Effect of monthly intermittent preventive treatment with dihydroartemisinin\u2013piperaquine with and without azithromycin versus monthly sulfadoxine\u2013pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial","volume":"401","author":"Madanitsa","year":"2023","journal-title":"Lancet"},{"key":"2025070104564141500_dkaf157-B28","author":"CLSI"},{"key":"2025070104564141500_dkaf157-B29","author":"CLSI"},{"key":"2025070104564141500_dkaf157-B30","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1080\/1040841X.2016.1208146","article-title":"Critical review on biofilm methods","volume":"43","author":"Azeredo","year":"2017","journal-title":"Crit Rev Microbiol"},{"key":"2025070104564141500_dkaf157-B31","doi-asserted-by":"publisher","first-page":"97.e1","DOI":"10.1016\/j.ajog.2007.06.039","article-title":"An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole","volume":"198","author":"Swidsinski","year":"2008","journal-title":"Am J Obstet Gynecol"},{"key":"2025070104564141500_dkaf157-B32","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1099\/mic.0.034280-0","article-title":"Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes","volume":"156","author":"Patterson","year":"2010","journal-title":"Microbiology (Reading)"},{"key":"2025070104564141500_dkaf157-B33","doi-asserted-by":"publisher","first-page":"12004","DOI":"10.3390\/ijms140612004","article-title":"Interactions between Lactobacillus crispatus and bacterial vaginosis (BV)-associated bacterial species in initial attachment and biofilm formation","volume":"14","author":"Machado","year":"2013","journal-title":"Int J Mol Sci"},{"key":"2025070104564141500_dkaf157-B34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41522-022-00285-0","article-title":"Identification and characterization of novel endolysins targeting Gardnerella vaginalis biofilms to treat bacterial vaginosis","volume":"8","author":"Arroyo-Moreno","year":"2022","journal-title":"NPJ Biofilms Microbiomes"},{"key":"2025070104564141500_dkaf157-B35","doi-asserted-by":"publisher","first-page":"17437","DOI":"10.1038\/s41598-024-68443-2","article-title":"Computational approach for drug discovery against Gardnerella vaginalis in quest for safer and effective treatments for bacterial vaginosis","volume":"14","author":"Fan","year":"2024","journal-title":"Sci Rep"},{"key":"2025070104564141500_dkaf157-B36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.1753-4887.2010.00362.x","article-title":"Folate metabolism pathway and Plasmodium falciparum malaria infection in pregnancy","volume":"69","author":"Chango","year":"2011","journal-title":"Nutr Rev"},{"key":"2025070104564141500_dkaf157-B37","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nm.4381","article-title":"Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic","volume":"23","author":"Blasco","year":"2017","journal-title":"Nat Med"},{"key":"2025070104564141500_dkaf157-B38","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.femsre.2005.03.004","article-title":"Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy","volume":"29","author":"de Koning","year":"2005","journal-title":"FEMS Microbiol Rev"},{"key":"2025070104564141500_dkaf157-B39","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/B978-0-7020-7167-6.00051-8","volume-title":"Medical Pharmacology and Therapeutics","author":"Waller","year":"2018"},{"key":"2025070104564141500_dkaf157-B40","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3390\/nu3010118","article-title":"Folate production by probiotic bacteria","volume":"3","author":"Rossi","year":"2011","journal-title":"Nutrients"},{"key":"2025070104564141500_dkaf157-B41","doi-asserted-by":"publisher","first-page":"7171","DOI":"10.1016\/S0021-9258(18)48220-8","article-title":"Folate transport in Lactobacillus salivarius. Characterization of the transport mechanism and purification and properties of the binding component","volume":"262","author":"Kumar","year":"1987","journal-title":"J Biol Chem"},{"key":"2025070104564141500_dkaf157-B42","doi-asserted-by":"publisher","first-page":"e2105014118","DOI":"10.1073\/pnas.2105014118","article-title":"Insights into the bilayer-mediated toppling mechanism of a folate-specific ECF transporter by cryo-EM","volume":"118","author":"Thangaratnarajah","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025070104564141500_dkaf157-B43","doi-asserted-by":"publisher","first-page":"e9917","DOI":"10.7717\/peerj.9917","article-title":"Evaluation of different culture media to support in vitro growth and biofilm formation of bacterial vaginosis-associated anaerobes","volume":"8","author":"Rosca","year":"2020","journal-title":"PeerJ"},{"key":"2025070104564141500_dkaf157-B44","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/jac\/dkx351","article-title":"Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms","volume":"73","author":"Dingsdag","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2025070104564141500_dkaf157-B45","doi-asserted-by":"publisher","first-page":"155","DOI":"10.4103\/0255-0857.40531","article-title":"Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis","volume":"26","author":"Nagaraja","year":"2008","journal-title":"Indian J Med Microbiol"},{"key":"2025070104564141500_dkaf157-B46","doi-asserted-by":"publisher","first-page":"1361825","DOI":"10.1155\/2020\/1361825","article-title":"Antimicrobial susceptibility testing of metronidazole and clindamycin against Gardnerella vaginalis in planktonic and biofilm formation","volume":"2020","author":"Li","year":"2020","journal-title":"Can J Infect Dis Med Microbiol"},{"key":"2025070104564141500_dkaf157-B47","doi-asserted-by":"publisher","first-page":"513","DOI":"10.18502\/ijm.v15i4.13505","article-title":"Prevalence of Gardnerella vaginalis infection and antibiotic resistance pattern of isolates of gynecology clinic patients at Shahriar Noor Hospital from January to June 2020 by PCR and culture methods","volume":"15","author":"Rashidifar","year":"2023","journal-title":"Iran J Microbiol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/7\/1972\/63243394\/dkaf157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/7\/1972\/63243394\/dkaf157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:56:50Z","timestamp":1751360210000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/7\/1972\/8138252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,5,20]]},"published-print":{"date-parts":[[2025,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf157","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,5,20]]}}}