{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:23:46Z","timestamp":1791120226463,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[1999,11,1]],"date-time":"1999-11-01T00:00:00Z","timestamp":941414400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1999,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and\/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of\n            <jats:italic>Candida<\/jats:italic>\n            species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of\n            <jats:italic>Candida<\/jats:italic>\n            . The MICs generally were determined to be in the range of 0.5 to 100 mg \u00b7 ml\n            <jats:sup>\u22121<\/jats:sup>\n            . Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of\n            <jats:italic>Candida<\/jats:italic>\n            by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg\/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several\n            <jats:italic>Candida<\/jats:italic>\n            species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with\n            <jats:italic>Candida<\/jats:italic>\n            is an attractive therapeutic option. Since fluconazole-resistant\n            <jats:italic>Candida<\/jats:italic>\n            species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.\n          <\/jats:p>","DOI":"10.1128\/aac.43.11.2635","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:33:39Z","timestamp":1539045219000},"page":"2635-2641","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":125,"title":["Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical\n            <i>Candida<\/i>\n            Isolates"],"prefix":"10.1128","volume":"43","author":[{"given":"M. E.","family":"Kuipers","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Section of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Studies, University Centre for Pharmacy, 9713 AV Groningen,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. G.","family":"de Vries","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Section of Medical Microbiology, University Hospital Groningen, 9713 GZ Groningen,2 The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Section of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Studies, University Centre for Pharmacy, 9713 AV Groningen,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. K. F.","family":"Meijer","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Section of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Studies, University Centre for Pharmacy, 9713 AV Groningen,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J.","family":"Swart","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Section of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Studies, University Centre for Pharmacy, 9713 AV Groningen,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199406000-00010"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/41.1.59"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/BF00189377","article-title":"Killing of Candida albicans by lactoferrin B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin.","volume":"182","author":"Bellamy W.","year":"1993","unstructured":"Bellamy W. Wakabayashi H. Takase M. Kawase K. Shimamura S. Tomita M. 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C.\n              Meijer\n              D. K. F.\n          Lactoferrin: antiviral activity of lactoferrin\n          Advances in lactoferrin research.\n              Spik\n              G.\n              Legrand\n              D.\n              Mazurier\n              J.\n              Pierce\n              A.\n              Perraudin\n              J.\n          1998\n          205\n          213\n          Plenum Press\n          New York N.Y","DOI":"10.1007\/978-1-4757-9068-9_24"},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/jac\/38.4.691","article-title":"Analysis of the risk factors associated with the emergence of azole resistant oral candidosis in the course of HIV infection.","volume":"38","author":"Tumbarello M.","year":"1996","unstructured":"Tumbarello M. Caldarola G. Tacconelli E. Morace G. Posteraro B. Cauda R. Ortona L. 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