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The efficacy of voriconazole might be hampered by the emergence of azole resistance. However, the combination of voriconazole with anidulafungin could improve therapeutic outcomes in azole-resistant invasive aspergillosis (IA). The<jats:italic>in vitro<\/jats:italic>interaction between voriconazole and anidulafungin was determined against voriconazole-susceptible and voriconazole-resistant (substitutions in the<jats:italic>cyp51A<\/jats:italic>gene, including single point [M220I and G54W] and tandem repeat [34-bp tandem repeat in the promoter region of the<jats:italic>cyp51A<\/jats:italic>gene in combination with substitutions at codon L98 and 46-bp tandem repeat in the promoter region of the<jats:italic>cyp51A<\/jats:italic>gene in combination with mutation at codons Y121 and T289] mutations) clinical<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>isolates using a checkerboard microdilution method with spectrophotometric analysis and a viability-based XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} assay within 2 h of exposure after 24 and 48 h of incubation at 35\u00b0C to 37\u00b0C. Fractional inhibitory concentration (FIC) indexes (FICis) were determined using different MIC endpoints and Bliss independence analysis performed based on the response surface calculation of the no-drug interaction. Significant synergistic interactions obtained based on measuring the FIC index were dependent on the MIC endpoint, in which FICs were inversely related to voriconazole and anidulafungin MICs and were influenced by the CYP51A genotype. A statistically significant difference was observed between FIC indexes of isolates harboring tandem repeat mutations and wild-type controls (<jats:italic>P<\/jats:italic>= 0.006 by one-way analysis of variance [ANOVA]), indicating that synergy is decreased in azole-resistant strains. Our results indicated that a combination of voriconazole and anidulafungin might be effective against infections caused by both azole-susceptible and azole-resistant<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>isolates, but the combination could possibly be less effective in voriconazole-resistant strains with high MICs. Studies<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro-in vivo<\/jats:italic>correlation investigations are required to validate the potential synergy of voriconazole and anidulafungin.<\/jats:p>","DOI":"10.1128\/aac.00980-12","type":"journal-article","created":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T06:27:56Z","timestamp":1353997676000},"page":"796-803","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["<i>In Vitro<\/i>Interaction of Voriconazole and Anidulafungin against Triazole-Resistant Aspergillus fumigatus"],"prefix":"10.1128","volume":"57","author":[{"given":"Seyedmojtaba","family":"Seyedmousavi","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Meletiadis","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J. 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