{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:48:35Z","timestamp":1790516915861,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"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":[[2015,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The majority of azole resistance mechanisms in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            correspond to mutations in the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene. As azoles are less effective against infections caused by multiply azole-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            isolates, new therapeutic options are warranted for treating these infections. We therefore investigated the\n            <jats:italic>in vitro<\/jats:italic>\n            combination of posaconazole (POSA) and caspofungin (CAS) against 20 wild-type and resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            isolates with 10 different resistance mechanisms. Fungal growth was assessed with the XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt] method. Pharmacodynamic interactions were assessed with the fractional inhibitory concentration (FIC) index (FICi) on the basis of 10% (FICi-0), 25% (FICi-1), or 53 0% (FICi-2) growth, and FICs were correlated with POSA and CAS concentrations. Synergy and antagonism were concluded when the FICi values were statistically significantly (\n            <jats:italic>t<\/jats:italic>\n            test,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) lower than 1 and higher than 1.25, respectively. Significant synergy was found for all isolates with mean FICi-0 values ranging from 0.28 to 0.75 (median, 0.46). Stronger synergistic interactions were found with FICi-1 (median, 0.18; range, 0.07 to 0.47) and FICi-2 (0.31; 0.07 to 0.6). The FICi-2 values of isolates with tandem-repeat-containing mutations or codon M220 were lower than those seen with the other isolates (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). FIC-2 values were inversely correlated with POSA MICs (\n            <jats:italic>\n              r\n              <jats:sub>s<\/jats:sub>\n            <\/jats:italic>\n            = \u22120.52,\n            <jats:italic>P<\/jats:italic>\n            = 0.0006) and linearly with the ratio of drug concentrations in combination over the MIC of POSA (\n            <jats:italic>\n              r\n              <jats:sub>s<\/jats:sub>\n            <\/jats:italic>\n            = 0.76,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001) and CAS (\n            <jats:italic>\n              r\n              <jats:sub>s<\/jats:sub>\n            <\/jats:italic>\n            = 0.52,\n            <jats:italic>P<\/jats:italic>\n            = 0.0004). The synergistic effect of the combination of POSA and CAS (POSA\/CAS) against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            isolates depended on the underlying azole resistance mechanism. Moreover, the drug combination synergy was found to be increased against isolates with elevated POSA MICs compared to wild-type isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.04469-14","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T18:35:13Z","timestamp":1423679713000},"page":"1738-1744","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["The Strength of Synergistic Interaction between Posaconazole and Caspofungin Depends on the Underlying Azole Resistance Mechanism of Aspergillus fumigatus"],"prefix":"10.1128","volume":"59","author":[{"given":"Eleftheria","family":"Mavridou","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Centre of Nijmegen, 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":"Antony","family":"Rijs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Centre of Nijmegen, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-4149","authenticated-orcid":false,"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Centre of Nijmegen, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Centre of Nijmegen, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2006.08.017"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1507.090043"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc061720"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.2.577-581.2003"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.7.2431-2438.2001"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.7.2747-2750.2004"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050219"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00231-09"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70265-8"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00185-11"},{"key":"e_1_3_1_12_2","article-title":"Azole-resistant Aspergillus fumigatus due to TR46\/Y121F\/T289A mutation emerging in Belgium, July 2012","volume":"29","author":"Vermeulen E","year":"2012","unstructured":"Vermeulen E, Maertens J, Schoemans H, Lagrou K. 2012. Azole-resistant Aspergillus fumigatus due to TR46\/Y121F\/T289A mutation emerging in Belgium, July 2012. Euro Surveil 29:17:pii=20326. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=20326.","journal-title":"Euro Surveil"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit320"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072280"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.5.1719-1726.2003"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/597465"},{"key":"e_1_3_1_17_2","volume-title":"Abstr 22nd Eur Congr Clin Microbiol Infect Dis","author":"Marr KA HS","year":"2012","unstructured":"Marr KA HS, Rottinghaus ST, Jagannatha S, Bow EJ, Wingard JR, Pappas P, Herbrecht R, Walsh TJ, Maertens J. 2012. A randomised, double-blind study of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis, poster LB 2812. Abstr 22nd Eur Congr Clin Microbiol Infect Dis."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1111\/j.1439-0507.2010.01985.x","article-title":"Caspofungin plus posaconazole as salvage therapy of invasive fungal infections in immunocompromised patients","volume":"54","author":"Lellek H","unstructured":"Lellek H, Waldenmaier D, Dahlke J, Ayuk FA, Wolschke C, Kroger N, Zander AR. Caspofungin plus posaconazole as salvage therapy of invasive fungal infections in immunocompromised patients. 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