{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:06:29Z","timestamp":1792137989209,"version":"4.4.0"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"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":[[2010,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The fractional inhibitory concentration (FIC) index range of 0.5 to 4 that is commonly used to define additivity results in no interactions in most combination studies of antifungal agents. These results may differ from those of\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies, where positive and negative interactions may be observed. We reassessed this\n                    <jats:italic>in vitro<\/jats:italic>\n                    FIC index range based on (i) the experimental variation of the checkerboard technique using multiple replicates, (ii) the ability to correctly determine purely additive self-drug and two-drug antagonistic combinations of amphotericin B (AMB) and voriconazole (VRC), (iii) Monte Carlo simulation analysis, and (iv)\n                    <jats:italic>in vitro<\/jats:italic>\n                    -\n                    <jats:italic>in vivo<\/jats:italic>\n                    correlation using experimental models of invasive pulmonary aspergillosis against the same\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    isolate based on visual, spectrophotometric, and colorimetric determinations of FICs after 24 and 48 h of incubation. FICs obtained after 24 h of incubation ranged from 0.5 to 1.25 for the self-drug additive combinations of AMB plus AMB and VRC plus VRC and from 2.25 to 4.25 for the antagonistic combination of AMB plus VRC. Monte Carlo simulation analysis showed that self-drug combinations were correctly classified as additive and that the combination of AMB plus VRC was correctly classified as antagonistic for &gt;85% of the simulated FICs when deviation of the 95% confidence interval (CI) of replicate FICs from the additivity range of 1 to 1.25 was used to assess interactions after 24 h.\n                    <jats:italic>In vitro<\/jats:italic>\n                    -\n                    <jats:italic>in vivo<\/jats:italic>\n                    correlation analysis showed that the 95% CIs of the FICs of the\n                    <jats:italic>in vivo<\/jats:italic>\n                    synergistic combination anidulafungin plus VRC determined after 24 h were lower than 1 and the 95% CIs of the FICs of the\n                    <jats:italic>in vivo<\/jats:italic>\n                    antagonistic combination AMB plus ravuconazole were higher than 1.25. Adequate insight into weak pharmacodynamic interactions with\n                    <jats:italic>in vivo<\/jats:italic>\n                    relevance may be obtained by demonstrating that triplicate FICs at 24 h are outside an inclusive additivity range of 1 to 1.25.\n                  <\/jats:p>","DOI":"10.1128\/aac.00999-09","type":"journal-article","created":{"date-parts":[[2009,12,8]],"date-time":"2009-12-08T00:28:12Z","timestamp":1260232092000},"page":"602-609","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":319,"title":["Defining Fractional Inhibitory Concentration Index Cutoffs for Additive Interactions Based on Self-Drug Additive Combinations, Monte Carlo Simulation Analysis, and\n                    <i>In Vitro<\/i>\n                    -\n                    <i>In Vivo<\/i>\n                    Correlation Data for Antifungal Drug Combinations against\n                    <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1128","volume":"54","author":[{"given":"Joseph","family":"Meletiadis","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Microbiology, Attikon University General Hospital, National and Kapodistrian University, Athens, Greece"},{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros","family":"Pournaras","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Thessaly, Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Roilides","sequence":"additional","affiliation":[{"name":"Third Department of Pediatrics, Aristotle University, Hippokration Hospital, Thessaloniki, Greece"},{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"i","volume":"48","year":"2004","unstructured":"American Society for Microbiology. 2004. Instructions to authors. Antimicrob. Agents Chemother.48:i-xxi.","journal-title":"Agents Chemother."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/142.3.476"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/19.2.271"},{"key":"e_1_3_2_5_2","first-page":"93","volume":"41","year":"1989","unstructured":"Berenbaum, M. C. 1989. What is synergy? Pharmacol. Rev.41:93-141.","journal-title":"Pharmacol. Rev."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.4867-4875.2005"},{"key":"e_1_3_2_7_2","unstructured":"Clinical and Laboratory Standards Institute. 2002. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. NCCLS document M38-A. 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