{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:30:14Z","timestamp":1658237414462},"reference-count":49,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"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":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Given the recent increase in aspergillosis caused by species other than\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            , micafungin, caspofungin, and liposomal amphotericin B (L-AmBi) were investigated as monotherapy or combination therapy for murine systemic or pulmonary\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus flavus<\/jats:named-content>\n            infection. Treatment for 3 or 6 days was begun at 24 h (intravenous [i.v.], 2.8 \u00d7 10\n            <jats:sup>4<\/jats:sup>\n            conidia) or 2 h (intranasal, 4.1 \u00d7 10\n            <jats:sup>6<\/jats:sup>\n            to 6.75 \u00d7 10\n            <jats:sup>6<\/jats:sup>\n            conidia) postchallenge as follows: 5 or 10 mg\/kg L-AmBi, 10 mg\/kg caspofungin, 15 mg\/kg micafungin, L-AmBi plus echinocandin, L-AmBi on days 1 to 3 and echinocandin on days 4 to 6, or echinocandin on days 1 to 3 and L-AmBi on days 4 to 6. Mice were monitored for survival, fungal burden, serum or tissue cytokines, and lung histopathology. In the systemic infection, micafungin or caspofungin was more effective than L-AmBi in prolonging survival (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05), and L-AmBi was associated with significantly elevated serum levels of interleukin-6 (IL-6), macrophage inflammatory protein 1\u03b1 (MIP-1\u03b1), and IL-12 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). In contrast, L-AmBi was significantly more effective than the echinocandins in reducing fungal growth in most tissues (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Concomitant therapies produced significantly enhanced survival, reduction in fungal burden, and low levels of proinflammatory cytokines, while antagonism was seen with some sequential regimens. In comparison, in the pulmonary infection, L-AmBi was significantly better (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) than caspofungin or the combination of L-AmBi and caspofungin in prolonging survival and reducing lung fungal burden. Caspofungin stimulated high lung levels of IL-1\u03b1, tumor necrosis factor alpha (TNF-\u03b1), and IL-6, with extensive tissue damage. In summary, systemic\n            <jats:italic>A flavus<\/jats:italic>\n            infection was treated effectively with L-AmBi plus micafungin or caspofungin provided that the drugs were administered concomitantly and not sequentially, while pulmonary\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n            infection responded well to L-AmBi but not to caspofungin.\n          <\/jats:p>","DOI":"10.1128\/aac.00607-11","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T04:10:31Z","timestamp":1317701431000},"page":"218-230","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Differences in Efficacy and Cytokine Profiles following Echinocandin or Liposomal Amphotericin B Monotherapy or Combination Therapy for Murine Pulmonary or Systemic Aspergillus flavus Infections"],"prefix":"10.1128","volume":"56","author":[{"given":"J. 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