PMC:7306567 / 17643-19217 JSONTXT

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    LitCovid-PD-FMA-UBERON

    {"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T22","span":{"begin":824,"end":831},"obj":"Body_part"}],"attributes":[{"id":"A22","pred":"fma_id","subj":"T22","obj":"http://purl.org/sig/ont/fma/fma7394"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PD-UBERON

    {"project":"LitCovid-PD-UBERON","denotations":[{"id":"T18","span":{"begin":824,"end":831},"obj":"Body_part"}],"attributes":[{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0003126"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PubTator

    {"project":"LitCovid-PubTator","denotations":[{"id":"201","span":{"begin":233,"end":245},"obj":"Chemical"},{"id":"202","span":{"begin":330,"end":344},"obj":"Chemical"},{"id":"203","span":{"begin":466,"end":472},"obj":"Chemical"},{"id":"204","span":{"begin":508,"end":514},"obj":"Chemical"},{"id":"205","span":{"begin":166,"end":179},"obj":"Disease"},{"id":"208","span":{"begin":1111,"end":1117},"obj":"Chemical"},{"id":"209","span":{"begin":703,"end":732},"obj":"Disease"}],"attributes":[{"id":"A201","pred":"tao:has_database_id","subj":"201","obj":"MESH:D065819"},{"id":"A202","pred":"tao:has_database_id","subj":"202","obj":"MESH:D005436"},{"id":"A203","pred":"tao:has_database_id","subj":"203","obj":"MESH:D001393"},{"id":"A204","pred":"tao:has_database_id","subj":"204","obj":"MESH:D001393"},{"id":"A205","pred":"tao:has_database_id","subj":"205","obj":"MESH:D060085"},{"id":"A208","pred":"tao:has_database_id","subj":"208","obj":"MESH:D001393"},{"id":"A209","pred":"tao:has_database_id","subj":"209","obj":"MESH:D001228"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PD-MONDO

    {"project":"LitCovid-PD-MONDO","denotations":[{"id":"T82","span":{"begin":169,"end":179},"obj":"Disease"},{"id":"T83","span":{"begin":715,"end":732},"obj":"Disease"}],"attributes":[{"id":"A82","pred":"mondo_id","subj":"T82","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A83","pred":"mondo_id","subj":"T83","obj":"http://purl.obolibrary.org/obo/MONDO_0021925"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PD-CLO

    {"project":"LitCovid-PD-CLO","denotations":[{"id":"T115","span":{"begin":78,"end":79},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T116","span":{"begin":275,"end":277},"obj":"http://purl.obolibrary.org/obo/CLO_0053733"},{"id":"T117","span":{"begin":571,"end":573},"obj":"http://purl.obolibrary.org/obo/CLO_0053799"},{"id":"T118","span":{"begin":616,"end":617},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T119","span":{"begin":774,"end":776},"obj":"http://purl.obolibrary.org/obo/CLO_0001000"},{"id":"T120","span":{"begin":1244,"end":1245},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PD-CHEBI

    {"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T121","span":{"begin":14,"end":24},"obj":"Chemical"},{"id":"T122","span":{"begin":89,"end":93},"obj":"Chemical"},{"id":"T123","span":{"begin":94,"end":98},"obj":"Chemical"},{"id":"T124","span":{"begin":233,"end":245},"obj":"Chemical"},{"id":"T125","span":{"begin":330,"end":344},"obj":"Chemical"},{"id":"T126","span":{"begin":466,"end":472},"obj":"Chemical"},{"id":"T127","span":{"begin":485,"end":489},"obj":"Chemical"},{"id":"T128","span":{"begin":508,"end":514},"obj":"Chemical"},{"id":"T129","span":{"begin":519,"end":524},"obj":"Chemical"},{"id":"T130","span":{"begin":588,"end":598},"obj":"Chemical"},{"id":"T131","span":{"begin":656,"end":666},"obj":"Chemical"},{"id":"T132","span":{"begin":927,"end":938},"obj":"Chemical"},{"id":"T133","span":{"begin":1060,"end":1071},"obj":"Chemical"},{"id":"T134","span":{"begin":1111,"end":1117},"obj":"Chemical"},{"id":"T135","span":{"begin":1142,"end":1150},"obj":"Chemical"},{"id":"T136","span":{"begin":1286,"end":1296},"obj":"Chemical"},{"id":"T137","span":{"begin":1360,"end":1375},"obj":"Chemical"},{"id":"T139","span":{"begin":1371,"end":1375},"obj":"Chemical"},{"id":"T140","span":{"begin":1399,"end":1412},"obj":"Chemical"},{"id":"T141","span":{"begin":1506,"end":1516},"obj":"Chemical"},{"id":"T142","span":{"begin":1560,"end":1564},"obj":"Chemical"}],"attributes":[{"id":"A121","pred":"chebi_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A122","pred":"chebi_id","subj":"T122","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A123","pred":"chebi_id","subj":"T123","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A124","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_10023"},{"id":"A125","pred":"chebi_id","subj":"T125","obj":"http://purl.obolibrary.org/obo/CHEBI_5098"},{"id":"A126","pred":"chebi_id","subj":"T126","obj":"http://purl.obolibrary.org/obo/CHEBI_68452"},{"id":"A127","pred":"chebi_id","subj":"T127","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A128","pred":"chebi_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/CHEBI_68452"},{"id":"A129","pred":"chebi_id","subj":"T129","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A130","pred":"chebi_id","subj":"T130","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A131","pred":"chebi_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A132","pred":"chebi_id","subj":"T132","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A133","pred":"chebi_id","subj":"T133","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A134","pred":"chebi_id","subj":"T134","obj":"http://purl.obolibrary.org/obo/CHEBI_68452"},{"id":"A135","pred":"chebi_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/CHEBI_48121"},{"id":"A136","pred":"chebi_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A137","pred":"chebi_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A138","pred":"chebi_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/CHEBI_86327"},{"id":"A139","pred":"chebi_id","subj":"T139","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A140","pred":"chebi_id","subj":"T140","obj":"http://purl.obolibrary.org/obo/CHEBI_57248"},{"id":"A141","pred":"chebi_id","subj":"T141","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A142","pred":"chebi_id","subj":"T142","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-sentences

    {"project":"LitCovid-sentences","denotations":[{"id":"T117","span":{"begin":0,"end":77},"obj":"Sentence"},{"id":"T118","span":{"begin":78,"end":414},"obj":"Sentence"},{"id":"T119","span":{"begin":415,"end":473},"obj":"Sentence"},{"id":"T120","span":{"begin":474,"end":575},"obj":"Sentence"},{"id":"T121","span":{"begin":576,"end":782},"obj":"Sentence"},{"id":"T122","span":{"begin":783,"end":965},"obj":"Sentence"},{"id":"T123","span":{"begin":966,"end":1199},"obj":"Sentence"},{"id":"T124","span":{"begin":1200,"end":1309},"obj":"Sentence"},{"id":"T125","span":{"begin":1310,"end":1390},"obj":"Sentence"},{"id":"T126","span":{"begin":1391,"end":1448},"obj":"Sentence"},{"id":"T127","span":{"begin":1449,"end":1574},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    LitCovid-PMC-OGER-BB

    {"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T141","span":{"begin":89,"end":93},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T142","span":{"begin":94,"end":98},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T143","span":{"begin":185,"end":186},"obj":"NCBITaxon:4932"},{"id":"T144","span":{"begin":186,"end":187},"obj":"NCBITaxon:562"},{"id":"T145","span":{"begin":233,"end":245},"obj":"CHEBI:10023;CHEBI:10023"},{"id":"T146","span":{"begin":330,"end":344},"obj":"CHEBI:5098;CHEBI:5098"},{"id":"T147","span":{"begin":485,"end":489},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T148","span":{"begin":508,"end":514},"obj":"CHEBI:68452;CHEBI:68452"},{"id":"T149","span":{"begin":519,"end":524},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T150","span":{"begin":703,"end":714},"obj":"NCBITaxon:5052"},{"id":"T151","span":{"begin":715,"end":732},"obj":"UBERON:0007196"},{"id":"T152","span":{"begin":750,"end":763},"obj":"UBERON:0001852"},{"id":"T153","span":{"begin":824,"end":831},"obj":"UBERON:0003126"},{"id":"T154","span":{"begin":927,"end":938},"obj":"CHEBI:67079;CHEBI:67079"},{"id":"T155","span":{"begin":986,"end":997},"obj":"NCBITaxon:5052"},{"id":"T156","span":{"begin":1021,"end":1032},"obj":"CHEBI:50905;CHEBI:50905"},{"id":"T157","span":{"begin":1037,"end":1046},"obj":"CHEBI:25435;CHEBI:25435"},{"id":"T158","span":{"begin":1060,"end":1071},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T159","span":{"begin":1081,"end":1090},"obj":"GO:0007565"},{"id":"T160","span":{"begin":1210,"end":1218},"obj":"GO:0007565"},{"id":"T161","span":{"begin":1360,"end":1370},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T162","span":{"begin":1371,"end":1375},"obj":"CHEBI:86327;CHEBI:86327"},{"id":"T163","span":{"begin":1399,"end":1412},"obj":"CHEBI:57248;CHEBI:57248"},{"id":"T164","span":{"begin":1506,"end":1516},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T165","span":{"begin":1560,"end":1564},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T5704","span":{"begin":89,"end":93},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T23687","span":{"begin":94,"end":98},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T76380","span":{"begin":185,"end":186},"obj":"NCBITaxon:4932"},{"id":"T2256","span":{"begin":186,"end":187},"obj":"NCBITaxon:562"},{"id":"T62223","span":{"begin":233,"end":245},"obj":"CHEBI:10023;CHEBI:10023"},{"id":"T32565","span":{"begin":330,"end":344},"obj":"CHEBI:5098;CHEBI:5098"},{"id":"T43236","span":{"begin":485,"end":489},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T38702","span":{"begin":508,"end":514},"obj":"CHEBI:68452;CHEBI:68452"},{"id":"T74202","span":{"begin":519,"end":524},"obj":"CHEBI:23888;CHEBI:23888"},{"id":"T48860","span":{"begin":703,"end":714},"obj":"NCBITaxon:5052"},{"id":"T84649","span":{"begin":715,"end":732},"obj":"UBERON:0007196"},{"id":"T69891","span":{"begin":750,"end":763},"obj":"UBERON:0001852"},{"id":"T67622","span":{"begin":824,"end":831},"obj":"UBERON:0003126"},{"id":"T4317","span":{"begin":927,"end":938},"obj":"CHEBI:67079;CHEBI:67079"},{"id":"T80540","span":{"begin":986,"end":997},"obj":"NCBITaxon:5052"},{"id":"T31714","span":{"begin":1021,"end":1032},"obj":"CHEBI:50905;CHEBI:50905"},{"id":"T16663","span":{"begin":1037,"end":1046},"obj":"CHEBI:25435;CHEBI:25435"},{"id":"T53462","span":{"begin":1060,"end":1071},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T49738","span":{"begin":1081,"end":1090},"obj":"GO:0007565"},{"id":"T22501","span":{"begin":1210,"end":1218},"obj":"GO:0007565"},{"id":"T23823","span":{"begin":1360,"end":1370},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T93737","span":{"begin":1371,"end":1375},"obj":"CHEBI:86327;CHEBI:86327"},{"id":"T6922","span":{"begin":1399,"end":1412},"obj":"CHEBI:57248;CHEBI:57248"},{"id":"T46107","span":{"begin":1506,"end":1516},"obj":"CHEBI:35718;CHEBI:35718"},{"id":"T54949","span":{"begin":1560,"end":1564},"obj":"CHEBI:23888;CHEBI:23888"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}

    2_test

    {"project":"2_test","denotations":[{"id":"32572532-28717040-47963442","span":{"begin":346,"end":348},"obj":"28717040"},{"id":"32572532-19361301-47963443","span":{"begin":571,"end":573},"obj":"19361301"},{"id":"32572532-27365388-47963444","span":{"begin":774,"end":776},"obj":"27365388"},{"id":"32572532-10525567-47963445","span":{"begin":778,"end":780},"obj":"10525567"},{"id":"32572532-29544767-47963446","span":{"begin":1191,"end":1193},"obj":"29544767"},{"id":"32572532-29623451-47963447","span":{"begin":1386,"end":1388},"obj":"29623451"},{"id":"T52416","span":{"begin":346,"end":348},"obj":"28717040"},{"id":"T67943","span":{"begin":571,"end":573},"obj":"19361301"},{"id":"T52492","span":{"begin":774,"end":776},"obj":"27365388"},{"id":"T28103","span":{"begin":778,"end":780},"obj":"10525567"},{"id":"T58235","span":{"begin":1191,"end":1193},"obj":"29544767"},{"id":"T25290","span":{"begin":1386,"end":1388},"obj":"29623451"}],"text":"Discussion on antifungal treatment options and challenges for IAPA in the ICU\nA specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood. Similar interactions have not been seen with other azoles. Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].\nAerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54]. However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy. The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55]. Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.\nThere is little evidence on the impact of ECMO on antifungal drug exposure [56]. For the echinocandins, an impact of ECMO is not expected. Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure."}