{"id":"https://openalex.org/W3181572811","doi":"https://doi.org/10.1093/jac/dkab223","title":"Efficacy of nikkomycin Z in murine CNS coccidioidomycosis: modelling sustained-release dosing","display_name":"Efficacy of nikkomycin Z in murine CNS coccidioidomycosis: modelling sustained-release dosing","publication_year":2021,"publication_date":"2021-06-11","ids":{"openalex":"https://openalex.org/W3181572811","doi":"https://doi.org/10.1093/jac/dkab223","mag":"3181572811","pmid":"https://pubmed.ncbi.nlm.nih.gov/34269392"},"language":"en","primary_location":{"id":"doi:10.1093/jac/dkab223","doi":"https://doi.org/10.1093/jac/dkab223","is_oa":false,"landing_page_url":"https://doi.org/10.1093/jac/dkab223","pdf_url":null,"source":{"id":"https://openalex.org/S124275759","display_name":"Journal of Antimicrobial Chemotherapy","issn_l":"0305-7453","issn":["0305-7453","1460-2091"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Antimicrobial Chemotherapy","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5031917496","display_name":"Gabriele Sass","orcid":"https://orcid.org/0000-0001-9829-2897","observed_orcids":["https://orcid.org/0000-0001-9829-2897"]},"institutions":[{"id":"https://openalex.org/I4210125992","display_name":"California Institute for Medical Research","ror":"https://ror.org/03cf9xg09","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210125992"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Gabriele Sass","raw_affiliation_strings":["California Institute for Medical Research, San Jose, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"California Institute for Medical Research, San Jose, CA, USA","institution_ids":["https://openalex.org/I4210125992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005543870","display_name":"David J. Larwood","orcid":"https://orcid.org/0000-0001-8202-0483","observed_orcids":["https://orcid.org/0000-0001-8202-0483"]},"institutions":[{"id":"https://openalex.org/I4210125992","display_name":"California Institute for Medical Research","ror":"https://ror.org/03cf9xg09","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210125992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David J Larwood","raw_affiliation_strings":["California Institute for Medical Research, San Jose, CA, USA","Valley Fever Solutions, Tucson, AZ, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"California Institute for Medical Research, San Jose, CA, USA","institution_ids":["https://openalex.org/I4210125992"]},{"raw_affiliation_string":"Valley Fever Solutions, Tucson, AZ, USA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108523852","display_name":"Marife Martinez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210125992","display_name":"California Institute for Medical Research","ror":"https://ror.org/03cf9xg09","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210125992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marife Martinez","raw_affiliation_strings":["California Institute for Medical Research, San Jose, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"California Institute for Medical Research, San Jose, CA, USA","institution_ids":["https://openalex.org/I4210125992"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022917298","display_name":"Pallabi Shrestha","orcid":"https://orcid.org/0000-0002-6490-0804","observed_orcids":["https://orcid.org/0000-0002-6490-0804"]},"institutions":[{"id":"https://openalex.org/I4210125992","display_name":"California Institute for Medical Research","ror":"https://ror.org/03cf9xg09","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210125992"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pallabi Shrestha","raw_affiliation_strings":["California Institute for Medical Research, San Jose, CA, USA"],"raw_orcid":"https://orcid.org/0000-0002-6490-0804","affiliations":[{"raw_affiliation_string":"California Institute for Medical Research, San Jose, CA, USA","institution_ids":["https://openalex.org/I4210125992"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5021143803","display_name":"David A. Stevens","orcid":"https://orcid.org/0000-0002-5861-5716","observed_orcids":["https://orcid.org/0000-0002-5861-5716"]},"institutions":[{"id":"https://openalex.org/I4210125992","display_name":"California Institute for Medical Research","ror":"https://ror.org/03cf9xg09","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210125992"]},{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David A Stevens","raw_affiliation_strings":["California Institute for Medical Research, San Jose, CA, USA","Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"California Institute for Medical Research, San Jose, CA, USA","institution_ids":["https://openalex.org/I4210125992"]},{"raw_affiliation_string":"Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA, USA","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5031917496"],"corresponding_institution_ids":["https://openalex.org/I4210125992"],"apc_list":{"value":2464,"currency":"GBP","value_usd":3696},"apc_paid":null,"fwci":1.0292,"has_fulltext":false,"cited_by_count":15,"citation_normalized_percentile":{"value":0.80150783,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"76","issue":"10","first_page":"2629","last_page":"2635"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11037","display_name":"Fungal Infections and Studies","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11037","display_name":"Fungal Infections and Studies","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10150","display_name":"Antifungal resistance and susceptibility","score":0.001500000013038516,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10873","display_name":"Bacterial Infections and Vaccines","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2404","display_name":"Microbiology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/nikkomycin-z","display_name":"nikkomycin Z","score":0.9750000238418579},{"id":"https://openalex.org/keywords/coccidioidomycosis","display_name":"coccidioidomycosis","score":0.984000027179718},{"id":"https://openalex.org/keywords/coccidioidal-meningitis","display_name":"coccidioidal meningitis","score":0.8679999709129333},{"id":"https://openalex.org/keywords/coccidioides-posadasii","display_name":"Coccidioides posadasii","score":0.9810000061988831},{"id":"https://openalex.org/keywords/chitin-synthase-inhibitors","display_name":"chitin synthase inhibitors","score":0.9539999961853027},{"id":"https://openalex.org/keywords/fluconazole","display_name":"fluconazole","score":0.7960000038146973},{"id":"https://openalex.org/keywords/antifungal-efficacy","display_name":"antifungal efficacy","score":0.6240000128746033},{"id":"https://openalex.org/keywords/survival","display_name":"survival","score":0.44600000977516174}],"concepts":[{"id":"https://openalex.org/C2780651595","wikidata":"https://www.wikidata.org/wiki/Q411478","display_name":"Fluconazole","level":3,"score":0.9036563634872437},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.6042301654815674},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.587770938873291},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.48693788051605225},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.4162026345729828},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3659544289112091},{"id":"https://openalex.org/C2779548794","wikidata":"https://www.wikidata.org/wiki/Q578726","display_name":"Antifungal","level":2,"score":0.23980873823165894},{"id":"https://openalex.org/C16005928","wikidata":"https://www.wikidata.org/wiki/Q171171","display_name":"Dermatology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000617","descriptor_name":"Aminoglycosides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000935","descriptor_name":"Antifungal Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D003045","descriptor_name":"Coccidioides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003047","descriptor_name":"Coccidioidomycosis","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003692","descriptor_name":"Delayed-Action Preparations","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1093/jac/dkab223","doi":"https://doi.org/10.1093/jac/dkab223","is_oa":false,"landing_page_url":"https://doi.org/10.1093/jac/dkab223","pdf_url":null,"source":{"id":"https://openalex.org/S124275759","display_name":"Journal of Antimicrobial Chemotherapy","issn_l":"0305-7453","issn":["0305-7453","1460-2091"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Antimicrobial Chemotherapy","raw_type":"journal-article"},{"id":"pmid:34269392","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34269392","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of antimicrobial chemotherapy","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":21,"referenced_works":["https://openalex.org/W1573823453","https://openalex.org/W1640787265","https://openalex.org/W1982083114","https://openalex.org/W1988195179","https://openalex.org/W2011781042","https://openalex.org/W2065870824","https://openalex.org/W2111229199","https://openalex.org/W2113995750","https://openalex.org/W2123472426","https://openalex.org/W2134944658","https://openalex.org/W2142512633","https://openalex.org/W2143811581","https://openalex.org/W2166675124","https://openalex.org/W2168468942","https://openalex.org/W2479157738","https://openalex.org/W2518021141","https://openalex.org/W3042161894","https://openalex.org/W3097240824","https://openalex.org/W3146180644","https://openalex.org/W4235080411","https://openalex.org/W4256407300"],"related_works":["https://openalex.org/W3182315526","https://openalex.org/W4317632565","https://openalex.org/W2111229199","https://openalex.org/W4401715932","https://openalex.org/W2101737286","https://openalex.org/W4411092247","https://openalex.org/W2120439302","https://openalex.org/W7100690317","https://openalex.org/W3097240824","https://openalex.org/W2166675124"],"abstract_inverted_index":{"OBJECTIVES:":[0],"Meningitis":[1],"is":[2,11,18],"the":[3,177,202,214],"most":[4],"feared":[5],"coccidioidomycosis":[6],"complication.":[7],"Nikkomycin":[8],"Z":[9],"(nikZ)":[10],"a":[12,223],"chitin":[13],"synthase":[14],"inhibitor.":[15],"A":[16],"concern":[17],"short":[19],"half-life,":[20],"necessitating":[21],"multiple":[22],"dose/day":[23],"regimens.":[24],"We":[25],"simulated":[26],"extended":[27],"release,":[28],"providing":[29],"nikZ":[30,69,95,114,122,145,171],"in":[31,75,90,98,109,135,160,180,225],"drinking":[32,76,99,167,191],"water.":[33,77,100],"Extended":[34],"release":[35,251],"would":[36],"enhance":[37],"convenience,":[38],"and":[39,88,107,113,117,140,192,256],"adherence,":[40],"for":[41],"patients.":[42],"METHODS:":[43],"Coccidioides":[44],"posadasii":[45],"was":[46,59,96,102,125,150,163,205],"injected":[47],"intracerebrally":[48],"into":[49],"mice.":[50],"Twelve":[51],"day":[52],"treatments":[53],"began":[54],"on":[55],"Day":[56,79],"3.":[57],"Fluconazole":[58],"given":[60],"100":[61,71,116,146],"mg/kg":[62],"once":[63],"daily":[64,240],"(gavage);":[65],"designed":[66,193,203],"doses":[67],"of":[68,142,158,216,242],"30,":[70,115],"or":[72,147,232],"300":[73,118,123,148],"mg/kg/day":[74,124,149],"On":[78],"30":[80],"post-treatment,":[81],"survivors":[82],"were":[83,133,247],"euthanized,":[84],"brain":[85],"cfu":[86,89],"quantitated":[87],"other":[91,161],"organs":[92,162],"assessed.":[93],"RESULTS:":[94],"stable":[97],"Survival":[101],"11%,":[103],"50%,":[104],"70%,":[105],"90%":[106],"100%":[108],"untreated":[110],"controls,":[111],"fluconazole":[112],"mg/kg/day,":[119],"respectively":[120],";":[121],"superior":[126,151,257],"(P":[127,152],"\u2264":[128,153],"0.01)":[129,154],"to":[130,155,173,188,207],"fluconazole.":[131,156],"Brains":[132],"sterilized":[134],"0%,":[136],"20%,":[137],"86%,":[138],"89%":[139],"80%":[141],"mice,":[143],"respectively;":[144],"Clearance":[157],"infection":[159],"similar.":[164],"All":[165],"decreased":[166],"after":[168],"infection,":[169],"causing":[170],"mice":[172],"ingest":[174],"less":[175,200],"than":[176,201],"desired":[178],"dose":[179,204],"early":[181],"therapy;":[182],"despite":[183],"this,":[184],"they":[185],"recovered":[186],"sufficiently":[187],"resume":[189],"pre-infection":[190],"drug":[194,228],"intakes.":[195],"Thus,":[196],"when":[197],"sickest,":[198],"even":[199],"sufficient":[206],"enable":[208],"recovery.":[209],"CONCLUSIONS:":[210],"This":[211],"efficacy":[212],"supports":[213],"development":[215],"sustained-release":[217],"nikZ.":[218],"Decreased":[219],"intake":[220],"wouldn't":[221],"be":[222],"factor":[224],"humans,":[226],"receiving":[227],"via":[229],"extended-release":[230],"pill":[231],"continuous":[233],"IV":[234],"infusion.":[235],"In":[236],"prior":[237],"studies":[238],"(twice":[239],"nikZ)":[241],"murine":[243],"coccidioidal":[244],"meningitis,":[245],"results":[246],"inferior,":[248],"suggesting":[249],"sustained":[250],"may":[252],"provide":[253],"both":[254],"convenience":[255],"outcomes.":[258]},"counts_by_year":[{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2021-07-19T00:00:00"}
