{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:28:05Z","timestamp":1763389685315,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Candidiasis is the most common cause of fungal sepsis, and new agents are of interest to ameliorate current deficiencies in therapy. Nikkomycin Z (NIKZ) is an inhibitor of chitin synthase, interfering with fungal cell wall development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives\/Methods<\/jats:title><jats:p>We studied NIKZ therapy of disseminated murine candidiasis, via continuous drug exposure, in drinking water, to compensate for rapid clearance of the drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Drinking, and thus drug intake in the NIKZ groups, as well as body weight, was affected by the degree of illness. NIKZ effect on survival, despite reduced drinking initially after infection, was highly efficacious and dose\u2010related, and comparable to fluconazole, though neither were curative with the regimens employed. The challenge was rapidly lethal to all untreated animals, whereas NIKZ groups achieved &gt;50% survival. Assays of residual fungal infection were consistent with impressions of efficacy based on survival. Although NIKZ MIC for <jats:italic>Candida albicans<\/jats:italic> appeared unpromising, mycelial formation assays more closely correlated with in vivo observations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In vitro<jats:italic>\u2010<\/jats:italic>in vivo disparity may be explained by NIKZ tissue concentration in the target tissue and\/or by enhanced NIKZ action on mycelial formation, a morphological change in vivo wherein chitin synthesis is more critical, compared to NIKZ activity in inhibiting planktonic growth. A sustained release oral form of NIKZ in drug development for humans could hold promise, possibly also in future exploring previously demonstrated synergy in vitro with other antifungals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13569","type":"journal-article","created":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T07:28:38Z","timestamp":1674286118000},"page":"378-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Continuous dosing of nikkomycin Z against systemic candidiasis, in vivo and in vitro correlates"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-2897","authenticated-orcid":false,"given":"Gabriele","family":"Sass","sequence":"first","affiliation":[{"name":"California Institute for Medical Research  San Jose California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Larwood","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research  San Jose California USA"},{"name":"Valley Fever Solutions  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marife","family":"Martinez","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research  San Jose California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research  San Jose California USA"},{"name":"Div. of Infectious Diseases and Geographic Medicine Stanford Univ. Medical School  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"e_1_2_8_2_1","article-title":"Burden of candidemia in the United States, 2017","volume":"71","author":"Tsay SV","year":"2020","journal-title":"Clin Infect Dis"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis021"},{"key":"e_1_2_8_4_1","first-page":"325","volume-title":"Cutaneous Antifungal Agents","author":"Fiedler H\u2010P","year":"1993"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040261"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.2026"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00285-21"},{"volume-title":"Analysis of Mouse Plasma, Brain and Lung Samples for Nikkomycin Z","year":"2020","author":"Catz P","key":"e_1_2_8_8_1"},{"key":"e_1_2_8_9_1","unstructured":"SwezeyRR HectorRF KhandwalaA et al.Pharmacokinetics and safety of nikkomycin Z after oral administration of single doses to normal volunteers. 37th Interscience conf. On antimicrobial agents and chemotherapy Toronto Canada 1997 American soc. microbiology Washington DC USA abstract F\u201087."},{"key":"e_1_2_8_10_1","unstructured":"NixDE HooverSE ThompsonC et al.Pharmacokinetics and safety of nikkomycin Z following multiple rising doses in healthy subjects. 50th Interscience Conf. on Antimicrobial Agents and Chemotherapy Boston Massachusetts September 12\u201315 2010 by American Soc. Microbiology Washington DC USA 2010 Abstract A1\u2010031."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu029"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00530-06"},{"volume-title":"Reference method for broth dilution antifungal susceptibility testing of Yeasts. 4th Edition: M27","year":"2017","author":"CLSI","key":"e_1_2_8_13_1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02344-20"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/126.4.353"},{"key":"e_1_2_8_16_1","first-page":"460","article-title":"Host\u2010parasite interactions in the pathogenesis of experimental renal candidiasis","volume":"49","author":"Barnes JL","year":"1983","journal-title":"Lab Invest"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470316474"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(99)00022-7"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1468-6708-3-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.2.183"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/02681219080000291"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.133.3.1472-1477.1978"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.9.1909"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/12.4.303"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-50-1-78"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05011-11"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-137-9-2155"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.6.1401"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.4.587"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00619-17"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/lam.13204"},{"key":"e_1_2_8_32_1","unstructured":"FloresME HectorRF.In vitroactivity of the antifungal nikkomycin Z (SP\u2010920704) in combination with fluconazole or itraconazole vs. yeasts. 36th Interscience Conf. on Antimicrobial Agents and Chemotherapy New Orleans Louisiana USA 1996 American Soc. for Microbiology Washington DC USA 1996 Abstract F\u2010190."},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/157.1.212"},{"key":"e_1_2_8_34_1","unstructured":"MihalceaE LicollariAA.Single oral dose range finding study followed by a 7\u2010day repeated dose and pharmacokinetic study of NikZ in mice. Nucro\u2010Technics Study no. 346295. Nucro\u2010Technics Scarborough Ontario Canada2019."},{"key":"e_1_2_8_35_1","unstructured":"MirdamadiK LicollariA TanA.Evaluation of plasma concentrations of nikkomycin following administration to mice in drinking water. Nucro\u2010Technics Study no. 374222. Nucro\u2010Technics Scarborough Ontario Canada2021."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01609-08"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab223"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/yea.837"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.6.1284"},{"key":"e_1_2_8_40_1","first-page":"365","volume-title":"Cutaneous Antifungal Agents","author":"Perfect JR","year":"1993"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.9.2547-2548.2000"},{"key":"e_1_2_8_42_1","unstructured":"HectorRF SabouniA.US Patent No. 5 789 387: Methods and Compositions for Treating Fungal Infections in Mammals. US Patent and Trademark Office1998."}],"container-title":["Mycoses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13569","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/myc.13569","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13569","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T12:42:02Z","timestamp":1693917722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/myc.13569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/myc.13569"],"URL":"https:\/\/doi.org\/10.1111\/myc.13569","archive":["Portico"],"relation":{},"ISSN":["0933-7407","1439-0507"],"issn-type":[{"type":"print","value":"0933-7407"},{"type":"electronic","value":"1439-0507"}],"subject":[],"published":{"date-parts":[[2023,1,30]]},"assertion":[{"value":"2022-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}