{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:39:54Z","timestamp":1774690794272,"version":"3.50.1"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"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":[[2000,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Coccidioidal meningitis is a devastating disease that requires long-term therapy with little hope of cure. A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of fluconazole (FCZ) and itraconazole (ITZ). Hydrocortisone-treated male New Zealand white rabbits were infected intracisternally with 5.0 \u00d7 10\n            <jats:sup>4<\/jats:sup>\n            to 5.4 \u00d7 10\n            <jats:sup>4<\/jats:sup>\n            arthroconidia of\n            <jats:italic>Coccidioides immitis<\/jats:italic>\n            . Oral treatment with polyethylene glycol 200 (PEG) (\n            <jats:italic>n<\/jats:italic>\n            = 9), FCZ (\n            <jats:italic>n<\/jats:italic>\n            = 8; 80 mg\/kg of body weight\/day), or ITZ (\n            <jats:italic>n<\/jats:italic>\n            = 8; 80 mg\/kg\/day) began 5 days after infection and continued for 28 consecutive days. Both FCZ and ITZ reduced the number of CFU of\n            <jats:italic>C. immitis<\/jats:italic>\n            organisms in the spinal cord and brain compared with the number in PEG-treated animals (\n            <jats:italic>P<\/jats:italic>\n            \u2264 0.003), but the results for FCZ and ITZ were not different from each other. Histopathologic severity (semiquantitative scoring system by an observer blinded to treatment) was equally reduced in both FCZ and ITZ treatment groups compared with that in controls (\n            <jats:italic>P<\/jats:italic>\n            \u2264 0.0004). Both treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of\n            <jats:italic>C. immitis<\/jats:italic>\n            from CSF compared with the results for PEG-treated controls. Neither drug affected CSF glucose levels. Both compounds were effective at reducing neurological and systemic signs and extending survival (\n            <jats:italic>P<\/jats:italic>\n            \u2264 0.014). FCZ was more effective at reducing head and body shakes, posture changes, and incontinence; ITZ was more effective at reducing continuous fever. Mean levels of FCZ and ITZ in the serum and CSF were determined by bioassay; at 17 to 26 h postdosing, levels were 28.1 to 40.0 and 22.4 to 29.9 \u03bcg\/ml, respectively, for FCZ and 0.77 to 2.51 and 0 \u03bcg\/ml, respectively, for ITZ. The sera of most animals developed antibody to\n            <jats:italic>C. immitis<\/jats:italic>\n            , but azole treatment attenuated antibody development in CSF and its titer. In conclusion, both FCZ and ITZ were efficacious, but neither was curative in a rabbit model of coccidioidal meningitis.\n          <\/jats:p>","DOI":"10.1128\/aac.44.6.1512-1517.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1512-1517","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Comparison of Fluconazole and Itraconazole in a Rabbit Model of Coccidioidal Meningitis"],"prefix":"10.1128","volume":"44","author":[{"given":"Kevin N.","family":"Sorensen","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center,1 and"},{"name":"<!--label omitted: 2-->California Institute for Medical Research,2 San Jose, California 95128;"},{"name":"<!--label omitted: 3-->Department of Medicine, Division of Infectious Diseases and Geographic Medicine,3 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond A.","family":"Sobel","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Department of Pathology,4 Stanford University, Stanford, California 94305;"},{"name":"<!--label omitted: 5-->Veterans Affairs Health Care System, Palo Alto, California 943045;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl V.","family":"Clemons","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center,1 and"},{"name":"<!--label omitted: 2-->California Institute for Medical Research,2 San Jose, California 95128;"},{"name":"<!--label omitted: 3-->Department of Medicine, Division of Infectious Diseases and Geographic Medicine,3 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demosthenes","family":"Pappagianis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 6-->Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California 956166; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center,1 and"},{"name":"<!--label omitted: 2-->California Institute for Medical Research,2 San Jose, California 95128;"},{"name":"<!--label omitted: 3-->Department of Medicine, Division of Infectious Diseases and Geographic Medicine,3 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul L.","family":"Williams","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->California Institute for Medical Research,2 San Jose, California 95128;"},{"name":"<!--label omitted: 7--> Kaweah Delta District Hospital, Visalia, California 932917"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/infdis\/157.1.178","article-title":"Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system.","volume":"157","author":"Arndt C. A. S.","year":"1988","unstructured":"Arndt C. A. S. Walsh T. J. McCully C. L. Balis F. M. Pizzo P. A. Poplack D. G. Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J. Infect. Dis. 157 1988 178 180","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"S318","DOI":"10.1093\/clinids\/12.Supplement_3.S318","article-title":"Pharmacokinetics and tissue penetration of fluconazole in humans.","volume":"12","author":"Brammer K. W.","year":"1990","unstructured":"Brammer K. W. Farrow P. R. Faulkner J. K. Pharmacokinetics and tissue penetration of fluconazole in humans. Rev. Infect. Dis. 12 (Suppl. 3) 1990 S318 S326","journal-title":"Rev. Infect. Dis."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.5.928"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.7326\/0003-4819-98-2-160","article-title":"High-dose ketoconazole for treatment of fungal infections of the central nervous system.","volume":"98","author":"Craven P. C.","year":"1983","unstructured":"Craven P. C. Graybill J. R. Jorgensen J. H. Dismukes W. E. Levine B. E. High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann. Intern. Med. 98 1983 160 167","journal-title":"Ann. Intern. Med."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-124-3-199602010-00004"},{"key":"e_1_3_2_7_2","first-page":"339","article-title":"Coccidioidal meningitis.","volume":"94","author":"Einstein H. E.","year":"1961","unstructured":"Einstein H. E. Holeman C. W. Jr. Candidge L. L. Holden D. H. Coccidioidal meningitis. Calif. Med. 94 1961 339 343","journal-title":"Calif. Med."},{"key":"e_1_3_2_8_2","unstructured":"Galgiani\n              J. N. Coccidioides immitis meningitis\n          In defense of the brain: current concepts in the immunopathogenesis and clinical aspects of CNS infections.\n              Peterson\n              P. K.\n              Remington\n              J. S.\n          1997\n          227\n          238\n          Blackwell Science Inc.\n          Malden Mass"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.7326\/0003-4819-119-1-199307010-00005","article-title":"Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group.","volume":"119","author":"Galgiani J. N.","year":"1993","unstructured":"Galgiani J. N. Catanzaro A. Cloud G. A. Higgs J. Friedman B. A. Larsen R. A. Graybill J. R. Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group. Ann. Intern. Med. 119 1993 28 35","journal-title":"Ann. Intern. Med."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.10.2224"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1001\/archinte.1986.00360220179029","article-title":"Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B.","volume":"146","author":"Labadie E. L.","year":"1986","unstructured":"Labadie E. L. Hamilton R. H. Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B. Arch Intern Med. 146 1986 2013 2018","journal-title":"Arch Intern Med."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1512"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1558"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.2111"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.3.3.247"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1001\/archinte.1995.00430150157016","article-title":"Fluconazole therapy in coccidioidal meningitis maintained with intrathecal amphotericin B.","volume":"155","author":"Perez J. A.","year":"1995","unstructured":"Perez J. A. Jr. Johnson R. H. Caldwell J. W. Arsura E. L. Nemecheck P. Fluconazole therapy in coccidioidal meningitis maintained with intrathecal amphotericin B. Arch. Intern. Med. 155 1995 1665 1668","journal-title":"Arch. Intern. Med."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/jac\/16.1.81","article-title":"Penetration of imidazoles and triazoles into cerebrospinal fluid of rabbits.","volume":"16","author":"Perfect J. R.","year":"1985","unstructured":"Perfect J. R. Durack D. T. Penetration of imidazoles and triazoles into cerebrospinal fluid of rabbits. J. Antimicrob. Chemother. 16 1985 81 86","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.29.4.579"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.5.846"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1056\/NEJM199504203321607","article-title":"Current concepts: coccidioidomycosis.","volume":"332","author":"Stevens D. A.","year":"1995","unstructured":"Stevens D. A. Current concepts: coccidioidomycosis. N. Engl. J. Med. 332 1995 1077 1082","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.7326\/0003-4819-112-2-108","article-title":"Itraconazole therapy for chronic coccidioidal meningitis.","volume":"112","author":"Tucker R. M.","year":"1990","unstructured":"Tucker R. M. Denning D. W. Dupont B. Stevens D. A. Itraconazole therapy for chronic coccidioidal meningitis. Ann. Intern. Med. 112 1990 108 112","journal-title":"Ann. Intern. Med."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.3.369"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1988.tb40443.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1093\/clinids\/9.Supplement_1.S43","article-title":"Itraconazole: pharmacologic studies in animals and humans.","volume":"9","author":"Van Cauteren H.","year":"1987","unstructured":"Van Cauteren H. Heykants J. De Coster R. Cauwenbergh G. Itraconazole: pharmacologic studies in animals and humans. Rev. Infect. Dis. 9 (Suppl. 1) 1987 S43 S46","journal-title":"Rev. Infect. Dis."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/clind\/16.2.247","article-title":"The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955\u20131958.","volume":"16","author":"Vincent T.","year":"1993","unstructured":"Vincent T. Galgiani J. N. Huppert M. Salkin D. The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955\u20131958. Clin. Infect. Dis. 16 1993 247 254","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.3.673"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/515689"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1023\/A:1016048100712","article-title":"Fluconazole distribution to the brain: a crossover study in freely-moving rats using in vivo microdialysis.","volume":"13","author":"Yang H.","year":"1996","unstructured":"Yang H. Wang Q. Elmquist W. F. Fluconazole distribution to the brain: a crossover study in freely-moving rats using in vivo microdialysis. Pharm. Res. 13 1996 1570 1575","journal-title":"Pharm. Res."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.6.1512-1517.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.6.1512-1517.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:53:44Z","timestamp":1645462424000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.44.6.1512-1517.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,6]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,6]]}},"alternative-id":["10.1128\/AAC.44.6.1512-1517.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.44.6.1512-1517.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,6]]},"assertion":[{"value":"1999-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}