title: Comparative in vitro and in vivo evaluation of himachalol in murine invasive aspergillosis.
abstract: Aspergilli are increasingly important infections in immunocompromised patients (ICP). The available antifungals often cause discrepancies in laboratory determination of MICs and a correlation in therapy. An effort was made to compare in vitro techniques for testing of antifungals, viz. polyenes, imidazoles, 5-fluorocytosine, amorolfine; and screened a phytoproduct- himachalol (a sesquiterpene alcohol) from Cedrus deodara (Roxb.) Loud against A. fumigatus clinical isolates (24) by macrobroth two-fold seal dilution (TFSD), microbroth microtitre (MT) and disc diffusion (DD) techniques using various broth/agar media at varying periods of incubation. The best activity in terms of geometric mean (GM) (GM.MIC < 0.39 microgrmas ml-1) was obtained with SCZ in the broth by both MT or TFSD technique followed by ECZ (GM.MIC 0.39 micrograms ml-1) and ITZ (GM.MIC 0.39-0.8 micrograms ml-1) in RPMI-1640. Overall RPMI-1640 was found to be the most suitable growth medium for testing of azoles or amorolfine, and YNB for polyene and 5-FC. MT technique was the most sensitive quantitative, reproducible, rapid and economical compared to other techniques. The treatment of Swiss mice with himachalol (200 mg kg-1, po) once a day, for 7 days, provided 60% protection concomitantly with increased MST (15 days) against invasive aspergillosis. A combination of himachalol (200 mgkg-1) plus SCZ (5 mgkg-1) showed better regimen in the therapy evidenced by enhanced survival (80%) of mice significantly (p < 0.001) with prolonged MST (> 15 days) compared to control. The treatments also reduced cfu (mean log10) burden of A. fumigatus from kidney.
authors.affiliation: Division of Medical Mycology, Central Drug Research Institute, Lucknow, India.
authors.forename: L
authors.initials: L
authors.lastname: Chowdhry
authors.forename: Z K
authors.initials: ZK
authors.lastname: Khan
authors.forename: D K
authors.initials: DK
authors.lastname: Kulshrestha
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001567:Benzocycloheptenes / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001567:Benzocycloheptenes; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C010185:himachalol