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.
Subject(s)
Animals , Antifungal Agents/pharmacology , Aspergillosis/drug therapy , Aspergillus fumigatus/drug effects , Benzocycloheptenes/pharmacology , Evaluation Studies as Topic , Male , Mice , Microbial Sensitivity Tests , Sesquiterpenes/pharmacologyABSTRACT
Alcoholics extracts of 266 botanically identified plant materials from 222 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings. Biological activities have been observed in 89 extracts. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported.