Antifungal agents and immunomodulators in systemic mycoses.

The rising incidence of fungal infections and the emergence of several fungi as opportunistic pathogens have reawakened interest in chemotherapeutic and prophylactic agents for mycoses. During the past decades significant advances have been made in the development of novel antifungal agents for treatment of systemic mycoses. This brief review presents an update of the available information on polyenes, imidazoles, triazoles, flucytosine, allylamines, echinocandins, nikkomycins, sordarins and immunomodulators. A reference has also been made to the work in antifungals done or in progress at the Central Drug Research Institute (CDRI), Lucknow. Currently, antifungals represent more than 6% of the total world market for anti-infective agents and with 20% annual expansion they are expected to cross the 15 billion US Dollars in value within a decade.

Comparative in vitro and in vivo evaluation of himachalol in murine invasive aspergillosis.

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.