Synergy of fluconazole with macrophages for antifungal activity against Candida albicans.
The possible between macrophages and fluconazole for antifungal activity against different isolates of C. albicans was studied. The susceptibility of C. albicans isolates to fluconazole (FCZ), when incubated in RPMI-1640 with 10% fetal bovine serum (FBS) and 10% fresh mouse serum (test medium, TM) was determined by using a quantitative culture methodology, Multiplication of isolate Sh27 was strongly inhibited by FCZ, even at 1.0 microgram/ml. However, FCZ even at 100 microgram/ml was not fungicidal. Resident murine peritoneal macrophages (MP) incubated for 48 h in RPMI-1640 + 10% FBS (tissue culture medium, TCM), then challenged with Sh27 in TM for 24 h, were fungistatic (20 +/ 9%, n = 4). Cultured macrophages synergized with FCZ (10 micrograms/ml) for fungicidal activity when co-cultured with sh27 in TM for 24 h (46 +/ 8%) and for 48 h (74 +/ 5%), n = 3. Macrophages and FCZ (10 micrograms/ml) could not synergize for significant killing of a less FCZ-sensitive C. albicans isolate 94-164. Multiplication of a FCZ-resistant isolate (94-20) was not inhibited by FCZ at 10 micrograms/ml TM; however, macrophages and FCZ (10 micrograms/ml) could synergize for fungistatic (64%), but not fungicidal, activity.
Garcha
U K
UK
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA.
Brummer
E
E
Stevens
D A
DA
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002478:Cells, Cultured; D004352:Drug Resistance, Microbial; D015725:Fluconazole / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000935:Antifungal Agents; D015725:Fluconazole