title: Synergy of fluconazole with macrophages for antifungal activity against Candida albicans.
abstract: 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.
authors.affiliation: Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA.
authors.forename: U K
authors.initials: UK
authors.lastname: Garcha
authors.forename: E
authors.initials: E
authors.lastname: Brummer
authors.forename: D A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole