Development of amphotericin B-resistant Candida tropicalis in a patient with defective leukocyte function.
Emergence, during therapy, of fungi resistant to amphotericin B is purportedly rare, as fungi with altered cell membrane ergosterol content are considered too fragile to survive normal host defenses. Progressive amphotericin B resistance arose in a strain of Candida tropicalis isolated repeatedly from the urine of a patient with pyelonephritis. The most resistant isolate (R-2) lacked cell membrane ergosterol, the usual attachment site for amphotericin B, and was not inhibited by greater than 500 micrograms/ml of the drug. R-2 infected and killed embryonated eggs, but was unable to produce progressive renal infection in steroid-treated mice because of a reduced capacity to produce pseudomycelia. Persistent infection of the patient by this altered fungus was attributed to defective leukocyte candidacidal activity, especially marked in autologous serum, and to defective Candida-related cell-mediated immunity. A literature review suggests that amphotericin B resistance may not be as rare as many authorities have indicated. It is apparent that few laboratories routinely monitor fungi for amphotericin B susceptibility. In patients with defective antimicrobial defenses, amphotericin B-resistant fungi may survive, produce progressive infection, and require alternative chemotherapy for eradication.
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002642:Chick Embryo; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011704:Pyelonephritis / Q000382:microbiology / Q000652:urine
D000666:Amphotericin B