Fluconazole and amphotericin B antifungal therapies do not negate the protective effect of endogenous tumor necrosis factor in a murine model of fatal disseminated candidiasis.
In systemic candidiasis, endogenously produced tumor necrosis factor (TNF)-alpha prolongs survival of the infected host. To determine whether endogenously produced TNF-alpha has a beneficial effect beyond that provided by antifungal therapy, survival was assessed in infected mice that received fluconazole or amphotericin B alone and in combination with anti-TNF-alpha antibody. Neutralization of serum TNF-alpha did not affect survival in fluconazole recipients; however, for amphotericin B recipients, it significantly shortened mean survival. For both fluconazole and amphotericin B recipients, colony counts in organs were significantly higher in animals that also received anti-TNF-alpha antibody. Administration of anti-TNF-alpha antibody with amphotericin B or fluconazole did not affect the morphology of fungi or the inflammatory response in kidneys. This study suggests that exogenous TNF-alpha and drugs that increase the endogenous production of TNF-alpha by the host may be useful adjuncts to fluconazole and amphotericin B for the treatment of systemic candidiasis.
Louie
A
A
Infectious Disease Section, Stratton VA Medical Center, Albany, New York.
Baltch
A L
AL
Smith
R P
RP
Franke
M A
MA
Ritz
W J
WJ
Singh
J K
JK
Gordon
M A
MA
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D015169:Colony Count, Microbial; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007668:Kidney / Q000382:microbiology; D007958:Leukocyte Count; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D007074:Immunoglobulin G; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B; D015725:Fluconazole