Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis

H. S. Jafari, X. Saez-Llorens, C. Severien, F. Parras, I. Friedland, S. Rinderknecht, S. Ehrett, K. D. Olsen, C. Abramowsky, G. H. McCracken

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Abstract

To assess the effects of antifungal therapy on the course of Candida albicans central nervous system infection and inflammation, we inoculated intracisternally 105 CFU of C. albicans into rabbits. Fluconazole (10 mg/kg of body weight) or amphotericin B (1 mg/kg) was infused intravenously daily for 14 days. Treatment was initiated 24 h or 5 days after infection. Cerebrospinal fluid (CSF) was repeatedly obtained to culture the organisms, assess the level of inflammation, and measure drug concentrations. Brain tissue was obtained at the end of therapy for culture, drug concentration determinations, and histopathology. The median number of days of treatment required to sterilize CSF cultures was 4 days for fluconazole therapy and 1 day for amphotericin B therapy (P = 0.037). There was a significant reduction in tumor necrosis factor alpha and leukocyte concentrations in the CSF of animals treated early versus those in untreated control animals (P < 0.05 and P < 0.001, respectively; analysis of variance). Compared with treated animals, a higher proportion of cultured CSF samples from untreated animals were positive for Candida (P < 0.001). A cultured brain sample from 1 of the 12 animals treated early with amphotericin B was positive for C. albicans (P < 0.01 versus controls); cultures of brain samples from 3 of 12 animals treated early with fluconazole were positive, whereas cultures of brain samples from 10 of 12 controls were positive (P < 0.05). The mean density of C. albicans was lower in the single culture-positive amphotericin B recipient (1 x 101 CFU/g of brain tissue) than in those treated with fluconazole (1 x 103 CFU/g) and in controls (8 x 104 CFU/g). In animals treated late, the density of C. albicans in the brain in relation to the number of days of therapy was significantly lower in amphotericin B recipients than in those treated with fluconazole (P < 0.01) and untreated controls (P < 0.01; analysis of covariance). By histopathology, a larger proportion of untreated animals compared with those treated early demonstrated features of severe infection such as perivasculitis, ventriculitis, and evidence of fungal organisms. Compared with amphotericin B-treated rabbits, those given fluconazole had a trend toward more severe pathologic lesions. Reduced susceptibility to both fluconazole and amphotericin B was observed in the C. albicans organisms isolated from the brain of one fluconazole-treated animal. These data suggest that amphotericin B is the preferred treatment for C. albicans infections of the central nervous system.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume38
Issue number1
StatePublished - 1994

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Fluconazole
Candida albicans
Meningitis
Amphotericin B
Histology
Inflammation
Brain
Cerebrospinal Fluid
Central Nervous System Infections
Therapeutics
Rabbits
Infection
Candida
Analysis of Variance
Leukocytes
Tumor Necrosis Factor-alpha
Body Weight
Drug Therapy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis. / Jafari, H. S.; Saez-Llorens, X.; Severien, C.; Parras, F.; Friedland, I.; Rinderknecht, S.; Ehrett, S.; Olsen, K. D.; Abramowsky, C.; McCracken, G. H.

In: Antimicrobial Agents and Chemotherapy, Vol. 38, No. 1, 1994, p. 83-89.

Research output: Contribution to journalArticle

Jafari, HS, Saez-Llorens, X, Severien, C, Parras, F, Friedland, I, Rinderknecht, S, Ehrett, S, Olsen, KD, Abramowsky, C & McCracken, GH 1994, 'Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis', Antimicrobial Agents and Chemotherapy, vol. 38, no. 1, pp. 83-89.
Jafari HS, Saez-Llorens X, Severien C, Parras F, Friedland I, Rinderknecht S et al. Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis. Antimicrobial Agents and Chemotherapy. 1994;38(1):83-89.
Jafari, H. S. ; Saez-Llorens, X. ; Severien, C. ; Parras, F. ; Friedland, I. ; Rinderknecht, S. ; Ehrett, S. ; Olsen, K. D. ; Abramowsky, C. ; McCracken, G. H. / Effects of antifungal therapy on inflammation, sterilization, and histology in experimental Candida albicans meningitis. In: Antimicrobial Agents and Chemotherapy. 1994 ; Vol. 38, No. 1. pp. 83-89.
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