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Successful Treatment of Murine Fusariosis with High Doses of Liposomal Amphotericin B.

ORTONEDA M, PASTOR FJ, PUJOL I, GUARRO J; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. J-1830.

Universitat Rovira i Virgili, Reus, Spain

Fusarium verticillioides is one of the most frequent species involved in fusarial disseminated infections. It has shown in vitro resistance to the available antifungal drugs and the optimal treatment regimen has not yet been established. Amphotericin B (AB) at doses of 1-2 mg/kg/d is the standard therapy, even though many cases of failure exist. Although the clinical data are still very scarce it has been argued that higher doses of lipid preparations of AB, that would reduce the toxicity of the drug, might be useful. We have compared the activity of liposomal amphotericin B (LAB) (AmBisome) at 20 mg/kg/d and (AB) at 1.5 mg/kg/d in a systemic infection by F. verticillioides in mice. Daily treatment was begun one day after IV infection with 2x10[8] conidia/mouse and continued for 10 days. Mean survival time (MST) of the different groups was estimated by the Kaplan-Meier method and compared using the log rank test. Survival on day 11 was 100% for LAB (MST = 11.0 d, P < 0.05), 62.5% for AB (MST = 8.6 d, P > 0.05) and 50% for the control group (MST = 8.6 d). Surviving mice were sacrificed on day 11 and tissue burden in liver, kidneys and spleen was compared among groups using the ANOVA analysis. There was a significant reduction (P < 0.05) of colony counts in liver and spleen for LAB (2.36 and 3.33 log CFU/g, respectively) compared to those of control group (4.76 and 5.67 log CFU/g, respectively). Clearance of the fungus from kidneys was not observed in any group. CONCLUSIONS: 1) LAB at high doses increased survival and reduced significantly tissue burden in liver and spleen of immunocompetent mice infected with F. verticillioides, while results with AB1.5 were similar to those obtained in the control group. 2) LAB has potential for treatment of systemic infections caused by F. verticillioides.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AmBisome
  • Amphotericin B
  • Animals
  • Antifungal Agents
  • Drug Carriers
  • Fusarium
  • In Vitro
  • Kidney
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Muridae
  • Spleen
  • drug therapy
  • therapy
Other ID:
  • GWAIDS0029157
UI: 102268789

From Meeting Abstracts




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