Amphotericin B resistance of Aspergillus terreus in a murine model of disseminated aspergillosis

Abstract

The in-vivo activity of amphotericin B and itraconazole against a clinical isolate of Aspergillus terreus was determined in a murine model of disseminated aspergillosis. MICs of amphotericin B and itraconazole for the strain, determined by an NCCLSbased technique, were 2 ìg=ml and 1 ìg=ml, respectively. Mice infected intravenously were treated with either itraconazole (50 or 100 mg=kg=day) or amphotericin B 4.5 mg=kg=day for 10 days. Treatment with both doses of itraconazole signi®cantly prolonged the survival rates compared with those for untreated mice. In comparison, mortality rate and median survival time were identical for mice treated with amphotericin B and for mice given no therapy, indicating that the strain was highly resistant to amphotericin B in this model. Analysis of sterol composition showed that the major sterol was ergosterol. This suggests that amphotericin B resistance was not related to a modi®ed sterol pro®le.

Comparison of the Etest and the Sensititre Colorimetric Methods with the NCCLS Proposed Standard for Antifungal Susceptibility Testing of Aspergillus Species

“…Furthermore, the MICs of amphotericin B for A. flavus, A. terreus, and three strains of A. nidulans determined by the Etest were very high (Ͼ16 mg/liter) compared with those determined by the NCCLS method (1 to 4 mg/liter). In vivo resistance to amphotericin B has been reported for A. flavus (24) and A. terreus (4,16), even though the MICs determined by the NCCLS method in vitro are low. Again, this indicates that the Etest method might be superior to the NCCLS method in detecting amphotericin B resistance (9), as has previously been found for yeasts (2,18,40).…”

Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyondCandida albicansandAspergillus fumigatus

“…In contrast to A. fumigatus, A. terreus is resistant in vitro and in vivo to the fungicidal effects of amphotericin B (Table 4) (14,20,47,96,105). Of note, the new triazoles and echinocandins all have excellent activities in vitro against A. terreus (Table 4).…”

“…The frequency of Aspergillus terreus as a cause of invasive aspergillosis varies from 3 to 12.5% (42,78). Infections due to this species appear to be increasing in recent years and are of concern given its apparent resistance in vitro to amphotericin B and poor clinical response to treatment with this agent (3,14,42,47,96). Environmental studies have found A. terreus in showerheads, hospital water storage tanks, and potted plants (1,48).…”

Presente y futuro de la micología médica

“…Así, es conocida la diferente susceptibilidad a los antifúngicos de las distintas especies de Candida y, sin duda, es previsible que algo parecido ocurra entre las diferentes especies de hongos filamentosos. Así por ejemplo, existen datos sobre la susceptibilidad disminuida de Aspergillus terreus a anfotericina B, cuando se compara con la de A. fumigatus [12][13][14][15][16] . Scedosporium apiospermum es sensible a varios antifúngicos mientras que la infección por S. prolificans es prácticamente intratable [17][18][19] .…”