+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

In vivo virulence of laboratory-selected azole-resistant Aspergillus fumigatus in a murine pulmonary aspergillosis model



In vivo virulence of laboratory-selected azole-resistant Aspergillus fumigatus in a murine pulmonary aspergillosis model



Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 41: 390-391



Previous studies had shown that laboratory-selected amphotericin B-resistant Aspergillus fumigatus isolates exhibited poor virulence in a murine pulmonary aspergillosis model. Thus, correlation of in vitro drug resistance with in vivo evaluation has been difficult. We investigated the virulence of laboratory-selected spontaneous mutants of A. fumigatus showing reduced susceptibility to voriconazole (MIC 6.33+-5.12 mug/ml). The cytochrome P450-dependent 14a-sterol demethylase from 5 of 6 resistant isolates showed specific amino acid alteration (G138R or G448S). Using a murine pulmonary aspergillosis model, we examined the virulence of a representative resistant isolate (VCZ-F10) and the results were compared with those obtained for the drug-susceptible parent (ATCC 208995). Mice were made neutropenic by three successive injections of cyclophosphamide (100 mg/kg/d) on day -3, -1 and 1 where day 0 is the day of infection. The immunosuppressed mice were challenged with 1X106 conidia/mouse and the infectivity of the isolates were evaluated by the survival and the fungal load of the infected animals. The animals infected with the parent (n=20) and the resistant (n=19) isolates survived 3.19+-1.01 day and 3.2+-0.92 day, respectively. Determination of fungal burden in the lungs of infected animals showed no significant difference between the parent (875+-670 CFU/lungs) and the resistant mutant (705+-442 CFU/lungs) groups. In another study, similar results were obtained for itraconazole resistant isolates. These results suggest that spontaneous azoleresistant isolates of A. fumigatus selected in the laboratory are virulent in a murine pulmonary aspergillosis model.

(PDF emailed within 1 workday: $29.90)

Accession: 035111472

Download citation: RISBibTeXText


Related references

Pharmacodynamics and dose-response relationships of liposomal amphotericin B against different azole-resistant Aspergillus fumigatus isolates in a murine model of disseminated aspergillosis. Antimicrobial Agents and ChemoTherapy 57(4): 1866-1871, 2013

Variation in virulence of Aspergillus fumigatus strains in a murine model of invasive pulmonary aspergillosis. Journal of Medical Microbiology 45(3): 186-191, 1996

Pulmonary aspergillosis caused by a pan-azole-resistant Aspergillus fumigatus in a 10-year-old boy. Pediatric Infectious Disease Journal 30(3): 268-270, 2011

Invasive pulmonary aspergillosis due to a multi-azole resistant Aspergillus fumigatus. Acta Clinica Belgica 67(1): 46-48, 2012

In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression Models of Invasive Aspergillosis. Antimicrobial Agents and ChemoTherapy 61(6): -, 2017

The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis. Infection and Immunity 61(5): 1650-1656, 1993

A new experimental murine aspergillosis model to identify strains of Aspergillus fumigatus with reduced virulence. Nihon Ishinkin Gakkai Zasshi 43(4): 203-213, 2002

Isavuconazole (BAL4815) pharmacodynamic target determination in an in vivo murine model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant isolates of Aspergillus fumigatus. Antimicrobial Agents and ChemoTherapy 57(12): 6284-6289, 2014

In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. EBGA Network. European research group on Biotypes and Genotypes of Aspergillus fumigatus. Journal of Medical Microbiology 48(12): 1087-1093, 1999

Dose optimization of voriconazole/anidulafungin combination against Aspergillus fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response surface analysis: clinical implications for azole-resistant aspergillosis. Journal of Antimicrobial ChemoTherapy 71(11): 3135-3147, 2016

High airborne level of Aspergillus fumigatus and presence of azole-resistant TR34/L98H isolates in the home of a cystic fibrosis patient harbouring chronic colonisation with azole-resistant H285Y A. fumigatus. Journal of Cystic Fibrosis 2019, 2019

Efficacy of LY303366 against amphotericin B-susceptible and -resistant Aspergillus fumigatus in a murine model of invasive aspergillosis. Antimicrobial Agents and ChemoTherapy 42(4): 873-878, 1998

Pharmacodynamics of Voriconazole against Wild-Type and Azole-Resistant Aspergillus flavus Isolates in a Nonneutropenic Murine Model of Disseminated Aspergillosis. Antimicrobial Agents and ChemoTherapy 61(1): -, 2016

Interactions of cortisone acetate and aspergillus fumigatus in a murine model of experimental pulmonary aspergillosis. Abstracts of the Annual Meeting of the American Society for Microbiology 90: 76, 1990

Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis. Infection and Immunity 62(12): 5247-5254, 1994