EFFICACY OF PTX3 AND POSACONAZOLE COMBINATION IN A RAT MODEL OF INVASIVE PULMONARY ASPERGILLOSIS

Ref ID: 19537

Author:

E Marra1, ML Pacello1, L Aurisicchio1, R Gaziano3, R De Santis2, G Salvatori2*

Author address:

1Biotechnology, Takis srl, Rome, Italy
2Biotechnology, Sigma-tau , Pomezia (RM), Italy
3Experimental Medicine, University Tor Vergata, Rome, Italy

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose/Methods:
Invasive pulmonary aspergillosis (IPA) remains a relevant clinical issue in patients with graft-versushost
disease, largely due to immunosuppressive treatments with high dosages of corticosteroids. The
mortality related to IPA infection can be up to 90% in heavily treated patients, thus underlining
the need for well tolerable prophylactic interventions aimed at reducing infection frequency.
posaconazole is the most recently approved triazole, with potent anti-Aspergillus activity, currently
used in the prophilaxis of IPA. Limitations to the use of posaconazole are related to drug-drug
interaction and considerable side effects. PTX3 is an innate immunity multimeric glycoprotein
characterized by an opsonic activity against Aspergillus and proven to prevent IPA in mouse and rat
models. In order to investigate the potential benefit of combining posaconazole antifungal activity
with the immune modulatory function of PTX3, the efficacy of the simultaneous administration of
these two molecules in prophylaxis was evaluated in rats immunosuppressed with Cortisone acetate
and intratracheally administered with A. fumigatus conidia to elicit pulmonary infection.
Results:
Overall survival (37% posaconazole, 35% PTX3 and 90% combination), mean survival time and
lung fungal burden indicate synergic activity of PTX3 and posaconazole. Similarly, evaluation of
myeloperoxidase (MPO) as a marker of neutrophils activity in the lungs of infected rats clearly
indicates a synergic function of PTX3 and posaconazole in strengthening immune response against
the fungus.
Conclusion:
The results highlight the potential clinical benefit of combining oosaconazole and PTX3, particularly
in those clinical cases where reduction of triazole dosage would be desirable to minimize side effects.

Abstract Number: 64

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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