Treating Resistant Filamentous Fungi Infections

Abstract

Resistance to treatment can be caused by intrinsic resistance to antifungal drugs, and also by the angioinvasive nature of some of these mycoses, which causes distal pulmonary infarction. As blood flow is blocked, antifungal drug penetraiton is decreased. Both considerations must be addressed. With the development of infarction, there is decreased penetration of polyenes and presumably all antifungal drugs into tissue. Inadequate delivery of antifungal drugs is one reason which causes in vitro susceptible pathogens, like Aspergillus species (triazoles) or zygomycetes (polyenes) to progress in the presence of antifungal therapy which “should be effective”. Management of clinical resistance in these patient can be improved at the outset, by accelerating the speed of diagnosis and initiating treatment more promptly. Tools for this include a) rapidlly identifying patients at high risk and b) intensive surveillance with serum (and now bronchoalveolar lavage) galactomannan, beta-D-glucan, and PCR. The former allows identification of groups for antifungal prophylaxis, and the latter allows for identifcation of patients ever earlier in the course of disease. There is room for considerable improvement in rapid diagnosis. Intrinsically high resistance to antifungals can be predicted for many (not all) isolates simply by identifying the fungal species. This is straightforward for polyene resistance of Aspergillus terreus, or almost pan-antifungal resistance of Scedosporium prolificans. Others, such as Fusarium or Paecilomyces species, are very challenging, but may respond to high levels of certain antifungals. For these patients animal studies and small clinical series may provde guidance. There is great temptation to use combinations of antifungal drugs, especially when synergy is suggested by in vitro studies. This area is complicated by the rarity of such isolates and inability to collect large series of infected patients. For some, recommendations may need to be individualls tailored. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive