Caspofungin: when and how? The microbiologist's view.

The echinocandins are antifungal agents, which act by inhibiting the synthesis of ß-(1,3)-D-glucan, an integral component of fungal cell walls. Caspofungin, the first approved echinocandin, demonstrates good in vitro and in vivo activity against a range of Candida species and is an alternative therapy for Aspergillus infections. Caspofungin provides an excellent safety profile and is therefore favoured in patients with moderately severe to severe illness, recent azole exposure and in those who are at high risk of infections due to Candida glabrata or Candida krusei. In vivo/in vitro resistance to caspofungin and breakthrough infections in patients receiving this agent have been reported for Candida and Aspergillus species. The types of pathogens and the frequency causing breakthrough mycoses are not well delineated. Caspofungin resistance resulting in clinical failure has been linked to mutations in the Fksp subunit of glucan synthase complex. European Committee for Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute need to improve the in vitro susceptibility testing methods to detect fks hot spot mutants. Caspofungin represents a significant advance in the care of patients with serious fungal infections.

Sexual reproduction in Aspergillus species of medical or economical importance: why so fastidious?

Heterothallism is dependent upon the obligatory cross-mating between self-sterile homokaryotic individuals and represents a common pattern of sexuality in yeasts and molds. Heterothallic reproductive cycles have recently been discovered in three Aspergillus species of medical and economic importance, namely Aspergillus fumigatus,A. parasiticus and A. flavus. Together with Aspergillus udagawae (Neosartorya udagawae), heterothallism has now been discovered in a total of four aspergilli that affect human health or economy. These fungi appear to express relatively low levels of fertility compared to other heterothallic or homothallic aspergilli and require unusually fastidious environmental parameters to complete the sexual cycle. Because the purpose of sex is to reproduce, we favor the hypothesis that while fertility of these species is on the decline this is compensated by their proficiency to reproduce asexually in a wider range of environmental conditions. Heterothallism in these species could provide an invaluable tool for the recombinational analysis of factors relevant to pathogenicity or toxin production. There is concern, however, whether extensive recombinational analysis can be very practical in light of the fact that formation of ascospores in these species requires a long period of time and the construction of genetically marked strains is likely to decrease fertility even further.