Candida parapsilosis, C. orthopsilosis y C. metapsilosisepidemiología de las candidemias, patrones de sensibilidad y mecanismos de resistencia a las equinocandinas

Resumen

In the study presented, a retrospective study was carried out in which the diagnosed candidemias were analysed over a 15-year period in the Microbiology Service of the Hospital de la Santa Creu I Sant Pau in Barcelona. The implication of C. parapsilosis complex as a causal agent of candidemia was evaluated, and also their percentage distribution according to other Candida species and their prevalence according to patient's age, as well as their evolution over the years and the prevalence of the three species comprising the complex: C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis. The susceptibility of C. parapsilosis to the nine antifungal approved systemic agents and their possible resistance mechanism, both intrinsic and acquired, to echinocandins was also studied. C. parapsilosis complex was the second most common species causing fungemia (20%), ahead of C. tropicalis (14.4%) and C. glabrata (11.7%) and only behind C. albicans (43.1%). A much higher incidence is shown in paediatric patients (less than 1 year: 66.7%; 2-14 year: 50%). During this period its incidence increased slightly over the years (0.33% per year). The susceptibility studies showed an excellent activity of the 9 antifungal agents tested against almost all the isolates, and only in the case of itraconazole, a considerably percentage of non-susceptible strains (23%) was detected. The percentage of echinocandin non-susceptible strains was low (1.5%) and caspofungin was the most active echinocandin against C. parapsilosis. To study the resistance mechanism against echinocandins, the FKS1 and FKS2 genes were analysed, which codify for the ß-(1,3)-D-glucan synthase and the possible activation of adaptive responses against the action of echinocandins was also analysed. A relative low frequency of acquired mutations in the FKS1 (11/78 isolates) was detected, being all mutations detected outside HS regions and no mutations were identified in the FKS2 gene. Only a single mutation (F1386S) in 1 out 6 non-susceptible isolates was identified, outside the HS regions, which may be associated with the phenotype resistant to echinocandins. The basal chitin content of the cell wall was very similar among the echinocandin susceptible (7.79%) and non-susceptible (8.14%) C. parapsilosis isolates, as well as among the 3 species of the complex: C. parapsilosis (7.96%), C. orthopsilosis (9.42%) and C. metapsilosis (9.53%). However all these values were significantly higher that those determined in the C. albicans control strains (4.61%). The vast majority of the strains increased their basal chitin content between 1% to 3%, after a treatment with caspofungin, with the exception of the two echinocandin resistant C. parapsilosis isolates that increased their chitin content by 7% and 11%. Of note is that these two isolates were the ones that showed the lowest basal chitin content and moreover, one of them showed the F1386S mutation. These results may suggest that a compensatory increase in the chitin production, as a consequence of the inhibition in the synthesis of ß-(1,3)-D-glucan caused by echinocandins, could be implied in the acquired resistance to these antifungal agents.