New approaches to the detection of echinocandin resistance in Candida glabrata in clinical diagnostic laboratories

Fraser, Mark (2019) New approaches to the detection of echinocandin resistance in Candida glabrata in clinical diagnostic laboratories. UWE https://researchdata.uwe.ac.uk/id/eprint/444/

Brief summary of project

Candidaemia is widely reported as the fourth most common form of bloodstream infection worldwide. Reports of cases of candidaemia whilst patients are in receipt of antifungal therapy are increasing, and this is especially relevant as prescribing practices change and develop. Given the elevation of echinocandin antifungal agents as first line treatment options over triazole agents and the use of echinocandin antifungal agents as prophylactic agents, it is important to maintain awareness of the potential difficulties surrounding emergent antifungal resistance. This study has designed and created a suitable assay for the specific detection of FKS gene mutations in Candida glabrata in the clinical diagnostic laboratory that can be used to indicate resistance using a pyrosequencing based platform. There exists the potential for this rapid molecular detection system to be used as a screening tool helping to provide clinicians with the information required to make appropriate therapeutic decisions for the management of bloodstream infections within 4 hours. This study has also attempted to demonstrate the potential of proteomic approaches, using LC MS/MS and MALDI-TOF MS, to indicate antifungal resistance as demonstrated by C. glabrata and the echinocandin antifungal agents, by the identification of proteins, the changing patterns of protein presence, absence or relative abundance. This study has solely focused on using techniques that are realistically accessible to a diagnostic microbiology laboratory so as to maintain a true clinical impact. No readily identifiable or reproducible patterns were found, however the importance of continuing to adapt and modify the capabilities of the modern clinical diagnostic laboratory as an era of increasing antimicrobial resistance is highlighted. This study also serves to demonstrate the continual low level of echinocandin resistance prevalent in C. glabrata in the United Kingdom.