Yamin, Dina Hussein Marzouq
(2022)
Clinical epidemiology and development of novel multilocus sequence typing scheme for candida parapsilosis associated with catheter-related bloodstream infections.
PhD thesis, Universiti Sains Malaysia.
Abstract
Candida parapsilosis has been increasingly reported as an important pathogen
causing healthcare associated infections, including catheter-related bloodstream
infections (CRBSIs). Given the paucity of information on this pathogen, this study
aimed to determine the prevalence of C. parapsilosis CRBSI and the associated risk
factors. As there is lack of genotyping method to study the molecular characteristics of
C. parapsilosis, this study included the development of multilocus sequence typing
(MLST) scheme for C. parapsilosis sensu stricto population. In this study, data for 208
C. parapsilosis candidemia were collected and recorded in a standard proforma. After
exclusion of 31 cases that were not catheterized, 177 episodes of C. parapsilosis
candidemia were included in analysis, from which, 30 cases of CRBSI were compared
to 147 non-CRBSI cases in terms of demographic, underlying diseases, invasive medical
procedures, and laboratory test values. The prevalence, clinical characteristics and risk
factors of C. parapsilosis CRBSIs were determined. Species identification of
C. parapsilosis sensu stricto was confirmed by sequencing the ITS region of the
ribosomal RNA genes. A novel MLST scheme was developed for genotyping clinical
C. parapsilosis population. Five representative non-related C. parapsilosis isolates were
used to test the potentially polymorphic loci for the presence of polymorphism. In MLST
development phase, a number of loci were screened based on previously published
MLST schemes and data from C. parapsilosis whole genome sequences. Seven most
polymorphic loci were selected. Neutrality test was performed on the selected loci and discriminatory power of the scheme was determined. Genetic diversity among
C. parapsilosis population and correlation with clinical outcomes and antifungal
resistance were determined. Results of this study revealed that C. parapsilosis was the
most predominant Candida species causing candidemia contributing to 29.2% of all
candidemia cases. The prevalence of C. parapsilosis CRBSI was 14.4% of all
C. parapsilosis candidemia, and 17.7% of catheterized candidemia patients. Out of 208
cases of C. parapsilosis candidemia, 30 cases were CRBSI, 112 were BSI and 66 were
catheter colonizer. Intensive care unit (ICU) admission and receipt of total parenteral
nutrition (TPN) were reported as independent risk factors of C. parapsilosis CRBSI.
Admission in non-ICU and receipt of TPN were significantly associated with the
development of C. parapsilosis CRBSI compared to non-CRBSI. Death due to
C. parapsilosis candidemia was reported in 19.1% of patients. The developed MLST
scheme demonstrated the ability to discriminate 19 C. parapsilosis sensu stricto strains
into 15 different DSTs with a discriminatory power of 0.942. Phylogenetic analysis
based on 4735 concatenated nucleotides of 19 C. parapsilosis sensu stricto strains were
grouped into four clusters. The associations of C. parapsilosis DSTs with outcomes and
antifungal resistance cannot be determined due to small number of strains in each
genotype. In conclusion, the prevalence of C. parapsilosis candidemia was the highest
among other Candida species, while the prevalence of C. parapsilosis CRBSI was low
compared to all C. parapsilosis candidemia. Admission to ICU and receiving TPN were independent risk factors for C. parapsilosis CRBSI, where non-ICU admission and TPN
receipt were significantly associated with development of CRBSI compared to non-
CRBSI. A novel MLST scheme for C. parapsilosis has been successfully developed.
This robust, highly discriminatory novel MLST scheme could be used as a molecular
genotyping tool for C. parapsilosis sensu stricto strains worldwide.
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