Abstract
Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates (n = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 μg/ml and micafungin = 8 μg/ml) and the infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city (P = 0.02, α <0.05) and Mashhad was significantly associated with mortality (P = 0.03, α <0.05). Overall, we found a low level of antifungal resistance for Iranian C. parapsilosis blood isolates, but the noted MDR strain can potentially become the source of future infections and challenge the antifungal therapy in antifungal-naïve patients. AFLP typing results warrants confirmation using other resolutive typing methods.
Highlights
The changing epidemiological landscape of candidemia driven by overuse of prophylactic antifungal drugs has resulted in an increasing incidence of non-albicans Candida (NAC) species (Sanglard, 2019)
Candida parapsilosis accounted for the vast majority of the blood isolates (n = 93; 94.9% from 86 patients), followed by C. orthopsilosis (n = 3; 3%) and one patient was concurrently infected with both C. parapsilosis and C. orthopsilosis (98 isolates from 90 patients) (Table 1, Supplementary Table 3)
There was no difference for C. parapsilosis candidemia between males (n = 45; 50%) and females (n = 45; 50%)
Summary
The changing epidemiological landscape of candidemia driven by overuse of prophylactic antifungal drugs has resulted in an increasing incidence of non-albicans Candida (NAC) species (Sanglard, 2019). Microbiologists and clinicians are heavily focused on multi-drug resistant Candida parapsilosis and Candida auris (Colombo et al, 2017), but an increasing number of publications are casting light on the importance of other NAC species, as well (Chakrabarti et al, 2015; Singh et al, 2019). Among these NAC species, Candida parapsilosis is the first to third common cause of candidemia depending on age, geographical location, and patient category (Chan et al, 2015; Da Matta et al, 2017; Sun et al, 2019). The closely related cryptic species of C. parapsilosis, i.e., C. orthopsilosis, is linked to numerous clinical failures (Wessel et al, 2013; Oliveira et al, 2014; Heslop et al, 2015; Charsizadeh et al, 2018b), and implicated in a wide range of clinical manifestations, including superficial infections (Feng et al, 2012), septic arthritis (Heslop et al, 2015), keratitis (Wessel et al, 2013), and fatal invasive bloodstream infections (Choi et al, 2010)
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