Candidiasis and antifungal drug resistance in the Asia-Pacific region

Posted by Dr. Truong Ngoc Hai - Resuscitation Doctor - Emergency Department - Vinmec Central Park International General Hospital

Population-based studies in Europe and the United States show that approximately 95% of candidaemia is caused by the following four strains: C.albicans , C.glabrata , C.parapsilosis and C.tropicalis . In which, C.albicans accounted for about 45-60% of all samples isolated from blood, followed by C. glabrata strain (18). In contrast, based on single-country studies, C.tropicalis appears to be predominant in Latin America as well as in Southeast Asia (19-21). However, these data are based on reports from small studies, with different methods of testing for antifungals. In particular, most of the published data is reported from Singapore, Thailand and Korea. Therefore, there is a gap in knowledge and expertise compared to other countries in the Asia-Pacific region.
Knowledge of the epidemiology of Candida strains is important when considering treatment, because susceptibility to fluconazole can often be predicted by identification of the causative organism. C.albicans generally responds to fluconazole, but natural resistance to fluconazole has recently been reported to be increased in C.glabrata , C.tropicalis (22) and C.parapsilosis (23) strains.
Susceptibility to fluconazole in the same Candida strain has been reported to vary from country to country or within countries, underscoring the importance of knowledge of the epidemiology and drug response in each country. local. Antifungal testing is not routinely performed in hospitals in the Asia-Pacific region. Clinicians often prescribe drugs empiric or based on response data from elsewhere, which is not applicable to the local epidemiology.
To complete the data for each region, a prospective, multicenter observational study was conducted across 13 centers in the Asia-Pacific region, over a 2-year period (2013-2015) and included A total of 861 Candida samples were isolated.

Table 1 - Distribution of Candida strains in the participating countries (17)

Research results on the distribution of Candida strains showed that the 4 most common strains were C.albicans (35.9%), C.tropicalis (30.7%), C.parapsilosis (15.7%) and C.glabrata (13.6). %).
C.albicans is the most common strain at centers in Korea, Singapore, Taiwan and Vietnam. C.tropicalis is common in centers in the Philippines and Thailand, while C.parapsilosis is most common in Brunei. It is worth noting that the proportion of non-albicans strains recorded was higher than that of C.albicans in most countries, except Taiwan.
In Vietnam, 6 common Candida strains are C.albicans (39.9%), C.tropicalis (39.2%), C.parapsilosis (7.8%), C.glabrata (7.8%), C.rugosa (3.9%). and C.guilliermondii (0.7%). In which, non-albicans strains accounted for 60.1%.

Table 2 - Antifungal susceptibility of the countries participating in the study( 17 )

C.albicans is also sensitive to fluconazole (99.7%). This susceptibility was lower in non-albicans strains, especially C.tropicalis (S=75.8%, S-DD= 6.1%, R=18.2%), C.glabrata (S-DD= 94.8%, R) = 5.2%) and C.parapsilosis (S= 94.8%, S-DD = 3% R=2.2%). There were regional differences in fluconazole susceptibility among non-albicans strains. C.tropicalis fluconazole resistance is highest in Thailand. (S=70.3%) and Vietnam (S=61.7%); meanwhile, fluconazole resistance of C. glabrata was highest in Brunei (S-DD= 80%) and Singapore (S-DD= 93.9%).
All isolated C.albicans samples were sensitive to voriconazole, but 16.7% of C.tropicalis had MICs in the S-DD range and 14% of C.tropicalis were resistant to voriconazole.
The activities of the 3 groups of echinocandins were still sensitive (S> 99%) to C.albicans, C.tropicalis and C.parapsilosis, but a small percentage of caspofungin resistance (low level) was observed. C.glabrata samples were isolated. A total of 12 isolates did not respond to caspofungin, of which 9 (75%) had MICs that fell into the intermediate response region. Resistance to caspofungin was most common in C. glabrata (n= 8) (S= 93.1%, S-DD= 5.2%, R= 1.7%), accounting for 62% of the total samples that did not respond. Most caspofungin unresponsive samples were tested for susceptibility to other echinocandins, because cross-resistance with any of the other two echinocandins was observed in only three strains (C.tropicalis, C.glabrata and C.krusei ). The gene mutations in the fks hotspot regions were identified in 2 isolates: C.glabrata (GenBank KT950827) and C.krusei (GenBank KT950828), and all 2 samples with the fks mutation showed cross-resistance with fks. at least 2 out of 3 echinocandins. The sensitivity to caspofungin was lowest in C. glabrata isolates from Korea (S= 77.8) and Singapore (S= 89.8%); however, the number of isolates with caspofungin resistance is not much.
There is no CLSI breakpoint for amphotericin B's antifungal activity against Candida strains. However, the MIC distribution range of amphotericin B against C.albicans (range 0.12-1.0 mg/l, MIC50 and MIC90= 0.5mg/l), C.tropicalis (0.25-1.0 mg/l, MIC50 and MIC90= 1.0 mg/l), C.parapsilosis (0.25-1.0 mg/l, MIC50= 0.5, MIC90= 1.0 mg/l) and C.glabrata (0.25-2.0 mg/l, MIC50 and MIC90= 1.0 mg/l) falls into the “wild-type” MIC distribution (24).
The results from this study are important for two reasons:
First, we found non-albicans strains to be the most frequent in the isolates from most cases of bacteremia in the pharynx. most of the countries in the Asia-Pacific region and of these, C.tropicalis and C.parapsilosis stand out.
Second, a significant proportion of C.tropicalis (and subsequently C.parapsilosis ) showed decreased susceptibility to fluconazole. It is implied that susceptibility to fluconazole in these non-albicans strains cannot be accurately predicted (25). These findings suggest that in the Asia-Pacific region, echinocandins should be selected in clinically unstable situations and in high-risk patients, with evidence of candidaemia (26). Routine antifungal treatment of non-albicans strains is recommended for appropriate use of azoles (27) and if fluconazole is considered empiric, then therapeutic dosing strategies should be implemented. appropriate treatment (28).

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