scholarly journals Comparison of In Vitro Killing Activity of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in RPMI-1640 in the Absence and Presence of Human Serum

2021 ◽  
Vol 9 (4) ◽  
pp. 863
Author(s):  
Renátó Kovács ◽  
Zoltán Tóth ◽  
Jeffrey B. Locke ◽  
Lajos Forgács ◽  
Gábor Kardos ◽  
...  
Keyword(s):  
South African ◽  
South Asian ◽  
Therapeutic Option ◽  
East Asian ◽  
Multidrug Resistant ◽  
South American ◽  
The South ◽  
Candida Auris ◽  
Asian Clade

Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.

scholarly journals Unpredictable In Vitro Killing Activity of Amphotericin B against Four Candida auris Clades

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 990
Author(s):  
Zoltán Papp ◽  
Andrew M. Borman ◽  
Lajos Forgács ◽  
Renátó Kovács ◽  
Zoltán Tóth ◽  
...  
Keyword(s):  
Amphotericin B ◽  
South African ◽  
South Asian ◽  
East Asian ◽  
South American ◽  
The South ◽  
Candida Auris ◽  
Killing Activity ◽  
Tract Infections

Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections.

scholarly journals Two Candida auris Cases in Germany with No Recent Contact to Foreign Healthcare—Epidemiological and Microbiological Investigations

2021 ◽  
Vol 7 (5) ◽  
pp. 380
Author(s):  
Joerg Steinmann ◽  
Thomas Schrauzer ◽  
Lisa Kirchhoff ◽  
Jacques F. Meis ◽  
Peter-Michael Rath
Keyword(s):  
South Asian ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Contact Precautions ◽  
Asian Clade ◽  
Care Facilities ◽  
Long Time ◽  
European Health ◽  
Healthcare Associated

Candida auris has become a global fungal public health threat. This multidrug-resistant yeast is associated with nosocomial intra- and interhospital transmissions causing healthcare-associated infections. Here, we report on two C. auris cases from Germany. The two patients stayed in Germany for a long time before C. auris was detected during their hospitalization. The patients were isolated in single rooms with contact precautions. No nosocomial transmissions were detected within the hospital. Both C. auris isolates exhibited high minimum inhibitory concentrations (MICs) of fluconazole and one isolate additionally high MICs against the echinocandins. Microsatellite genotyping showed that both strains belong to the South Asian clade. These two cases are examples for appropriate in-hospital care and infection control without further nosocomial spread. Awareness for this emerging, multidrug-resistant pathogen is justified and systematic surveillance in European health care facilities should be performed.

scholarly journals Identification of Candida auris by Use of the Updated Vitek 2 Yeast Identification System, Version 8.01: a Multilaboratory Evaluation Study

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Georges Ambaraghassi ◽  
Philippe J. Dufresne ◽  
Simon F. Dufresne ◽  
Émilie Vallières ◽  
José F. Muñoz ◽  
...  
Keyword(s):  
Evaluation Study ◽  
Multidrug Resistant ◽  
Identification System ◽  
Correct Identification ◽  
South American ◽  
The South ◽  
Candida Auris ◽  
Yeast Identification ◽  
Content Type ◽  
Vitek 2

ABSTRACT Candida auris is an emerging multidrug-resistant yeast that has been systematically incorrectly identified by phenotypic methods in clinical microbiology laboratories. The Vitek 2 automated identification system (bioMérieux) recently included C. auris in its database (version 8.01). We evaluated the performance of the Vitek 2 YST ID card to identify C. auris and related species. A panel of 44 isolates of Candida species (C. auris, n = 35; Candida haemulonii, n = 5; Candida duobushaemulonii, n = 4) were tested by three different hospital-based microbiology laboratories. Among 35 isolates of C. auris, Vitek 2 yielded correct identification in an average of 52% of tested samples. Low-discrimination (LD) results with an inability to distinguish between C. auris, C. duobushaemulonii, and Candida famata were obtained in an average of 27% of samples. Incorrect identification results were obtained in an average of 21% of samples, the majority (91%) of which were reported as C. duobushaemulonii and the remaining 9% of which were reported as Candida lusitaniae/C. duobushaemulonii. The proportion of correct identification was not statistically different across different centers (P = 0.78). Stratification by genetic clades demonstrated that 100% (n = 8) of the strains of the South American clade were correctly identified compared to 7% (n = 10) and 0% (n = 4) from the African and East Asian clades, respectively. None of the non-auris Candida strains (n = 9) were incorrectly identified as C. auris. Our results show that the Vitek 2 (version 8.01) yeast identification system has a limited ability to correctly identify C. auris. These data suggest that an identification result for C. duobushaemulonii should warrant further testing to rule out C. auris. The overall performance of the Vitek 2 seems to differ according to C. auris genetic clade, with the South American isolates yielding the most accurate results.

scholarly journals In-vitro antifungal resistance of Candida auris isolates from bloodstream infections, South Africa

2021 ◽  
Author(s):  
Tsidiso G. Maphanga ◽  
Serisha D. Naicker ◽  
Stanford Kwenda ◽  
Jose F. Muñoz ◽  
Erika van Schalkwyk ◽  
...  
Keyword(s):  
Amphotericin B ◽  
South African ◽  
Antifungal Agent ◽  
National Laboratory ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Reference Laboratory ◽  
Candida Auris ◽  
The Common

Introduction Candida auris is a multidrug-resistant fungal pathogen endemic in South African hospitals. Materials and methods We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidaemia, 2016-2017. We confirmed species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole and flucytosine using broth microdilution (BMD) and Etest. We interpreted minimum inhibitory concentrations (MICs) using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared to the C. auris B8441 reference strain. Results Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (85%) to fluconazole alone (MIC of ≥32 mg/L), 19 (5%) to fluconazole and amphotericin B (MIC ≥2 mg/L) and one (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (fluconazole, amphotericin B, echinocandins). Of 93 isolates selected for whole genome sequencing, 78 clustered in clade III including the pan-resistant isolates, 13 in clade I and two in clade IV. Eighty-four of these (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, E343D in ERG11 ; N647T in MRR1; A651P, A657V, S195G in TAC1b; S639P in FKS1; and S58T in ERG3 genes. Conclusions Most South African C. auris isolates were resistant to azoles, though resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically-susceptible isolates.

scholarly journals Candida auris Isolates of the Southern Asian and South African Lineages Exhibit Different Phenotypic and Antifungal Susceptibility Profiles In Vitro

2019 ◽  
Vol 57 (5) ◽  
Author(s):  
Adrien Szekely ◽  
Andrew M. Borman ◽  
Elizabeth M. Johnson
Keyword(s):  
United Kingdom ◽  
South African ◽  
Antifungal Susceptibility ◽  
The South ◽  
Candida Auris ◽  
Content Type ◽  
African Lineage ◽  
The United Kingdom ◽  
Asian Lineage

ABSTRACT Candida auris is a serious nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Sequence analyses of outbreak isolates revealed that C. auris has simultaneously emerged as four distinct continentally restricted clonal lineages. We previously reported multiple independent introductions of C. auris isolates from at least three of these lineages (the Southern Asia, South African, and Japanese/Korean lineages) into hospitals across the United Kingdom and that isolates circulating in the United Kingdom displayed two different cell phenotypes which correlated with differences in virulence in Galleria mellonella wax moths. Here, we compared the phenotypic characteristics and antifungal susceptibilities of isolates representative of the three geographic clades circulating in the United Kingdom. Isolates of the South African and Japanese/Korean lineages, but not those of the Southern Asian lineage, grew well on media containing actidione. However, unlike Southern Asian lineage isolates, they were unable to produce even rudimentary pseudohyphae in culture. Importantly, although all isolates were fluconazole resistant in vitro, fluconazole and voriconazole exhibited significantly higher MICs against isolates of the South African lineage than against isolates of the Southern Asian lineage. A similar trend was seen with minimum fungicidal concentrations (MFCs), with higher MFCs of the triazole antifungal agents being seen for the South African lineage isolates. Finally, the formation of large cellular aggregates was seen only with isolates of the South African and Japanese/Korean lineages, which correlates with the reduced virulence observed previously in Galleria wax moths inoculated with such isolates. Intriguingly, aggregation could be reversibly induced in isolates of the Southern Asian lineage by exposure to triazole and echinocandin antifungals but not by exposure to amphotericin B or flucytosine.

Insulating Peace: Managerial Coordination in Durable Security Complexes

2021 ◽  
Author(s):  
Konstantinos Travlos
Keyword(s):  
South Asian ◽  
Regional Security ◽  
Collective Intentionality ◽  
South American ◽  
Proof Of Concept ◽  
The South ◽  
Mapping Tool ◽  
Region I ◽  
The Face ◽  
Future Evaluation

Abstract I argue that insulation via managerial coordination is a key element in any explanation about the formation of political regions among states. The key role it plays is as a tool for the maintenance of intra-regional pacific relations in the face of diffusion and contagion processes, resulting from continued security linkages with excluded extra-regional states. In order to explore these dynamics, I propose a new reconceptualization of the concept of managerial coordination based on the basic framework concept mapping tool. This leads to clarity about what managerial coordination does as a dimension of insulation. It also necessitates a revamp of the scale of interstate managerial coordination as a measuring instrument of the intensity of collective intentionality toward insulation among the members of a region. I then map the region concept of durable security complex (DSC) as the scope for the enactment of managerial coordination, based on a review of existing region concepts in the new regionalist literature. I then conduct an ideographic proof-of-concept exercise on three DSCs in the presence or absence of managerial coordination. These are the Scandinavian states, the South Asian regional security complex, and the South American Norther Tier local hierarchy. The exercise provides indicators for a number of theoretical propositions worthy of future evaluation.

Economic Implications of Asian Integration

2008 ◽  
Vol 8 (3) ◽  
pp. 1850139 ◽  
Author(s):  
Joseph F. Francois ◽  
Ganeshan Wignaraja
Keyword(s):  
East Asia ◽  
South Asian ◽  
Regional Integration ◽  
East Asian ◽  
The South ◽  
Economic Implications ◽  
Spider Web ◽  
Integration Schemes ◽  
Asian Economies ◽  
Northeast Asian

The Asian countries are once again focused on options for large, comprehensive regional integration schemes. In this paper we explore the implications of such broad-based regional trade initiatives in Asia, highlighting the bridging of the East and South Asian economies. We place emphasis on the alternative prospects for insider and outsider countries. We work with a global general equilibrium model of the world economy, benchmarked to a projected 2017 sets of trade and production patterns. We also work with gravity-model based estimates of trade costs linked to infrastructure, and of barriers to trade in services. Taking these estimates, along with tariffs, into our CGE model, we examine regionally narrow and broad agreements, all centered on extending the reach of ASEAN to include free trade agreements with combinations of the northeast Asian economies (PRC, Japan, Korea) and also the South Asian economies. We focus on a stylized FTA that includes goods, services, and some aspects of trade cost reduction through trade facilitation and related infrastructure improvements. What matters most for East Asia is that China, Japan, and Korea be brought into any scheme for deeper regional integration. This matter alone drives most of the income and trade effects in the East Asia region across all of our scenarios. The inclusion of the South Asian economies in a broader regional agreement sees gains for the East Asian and South Asian economies. Most of the East Asian gains follow directly from Indian participation. The other South Asian players thus stand to benefit if India looks East and they are a part of the program, and to lose if they are not. Interestingly, we find that with the widest of agreements, the insiders benefit substantively in terms of trade and income while the aggregate impact on outside countries is negligible. Broadly speaking, a pan-Asian regional agreement would appear to cover enough countries, with a great enough diversity in production and incomes, to actually allow for regional gains without substantive third-country losses. However, realizing such potential requires overcoming a proven regional tendency to circumscribe trade concessions with rules of origin, NTBs, and exclusion lists. The more likely outcome, a spider web of bilateral agreements, carries with it the prospect of significant outsider costs (i.e. losses) both within and outside the region.

scholarly journals In Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No Antagonism

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui
Keyword(s):  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Resistant Mutants ◽  
Hospital Acquired

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

Whole genome sequence of first Candida auris strain, isolated in Russia

2019 ◽  
Vol 58 (3) ◽  
pp. 414-416 ◽  
Author(s):  
Ivan M Pchelin ◽  
Daniil V Azarov ◽  
Maria A Churina ◽  
Igor A Ryabinin ◽  
Irina V Vibornova ◽  
...  
Keyword(s):  
South Asian ◽  
Genome Sequence ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Candida Auris ◽  
Fluconazole Resistance ◽  
Russian Strain ◽  
Resistant Strains ◽  
Original Species

Abstract Candida auris is an emergent yeast pathogen, easily transmissible between patients and with high percent of multidrug resistant strains. Here we present a draft genome sequence of the first known Russian strain of C. auris, isolated from a case of candidemia. The strain clustered within South Asian C. auris clade and seemingly represented an independent event of dissemination from the original species range. Observed fluconazole resistance was probably due to F105L and K143R mutations in ERG11.

scholarly journals Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris

2019 ◽  
Vol 57 (4) ◽  
Author(s):  
Rory M. Welsh ◽  
D. Joseph Sexton ◽  
Kaitlin Forsberg ◽  
Snigdha Vallabhaneni ◽  
Anastasia Litvintseva
Keyword(s):  
Large Scale ◽  
East Asian ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type ◽  
New Information ◽  
Asian Clade ◽  
Single Region ◽  
Invasive Infections ◽  
Unique Nature

ABSTRACT The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. C. auris consists of four discrete clades, based on where the first isolates of the clade were reported, South Asian (clade I), East Asian (clade II), African (clade III), and South American (clade IV). These clades have unique genetic and biochemical characteristics that are important to understand and inform the global response to C. auris. Clade II has been underrepresented in the literature despite being the first one discovered. In this issue of the Journal of Clinical Microbiology, Y. J. Kwon et al. (J Clin Microbiol 57:e01624-18, 2019, https://doi.org/10.1128/JCM.01624-18) describe the largest collection of clinical isolates from Clade II, which is also the longest-running span of clinical cases, 20 years, from any single region to date. Clade II appears to have a propensity for the ear that is uncharacteristic of the other clades, which typically cause invasive infections and large-scale outbreaks. This study provides new information on an understudied lineage of C. auris and has important implications for future surveillance.

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