Emerging Multidrug-Resistant
                    Candida duobushaemulonii
                    Infections in Panama Hospitals: Importance of Laboratory Surveillance and Accurate Identification

ABSTRACT Candida duobushaemulonii , a yeast closely related to Candida auris , is thought to cause infections in rare cases and is often misidentified. In October 2016, the Panamanian Ministry of Health implemented laboratory surveillance for C. auris . Suspected C. auris isolates were forwarded to the national reference laboratory for identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry and antifungal susceptibility testing. Between November 2016 and May 2017, 17 of 36 (47%) isolates suspected to be C. auris were identified as C. duobushaemulonii. These 17 isolates were obtained from 14 patients at six hospitals. Ten patients, including three children, had bloodstream infections, and MICs for fluconazole, voriconazole, and amphotericin B were elevated. No resistance to echinocandins was observed. C. duobushaemulonii causes more invasive infections than previously appreciated and poses a substantial problem, given its resistance to multiple antifungals. Expanded laboratory surveillance is an important step in the detection and control of such emerging pathogens.

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Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

Journal of Clinical Microbiology ◽

10.1128/jcm.00367-15 ◽

2015 ◽

Vol 53 (6) ◽

pp. 1823-1830 ◽

Cited By ~ 246

Author(s):

Shallu Kathuria ◽

Pradeep K. Singh ◽

Cheshta Sharma ◽

Anupam Prakash ◽

Aradhana Masih ◽

...

Keyword(s):

Antifungal Susceptibility ◽

Laser Desorption ◽

Multidrug Resistant ◽

Laser Desorption Ionization ◽

Candida Auris ◽

Ionization Time ◽

Content Type ◽

Flight Mass Spectrometry ◽

Vitek 2 ◽

Matrix Assisted Laser

Candida aurisis a multidrug-resistant yeast that causes a wide spectrum of infections, especially in intensive care settings. We investigatedC. aurisprevalence among 102 clinical isolates previously identified asCandida haemuloniiorCandida famataby the Vitek 2 system. Internal transcribed spacer region (ITS) sequencing confirmed 88.2% of the isolates asC. auris, and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) easily separated all related species,viz.,C. auris(n= 90),C. haemulonii(n= 6),C. haemuloniivar.vulnera(n= 1), andCandida duobushaemulonii(n= 5). Thein vitroantifungal susceptibility was determined using CLSI broth microdilution (CLSI-BMD), the Vitek 2 antifungal susceptibility test, and the Etest method.C. aurisisolates revealed uniformly elevated fluconazole MICs (MIC50, 64 μg/ml), and an alarming percentage of isolates (37%) exhibited elevated caspofungin MICs by CLSI-BMD. Notably, 34% ofC. aurisisolates had coexisting elevated MICs (≥2 μg/ml) for both fluconazole and voriconazole, and 10% of the isolates had elevated coexisting MICs (≥2 μg/ml) to two additional azoles, i.e., posaconazole and isavuconazole. In contrast to reduced amphotericin B MICs by CLSI-BMD (MIC50, 1 μg/ml) forC. auris, elevated MICs were noted by Vitek 2 (MIC50, 8 μg/ml), which were statistically significant.Candida aurisremains an unnoticed pathogen in routine microbiology laboratories, as 90% of the isolates characterized by commercial identification systems are misidentified asC. haemulonii. MALDI-TOF MS proved to be a more robust diagnostic technique for rapid identification ofC. auris. Considering that misleading elevated MICs of amphotericin B by the Vitek AST-YS07 card may lead to the selection of inappropriate therapy, a cautionary approach is recommended for laboratories relying on commercial systems for identification and antifungal susceptibility testing of rare yeasts.

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Multilocus sequence typing of azole-resistant Candida auris strains, South Africa

Southern African Journal of Infectious Diseases ◽

10.4102/sajid.v35i1.116 ◽

2020 ◽

Vol 35 (1) ◽

Author(s):

Rindidzani Magobo ◽

Mabatho Mhlanga ◽

Craig Corcoran ◽

Nelesh P. Govender

Keyword(s):

Multilocus Sequence Typing ◽

Genetic Relatedness ◽

Antifungal Susceptibility ◽

Venous Catheter ◽

Multidrug Resistant ◽

Reference Laboratory ◽

Candida Auris ◽

Patient Demographics ◽

Male Patients ◽

And Cluster Analysis

Background: Candida auris is an emerging multidrug-resistant fungal pathogen associated with high mortality.Methods: We investigated the genetic relatedness of clinical C. auris isolates from patients admitted to either public- or private-sector hospitals, which were submitted to a reference laboratory from 2012 to 2015. Patient demographics and clinical details were recorded. We performed antifungal susceptibility testing, sequencing of the hotspot 1 and 2 regions of the FKS1 and FKS2 genes for all isolates with an echinocandin minimum inhibitory concentration (MIC) of ≥1 µg/mL and cluster analysis using multilocus sequence typing.Results: Eighty-five isolates were confirmed as C. auris. The median patient age was 59 years [inter-quartile range (IQR): 48–68 years], with male patients accounting for 68% of cases. Specimen types included urine (29%), blood (27%), central venous catheter tips (25%), irrigation fluid (7%), tissue (5%), respiratory tract specimens (4%) and other (3%). Ninety-seven per cent of isolates were resistant to fluconazole, 7% were resistant to both fluconazole and voriconazole, 8% were resistant to both fluconazole and echinocandins (considered multidrug resistant) and all were susceptible to amphotericin B. Of the 15 randomly selected fluconazole-resistant isolates, 14 isolates had an isavuconazole MIC ≤ 1 µg/mL. No FKS mutations were detected. Multilocus sequence typing (MLST) analysis grouped isolates into two clusters: cluster 1 and cluster 2 comprising 83 and 2 isolates, respectively.Conclusions: Azole-resistant C. auris strains circulating in South African hospitals were related by MLST, but the possibility of nosocomial transmission should be explored using a more discriminatory technique, for example, whole genome sequencing.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00517-21 ◽

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.

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Metagenomic Sequencing for Direct Identification of Candida auris Colonization

mSphere ◽

10.1128/msphere.00638-21 ◽

2021 ◽

Author(s):

Teresa R. O’Meara

Keyword(s):

Bloodstream Infections ◽

Multidrug Resistant ◽

Skin Microbiome ◽

Metagenomic Sequencing ◽

Nursing Facilities ◽

Candida Auris ◽

Direct Identification ◽

Skilled Nursing ◽

Content Type ◽

Skin Colonization

Candida auris is an emerging multidrug-resistant yeast that is associated with skin colonization and deadly bloodstream infections, especially in ventilator skilled nursing facilities. An ongoing question is how this organism colonizes the skin of these patients and whether the skin microbiome provides a measure of colonization resistance against C. auris .

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Facile Bio-Fabrication of Ag-Cu-Co Trimetallic Nanoparticles and Its Fungicidal Activity against Candida auris

Journal of Fungi ◽

10.3390/jof7010062 ◽

2021 ◽

Vol 7 (1) ◽

pp. 62 ◽

Cited By ~ 1

Author(s):

Majid Rasool Kamli ◽

Vartika Srivastava ◽

Nahid H. Hajrah ◽

Jamal S. M. Sabir ◽

Khalid Rehman Hakeem ◽

...

Keyword(s):

Electron Microscopy ◽

Antimicrobial Properties ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Biologically Active ◽

Phase Cell ◽

Candida Auris ◽

Medical Problems ◽

One Pot ◽

X Ray

Candida auris is an emergent multidrug-resistant pathogen that can lead to severe bloodstream infections associated with high mortality rates, especially in hospitalized individuals suffering from serious medical problems. As Candida auris is often multidrug-resistant, there is a persistent demand for new antimycotic drugs with novel antifungal action mechanisms. Here, we reported the facile, one-pot, one-step biosynthesis of biologically active Ag-Cu-Co trimetallic nanoparticles using the aqueous extract of Salvia officinalis rich in polyphenols and flavonoids. These medicinally important phytochemicals act as a reducing agent and stabilize/capping in the nanoparticles’ fabrication process. Fourier Transform-Infrared, Scanning electron microscopy, Transmission Electron Microscopy, Energy dispersive X-Ray, X-ray powder diffraction and Thermogravimetric analysis (TGA) measurements were used to classify the as-synthesized nanoparticles. Moreover, we evaluated the antifungal mechanism of as-synthesized nanoparticles against different clinical isolates of C. auris. The minimum inhibitory concentrations and minimum fungicidal concentrations ranged from 0.39–0.78 μg/mL and 0.78–1.56 μg/mL. Cell count and viability assay further validated the fungicidal potential of Ag-Cu-Co trimetallic nanoparticles. The comprehensive analysis showed that these trimetallic nanoparticles could induce apoptosis and G2/M phase cell cycle arrest in C. auris. Furthermore, Ag-Cu-Co trimetallic nanoparticles exhibit enhanced antimicrobial properties compared to their monometallic counterparts attributed to the synergistic effect of Ag, Cu and Co present in the as-synthesized nanoparticles. Therefore, the present study suggests that the Ag-Cu-Co trimetallic nanoparticles hold the capacity to be a lead for antifungal drug development against C. auris infections.

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In VitroandIn VivoAntimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01519-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 5961-5970 ◽

Cited By ~ 72

Author(s):

Luísa C. S. Antunes ◽

Francesco Imperi ◽

Fabrizia Minandri ◽

Paolo Visca

Keyword(s):

Human Serum ◽

Acinetobacter Baumannii ◽

Galleria Mellonella ◽

Therapeutic Potential ◽

Survival Rates ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Gallium Nitrate ◽

Content Type ◽

Bacterial Physiology

ABSTRACTMultidrug-resistantAcinetobacter baumanniiposes a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumanniichemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO3)3, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58A. baumanniistrains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO3)3delayed the entry ofA. baumanniiinto the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)3activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO3)3also protectedGalleria mellonellalarvae from lethalA. baumanniiinfection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO3)3inhibited the growth in human serum of 76% of the multidrug-resistantA. baumanniiisolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment ofA. baumanniibloodstream infections. Ga(NO3)3also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistantA. baumannii.

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Genomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal Sepsis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00898-18 ◽

2018 ◽

Vol 62 (11) ◽

Cited By ~ 11

Author(s):

Glen P. Carter ◽

James E. Ussher ◽

Anders Gonçalves Da Silva ◽

Sarah L. Baines ◽

Helen Heffernan ◽

...

Keyword(s):

Neonatal Sepsis ◽

Neonatal Intensive Care ◽

Genomic Analysis ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Comparative Genomic ◽

Coagulase Negative Staphylococci ◽

Content Type ◽

Staphylococcus Capitis ◽

Hospital Infection Control

ABSTRACT Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

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Environmental Isolation of Candida auris from the Coastal Wetlands of Andaman Islands, India

mBio ◽

10.1128/mbio.03181-20 ◽

2021 ◽

Vol 12 (2) ◽

Cited By ~ 1

Author(s):

Parth Arora ◽

Prerna Singh ◽

Yue Wang ◽

Anamika Yadav ◽

Kalpana Pawar ◽

...

Keyword(s):

Salt Marsh ◽

Coastal Wetlands ◽

Ecological Niche ◽

Multidrug Resistant ◽

Sandy Beaches ◽

Andaman Islands ◽

Human Pathogen ◽

Candida Auris ◽

Content Type ◽

The Indian Ocean

ABSTRACT Candida auris is a multidrug resistant pathogen that presents a serious global threat to human health. As C. auris is a newly emerged pathogen, several questions regarding its ecological niche remain unexplored. While species closely related to C. auris have been detected in different environmental habitats, little is known about the natural habitat(s) of C. auris. Here, we explored the virgin habitats around the very isolated Andaman Islands in the Indian Ocean for evidence of C. auris. We sampled coastal wetlands, including rocky shores, sandy beaches, tidal marshes, and mangrove swamps, around the Andaman group of the Andaman & Nicobar Islands, Union Territory, in India. Forty-eight samples of sediment soil and seawater were collected from eight sampling sites representing the heterogeneity of intertidal habitats across the east and west coast of South Andaman district. C. auris was isolated from two of the eight sampling sites, a salt marsh and a sandy beach. Interestingly, both multidrug-susceptible and multidrug-resistant C. auris isolates were found in the sample. Whole-genome sequencing analysis clustered the C. auris isolates into clade I, showing close similarity to other isolates from South Asia. Isolation of C. auris from the tropical coastal environment suggests its association with the marine ecosystem. The fact that viable C. auris was detected in the marine habitat confirms C. auris survival in harsh wetlands. However, the ecological significance of C. auris in salt marsh wetland and sandy beaches to human infections remains to be explored. IMPORTANCE Candida auris is a recently emerged multidrug-resistant fungal pathogen capable of causing severe infections in hospitalized patients. Despite its recognition as a human pathogen a decade ago, so far the natural ecological niche(s) of C. auris remains enigmatic. A previous hypothesis suggested that C. auris might be native to wetlands, that its emergence as a human pathogen might have been linked to global warming effects on wetlands, and that its enrichment in that ecological niche was favored by the ability of C. auris for thermal tolerance and salinity tolerance. To understand the mystery of environmental niches of C. auris, we explored the coastal wetland habitat around the very isolated Andaman Islands in the Indian Ocean. C. auris was isolated from the virgin habitats of salt marsh area with no human activity and from a sandy beach. C. auris isolation from the marine wetlands suggests that prior to its recognition as a human pathogen, it existed as an environmental fungus.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01393-19 ◽

2019 ◽

Vol 63 (12) ◽

Cited By ~ 8

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.

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Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01466-19 ◽

2019 ◽

Vol 64 (2) ◽

Cited By ~ 2

Author(s):

Ayesha Khan ◽

William C. Shropshire ◽

Blake Hanson ◽

An Q. Dinh ◽

Audrey Wanger ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Susceptibility Testing ◽

Multidrug Resistant ◽

Critically Ill Patient ◽

Whole Genome ◽

Candida Auris ◽

Content Type ◽

Simultaneous Infection ◽

Polymicrobial Infections ◽

Selection Of

ABSTRACT We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris. A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.

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