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11 pages, 886 KiB

Open AccessArticle

A Cluster of Candida auris Blood Stream Infections in a Tertiary Care Hospital in Oman from 2016 to 2019

by Jalila Mohsin, Sanjeewani Weerakoon, Sarah Ahmed, Ynze Puts, Zainab Al Balushi, Jacques F. Meis and Abdullah M.S. Al-Hatmi

Antibiotics 2020, 9(10), 638; https://doi.org/10.3390/antibiotics9100638 - 24 Sep 2020

Cited by 27 | Viewed by 3292

Abstract

(1) Background: Candida auris has been reported as emerging yeast pathogen that can cause invasive bloodstream infections in healthcare settings. It is associated with high mortality rates and resistance to multiple classes of antifungal drugs and is difficult to identify with standard laboratory [...] Read more.

(1) Background: Candida auris has been reported as emerging yeast pathogen that can cause invasive bloodstream infections in healthcare settings. It is associated with high mortality rates and resistance to multiple classes of antifungal drugs and is difficult to identify with standard laboratory methods. (2) Methods: We conducted a retrospective review of epidemiological, clinical, and microbiological records for 23 C. auris fungemia cases at the Royal Hospital, a tertiary care facility in Oman, between 2016 and 2018. Demographic data, risk factors associated with mortality, microbiology investigation and treatment regimens are described. Yeasts were identified by MALDI-TOF. (3) Results: We identified 23 patients with C. auris fungemia. All positive samples from patients were confirmed as C. auris using MALDI-TOF, and ITS-rDNA sequencing. Microsatellite genotyping showed that the Omani isolates belong to the South Asian clade I. The majority of patients had multiple underlying illnesses and other risk factors that have been associated with fungemia. All isolates were non-susceptible to fluconazole. Isolates from all patients were sensitive to echinocandins and these were used as first line therapy. (4) Conclusions: Candida auris affects adults and children with a variety of risk factors including central venous catheters and overuse of antibiotics. Infections occur in both immunocompromised and immunocompetent individuals. Mortality was high in this series, and the organism can be transmitted in healthcare settings. Programs for raising awareness in Oman hospitals are warranted. Caspofungin remains 1st line therapy as MICs are still low despite its wide use. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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10 pages, 1406 KiB

Open AccessArticle

Characteristics and Management of Candidaemia Episodes in an Established Candida auris Outbreak

by Juan V. Mulet Bayona, Nuria Tormo Palop, Carme Salvador García, Paz Herrero Rodríguez, Vicente Abril López de Medrano, Carolina Ferrer Gómez and Concepción Gimeno Cardona

Antibiotics 2020, 9(9), 558; https://doi.org/10.3390/antibiotics9090558 - 30 Aug 2020

Cited by 34 | Viewed by 3663

Abstract

The multi-resistant yeast Candida auris has become a global public health threat because of its ease to persist and spread in clinical environments, especially in intensive care units. One of the most severe manifestations of invasive candidiasis is candidaemia, whose epidemiology has evolved [...] Read more.

The multi-resistant yeast Candida auris has become a global public health threat because of its ease to persist and spread in clinical environments, especially in intensive care units. One of the most severe manifestations of invasive candidiasis is candidaemia, whose epidemiology has evolved to more resistant non-albicansCandida species, such as C. auris. It is crucial to establish infection control policies in order to control an outbreak due to nosocomial pathogens, including the implementation of screening colonisation studies. We describe here our experience in managing a C. auris outbreak lasting more than two and a half years which, despite our efforts in establishing control measures and surveillance, is still ongoing. A total of 287 colonised patients and 47 blood stream infections (candidaemia) have been detected to date. The epidemiology of those patients with candidaemia and the susceptibility of C. auris isolates are also reported. Thirty-five patients with candidaemia (74.5%) were also previously colonised. Forty-three patients (91.5%) were hospitalised (61.7%) or had been hospitalised (29.8%) in the ICU before developing candidaemia. Antifungal therapy for candidaemia consisted of echinocandins in monotherapy or in combination with amphotericin B or isavuconazole. The most common underlying disease was abdominal surgery (29.8%). The thirty-day mortality rate was 23.4% and two cases of endophtalmitis due to C. auris were found. All isolates were resistant to fluconazole and susceptible to echinocandins and amphotericin B. One isolate became resistant to echinocandins two months after the first isolate. Although there are no established clinical breakpoints, minimum inhibitory concentrations for isavuconazole were low (≤ 1 μg/mL). Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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11 pages, 768 KiB

Open AccessArticle

Candida auris Bloodstream Infections in Russia

by Natalia E. Barantsevich, Antonina V. Vetokhina, Natalia I. Ayushinova, Olga E. Orlova and Elena P. Barantsevich

Antibiotics 2020, 9(9), 557; https://doi.org/10.3390/antibiotics9090557 - 30 Aug 2020

Cited by 16 | Viewed by 3088

Abstract

Candida auris—a fungus (yeast) that can cause hospital outbreaks was first recognized in 2009. The authors report data on 38 cases of C. auris bloodstream infections in multidisciplinary hospitals situated in two distantly located regions of Russia, considering predisposing factors, antifungal susceptibility [...] Read more.

Candida auris—a fungus (yeast) that can cause hospital outbreaks was first recognized in 2009. The authors report data on 38 cases of C. auris bloodstream infections in multidisciplinary hospitals situated in two distantly located regions of Russia, considering predisposing factors, antifungal susceptibility of isolates, treatment, and outcomes. Interhospital transfers of patients and labor migration contributed to the spread of C. auris. The South Asian lineage of the studied strains was indicated by K143R substitution in ERG11 gene and phylogenetic analysis of internal transcribed spacer and D1-D2 domain. All isolates from C. auris candidemia cases were susceptible to echinocandins. High-level resistance to fluconazole and resistance to amphotericin B were present in the majority of strains. The overall all-cause mortality rate in C. auris bloodstream infections was 55.3% and the 30-day all-cause mortality rate 39.5%. The attributable mortality was 0%. Eradication of C. auris from blood was associated with the favourable outcomes in patients. It was achieved irrespective of whether antifungal preparations within or outside the susceptibility range were administered. Further international surveillance and studies providing consensus guidelines for the management of C. auris infections are needed. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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7 pages, 982 KiB

Open AccessCommunication

Derivates of the Antifungal Peptide Cm-p5 Inhibit Development of Candida auris Biofilms In Vitro

by Dennis Kubiczek, Heinz Raber, Melaine Gonzalez-García, Fidel Morales-Vicente, Ludger Staendker, Anselmo J. Otero-Gonzalez and Frank Rosenau

Antibiotics 2020, 9(7), 363; https://doi.org/10.3390/antibiotics9070363 - 27 Jun 2020

Cited by 23 | Viewed by 3676

Abstract

Growth in biofilms as a fascinating and complex microbial lifestyle has become widely accepted as one of the key features of pathogenic microbes, to successfully express their full virulence potential and environmental persistence. This also increases the threat posed by Candida auris, [...] Read more.

Growth in biofilms as a fascinating and complex microbial lifestyle has become widely accepted as one of the key features of pathogenic microbes, to successfully express their full virulence potential and environmental persistence. This also increases the threat posed by Candida auris, which has a high intrinsic ability to persist on abiotic surfaces including those of surgical instruments and medical tubing. In a previous study, cyclic and helical-stabilized analogues of the antifungal peptide Cm-p5 were designed and synthetized, and proved to have increased activities against C. albicans and C. parapsilosis, but not against planktonic C. auris cells cultivated in suspension cultures. Here, we demonstrate, initially, that these derivatives, however, exhibited semi-inhibitory concentrations between 10–21 µg/mL toward C. auris biofilms. Maturated biofilms were also arrested between 71–97%. These novel biofilm inhibitors may open urgently needed new routes for the development of novel drugs and treatments for the next stage of fight against C. auris. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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Review

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15 pages, 1001 KiB

Open AccessReview

Candida auris Urinary Tract Infections and Possible Treatment

by Nicole Griffith and Larry Danziger

Antibiotics 2020, 9(12), 898; https://doi.org/10.3390/antibiotics9120898 - 12 Dec 2020

Cited by 18 | Viewed by 5468

Abstract

Candida auris is a globally emerging pathogen that has been identified in urinary tract infections (UTIs) worldwide. The novel pathogen is characterized by common misidentification, difficult eradication, and multidrug resistance. To date, there is a paucity of data to guide the optimal management [...] Read more.

Candida auris is a globally emerging pathogen that has been identified in urinary tract infections (UTIs) worldwide. The novel pathogen is characterized by common misidentification, difficult eradication, and multidrug resistance. To date, there is a paucity of data to guide the optimal management of C. auris UTIs. This review provides an overview of C. auris as an etiologic agent of UTIs, a comprehensive review of published data on C. auris UTIs, and a proposed treatment algorithm based on patient clinical status, the presence or absence of clinical infection, comorbidities, infection, and therapy history. Echinocandin and liposomal amphotericin B are recommended as first-line agents for most patients with C. auris isolated in the urine, with a focus on infection control measures and appropriate follow-up criteria. A variety of combination therapies, flucytosine, and amphotericin B bladder irrigations are offered as potential alternatives in the event of infection persistence or recurrence. The treatment approach centers on the aggressive treatment of C. auris in most patients, with the goal of preventing subsequent invasive spread, multi-drug resistance, and ultimate mortality. Published literature on C. auris urinary isolation and treatment is imperative for the future evolution of evidence-based treatment recommendations for this unique pathogen of concern. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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14 pages, 528 KiB

Open AccessReview

Candida auris: An Overview of How to Screen, Detect, Test and Control This Emerging Pathogen

by Teresa Fasciana, Andrea Cortegiani, Mariachiara Ippolito, Antonino Giarratano, Orazia Di Quattro, Dario Lipari, Domenico Graceffa and Anna Giammanco

Antibiotics 2020, 9(11), 778; https://doi.org/10.3390/antibiotics9110778 - 5 Nov 2020

Cited by 40 | Viewed by 8331

Abstract

The multidrug-resistant yeast Candida auris is associated with invasive infections in critically ill patients and has been isolated in different countries worldwide. Ease of spread, prolonged persistence in the environment and antifungal drug resistance pose a significant concern for the prevention of transmission [...] Read more.

The multidrug-resistant yeast Candida auris is associated with invasive infections in critically ill patients and has been isolated in different countries worldwide. Ease of spread, prolonged persistence in the environment and antifungal drug resistance pose a significant concern for the prevention of transmission and management of patients with C. auris infections. Early and correct identification of patients colonized with C. auris is critical in containing its spread. However, this may be complicated by C. auris strains being misidentified as other phylogenetically related pathogens. In this review, we offer a brief overview highlighting some of the critical aspects of sample collection, laboratory culture-dependent and independent identification and the susceptibility profile of C. auris. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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16 pages, 516 KiB

Open AccessReview

Antifungal Resistance in Candida auris: Molecular Determinants

by María Guadalupe Frías-De-León, Rigoberto Hernández-Castro, Tania Vite-Garín, Roberto Arenas, Alexandro Bonifaz, Laura Castañón-Olivares, Gustavo Acosta-Altamirano and Erick Martínez-Herrera

Antibiotics 2020, 9(9), 568; https://doi.org/10.3390/antibiotics9090568 - 2 Sep 2020

Cited by 39 | Viewed by 7265

Abstract

Since Candida auris integrates strains resistant to multiple antifungals, research has been conducted focused on knowing which molecular mechanisms are involved. This review aims to summarize the results obtained in some of these studies. A search was carried out by consulting websites and [...] Read more.

Since Candida auris integrates strains resistant to multiple antifungals, research has been conducted focused on knowing which molecular mechanisms are involved. This review aims to summarize the results obtained in some of these studies. A search was carried out by consulting websites and online databases. The analysis indicates that most C. auris strains show higher resistance to fluconazole, followed by amphotericin B, and less resistance to 5-fluorocytosine and caspofungin. In C. auris, antifungal resistance to amphotericin B has been linked to an overexpression of several mutated ERG genes that lead to reduced ergosterol levels; fluconazole resistance is mostly explained by mutations identified in the ERG11 gene, as well as a higher number of copies of this gene and the overexpression of efflux pumps. For 5-fluorocytosine, it is hypothesized that the resistance is due to mutations in the FCY2, FCY1, and FUR1 genes. Resistance to caspofungin has been associated with a mutation in the FKS1 gene. Finally, resistance to each antifungal is closely related to the type of clade to which the strain belongs. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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13 pages, 1440 KiB

Open AccessReview

Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

by Mahmoud Ghannoum, Maiken Cavling Arendrup, Vishnu P. Chaturvedi, Shawn R. Lockhart, Thomas S. McCormick, Sudha Chaturvedi, Elizabeth L. Berkow, Deven Juneja, Bansidhar Tarai, Nkechi Azie, David Angulo and Thomas J. Walsh

Antibiotics 2020, 9(9), 539; https://doi.org/10.3390/antibiotics9090539 - 25 Aug 2020

Cited by 57 | Viewed by 8861

Abstract

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are [...] Read more.

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC₅₀ and MIC₉₀) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections. Full article

(This article belongs to the Special Issue Diagnosis,Resistance and Treatment of Infections by Candida auris)

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