Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents

Jacobs, Samantha; Jacobs, Jonathan L.; Dennis, Emily K.; Taimur, Sarah; Rana, Meenakshi; Patel, Dhruv; Gitman, Melissa R.; Patel, Gopi; Schaefer, Sarah; Iyer, Kishore; Moon, Jang; Adams, Victoria; Lerner, Polina; Walsh, Thomas J.; Zhu, YanChun; Anower, Mohammed Rokebul; Vaidya, Mayuri M; Chaturvedi, Sudha

doi:10.1128/aac.00053-22

Cited by 53 publications

(40 citation statements)

References 58 publications

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“…A number of studies have described the molecular mechanisms in C. auris that result in antifungal resistance and clinical failures of azoles and echinocandins. Resistance to azoles was shown to be mediated by mutations in ERG11 (F126L, Y132F and K143R) [ 3 , 51 , 106 , 114 , 115 ] and in CDR1 (V704L) [ 115 ]; and resistance to echinocandins, by mutations in FKS1 (S639P, S639F, S639Y, F635C, S635P and S635T) [ 51 , 52 , 115 , 116 , 117 , 118 ]. Analysis of pan-resistant C. auris strains suggested a fitness cost in some strains [ 118 ].…”

Section: C Auris Antifungal Resistance and Therapeutic Optionsmentioning

confidence: 99%

Navigating the New Reality: A Review of the Epidemiological, Clinical, and Microbiological Characteristics of Candida auris, with a Focus on Children

Ashkenazi‐Hoffnung

Danziger

2023

JoF

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During the past decade, Candida auris emerged across the world, causing nosocomial outbreaks in both pediatric and adult populations, particularly in intensive care settings. We reviewed the epidemiological trends and the clinical and microbiological characteristics of C. auris infection, focusing on the pediatric population. The review is based on 22 studies, which included about 250 pediatric patients with C. auris infection, across multiple countries; neonates and premature babies were the predominant pediatric patient group affected. The most common type of infection reported was bloodstream infection, which was associated with exceptionally high mortality rates. Antifungal treatment varied widely between the patients; this signifies a serious knowledge gap that should be addressed in future research. Advances in molecular diagnostic methods for rapid and accurate identification and for detection of resistance may prove especially valuable in future outbreak situations, as well as the development of investigational antifungals. However, the new reality of a highly resistant and difficult-to-treat pathogen calls for preparedness of all aspects of patient care. This spans from laboratory readiness, to raising awareness among epidemiologists and clinicians for global collaborative efforts to improve patient care and limit the spread of C. auris.

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Section: C Auris Antifungal Resistance and Therapeutic Optionsmentioning

confidence: 99%

Navigating the New Reality: A Review of the Epidemiological, Clinical, and Microbiological Characteristics of Candida auris, with a Focus on Children

Ashkenazi‐Hoffnung

Danziger

2023

JoF

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“…Candida auris is an emerging fungal pathogen that has caused outbreaks of invasive healthcare-associated infections worldwide [6]. Candida auris is frequently resistant to fluconazole, and multidrug-resistant and even pandrug-resistant C. auris isolates have also been described, thus leaving very few treatment options [6][7][8]. In Europe, the UK and Spain were the first countries to report outbreaks [9].…”

Section: Discussionmentioning

confidence: 99%

Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021

2022

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The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.

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“…Despite the need for an effective and reliable approach to treatment, the clinical practice guidelines of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Confederation of Medical Mycology (ECMM), and the Infection Disease Society of America (IDSA) still recommend echinocandin-based monotherapy for the majority of these infections [ 31 , 32 ]. The emergence of echinocandin resistance is, therefore, a relevant concern [ 24 , 33 ]. Based on the cutoff values suggested by the CDC, the resistance rate to echinocandins is approximately 5% [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interaction of Caspofungin Combined with Posaconazole against FKS Wild-Type and Mutant Candida auris Planktonic Cells and Biofilms

et al. 2022

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Candida auris is a potential multidrug-resistant pathogen able to cause biofilm-associated outbreaks, where frequently indwelling devices are the source of infections. The number of effective therapies is limited; thus, new, even-combination-based strategies are needed. Therefore, the in vitro efficacy of caspofungin with posaconazole against FKS wild-type and mutant Candida auris isolates was determined. The interactions were assessed utilizing the fractional inhibitory concentration indices (FICIs), the Bliss model, and a LIVE/DEAD assay. Planktonic minimum inhibitory concentrations (pMICs) for the caspofungin–posaconazole combination showed a 4- to 256-fold and a 2- to 512-fold decrease compared to caspofungin and posaconazole alone, respectively. Sessile minimum inhibitory concentrations (sMICs) for caspofungin and posaconazole in combination showed an 8- to 128-fold and a 4- to 512-fold decrease, respectively. The combination showed synergy, especially against biofilms (FICIs were 0.033–0.375 and 0.091–0.5, and Bliss cumulative synergy volumes were 6.96 and 32.39 for echinocandin-susceptible and -resistant isolates, respectively). The caspofungin-exposed (4 mg/L) C. auris biofilms exhibited increased cell death in the presence of posaconazole (0.03 mg/L) compared to untreated, caspofungin-exposed and posaconazole-treated biofilms. Despite the favorable effect of caspofungin with posaconazole, in vivo studies are needed to confirm the therapeutic potential of this combination in C. auris-associated infections.

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Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents

Abstract: Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area.

Cited by 53 publications

References 58 publications

Navigating the New Reality: A Review of the Epidemiological, Clinical, and Microbiological Characteristics of Candida auris, with a Focus on Children

Navigating the New Reality: A Review of the Epidemiological, Clinical, and Microbiological Characteristics of Candida auris, with a Focus on Children

Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021

Synergistic Interaction of Caspofungin Combined with Posaconazole against FKS Wild-Type and Mutant Candida auris Planktonic Cells and Biofilms

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