In vivo evolution to echinocandin resistance and increasing clonal heterogeneity in Candida auris during a difficult-to-control hospital outbreak, Italy, 2019 to 2022

Codda, Giulia; Willison, Edward; Magnasco, Laura; Morici, Paola; Giacobbe, Daniele Roberto; Mencacci, Antonella; Marini, Daniele; Mikulska, Małgorzata; Bassetti, Matteo; Marchese, Anna; Pilato, Vincenzo Di

doi:10.2807/1560-7917.es.2023.28.14.2300161

Cited by 20 publications

(8 citation statements)

References 18 publications

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“…Antifungal drug resistance is thought to be an acquired as well as a shared trait, with the potential to develop over time when fungi are exposed to antifungals [ 94 95 ]. The emergence of echinocandin resistance, detected by WGS and phenotypically, within an ongoing prolonged outbreak is concerning [ 96 ]. C. auris has an intrinsic ability to exhibit or develop resistance very rapidly even while the patient is still undergoing treatment, which is why it is essential to use the antifungals at the right time and at the correct dosage [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England

Jones,

Neill,

Borman

et al. 2024

Journal of Medical Microbiology

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The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.

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Section: Methodsmentioning

confidence: 99%

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England

Jones,

Neill,

Borman

et al. 2024

Journal of Medical Microbiology

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“…Further, investigations of potential outbreaks relied on older, less discriminatory genotyping methods or only on clinical epidemiological data. This all changed with the incursion of C. auris into multiple regions when it was recognized that this modern Candida species was capable of rapid patient-to-patient transmission, could colonize and persist in the hospital environment, and could cause invasive infection and be associated with antifungal drug resistance [89,92]. This section covers the main epidemiological features of healthcare-associated nosocomial outbreaks caused by Candida spp.…”

Section: Yeastsmentioning

confidence: 99%

“…auris is known to often be resistant to fluconazole, and traditionally, echinocandins have been the empiric therapy of choice for C. auris infections [302]. Concerningly, descriptions of emergent resistance to echinocandins have been described in the setting of established hospital endemicity [89]. This highlights the need for health services to double their efforts in preventing nosocomial transmission, as well as the need for antifungal susceptibility testing to identify drug resistance.…”

Section: Pathogenmentioning

confidence: 99%

Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management

Douglas,

Stewart,

Halliday

et al. 2023

JoF

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Nosocomial clusters of fungal infections, whilst uncommon, cannot be predicted and are associated with significant morbidity and mortality. Here, we review reports of nosocomial outbreaks of invasive fungal disease to glean insight into their epidemiology, risks for infection, methods employed in outbreak detection including genomic testing to confirm the outbreak, and approaches to clinical and infection control management. Both yeasts and filamentous fungi cause outbreaks, with each having general and specific risks. The early detection and confirmation of the outbreak are essential for diagnosis, treatment of affected patients, and termination of the outbreak. Environmental sampling, including the air in mould outbreaks, for the pathogen may be indicated. The genetic analysis of epidemiologically linked isolates is strongly recommended through a sufficiently discriminatory approach such as whole genome sequencing or a method that is acceptably discriminatory for that pathogen. An analysis of both linked isolates and epidemiologically unrelated strains is required to enable genetic similarity comparisons. The management of the outbreak encompasses input from a multi-disciplinary team with epidemiological investigation and infection control measures, including screening for additional cases, patient cohorting, and strict hygiene and cleaning procedures. Automated methods for fungal infection surveillance would greatly aid earlier outbreak detection and should be a focus of research.

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“…The phylogenetic structure of C. auris consists of 5 major clades with different genomic and phenotypic characteristics. For instance, clade I, originated in South Asia, is characterized by its rapid dissemination in clinical settings and is responsible for outbreaks that are difficult to eradicate worldwide (Chow et al, 2018;Thatchanamoorthy et al, 2022;Codda et al, 2023). In contrast, strains belonging to clade V have only been detected in individuals from Iran (Spruijtenburg et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Of these, Spain is the largest contributor with 50.5% of the total (Kohlenberg et al, 2022). National genomic surveillance studies in Italy have identified the emergence of multidrug-resistant strains in a large hospital in Liguria since 2019, all belonging to clade I (Codda et al, 2023). The situation in Spain is similar.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Evolution and Dispersal Patterns of Fluconazole-Resistance inCandida aurisclade III

Cancino-Muñoz,

Mulet-Bayona,

Salvador-García

et al. 2024

Preprint

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The rapid increase of infections caused by the emerging fungal pathogen Candida auris is of global concern, and understanding its expansion is a priority. The phylogenetic diversity of the yeast is clustered in five major clades, among which clade III is particularly relevant, as most of its strains exhibit resistance to fluconazole, reducing the therapeutic alternatives and provoking outbreaks that are difficult to control. In this study, we have investigated the phylogenetic structure of clade III by analyzing a global collection of 566 genomes. We have identified three subgroups within clade III, among which two are genetically most closely related. Moreover, we have estimated the evolutionary rate of clade III to be 2.25e-7 substitutions/site/year (2.87 changes per year). We found that one of these subgroups shows intrinsic resistance to fluconazole and is responsible for the majority of cases within this clade globally. We inferred that this subgroup may have originated around December 2010 (95% CI: April 2010 - June 2011), and since then it has spread across continents, generating multiple large outbreaks, each with a unique pattern of transmission and dissemination. These results highlight the remarkable ability of the pathogen to adapt to its environment and its rapid global spread, underscoring the urgent need to effectively address this epidemiological challenge.

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In vivo evolution to echinocandin resistance and increasing clonal heterogeneity in Candida auris during a difficult-to-control hospital outbreak, Italy, 2019 to 2022

Cited by 20 publications

References 18 publications

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England

Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management

Short-Term Evolution and Dispersal Patterns of Fluconazole-Resistance inCandida aurisclade III

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