Lockhart, Shawn R.

ABSTRACT Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host’s immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428–e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8 ], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, “rhinocerebral mucormycosis.” A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

ABSTRACT The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

Context.— Candida auris is an emerging yeast species that was first described in 2009. This ascomycetous yeast is notable for resistance to azole antifungal agents, for environmental persistence, and for its ability to contaminate health care environments, resulting in patient colonization and nosocomial infections. Objective.— To review the state of current knowledge addressing challenges in the accurate identification of C auris in the diagnostic microbiology laboratory, including application of phenotypic, proteomic, and genomic methodologies; characteristics that may predispose the human host to acquiring C auris; transmission; clinical presentations; treatment modalities; environmental decontamination; and infection prevention in health care settings. Data Sources.— The PubMed search engine was used to access peer-reviewed literature published from 2009 to 2019. Conclusions.— The rapid emergence of C auris has presented unique challenges for the areas of laboratory diagnostics and infection prevention and in options for antifungal treatment, which are limited. The current lack of established antifungal susceptibility test breakpoints complicates therapeutic decision making. Enhanced awareness of this pathogen is essential to monitor outbreaks and to reduce the risk of spread within health care environments.

ABSTRACTNeither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established forCandidaspp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable.Candidaspecies wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007Candida albicans, 186C. dubliniensis, 3,188C. glabratacomplex, 119C. guilliermondii, 493C. krusei, 205C. lusitaniae, 3,136C. parapsilosiscomplex, and 1,016C. tropicalisisolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml forC. albicans, 0.12, 0.25, and 0.03 μg/ml forC. glabratacomplex, 4, 2, and 4 μg/ml forC. parapsilosiscomplex, 0.5, 0.25, and 0.06 μg/ml forC. tropicalis, 0.25, 1, and 0.25 μg/ml forC. krusei, 0.25, 1, and 0.12 μg/ml forC. lusitaniae, 4, 2, and 2 μg/ml forC. guilliermondii, and 0.25, 0.25, and 0.12 μg/ml forC. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81Candidaisolates with identifiedfksmutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities ofCandidaspp. to caspofungin by reference methodologies is not recommended.

ABSTRACT Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans , C. tropicalis , and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata , non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata , ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender.