Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations

International audienceSince echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species

International audienceInvasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France over 17 years. The antifungal susceptibility profiles were all determined at the National Reference Center for Invasive Mycoses and Antifungals based on the EUCAST broth microdilution method. The centralized collection and analysis allowed us to describe the trends of azoles susceptibility of isolates belonging to common species, confirming the high susceptibility for C. albicans (n=3,295), C. tropicalis (n=641), C. parapsilosis (n=820), and decreased susceptibility for C. glabrata (n=1,274), and P. kudriavzevii (n=343). They also provide interesting data concerning azole susceptibility of Cr. neoformans species complex: showing comparable MICs distribution for the three species but lower MIC50 and MIC90 for serotype D (n=208) compared to serotype A (n=949) and AD hybrids (n=177). Finally, these data provide useful information for rare and/or emerging species such as C. lusitaniae (n=221), S. clavata (n=184), M. guilliermondii complex (n=150), C. haemulonii complex (n=87), R. mucilaginosa (n=55), W. anomalus (n=36)

The risk and clinical outcome of candidemia depending on underlying malignancy

International audiencePURPOSE:To assess the risk factors and outcomes associated with fungemia caused by the six most commonly occurring Candida species in patients with and without malignancies.METHODS:Analysis of the episodes of fungemia due to common Candida species in adults, based on an active hospital-based surveillance program (Paris area, France, 2002 to 2014).RESULTS:Of the 3417 patients (3666 isolates), 1164 (34.1%) had a solid tumor (45.7% digestive tract) and 586 (17.1%) a hematological malignancy (41.8% lymphoma, 33.5% acute leukemia). The hematology patients were significantly younger, more often pre-exposed to antifungals, more often infected by C. tropicalis, C. krusei, or C. kefyr, and more often treated in the first instance with an echinocandin. Compared with inpatients who were not in ICU at the time of fungemia, those in ICU were less frequently infected by C. parapsilosis (p < 0.02), had more recent surgery (p < 0.03), and died more frequently before day 8 and day 30 (p < 0.0001). An increase in crude mortality over time in ICU was observed only in oncology patients (p < 0.04). For all patients, lack of prescription of antifungals despite knowledge of positive blood culture increased the risk of death. The odds of being infected by a given Candida species compared with C. albicans were uneven regarding age, gender, type of malignancy, hospitalization in ICU, central venous catheter, HIV status, intravenous drug addiction, and previous exposure to antifungal drugs. Compared with C. albicans, C. glabrata (OR = 0.69 [0.54-0.89]) and C. parapsilosis (OR = 0.49 [0.35-0.67]) were associated with a decreased risk of death by day 8 and day 30.CONCLUSION:The clinical context of underlying malignancy and hospitalization in ICU may be relevant to the initial management of candidemia

Changes in the epidemiological landscape of invasive mould infections and disease

Although a wide variety of pathogens are associated with invasive mould diseases, Aspergillus spp. have historically been one of the most common causative organisms. Most invasive mould infections are caused by members of the Aspergillus fumigatus species complex and an emerging issue is the occurrence of azole resistance in A. fumigatus, with resistance to amphotericin B documented in other Aspergillus spp. The epidemiology of invasive fungal disease has shifted in recent years as non-A. fumigatus Aspergillus spp. and other moulds have become progressively more important, although there are no consolidated data on the prevalence of less common species of moulds. The incidence of mucormycosis may have been underestimated, which is a potential concern since species belonging to the order Mucorales are more resistant to antifungal agents than Aspergillus spp. All species of Mucorales are unaffected by voriconazole and most show moderate resistance in vitro to echinocandins. Fusarium spp. may be the second most common nosocomial fungal pathogen after Aspergillus in some tertiary hospitals, and show a susceptibility profile marked by a higher level of resistance than that of Aspergillus spp. Recently, Scedosporium aurantiacum has been reported as an emerging opportunistic pathogen, against which voriconazole is the most active antifungal agent. Other mould species can infect humans, although invasive fungal disease occurs less frequently. Since uncommon mould species exhibit individual susceptibility profiles and require tailored clinical management, accurate classification at species level of the aetiological agent in any invasive fungal disease should be regarded as the standard of care.This Supplement was funded by Basilea Pharmaceutica International Ltd, Basel, Switzerland.S

Diversity of coelomycetous fungi in human infections: A 10-y experience of two European reference centres

International audienceThe coelomycetous fungi are difficult to properly identify from their phenotypic characterization and their role as etiologic agents of human infections is not clear. We studied the species distribution of these fungi among clinical isolates that had been collected and stored over a ten-year period in two European reference laboratories (France and Spain). We identified phenotypically and molecularly 97 isolates by sequencing the D1-D2 fragment of the 28S nrRNA (LSU) gene and we provided the in vitro antifungal susceptibility pattern of seven antifungals against 46 isolates. Species of the orders Pleosporales and Glomerellales were present in both collections, and Botryosphaeriales and Diaporthales only in the French one. The most prevalent species were Medicopsis romeroi, Neocucurbitaria keratinophila, Neocucurbitaria unguis-hominis and Paraconiothyrium cyclothyrioides, which had been recovered primarily from superficial tissues. The Didymellaceae was the most common family represented, with 27 isolates distributed into five genera. Most of the isolates tested were susceptible to antifungals, and only the geometric mean (GM) and minimal inhibitory concentration (MIC) values of itraconazole and caspofungin had higher values. This study provides a good picture of the great diversity of coelomycetous fungi in the European clinical context, and the basis for future studies on this interesting but neglected group of fungi