When method-dependent categorical endpoints are available, namely either BPs or ECVs, MICs could aid in selecting the best treatment agent(s). BPs can categorize an isolate as either susceptible or ...resistant while the ECVs/ECOFFs can distinguish the wild type (WT, no known resistance mechanisms) from the Non-WT (NWT, harboring resistant mechanisms). Our literature review focused on the
species complex (SC) and the available methods and categorization endpoints. We also covered the incidence of these infections as well as the numerous
SC and
SC genotypes. The most important agents to treat cryptococcal infections are fluconazole (widely used), amphotericin B, and flucytosine. We provide data from the collaborative study that defined CLSI fluconazole ECVs for the most common cryptococcal species or genotypes and modes. EUCAST ECVs/ECOFFs are not yet available for fluconazole. We have summarized the incidence of cryptococccal infections (2000-2015) where fluconazole MICs were obtained by reference and commercial antifungal susceptibility tests. This occurrence is documented all over the world and those fluconazole MICs are mostly categorized by available CLSI ECVs/BPs as "resistant" instead of non-susceptible strains, including those by the commercial methods. As expected, the agreement between the CLSI and commercial methods is variable because SYO and Etest data could yield low/variable agreement (<90%) versus the CLSI method. Therefore, since BPs/ECVs are species and method dependent, why not gather sufficient MICs by commercial methods and define the required ECVs for these species?
We determined the
activity of fenticonazole against 318 vaginitis isolates of
and bacterial species and selected 28 isolates for time-kill studies. At concentrations equal to 4× MIC, fenticonazole ...reached the 99.9% killing endpoint by ∼10 h for
,
, and
and by ∼17 h for
and
; and at concentrations equal to 8× MIC, by ∼19 and ∼20 h for
and
, respectively. At concentrations equal to 2× MIC, fenticonazole required ∼20 h to reach the above endpoint against
in mixed culture with
,
, or
versus ∼17 h against
in pure culture. Supra-MICs are achievable in topically treated patients' vaginal surfaces.
•All Candida auris isolates showed fluconazole MICs >64 mg/L.•Posaconazole was the most active azole, followed by isavuconazole and itraconazole.•Echinocandin MICs were ≤1 mg/L by all three ...susceptibility testing methods.•Essential agreement between EUCAST and Sensititre® YeastOne® was >93% for all antifungals.•The number of non-wild-type isolates depended on the epidemiological cut-off value applied.
Candida auris is an emerging pathogen causing candidaemia outbreaks in several countries for which azole, amphotericin B (AmB) and echinocandin resistance has been reported. In this study, the antifungal susceptibilities of 73 Spanish C. auris isolates (56 bloodstream and 17 urine) to eight antifungal agents were determined using three methods. Isolates were identified by internal transcribed spacer (ITS) sequencing, and minimum inhibitory concentrations (MICs) of fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, anidulafungin, micafungin and AmB were determined by EUCAST methodology and Sensititre® YeastOne® (SYO) (bloodstream isolates) and Liofilchem® MIC Test Strip (all isolates). Agreement between the methods was analysed and the MICs (ours and published data) were categorised using recently proposed epidemiological cut-off values (ECVs). Fluconazole MICs were >64 mg/L, whilst >60% of voriconazole MICs were >1 mg/L by the three methods. Posaconazole was the most active azole (EUCAST geometric mean MIC, 0.053 mg/L), followed by isavuconazole (0.066 mg/L) and itraconazole (0.157 mg/L). Echinocandins MICs were ≤0.5 mg/L by SYO and EUCAST. The overall lowest AmB MICs (≤0.25 mg/L) were obtained by EUCAST. Essential agreement (±2 dilutions) between EUCAST and SYO was >93% for the eight antifungals. For this new C. auris clade, all isolates were resistant to fluconazole, and MICs for anidulafungin, micafungin and AmB were ≤1 mg/L using dilution methods. Voriconazole MICs were method-dependent. The number of non-wild-type (non-WT) isolates depended on the ECV applied; by the 97.5% ECV all isolates were WT except for isavuconazole (1.8% non-WT). Good essential agreement (>93%) was observed between EUCAST and SYO.
Fungal diseases and antifungal resistance continue to increase, including those caused by rare or emerging species. However, the majority of the published in vitro susceptibility data are for the ...most common fungal species. We reviewed the literature in order to pool reference minimal inhibitory concentration (MIC) data (Clinical and Laboratory Standards Institute-CLSI and European Committee on Antimicrobial Susceptibility-EUCAST) for rare/non-prevalent
and other yeast species. MIC results were compared with those for
,
, and
. Data were listed for twenty rare and emerging
spp., including
, as well as two
spp., two
spp.,
and five
spp. The best detectors of antimicrobial resistance are the breakpoints, which are not available for the less common
species. However, epidemiological cutoff values (ECVs/ECOFFs) have been calculated using merely in vitro data for both reference methods for various non-prevalent yeasts and recently the CLSI has established ECVs for other
species. The ECV could identify the non-wild type (NWT or mutants) isolates with known resistance mechanisms. Utilizing these ECVs, we were able to report additional percentages of NWT, especially for non-prevalent species, by analyzing the MIC distributions in the literature. In addition, since several antifungal drugs are under development, we are listing MIC data for some of these agents.
Anidulafungin, caspofungin, and micafungin killing activities against Candida glabrata, Candida bracarensis, and Candida nivariensis were evaluated by the time-kill methodology. The concentrations ...assayed were 0.06, 0.125, and 0.5 μg/ml, which are achieved in serum. Anidulafungin and micafungin required between 13 and 26 h to reach the fungicidal endpoint (99.9% killing) against C. glabrata and C. bracarensis. All echinocandins were less active against C. nivariensis.
Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and is associated with high mortality. It is typically resistant to fluconazole and voriconazole and, some ...cases, also to echinocandins and amphotericin B. This species, phylogenetically related to Candida haemulonii, is frequently misidentified by commercial identification techniques in clinical laboratories; therefore, the real prevalence of C. auris infections may be underestimated.
To describe the clinical and microbiological features of the first four cases of C. auris fungemia episodes observed in the European continent.
The four patients were hospitalized in the adult surgical intensive care unit. A total of 8 isolates (two per patient) from blood and catheter tip were analyzed.
All isolates were misidentified as Saccharomyces cerevisiae by AuxaColor 2, and as Candida sake by API ID20C. VITEK MS technology misidentified one isolate as Candida lusitaniae, another as C. haemulonii and could not identify the other six. C. auris identification was confirmed by ITS rDNA sequencing. All isolates were fluconazole (MIC >256mg/l) and voriconazole (MIC 2mg/l) resistant and susceptible to posaconazole, itraconazole, echinocandins and amphotericin B.
C. auris should be regarded as an emerging pathogen, which requires molecular methods for definitive identification. Our isolates were highly resistant to fluconazole and resistant to voriconazole, but susceptible to the other antifungals tested, which emphasizes the importance of accurately identifying this species to avoid therapeutic failures.
Abstract Candida albicans remains the most common fungal pathogen. This species is closely related to 2 phenotypically similar cryptic species, Candida dubliniensis and Candida africana . This study ...aims to compare the antifungal activities of echinocandins against 7 C. albicans , 5 C. dubliniensis , and 2 C. africana strains by time–kill methodology. MIC values were similar for the 3 species; however, differences in killing activity were observed among species, isolates, and echinocandins. Echinocandins produced weak killing activity against the 3 species. In all drugs, the fungicidal endpoint (99.9% mortality) was reached at ≤31 h with ≥0.5 μg/mL for anidulafungin in 4 C. albicans and 1 C. dubliniensis , for caspofungin in 1 C. albicans and 2 C. dubliniensis , and for micafungin in 4 C. albicans and 1 C. dubliniensis . None of echinocandins showed lethality against C. africana . Identification of these new cryptic species and time–kill studies would be recommendable when echinocandin treatment fails.
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