Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Candida auris in Austria-What Is New and What Is Different.

Candida auris is a novel and emerging pathogenic yeast which represents a serious global health threat. Since its first description in Japan 2009, it has been associated with large hospital outbreaks all over the world and is often resistant to more than one antifungal drug class. To date, five C. auris isolates have been detected in Austria. Morphological characterization and antifungal susceptibility profiles against echinocandins, azoles, polyenes and pyrimidines, as well as the new antifungals ibrexafungerp and manogepix, were determined. In order to assess pathogenicity of these isolates, an infection model in Galleria mellonella was performed and whole genome sequencing (WGS) analysis was conducted to determine the phylogeographic origin. We could characterize four isolates as South Asian clade I and one isolate as African clade III. All of them had elevated minimal inhibitory concentrations to at least two different antifungal classes. The new antifungal manogepix showed high in vitro efficacy against all five C. auris isolates. One isolate, belonging to the African clade III, showed an aggregating phenotype, while the other isolates belonging to South Asian clade I were non-aggregating. In the Galleria mellonella infection model, the isolate belonging to African clade III exhibited the lowest in vivo pathogenicity. As the occurrence of C. auris increases globally, it is important to raise awareness to prevent transmission and hospital outbreaks.

Efficacy of octenidine against emerging echinocandin-, azole- and multidrug-resistant Candida albicans and Candida glabrata.

OBJECTIVES: Infections due to Candida species represent a serious threat to healthcare facilities. Only a few classes of antifungal agents are available, and the rapid emergence of (multi)drug resistance eliminates effective treatment options for successful patient outcome. Topically applied antiseptics may represent a suitable tool for infection control and local therapy. This study aimed to investigate the in vitro efficacy of the widely used antiseptic octenidine (OCT) against clinical isolates of emerging azole-, echinocandin- and multi-resistant Candida albicans and Candida glabrata. METHODS: The antifungal activity of different concentrations of OCT ranging from 0.001% to 0.05% and of OCT-containing ready-to-use products was determined against well-characterised (multidrug) resistant C. albicans and C. glabrata isolates, including susceptible wild-type strains. Quantitative suspension tests were performed under "clean conditions" (0.3 g/L bovine serum albumin) and under "dirty conditions" (3 g/L albumin + 3 mL/L defibrinated sheep blood) as well as various contact times (30 s, 1 min, 2 min) according to EN13624:2013. RESULTS: Even in the presence of a high organic load, pure OCT at 0.05% and a contact time of 30 s was fully effective for all Candida strains, with growth kinetics indicating a time- and concentration-dependent activity. Importantly, commercially available OCT-based products achieved the required reduction of ≥4 log10 for all Candida isolates under the most challenging dirty conditions within two minutes, which makes them suitable for routine clinical use. CONCLUSION: These results encourage consideration of the well-tolerated antiseptic molecule OCT in the eradication of emerging (multidrug) resistant C. albicans and C. glabrata.

Do Candida albicans Isolates with Borderline Resistant Micafungin MICs Always Harbor FKS1 Hot Spot Mutations?

Antifungal susceptibility testing is important in guiding patient therapy due to an increasing number of resistant Candida isolates. In the clinical strain collection of the Austrian resistance report (AURES), a high number of micafungin-resistant C. albicans isolates (18.2% 49/269) was detected in seven different centres in Austria from 2011-2016. Most of these isolates showed a micafungin MIC value that was just above the clinical breakpoint (CB) established by EUCAST (0.016 mg/L). The aim of this study was to analyse whether C. albicans strains showing a micafungin MIC value of 1-2 dilutions above the CB (0.032 mg/L and 0.064 mg/L) are associated with mutations in FKS1 hotspot (HS) regions. 115 C. albicans candidemia strains showing a micafungin MIC one or two dilutions above the EUCAST CB (0.032 mg/L and 0.064 mg/L) were categorized as borderline resistant and screened for mutations in FKS1 HS1, HS2, and HS3 regions, which are known locations for the development of echinocandin resistance. For this purpose, we implemented targeted resequencing utilizing a next generation sequencing technology. No missense mutations could be detected in FKS1 HS1, HS2, and HS3 in any of the 115 isolates, which indicated that resistance conferred by alteration of FKS1 seems unlikely.

Molecular Methods for the Diagnosis of Invasive Candidiasis.

Invasive infections caused by members of the genus Candida are on the rise. Especially patients in intensive care units, immunocompromised patients, and those recovering from abdominal surgery are at risk for the development of candidemia or deep-seated candidiasis. Rapid initiation of appropriate antifungal therapy can increase survival rates significantly. In the past, most of these infections were caused by C. albicans, a species that typically is very susceptible to antifungals. However, in recent years a shift towards infections caused by non-albicans species displaying various susceptibly patterns has been observed and the prompt diagnosis of the underlying species has become an essential factor determining the therapeutic outcome. The gold standard for diagnosing invasive candidiasis is blood culture, even though its sensitivity is low and the time required for species identification usually exceeds 48 h. To overcome these issues, blood culture can be combined with other methods, and a large number of tests have been developed for this purpose. The aim of this review was to give an overview on strengths and limitations of currently available molecular methods for the diagnosis of invasive candidiasis.

Clinical evaluation of an in-house panfungal real-time PCR assay for the detection of fungal pathogens.

PURPOSE: Due to an increasing incidence of invasive fungal infections, the availability of reliable diagnostic tools for the fast detection of a wide spectrum of fungal pathogens is of vital importance. In this study, we aimed to conduct an extensive clinical evaluation of a recently published in-house panfungal PCR assay on samples from suspected invasive fungal infections. METHODS: Overall 265 clinical samples from 232 patients with suspected invasive fungal disease (96 deep airway samples, 60 sterile fluids, 50 tissue biopsies, and 59 blood samples) were included. All samples underwent standard culture-based diagnostics and were additionally analyzed with our panfungal PCR assay. RESULTS: Overall, 55.1% of agreement between culture and the panfungal PCR was observed; in 17% of all samples partial concordance was noted, while results between culture and our PCR assay were not in agreement in 27.9%. Our panfungal assay performed better in samples from normally sterile sites, while samples from the deep airways yielded the highest rate of discordant (39.6%) results. In two tissue and three blood samples an invasive pathogen was only detected by PCR while cultures remained negative. CONCLUSION: In combination with routine methods, our panfungal PCR assay is a valuable diagnostic tool. Patients at risk for invasive fungal infections might profit from the reduced time to pathogen identification.