scholarly journals The Emergence of Echinocandin-Resistant Candida glabrata Exhibiting High MICs and Related FKS Mutations in Turkey

2021 ◽  
Vol 7 (9) ◽  
pp. 691
Author(s):  
Ali Korhan Sig ◽  
Meliha Cagla Sonmezer ◽  
Dolunay Gülmez ◽  
Serhat Duyan ◽  
Ömrüm Uzun ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Venous Catheter ◽  
High Dose ◽  
High Morbidity ◽  
First Case ◽  
Hospitalization Period ◽  
Echinocandin Resistance

The frequency of invasive fungal infections shows a rising trend as well as a high morbidity and mortality. Among the causative agents, a shift toward the non-albicans Candida species including Candida glabrata species complex is being observed in several centers. Echinocandin resistance is increasingly published; however, isolates presenting with an in vitro resistance have not yet been reported from Turkey. We, herein, report the first FKS mutant and phenotypically echinocandin-resistant C. glabrata clinical strains from a single center in Turkey. In a 43-year-old female patient, several enterocutaneous fistulae developed after a long term hospitalization period and several complicated surgeries. She eventually required parenteral nutrition via a tunneled central venous catheter (CVC). Following a number of bacteremic and fungemic episodes as well as intensive antimicrobial interventions (including fluconazole, caspofungin and anidulafungin), a CVC-related candidemia caused by C. glabrata was detected. The isolated strain yielded high minimum inhibitory concentration (MIC) values for echinocandins and was categorized as resistant. A resistance-related mutation was detected in FKS2 HS1 (D666V). Blood cultures remained negative after the removal of the CVC and treatment with caspofungin and high-dose fluconazole. Following this first case, two additional C. glabrata strains with high echinocandin MICs were isolated from the urine cultures of two unrelated patients from different wards with different mutations in FKS2 HS1 (S663P and delF659). Our findings indicate that routine antifungal susceptibility testing is crucial and underlines the need for attention for the increasing trend of acquired echinocandin resistance in C. glabrata.

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

scholarly journals In-Vitro Activity of Nano Fluconazole and Conventional Flucon-azole against Clinically Important Dermatophytes

2020 ◽  
Author(s):  
Najmossadat MUSAVI BAFRUI ◽  
Seyed Jamal HASHEMI HAZAVEH ◽  
Mansour BAYAT
Keyword(s):  
Zeta Potential ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Nano Particles ◽  
Medical Sciences ◽  
Particle Structure ◽  
Epidermophyton Floccosum ◽  
Dermatophyte Species ◽  
Better Than

Background: Dermatophytosis is one of the most common fungal infections in humans. Antifungals such as fluconazole are effectively used for treating dermatophytosis; however, drug resistance was observed in many cases. Therefore, a newer treatment strategy is essential. Methods: This study (Conducted in the Laboratory of the School of Public Health, Tehran University of Medical Sciences, Tehran, Iran in 2018) evaluated the antifungal susceptibility of nano fluconazole compared to conventional fluconazole on dermatophyte isolates using CLSI M38-A2guidelines. Dermatophyte species isolated from clinical cases of dermatophytosis were identified using PCR sequencing techniques. Zeta potential and size of the nano particles containing fluconazole were measured; scanning electron microscope (SEM) was used to determine nano particle structure. Results: The size of liposomal fluconazole obtained was 88.9  12.14 nm with –20.12  3.8 mV for zeta potential. The encapsulation rate for fluconazole was 75.1  4.2%. MIC50 for the three tested species was 32, 16, and 8 μg/ml for Trichophyton interdigitale, T. rubrum, and Epidermophyton floccosum isolates, respectively. The corresponding values for nano fluconazole were 8 μg/ml for the three tested species. Conclusion: MIC value for nano-fluconazole was lower than conventional fluconazole in all dermatophytes species tested; therefore, nano-fluconazole could inhibit the growth of dermatophytes better than fluconazole at a lower concentration of the drug.

Identification and in Vitro Susceptibility Pattern of Fungal Pathogens in Immunocompromised Patients with invasive Fungal Infections

2021 ◽  
Vol 30 (3) ◽  
pp. 127-134
Author(s):  
Shaimaa A.S. Selem ◽  
Neveen A. Hassan ◽  
Mohamed Z. Abd El-Rahman ◽  
Doaa M. Abd El-Kareem
Keyword(s):  
Intensive Care ◽  
Fungal Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
University Hospitals ◽  
Vitek 2

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.

scholarly journals In Vitro Activity of a Novel Antifungal Compound, MYC-053, against Clinically Significant Antifungal-Resistant Strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp.

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
G. Tetz ◽  
M. Collins ◽  
D. Vikina ◽  
V. Tetz
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Glabrata ◽  
Fungal Infections ◽  
Antifungal Compound ◽  
Candida Auris ◽  
Content Type ◽  
Treatment And Prevention ◽  
Resistant Strains ◽  
Clinically Significant

ABSTRACT An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with MICs of 0.125 to 4.0 μg/ml. Notably, unlike other antifungals such as azoles, polyenes, and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocystis spp., Candida spp., and Cryptococcus spp. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.

scholarly journals In Vitro Exposure to Increasing Micafungin Concentrations Easily Promotes Echinocandin Resistance in Candida glabrata Isolates

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
María Ángeles Bordallo-Cardona ◽  
Pilar Escribano ◽  
Elia Gómez G. de la Pedrosa ◽  
Laura Judith Marcos-Zambrano ◽  
Rafael Cantón ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Content Type ◽  
Inhibition Of Growth ◽  
Direct Exposure ◽  
In Vitro Exposure ◽  
Echinocandin Resistance

ABSTRACT We assessed the in vitro susceptibility of five echinocandin-susceptible Candida glabrata isolates after exposure to micafungin. The direct exposure to plates at different micafungin concentrations resulted in the inhibition of growth at 0.062 μg/ml. The progressive exposure was performed on plates using 0.031 μg/ml of micafungin and sequential propagation on plates containing the next 2-fold concentration; the MICs of micafungin and anidulafungin increased sequentially, and all the isolates became echinocandin resistant, showing fks2 mutations.

scholarly journals Combination Treatment of Invasive Fungal Infections

2005 ◽  
Vol 18 (1) ◽  
pp. 163-194 ◽  
Author(s):  
Pranab K. Mukherjee ◽  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Treatment Outcome ◽  
Combination Therapy ◽  
Fungal Infections ◽  
Clinical Success ◽  
Treatment Strategies ◽  
Historical Review ◽  
Invasive Fungal Infections ◽  
High Morbidity ◽  
Interpretation Criteria

SUMMARY The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.

scholarly journals Hyperthermic intraperitoneal chemoperfusion with high dose oxaliplatin: Influence of perfusion temperature on postoperative outcome and survival

F1000Research ◽  
2015 ◽  
Vol 2 ◽  
pp. 179
Author(s):  
Johanna Verhulst
Keyword(s):  
Proportional Hazards ◽  
Negative Binomial ◽  
Randomized Study ◽  
Cox Proportional Hazards ◽  
High Dose ◽  
High Morbidity ◽  
Anastomotic Leaks ◽  
Major Complications ◽  
Post Operative Survival

Introduction: Hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming a standard therapy in the treatment of peritoneal carcinomatosis (PC). Compared to systemic chemotherapy, HIPEC improves survival in patients with PC. This therapy has high morbidity rates (up to 41%). In vitro it has been demonstrated that hyperthermia has a toxic effect on malign cells. However, hyperthermia also affects normal tissue. To my knowledge, any additional effect of hyperthermia combined with chemotherapy has never been demonstrated in a clinical setting. In this study, the effects of hyperthermia on outcome and survival were analyzed. Methods: Patients with PC from any origin who were treated with HIPEC were included in this retrospective, non-randomized study. Data on patient characteristics, tumor characteristics, features of the surgery and postoperative complications were extracted from patient files. Models predicting time to removal of nasogastric tube (TRNT), post-operative major complications, the occurrence of anastomotic leaks and post-operative survival were built, using negative binomial regression, logistic regression or Cox proportional hazards regression as appropriate. Results: 138 patients treated with HIPEC were included. Maximal temperature during the operation was not statistically significantly associated with anastomotic leaks or post-operative major complications. Maximal temperature during the operation was negatively associated with post-operative survival (P=0.01). Conclusion: The results suggest that hyperthermia may negatively affect survival in patients who are treated with HIPEC for PC of various origins. This study has the classical limitations of a retrospective study. Therefore, randomized trials are required to confirm the results.

scholarly journals In vitro activity of a novel antifungal compound, MYC-053, against clinically significant antifungal-resistant strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp

2018 ◽  
Author(s):  
G Tetz ◽  
M Collins ◽  
D Vikina ◽  
V Tetz
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Glabrata ◽  
Fungal Infections ◽  
Therapeutic Window ◽  
Antifungal Compound ◽  
Antifungal Compounds ◽  
Candida Auris ◽  
Treatment And Prevention ◽  
Resistant Strains

ABSTRACTAn urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with the minimum inhibitory concentrations (MIC) of 0.125–4.0 μg/mL. Notably, unlike other antifungal compounds, MYC-053 was effective against Pneumocystis isolates. MYC-053 was highly effective against preformed 48-h-old yeast biofilms, with the minimal biofilm eradication concentrations equal to 1–4 times MIC. The compound was not cytotoxic against L2 and A549 cell lines at concentrations over 100 μg/ml. Further, it possessed no apparent hemolytic activity up to 1000 μg/ml (the highest concentration tested). Overall, these data indicated that MYC-053 has a broad therapeutic window and may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi in neutropenic patients.

scholarly journals 680. Month Long Fungemia due to Candida auris Endocarditis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S443-S443
Author(s):  
Haseeba khan ◽  
Christy Varughese ◽  
Hemil Gonzalez
Keyword(s):  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Acute Care Hospital ◽  
Sigmoid Resection ◽  
Blood Cultures ◽  
Multi Drug Resistance ◽  
Care Hospital ◽  
Candida Auris ◽  
Candida Spp ◽  
First Case

Abstract Background Candida auris (C. auris) is a multidrug resistant Candida species, reported to cause persistent fungemia along with a multitude of invasive fungal infections. We report the first case of C. auris fungemia due to endocarditis. Methods 61 year old man with a history of diverticulitis that required sigmoid resection and was complicated by abdominal abscesses due to multi drug resistant organisms warranting heavy antibiosis. Prolonged hospitalisation for that surgery was followed by a stay at a long term acute care hospital. He was readmitted at an outside hospital with sepsis where blood cultures grew C.auris. Upon evaluation, was found to have aortic valve endocarditis. Per patient’s preference, surgery was initially deferred. Despite escalation of therapy with a combination of antifungals, he remained fungemic for five weeks with repeat blood cultures showing changing antifungal susceptibility patterns. Patient eventually underwent surgical intervention at our facility, with valve cultures being positive for C.auris. After the surgery he was treated with 6 weeks of intravenous combination antifungal therapy. Results C.auris’s pathogenicity stems from multiple mechanisms with multi drug resistance being most pertinent. What adds to the complexity of the management is the absence of C.auris specific minimum inhibitory concentration breakpoints. Therefore treatment is based on Center for Disease Control’s (CDC) proposed breakpoints that have been extrapolated from other Candida spp. It is further complicated by lack of C.auris specific data showing essential agreement among different commercially available antifungal susceptibility testing (AFST). Heteroresistance of the microbial population is an issue that must be considered in such protracted fungemia. Conclusion Invasive infections due to Candida auris presents as a diagnostic and therapeutic challenge to clinicians. Disclosures All Authors: No reported disclosures

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