Fluconazole-resistant Candida Krusei Research Articles

1,3-Oxazole derivatives of cytisine as potential inhibitors of glutathione reductase of Candida spp.: QSAR modeling, docking analysis and experimental study of new anti-Candida agents

Natural products as well as their derivatives play a significant role in the discovery of new biologically active compounds in the different areas of our life especially in the field of medicine. The synthesis of compounds produced from natural products including cytisine is one approach for the wider use of natural substances in the development of new drugs. QSAR modeling was used to predict and select of biologically active cytisine-containing 1,3-oxazoles. The eleven most promising compounds were identified, synthesized and tested. The activity of the synthesized compounds was evaluated using the disc diffusion method against C. albicans M 885 (ATCC 10,231) strain and clinical fluconazole-resistant Candida krusei strain. Molecular docking of the most active compounds as potential inhibitors of the Candida spp. glutathione reductase was performed using the AutoDock Vina. The built classification models demonstrated good stability, robustness and predictive power. The eleven cytisine-containing 1,3-oxazoles were synthesized and their activity against Candida spp. was evaluated. Compounds 10, 11 as potential inhibitors of the Candida spp. glutathione reductase demonstrated the high activity against C. albicans M 885 (ATCC 10,231) strain and clinical fluconazole-resistant Candida krusei strain. The studied compounds 10, 11 present the interesting scaffold for further investigation as potential inhibitors of the Candida spp. glutathione reductase with the promising antifungal properties. The developed models are publicly available online at http://ochem.eu/article/120720 and could be used by scientists for design of new more effective drugs.

In vitro inhibitory activities of magnolol against Candida spp.

Candida spp. cause various infections involving the skin, mucosa, deep tissues, and even life-threatening candidemia. They are regarded as an important pathogen of nosocomial bloodstream infection, with a high mortality rate. As a result of prolonged exposure to azoles, the therapeutic failure associated with azoles resistance has become a serious challenge in clinical situations. Therefore, novel, alternative antifungals are required urgently. In the present study, the CLSI M-27A broth microdilution method and the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay were used to evaluate the antifungal effects of magnolol against various standard Candida strains in planktonic mode and biofilm formation, respectively. The antifungal activity of magnolol was demonstrated in planktonic C. albicans and non-albicans Candida species, especially fluconazole-resistant Candida krusei, with the minimum inhibitory concentrations ranging from 10 to 40 μg/mL. The BMIC90 (minimum concentration with 90% Candida biofilm inhibited) values of magnolol ranged from 20 to 160 μg/mL, whereas the BMIC90 values of fluconazole were more than 128 μg/mL. As an alternative and broad-spectrum antifungal agent, magnolol might be of benefit to the treatment of refractory Candida infection.

Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole.

Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person's ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed.

Amphotericin B in the management of fungal infections in a neonatal intensive care unit: experiences in a teaching hospital

Invasive systemic fungal infections have emerged as serious nosocomial threats to neonates in the neonatal intensive care unit (NICU). Candidaemia due to fluconazole-resistant Candida krusei necessitated the use of amphotericin B in the NICU at Dr George Mukhari Hospital. The use of amphotericin B 1 mg/kg/dose in the first 20 patients was monitored. Response to treatment and side effects related to the use of amphotericin B in this population were documented and described. Nephrotoxicity, a common and well described side effect of amphotericin B, was not observed in this study - rather hepatotoxicity. To ensure uniformity in monitoring adverse effects, a monitoring tool has been developed for use in the NICU.

Synthesis and evaluation of novel 1-(1 H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as antifungal agents

A series of 1-(1 H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure–activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS, 1H NMR and 13C NMR. Results of preliminary antifungal tests against six human pathogenic fungi ( Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole-resistant Candida krusei, Candida glabrata) in vitro showed that all title compounds exhibited activity against fungi tested to some extent except against C. tropicalis. Compound 5b showed higher activity against C. albicans, C. parapsilosis and C. krusei than fluconazole, and its MIC values were determined to be 0.5 μg/mL, 1 μg/mL and 4 μg/mL, respectively. Compound 5k showed higher activities against Torulopsis glabrata than fluconazole (with the MIC value of 2 μg/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities against C. parapsilosis than fluconazole (with the MIC values of 2 μg/mL, 2 μg/mL, 2 μg/mL, 1 μg/mL and 2 μg/mL, respectively).

An unusual case of Candida tropicalis and Candida krusei arthritis in a patient with acute myelogenous leukemia before chemotherapy

A 79-year-old male with acute myelogenous leukemia developed acute right knee arthritis during admission, after the use of broad-spectrum antibiotics before chemotherapy. The initial synovial fluid sample appeared to be mildly inflammatory with a low white cell count. The fungal septic arthritis was not diagnosed until Candida tropicalis, a rare species of Candida, was isolated in the synovial fluid. Although fluconazole is effective in treating the microorganism, the untreated leukemia rendered the infection incurable and led to the growth of fluconazole-resistant Candida krusei. We reported the unusual case of fungal arthritis and reviewed the literature.

Candida krusei pneumonia as a complication of a tuboovarian abscess treatment – case report

Background: Frequency of infections, caused by Candida glabrata and Candida krusei, which are more resistant to fluconazole, is increasing among hospitalised patients, especially among patients in intensive care units (ICU). Systemic Candida infections are particularly dangerous. Pneumonia, caused by Candida species, most commonly albicans, rarely others, is a serious infection especially for immunocompromised patients. It’s often fatal. We present a case report of a serious lung infection with fluconazole resistant Candida krusei in a 42-year-old previously healthy patient with perforated tuboovarian abscess (TOA), consecutive severe sepsis and septic shock. Patient used intrauterine device (IUD) for 17 years without any gynaecological controls. Ascending genital infection with E.colli and Staph. chromogenes led to TOA. In spite of empirical antibiotic treatment, surgical and intensive care supportive therapy of affected organs, patient’s condition critically deteriorated until exact fungus specification was made and specific antifungal therapy for Candida krusei with voriconazol was started. After that patient’s condition improved. Conclusions: Connection between patient’s age, IUD use duration and severity of the pelvic inflammatory disease (PID) was seen as multiorgan septic dysfunction with dominant lung failure. Candida pneumonia is rare with non-neutropenic patients. Especially with »non albicans« species. We believe Candida krusei infection in our patient is related to general weakness and immunocompromised condition because of prolonged and severe PID. Candida krusei infection needs immediate specific antifungal treatment. It was the first Candida krusei infection in our ICU.

Antifungal activity of 3'-deoxyadenosine (cordycepin).

The antifungal activity of the nucleoside analog 3'-deoxyadenosine (cordycepin) was studied in a murine model of invasive candidiasis. When protected from deamination by either deoxycoformycin or coformycin, both of which are adenosine deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as demonstrated by prolongation of survival and a decrease in CFU in the kidneys of mice treated with cordycepin plus an adenosine deaminase inhibitor. The antifungal effect was seen with three different Candida isolates: Candida albicans 64, a relatively fluconazole-resistant clinical isolate of C. albicans (MIC, 16 micrograms/ml), and the fluconazole-resistant Candida krusei. Cordycepin and related compounds may provide another avenue for the discovery of clinically useful antifungal drugs.

Species differentiation by internally transcribed spacer PCR and HhaI digestion of fluconazole-resistant Candida krusei, Candida inconspicua, and Candida norvegensis strains.

PCR amplification of the regions containing the internally transcribed spacers and 5.8S rRNA gene of Candida krusei, C. inconspicua, and C. norvegensis yielded fragments of 510, 460, and 500 bp, respectively. HhaI digestion of these fragments yielded species-specific bands. Random amplification of polymorphic DNA with primer R108 showed interspecific discriminatory band patterns. Susceptibilities to fluconazole and amphotericin B were determined.