- Neuroinfections caused by fungi. [Review]
- IInfection 2018 May 21
- CONCLUSIONS: Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
- Isolated Pulmonary Valve Fungal Endocarditis with Candida parapsilosis: Management Considerations of a Rare Case. [Journal Article]
- JHJ Heart Valve Dis 2017; 26(5):581-584
- Pulmonary valve infections without the involvement of other valves account for only 1.5- 2% of all infective endocarditis cases. Isolated pulmonary valve endocarditis due to fungus is extremely rare....
Pulmonary valve infections without the involvement of other valves account for only 1.5- 2% of all infective endocarditis cases. Isolated pulmonary valve endocarditis due to fungus is extremely rare. The case is presented of a 36-year-old male who was found to have isolated pulmonary valve endocarditis caused by a very rare organism, Candida parapsilosis, and that was solely managed with medical therapy. The patient was evaluated for three weeks of lowgrade fever, generalized rash and fatigue, and found to have C. parapsilosis in the blood. Transesophageal echocardiography (TEE) demonstrated a 4.5 cm vegetation on the pulmonary valve, without involvement of other valves. The patient was deemed not to be a surgical candidate and was subsequently started on intravenous liposomal amphotericin B and 5-flucytosine, with excellent clinical outcome. Based on these case details, it must be emphasized that in selective cases and if there are no known complications, fungal endocarditis can be managed successfully using anti-fungal agents.
- Detection of Candida species in pregnant Chinese women with a molecular beacon method. [Journal Article]
- JMJ Med Microbiol 2018 Apr 20
- CONCLUSIONS: By exhibiting good sensitivity and specificity, the molecular assay may offer a fast and accurate Candida screening platform for pregnant women.
- The in vitro efficacy of SunSmile® Fruit & Vegetable Rinse against pathogenic strains of Prototheca algae that cause mastitis in cows. [Journal Article]
- JMJ Mycol Med 2018 Apr 16
- The research concerns algae of the genus Prototheca. They are found in the natural environment and they can cause a disease in animals and humans called protothecosis. The aim of the study was to eva...
The research concerns algae of the genus Prototheca. They are found in the natural environment and they can cause a disease in animals and humans called protothecosis. The aim of the study was to evaluate the in vitro activity of the fruit and vegetable rinse agent SunSmile® Fruit & Vegetable Rinse (Sunrider International) against P. zopfii isolates. The materials consisted of ten P. zopfii strains isolated from the milk of cows with mastitis. The following antifungal chemotherapeutic agents were also used in the study for comparison: nystatin, ketoconazole, amphothericin B, miconazole, clotrimazole, econazole, fluconazole, and flucytosine. The tube dilution method were used to evaluate the effect of a fruit and vegetable rinse agent and the disc-diffusion method to evaluate the effect of antifungal chemotherapeutic agents on P. zopfii strains. All tested strains of P. zopfii were susceptible to the action of the SunSmile® agent. The MMC was in the range of 0.0024-0.0190%. The SunSmile® Fruit & Vegetable Rinse can be used in prevention of mastitis in cows and in human protothecosis due to its safe, natural composition and efficacy.
- Developmental toxicity of flucytosine following administration to pregnant rats at a specific time point of organogenesis. [Journal Article]
- CACongenit Anom (Kyoto) 2018 Apr 13
- To investigate the abnormalities that are specific to administration of flucytosine at one time point during embryonic organogenesis, flucytosine was administered orally to pregnant Sprague Dawley (S...
To investigate the abnormalities that are specific to administration of flucytosine at one time point during embryonic organogenesis, flucytosine was administered orally to pregnant Sprague Dawley (SD) rats in a single dose on day 11 of pregnancy at 25 or 35 mg/kg. Fetuses on day 20 of pregnancy were externally, viscerally, and skeletally examined. Maternal body weight gain and food consumption were suppressed the day after administration of a 35 mg/kg. Fetal examinations revealed various alterations in both dose groups: externally preaxial polydactyly in the hind limb; skeletally fused lumbar centrum, absent sacral centrum, supernumerary sacral vertebra, and absent ribs. Our findings indicated that specific types of external and skeletal anomalies were induced following flucytosine administration on day 11 of pregnancy.
- Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus. [Journal Article]
- AAAntimicrob Agents Chemother 2018; 62(6)
- The antifungal drug 5-flucytosine (5FC), a derivative of the nucleobase cytosine, is licensed for the treatment of fungal diseases; however, it is rarely used as a monotherapeutic to treat Aspergillu...
The antifungal drug 5-flucytosine (5FC), a derivative of the nucleobase cytosine, is licensed for the treatment of fungal diseases; however, it is rarely used as a monotherapeutic to treat Aspergillus infection. Despite being potent against other fungal pathogens, 5FC has limited activity against Aspergillus fumigatus when standard in vitro assays are used to determine susceptibility. However, in modified in vitro assays where the pH is set to pH 5, the activity of 5FC increases significantly. Here we provide evidence that fcyB, a gene that encodes a purine-cytosine permease orthologous to known 5FC importers, is downregulated at pH 7 and is the primary factor responsible for the low efficacy of 5FC at pH 7. We also uncover two transcriptional regulators that are responsible for the repression of fcyB and, consequently, mediators of 5FC resistance, the CCAAT binding complex (CBC) and the pH regulatory protein PacC. We propose that the activity of 5FC might be enhanced by the perturbation of factors that repress fcyB expression, such as PacC or other components of the pH-sensing machinery.
- Cryptococcal meningitis in AIDS. [Journal Article]
- HCHandb Clin Neurol 2018; 152:139-150
- Cryptococcal meningitis remains a significant cause of morbidity and mortality amongst patients living with human immunodeficiency virus (HIV). The prevalence in the developed world has decreased as ...
Cryptococcal meningitis remains a significant cause of morbidity and mortality amongst patients living with human immunodeficiency virus (HIV). The prevalence in the developed world has decreased as HIV is being diagnosed earlier, but is still significant, and the prevalence in resource-limited settings is exceedingly high. The presenting symptoms usually include a headache, fever, and, less often, cranial nerve abnormalities. Space-occupying lesions do occur, but are rare. Once diagnosed, patients should be treated with a combination of amphotericin and flucytosine, with step-down therapy to fluconazole for a minimum of a year, or until the CD4 count is above 100 cells/μL, whichever is longer. In the acute phase of treatment increased opening pressure is common, which should be managed aggressively with frequent lumbar punctures, or through neurosurgical interventions (lumbar drains, ventriculoperitoneal shunts) if those fail. Antiretrovirals should be delayed at least 2 weeks, but maybe as many as 10 weeks, after initiation of antifungal therapy in order to prevent clinical or subclinical immune reconstitution inflammatory syndrome (IRIS), which may lead to increased mortality. However, if IRIS does develop, there is no role for antiretroviral interruption, and the condition should be managed supportively by use of anti-inflammatories and aggressive management of elevated opening pressure, if present. Steroids should be administered for specific indications only (IRIS or cryptococcoma with cerebral edema and risk of herniation) as routine use of steroids increases mortality in cryptococcal meningitis.
- Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. [Journal Article]
- EMEmerg Microbes Infect 2018 Mar 29; 7(1):43
- Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris oc...
Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris occurred in a specialized cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak in the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina platforms to detect antifungal resistance alleles and reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin; the outbreak showed similar genetic diversity to that of the entire clade, and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations add to a growing body of research on multiple antifungal drug targets in this organism. Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission and implement outbreak control measures.
- Triple therapy versus amphotericin B plus flucytosine for the treatment of non-HIV- and non-transplant-associated cryptococcal meningitis: retrospective cohort study. [Journal Article]
- NRNeurol Res 2018; 40(5):398-404
- Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, es...
Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, especially when two antifungal drugs are at sub-therapeutic doses. Methods In this study of induction therapy, all non-HIV-infected, non-transplant patients with a first episode of cryptococcal meningitis were divided into two groups. In group I, the patients received amphotericin B plus 5-flucytosine. In group II, in addition to amphotericin B and 5-flucytosine, the patients also received fluconazole. Results In this study, 32 patients were included in group I, and the other 30 were in group II. Although patients from group II had higher fungal burdens with approximately 2100 Cryptococci/ml CSF before treatment, they had a significantly higher frequency of satisfactory outcomes (80% vs. 50%, respectively, P = 0.014). Less time for more patients in group II to have CSF sterilization (P = 0.021; P = 0.046). And more patients in group II had improved neurological function circumstances evaluated by comparing the BMRC staging between patients at discharge and follow-up 10 weeks (P = 0.032). No significant difference was observed in the incidence of adverse events between the two groups. Conclusion Triple therapy a superior alternative induction regimen for patients with non-HIV- and non-transplant-associated cryptococcal meningitis.
New Search Next
- Flucytosine resistance in Cryptococcus gattii is indirectly mediated by the FCY2-FCY1-FUR1 pathway. [Journal Article]
- MMMed Mycol 2018 Mar 15
- Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widel...
Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widely used antifungals against Cryptococcus spp., yet very few studies have looked at the molecular mechanisms responsible for 5FC resistance in this pathogen. In this study, we examined 11 C. gattii clinical isolates of the major molecular type VGIII based on differential 5FC susceptibility and asked whether there were genomic changes in the key genes involved in flucytosine metabolism. Susceptibility assays and sequencing analysis revealed an association between a point mutation in the cytosine deaminase gene (FCY1) and 5FC resistance in two of the studied 5FC resistant C. gattii VGIII clinical isolates, B9322 and JS5. This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino acids. Heterologous expression of FCY1 and spot sensitivity assays, however, demonstrated that this point mutation did not have any effect on FCY1 activities and was not responsible for 5FC resistance. Comparative sequence analysis further showed that no changes in the amino acid sequence and no genomic alterations were observed within 1 kb of the upstream and downstream sequences of either cytosine permeases (FCY2-4) or uracil phosphoribosyltransferase (FUR1) genes in 5FC resistant and 5FC susceptible C. gattii VGIII isolates. The herein obtained results suggest that the observed 5FC resistance in the isolates B9322 and JS5 is due to changes in unknown protein(s) or pathway(s) that regulate flucytosine metabolism.