Systemic Yeast Infections Research Articles

Systemic infection by Spencermartinsiella sp. in a Nile crocodile (Crocodylus niloticus)

Um crocodilo macho adulto (Crocodylus niloticus) foi diagnosticado com infecção fúngica sustêmica. Histologicamente, havia extensas áreas de necrose no pulmão, que estavam associadas com infiltrado inflamatório linfo-plasmo-histiocitário, com numerosas células gigantes multinucleadas e miríade de pseudo-hifas e organismos leveduriformes intralesionais, dentro de favéolas distendidas. Focos necróticos também foram observados na mucosa do trato digestório, traquéia, túnica íntima de artérias, fígado e coração, com acentuado infiltrado inflamatório linfo-histiocitário, com grande número de macrófagos epitelioides e células gigantes e hifas e organismos leveduriformes intralesionais e intravasculares. Cortes corados por PAS e GMS evidenciaram estruturas leveduriformes ovais com 4 a 6 μm de diâmetro e pseudo-hifas de paredes espessas e paralelas com 5 a 8 μm. PCR realizado com DNA extraído de material parafinizado amplificou os domínios D1/D2 da subunidade maior do gene rRNA, cuja sequencia foi idêntica a sequências de uma nova espécie, isolada no Brasil de madeira em decomposição, do gênero Spencermartinsiella, cuja espécie mais próxima é Spencermartinsiella cellulosicola.

Synthesis and Antifungal Activity of Some 4,6-Dimethylisoxazolo[3,4- b]pyridin-3(1H)-one Derivatives

Cutaneous and invasive fungal infections are constant threats to human health that substantiate the need for the development of new efficacious and safe antimycotics. A series of N1-alkyl, N1-acyl and N1-sulfonyl derivatives of 4,6- dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were synthesized. The antimicrobial activities of title compounds against 21 pathogenic yeast-like fungal clinical isolates and 5 reference strains were evaluated by means of a broth microdilution method. Among the compounds tested, the newly prepared N1-benzoyl (2m) and N1-(4-fluorobenzoyl) (2n) derivatives of 1 showed 81% and 95% inhibitory efficacy, respectively, against the clinical isolates, which were comparable to that of the reference drug fluconazole. The strains that exhibited the highest susceptibility to the compound 2n included Candida utilis (MIC < 6.2 μg/mL), C. parapsilosis (MIC in the range <6.2 - 12.5 μg/mL), Geotrichum candidum (MIC = 12.5 μg/mL) as well as C. lusitaniae and Rhodotorula mucilaginosa (MIC = 25 μg/mL). In terms of MIC, compound 2n proved to be four times more active against the clinical isolates of Candida albicans and C. albicans ATCC 10231 standard strain than fluconazole, the widely prescribed antifungal agent for mucosal and systemic yeast infections (MIC = 50 vs 200 μg/mL).

Infecção sistêmica por Spencermartinsiella sp. em um crocodilo do Nilo (Crocodylus niloticus)

A male adult crocodile (Crocodylus niloticus) was diagnosed with systemic yeast infection. Histologically, there were extensive areas of necrosis in the lung, which were associated with a diffuse severe lympho-plasmo-histiocytic inflammatory infiltrate, with numerous multinucleated giant cells, and myriads of intralesional pseudo-hyphae and yeast like organisms within distended foveolae. Necrotic foci were also observed in the mucosa of the digestive tract, trachea, tunica intima of arteries, liver, and heart, with a marked inflammatory lympho-histiocytic infiltrate, with large numbers of epithelioid macrophages and giant cells, and intralesional and intravascular pseudo-hyphae and yeast-like organisms. Oval yeast structures with 4 to 6 m in diameter and 5 to 8 m thick paralleled-wall pseudo-hyphae were observed in PAS or GMS stained sections. PCR with DNA template extracted from paraffin embedded tissues amplified the D1/D2 domains of the large subunit rRNA gene, which was sequenced and found to be identical to sequences of a new species, isolated from rotting wood in Brazil, of the genus Spencermartinsiella, which its closest relative is Spencermartinsiella cellulosicola.

Spectrum of Systemic Yeast Infections in Leukemia Patients in Cameroon and Sensitivity of Isolates to Griseofulvin, Ketoconazole and Organic Extracts of Four Medicinal Plants

Clinical management of leukemia patients with hydroxyurea - based chemotherapy drugs and radiotherapy often does not yield very quick therapeutic benefits in patients, especially in tropical resource limited countries. Evidence based supportive and palliative care plan is critical in the clinical management of leukemia patients, which clinicians and oncologists in Africa often do not adequately implement during in-patient management in hospitals for a number of reasons including cost and knowledge. The spectrum of opportunistic infections in leukemia conditions is not well known and considered during management plans. In this study, we report the spectrum of systemic yeast infections amongst leukemia patients attending Phytobiotechnology Research Foundation clinic in Cameroon from June 2012 to June 2015 for the presence of various opportunistic systemic mycoses. All the patients in this study were already receiving hydroxyurea therapy for more than one year at the hospitals in Cameroon. The screening and testing were done through visual observation, KOH microscopy, in addition to culture tests on potato and malt extract agars. Twenty patients screened, were found with systemic yeast infections. Culture of urine, mouth swabs, vaginal fluids and blood yielded a 80% isolates of Candida albicans, and 20% Non Albicans Candida (NAC) including Cryptococcus species isolated from oral swab only. The results generally show that systemic yeasts are prevalent in leukemia patients and its co morbidity may possibly complicate effective chemotherapy treatment. The anti-yeast activity of Persea americana, magnifera indica, Moringa oleifera, and Allium sativum was significant with zones of inhibitions exhibited by Moringa oleifera and Allium sativum showing a better ant yeast activities than with ketoconazole and griseofulvin. The results also suggested the need to exploit alternative botanicals in the comanagement of leukemia as well as its attending opportunistic infections is a critical step toward generating a better treatment for leukemia.

Mycoses in the elderly

Infections with dermatophytes are more prevalent in the elderly than in non-elderly adults; risk factors include local trophic disturbances, underlying diseases such as diabetes and a reduced oxygen supply due to diminished blood circulation. Vaginal mycoses are seldom found. In systemic yeast infections in patients of advanced age, Candida glabrata plays a relatively important role. The dimorphic fungus Coccidioides immitis is more prevalent in the elderly in endemic areas. Although there is no higher susceptibility to moulds in this age group, there are certain situations increasing the risk. The manifestations and symptoms of infection often differ from those of younger patients, which may hamper diagnosis. Deficits in organ function may influence the antifungal drug therapy. Preventive measures such as altering the social environment, avoiding malnutrition, as well as efforts to retard immunosenescence and to improve hygiene are important.

Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys

Systemic infection by an unclassified yeast-like organism has been encountered sporadically in wild-caught owl monkeys (Aotus sp.) from South America. The infection is presumably acquired in the wild; the incubation period ranges from months to years. The disease is indolent and clinical signs are non-specific. The diagnosis is based on histopathologic observation of yeast-like cells in multiple internal organs. Most cells appear to be phagocytized by macrophages, however, many are apparently free in the extracellular space. Other inflammatory infiltrates, including neutrophils, lymphocytes, plasma cells, and multinucleated giant cells, are conspicuously absent. Cells are thick-walled, globose to oval, range from 5 to 8 μm in diameter, and reproduce by narrow-based budding of single daughter cells. Attempts to cultivate the organism on artificial media have failed. Yeast cell ultrastructure was studied using transmission electron microscopy. The cell wall is multilayered, and the internal structure is markedly heterogenous. In some cells, the cytoplasm is lightly electron-opaque, finely granular and lacks recognizable organelles or nuclei. In others, the cytoplasm is electron dense and contains mitochondria, ribosome-like granules, and a multilobulated nucleus. This organism differs from other recognized pathogenic yeast in its combined light microscopic appearance, organ involvement and host response. Ultrastructurally, it most closely resembles Loboa loboi.

Yeast identification – past, present, and future methods

The focus of this review is the evolution of biochemical phenotypic yeast identification methods with emphasis on conventional approaches, rapid screening tests, chromogenic agars, comprehensive commercial methods, and the eventual migration to genotypic methods. As systemic yeast infections can be devastating and resistance is common in certain species, accurate identification to the species level is paramount for successful therapy and appropriate patient care.

Antifungal and multidrug resistance modulatory effects of diterpenic and phenolic compounds

Azoles (fluconazole, itraconazole and ketoconazole) are among the few classes of antifungals available for the treatment of systemic yeast infections. Nowadays, due to the global AIDS pandemic and the use of immunosuppressive drugs in anticancer chemotherapy, the incidence of fungal infection as increased [1]. For these reasons, the resistance of yeasts to treatment is very common and the effectiveness of antifungal drugs is reduced by the activity of multidrug transporters from the ATP-binding cassette superfamily, such as Cdr1p and Cdr2p of the major human fungal pathogen Candida albicans. These proteins reduce intracellular drug concentration by actively extruding them out of cells. One of the strategies employed to overcome this type of resistance is the combination treatment with efflux pump inhibitors.

Subtypes of genotype A Candida albicans isolates determined by restriction endonuclease and sequence analyses

Systemic yeast infections are the Leading cause of mortality and morbidity in immunocompromized patients. Candida albicans, being the most frequently isolated fungal pathogen in these patients, can be divided into three genotypes (genotypes A, B and C) by 25S intron analysis. In our study, we found that molecular sizes of genotype A C. albicans isolates were heterogeneous. In order to determine the molecular basis of this difference, Haelll digestion was applied, and strains forming different band patterns were analyzed by automated sequence analysis. As a result of sequence analysis, eight different subtypes (a --> h) were found among genotype A C. albicans strains and an easy differentiation scheme consisting of Haelll and MspI digestions was constructed.

Prospective study of Candida species in patients at a comprehensive cancer center.

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non-albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC > or = 64 microg/ml) and itraconazole (MIC > or = 1 microg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans (P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates (P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.

Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys

Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys

Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys

Systemic infection by an unclassified yeast-like organism has been encountered sporadically in wild-caught owl monkeys (Aotus sp.) from South America. The infection is presumably acquired in the wild; the incubation period ranges from months to years. The disease is indolent and clinical signs are non-specific. The diagnosis is based on histopathologic observation of yeast-like cells in multiple internal organs. Most cells appear to be phagocytized by macrophages, however, many are apparently free in the extracellular space. Other inflammatory infiltrates, including neutrophils, lymphocytes, plasma cells, and multinucleated giant cells, are conspicuously absent. Cells are thick-walled, globose to oval, range from 5 to 8 micron in diameter, and reproduce by narrow-based budding of single daughter cells. Attempts to cultivate the organism on artificial media have failed. Yeast cell ultrastructure was studied using transmission electron microscopy. The cell wall is multilayered, and the internal structure is markedly heterogenous. In some cells, the cytoplasm is lightly electron-opaque, finely granular and lacks recognizable organelles or nuclei. In others, the cytoplasm is electron dense and contains mitochondria, ribosome-like granules, and a multilobulated nucleus. This organism differs from other recognized pathogenic yeast in its combined light microscopic appearance, organ involvement and host response. Ultrastructurally, it most closely resembles Loboa loboi.

Causative pathogens in onychomycosis and the possibility of treatment resistance: A review

Onychomycosis is caused primarily by dermatophytes, Candida species, and nondermatophytic molds. Dermatophytes, particularly Trichophyton rubrum , are by far the most common pathogens. There is some question as to whether Candida actually breaks down nail material or only invades the proximal nail bed. Similarly, the clinical significance of molds is unknown, because they may be colonizing organisms rather than destructive pathogens. It is, therefore, important to identify the pathogen in the array of organisms that may be isolated in culture. The increasing use of fluconazole in prophylaxis and treatment of systemic yeast infections and infections in patients with AIDS has been associated with the emergence of resistant Candida albicans , as well as previously minority species of Candida , such as C. glabrata and C. krusei . This may be of relevance to the treatment of onychomycosis with azole antifungals. (J Am Acad Dermatol 1998;38:S32-6.)

Current therapy of dermatophytosis

In the past dermatophytes were treated with topical agents or, in the case of more recalcitrant or extensive disease, with oral antifungals (griseofulvin or ketoconazole). Topical therapies may beeffectiveinraanycases,buttheyhavelimitations.Theyniaybeviewed as inconvenient by the patient, thereby affecting compliance. Therapy with early oral antifungals entails long treatment periods until complete cure is obtained. For ketoconazole rare but serious side effects can occur, particularly with prolonged use. Griseofulvin is still the drug of choice for the treatment of tinea capitis of the Microsporum type. In recent years a few new antimy-cotic agents have been developed for systemic therapy of superficial fungal infections. Itraconazole is a broad-spectrum triazole. Fluconazole belongs to the same chemical class and was used mainly in systemic yeast infections and mucosal candidosis. Terbinafine is an al-lylamine and has been found to be effective and safe in brief therapy of dermatophyte infections. Short-duration therapy of most dermatophyte infections is also possible with itraconazole. The high and specific activity against the causative agents, together with their pharmacokinetic properties, explains the good results obtained with these new drugs and their improved safety profile. Their mode of action, pharmacokinetics, and treatment schedules will be discussed.

The postantibiotic effect of antifungal agents against common pathogenic yeasts.

A total of ten strains of Candida spp. and Cryptococcus neoformans were examined for the presence of the postantibiotic effect (PAE) after 0.5-2 h exposure to amphotericin B, 5-fluorocytosine, miconazole and ketoconazole. Significant PAEs were observed for amphotericin B and 5-fluorocytosine, but none for the imidazoles. The duration of the PAEs of amphotericin B ranged from 0.5-10.4 h for the Candida spp. and 2.8-10.6 h for the cryptococcos, while 5-fluorocytosine induced PAEs from 0.8-7.4 h and 2.4-5.4 h, respectively. Even though no PAEs were demonstrated for the imidazoles, the growth rate was persistently reduced by continuous exposure to concentrations as low as 1/1000 of the MIC of these agents. These findings may have implications for dosing antifungal agents in systemic yeast infections.

Treatment of systemic yeast infection with fluconazole

Journal Article Treatment of systemic yeast infection with fluconazole Get access J. COHEN J. COHEN Hammersmith HospitalDu Cane Road, London W12 0HS, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 23, Issue 2, February 1989, Pages 294–295, https://doi.org/10.1093/jac/23.2.294 Published: 01 February 1989

Amphotericin B-resistant yeast infection in severely immunocompromised patients

Systemic yeast infections are a major cause of morbidity and mortality in severely immunocompromised patients. The in vitro susceptibility to amphotericin B of 29 yeasts causing fungemia was examined in 26 patients undergoing allogeneic or autologous bone marrow transplantation and/or myelosuppressive chemotherapy. The minimal inhibitory concentrations (MICs) of amphotericin B observed with blood isolates from these patients were significantly higher than those observed with blood, sputum, or skin isolates from non-immunocompromised patients (p <0.01). All episodes (10 of 10) of bloodstream infection in immunocompromised patients caused by isolates with MICs greater than 0.8 μg/ml were fatal, versus eight of 17 episodes of bloodstream infection caused by yeasts with MICs of 0.8 μg/ml or less (p = 0.04). Although 15 of 26 patients received empiric treatment with amphotericin B before laboratory evidence of fungemia developed, the amphotericin B susceptibilities of their isolates were not significantly different from those of patients who had not received empiric amphotericin B treatment. It is concluded that yeast fungemia in severely immunocompromised patients is often caused by organisms resistant to the usual concentrations of amphotericin B obtainable in vivo, and that this finding is clinically significant.

Torulopsis glabrata fungemia--a clinical pathological study.

The clinical findings, pathologic features, and outcome were investigated in 46 patients in whom Torulopsis glabrata was isolated in 131 specimens of blood. Nineteen of the patients had only a single positive blood culture and no evidence of systemic yeast infection, while 27 patients had a clinically significant fungemia based upon the occurrence of 2 or more positive blood cultures, or the combination of a positive blood culture and isolation of the organism from a closed body cavity or demonstration of the yeast in tissue sections. The predisposing factors to the development of fungemia included the presence of intravenous lines, indwelling Foley catheters, antibiotics and surgery, especially when the gastrointestinal tract was involved. Only 22% of patients received either steroids or cytostatic agents. Possible portals of entry were suggested by the prior isolation of the organism from urine, sputum, wounds, and central venous catheter tips in most of the patients. Twelve of 27 patients with clinically significant fungemia were treated. The initial mode of therapy in nine patients was removal of intravenous lines because of the clinical suspicion of catheter related sepsis. Seven of the patients improved rapidly and one more after amphotericin B was subsequently administered. Amphotericin B was the initial therapy in three cases. One patient was cured while another died of an unrelated infection. Five patients were not treated although the isolation of T. glabrata had been reported; the fact that the presence of the organism was felt to be unimportant was considered to be a factor in the delay of treatment. In the remaining 10 patients the organism was isolated only after the patient had died. Division of the patients into four groups based upon whether the individuals survived, died of unrelated disease, died with potentially lethal infection, or died with T. glabrata infection significantly contributing to death, revealed a spectrum of disease, certain signs of which appeared to be of predictive value as prognostic indices of survival and severity of the infection. Seven patients with transient fungemia experienced an acute episode of high spiking fever (greater than 102.5 degrees F), rigors and/or hypotension, six of whom improved after the intravenous catheter was removed, suggesting a catheter-related sepsis. In contrast, persistent low grade fever (less than 102.5 degrees F) characterized eight of the nine patients in whom T. glabrata infection was considered either potentially lethal, or contributing significantly to death. A deteriorating clinical course with organ failure was also associated with this latter category of patients. Catheter-induced specticemia was considered in only two patients in this category. The autopsy and clinical findings in this investigation as well as reported experimental studies suggest that T. glabrata is an organism of low virulence. The patients' underlying disease (e.g., neoplasia) and coexisting bacterial infection are the most important factors responsible for death.

Clinical aspects of Candida infection in denture wearers

Candida-induced denture stomatitis usually does not reflect any deep-seated, systemic abnormality, the dentures being the primary predisposing condition. However, infection with C albicans should be recognized as an extremely common complication to the wearing of dentures. Most cases are treated relatively easily, but recurrences are frequent and the infection often spreads to other parts of the oral mucosa. Therefore, preventive measures should be taken against colonization by Candida of the palatal mucosa and the dentures. In healthy persons, Candida-induced denture stomatitis is not serious; however, it should be considered a possible spearhead of systemic yeast infections in seriously ill patients, especially in those subjected to prolonged treatment with antibiotics, corticosteroids, or immunosuppressive drugs.