The frequency of severe systemic fungal diseases has increased in the last few decades. The clinical use of antibacterial drugs, immunosuppressive agents after organ transplantation, cancer chemotherapy, and advances in surgery are associated with increasing risk of fungal infections. Opportunistic pathogens from the genera Candida and Aspergillus as well as pathogenic fungi from the genus Cryptococcus can invade human organism and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. Nowadays, there are some effective antifungal agents, but, unfortunately, some of the pathogenic species show increasing resistance. The identification of fungal virulence factors and recognition of mechanisms of pathogenesis may lead to development of new efficient antifungal therapies. This review is focused on major virulence factors of the most common fungal pathogens of humans: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The adherence to host cells and tissues, secretion of hydrolytic enzymes, phenotypic switching and morphological dimorphism contribute to C. albicans virulence. The ability to grow at 37 degrees C, capsule synthesis and melanin formation are important virulence factors of C. neoformans. The putative virulence factors of A. fumigatus include production of pigments, adhesion molecules present on the cell surface and secretion of hydrolytic enzymes and toxins.

Fungi pathogenic to humans : molecular bases of virulence of Candida

/pdf/fungi-pathogenic-to-humans-molecular-bases-of-virulence-of-3z22urzkmx.pdf

Fungi pathogenic to humans: molecular bases of virulence of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with underlying risk factors (e.g., neutropenia, cancer chemotherapy, transplantation, AIDS). Although Candida species remain a relevant cause of IFI, other organisms (particularly moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections although other moulds including Fusarium species and Zygomycetes are increasing in frequency, and are associated with a high mortality rate. Options available for the prevention and treatment of these infections include standard and liposomal formulations of amphotericin B, but toxicity concerns limit their use; fluconazole is effective for the prevention and treatment of candidiasis but its inactivity against moulds and increasing resistance are limiting factors. Newer azoles, particularly voriconazole and posaconazole, have an enhanced spectrum of activity that includes Candida species, Aspergillus species, Cryptococcus species, dimorphic fungi, Fusarium species, and, for posaconazole, Zygomycetes. Recent data suggest that these agents are highly effective in a variety of clinical settings. Echinocandins have good activity against Candida species and Aspergillus species but their spectrum generally does not include Fusarium species, Cryptococcus species, Trichosporon species, Zygomycetes, and dematiaceous moulds. While these agents are unlikely to exhibit crossresistance with polyenes or azoles, they must be administered intravenously. Knowledge of the pathogenesis of IFIs and the activity, efficacy, and limitations of available treatment options will allow the selection of an appropriate antifungal agent for individual patients.

/pdf/aspergillus-to-zygomycetes-causes-risk-factors-prevention-54h6hpmay6.pdf

Aspergillus to Zygomycetes: Causes, Risk Factors, Prevention, and Treatment of Invasive Fungal Infections

https://www.scielo.br/pdf/bjm/v38n3/v38n3a01.pdf

The use of standard methodology for determination of antifungal activity of natural products against medical yeasts Candida sp and Cryptococcus sp

Cryptococcosis is a potential fatal disease, especially in immunocompromised patients. In China, the profile of cryptococcosis is unclear. Therefore, we summarize the epidemiology and therapy of cryptococcosis in china. All cases reports about cryptococcosis in China were collected from CBMdisk database (China Biology and Medicine data disc) with key words of cryptococcosis, or cryptococcal infection, or cryptococcus, and case. The features of the cryptococcosis were retrospectively analyzed. There were 1,032 reports about cryptococcosis, including 8,769 cases. Among them, there were 16% patient with AIDS/HIV, and 17% ones without underlying diseases. There were 2,371 cases of CNS infection. Among them of 2,068 cases, the treatment protocols and outcome were clearly described. The percentages of patients who received intrathecal treatment of amphotericin B(AmB), AmB + 5-FC(5-fluorocytosine), AmB + FCZ(fluconazole), and AmB + 5-FU + FCZ in each medication group were 10, 43, 53, and 33%, respectively. The mortalities were significantly lower in the AmB, Amb + 5-FC, AmB + FCZ intrathecal treatment groups compared with their non-intrathecal treatment controls (6% vs. 23%, 25% vs. 35%, 20% vs. 30%, respectively, P   0.05). The Chinese cryptococcosis had its own special clinical features, such as more patients without identifiable underlying diseases. Intrathecal injection of amphotericin B was effective treatment method for cryptococcal CNS infection in China.

Cryptococcosis in China (1985–2010): Review of Cases from Chinese Database

Cryptococcus neoformans is an important fungal pathogen causing invasive infection especially of the central nervous system in this era of the HIV/AIDS epidemic. The choice of treatment depends on site(s) of infection and the patients immune status. Use of appropriate antifungal agents decreases mortality significantly but requires continued therapy and long-term maintenance to prevent relapses. The use of liposomal amphotericin B (L Amp B) has overcome some of the difficulties usually found in this setting. The major advantage of these liposomal formulations are faster clearance of C. neoformans [cerebrospinal fluid (CSF) negative] and a reduction in a amphotericin toxicity. The majority of clinical efficacy data related to L Amp B are derived from compassionate use studies and case series. Use of liposomal amphotericin has also shown to be a cost effective approach. (authors)

S Subramanian

Papers

Clinical manifestations and management of cryptococcal infection.

Community-acquired, fatal extended spectrum beta lactamase producing Klebsiella pneumoniae splenic abscess and sepsis.