Zygomycosis Caused by Rhizopus microsporus and Rhizopus oryzae in Madhya Pradesh (M.P.) Central India: A Report of Two Cases

Zygomycosis encompasses infections due to two distinct orders of fungi, Mucorales and Entomophthorales. With rare exception, Entomophthorales are restricted to tropical areas. By contrast, mucorales are ubiquitous opportunistic fungi, which play a crucial part in the natural decay process. In human pathology, they may be opportunistic agents and be responsible for rare infection called (Mucormycosis) zygomycosis. We report two cases of zygomycosis from Madhya Pradesh, Central India, one caused by Rhizopus oryzae in a diabetic patient and another caused by Rhizopus microsporus in an apparently healthy patient. The cases were diagnosed by direct microscopy, histopathological examination and culture. Both the patients were successfully treated with liposomal amphotericin B. Rhizopus microsporus is, for the first time reported from Madhya Pradesh, India, causing rhino-maxillary orbital zygomycosis.     

Gastrointestinal zygomycosis: a report of three cases

Three cases of gastrointestinal zygomycosis, probably caused by Basidiobolus ranarum, are described. The diagnosis was based on morphology of the fungal elements in infected tissues and histopathologic findings. All the three patients responded favorably to management strategy that included surgical resection of the infected portion of the bowel and institution of specific antifungal therapy.     

The role of second-generation triazole antifungal agents voriconazole and posaconazole in patients with hematologic malignancies

The second-generation triazoles, voriconazole and posaconazole, have found important roles in the management of invasive fungal infections in high-risk patients. Both agents are more active against Candida albicans and the non-albicans Candida species than the first-generation triazoles. They are active against Aspergillus species, including those species less susceptible to polyenes, and against a variety of non-Aspergillus molds. In contrast to posaconazole, voriconazole has no activity against the zygomycetes, and breakthrough infections have been observed. Both are well absorbed, but considerable intra- and interpatient pharmacokinetic variability has raised the question of therapeutic drug monitoring. Both inhibit hepatic cytochrome P450 isoenzymes, which are important in the metabolism of various drugs coadministered in the management of high-risk patients. Clinical trials have demonstrated the safety and efficacy of both agents for antifungal prophylaxis and treatment in invasive candidiasis, invasive aspergillosis, and in invasive fungal infections caused by a variety of non-Aspergillus molds. Posaconazole is the only triazole approved for use in the treatment of invasive zygomycosis. Voriconazole is the accepted standard first-line therapy for invasive aspergillosis.     

Basidiobolomycosis of the Nose and Face: A Case Report and a Mini-Review of Unusual Cases of Basidiobolomycosis

Background  

Subcutaneous zygomycosis is a chronic infection caused by fungus of the order Entomophthorales. It can have varying presentations and presents in the nose and face area with gradually progressing subcutaneous swelling that may be difficult to diagnose unless a strong suspicion of fungal involvement is maintained. We present a case of subcutaneous zygomycosis in a 35-year-old male patient, resident of a North Indian state. The patient was diagnosed to be suffering from subcutaneous zygomycosis, the causative agent being Basidiobolus ranarum identified on culture and lactophenol cotton blue mount preparation. He responded well to treatment with Itraconazole and Terbinafine and is asymptomatic on follow-up.     

The role of adjuvant agents in treating fungal diseases

Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality despite the recent introduction of new antifungal medications. In this review, the available data on the use of adjuvant agents for the treatment of IFIs are discussed. Cytokines such as interferon-γ, colony-stimulating factors, granulocyte transfusions, and the monoclonal antibody efungumab may have in a role in the management of IFIs through augmentation of the host immune response, whereas pathogen-specific vaccines may help prevent infection. Pentraxin 3, an acute phase protein, may assist in the prevention and treatment of aspergillosis. Deferasirox, an iron chelator, is being investigated as an adjunctive therapy for the treatment of zygomycosis. Lactoferrin, an ironbinding protein, appears to have activity in Candida and Aspergillus infections, and omiganan may help prevent fungal catheter-related infections. Although none of these agents are currently approved for the treatment of IFIs, they may be involved in current and/or future treatment options when used in combination with antifungal drugs.     

Infección múltiple fúngica en un paciente diabético

BackgroundMixed fungal infections although undervalued, are more common than mentioned in the scientific literature. These infections have a poor prognosis for the patient.ObjectivesWe present an unusual case of a 61-year-old diabetic male who had a rhino-orbito-sinusal zygomycosis in 2001. After surgical debridement of the infected parts, along with antifungal therapy with liposomal amphotericin B, the patient started improving. Several years later the patient was hospitalized due to a similar problem and was diagnosed of rhino-orbito-cerebral zygomycosis.MethodsIn both episodes, a histopathological examination and cultures were performed on the sinus lesions. Tissue sections were stained with haematoxylin and eosin, Giemsa, periodic acid-Schiff (PAS) and Grocott's methenamine silver, and cultures specific for fungi were performed.ResultsThe histopathology studies revealed the presence of bacteria, actinomyces and a mixed infection by at least four different fungi, all of them well differentiated by their morphology. Despite the rapid diagnosis the patient died due to spreading to the central nervous system.ConclusionsMixed infections by fungi are rare, but due to the high incidence of immunodeficiencies they could occur more often than reported. We would like to alert on the possibility of acquired mixed infection by fungi which have shown to be high aggressive and have a worse prognostic in patients with underlying diseases.     

Gastrointestinal entomophthoramycosis caused by Basidiobolus haptosporus

There was described the first cultural proven case of gastrointestinal entomophthoramycosis caused by B. haptosporus. A review of the literature on gastrointestinal zygomycosis led us to presume that similar clinical reported cases have been also caused by this fungus. A commentary on the designation of the clinical forms of the infections caused by Zygomycetes was also made.Reprints request (Dr. Londero) Tuiuti 1809/201, 97100 Santa Maria, RS, Brazil.     

Animal models of Zygomycosis – Absidia,Rhizopus, Rhizomucor,and Cunninghamella

Infections caused by zygomycetes, which have been increasing in recent years, are known for their difficulty of diagnosis and treatment. Because little is known about this fungus and its infection, vigorous research is now in serious demand. As in many other systemic mycoses, animal model studies are essential in the investigation of zygomycosis, particularly for the study of pathogenesis, diagnosis and treatment. Unfortunately, such studies have been limited when compared with those of aspergillosis. To help investigating the disease, here in this review article, the profile of human zygomycosis is briefly described, followed by a review of the heretofore used animal models of zygomycosis. Among clinically important zygomycetes causing human infection, animal models are available for Absidia corymbifera,Rhizopus oryzae,R. microsporus var.rhizopodiformis, Rhizomucor pusillus and Cunninghamella bertholletiae. Mice are the most commonly used animals, but models using guinea pigs and rabbits are also available. Pretreatment of animals with cyclophosphamide, corticosteroid, alloxan or streptozocine is frequently done to create an immunocompromised state. Treatment with desferrioxamine, an iron chelator, is also used to make animal models. In terms of the route of infection, the airborne route is used for pathophysiological studies in pulmonary infection models, but sometimes intravenous injection is preferred, particularly for antifungal drug studies. When pathophysiological analysis is the purpose of the study, the animals must be cautiously examined both histopathologically and mycologically. For the most part, zygomycosis model studies can be performed in a similar manner to those of aspergillosis. However, Aspergillus spp. and zygomycetes are completely different fungi, and researchers should be aware of the specific, critical aspects when handling zygomycosis models, such as homogenization of infected organs and staining of pathological samples. This revised version was published online in August 2006 with corrections to the Cover Date.     

Clinical efficacy of new antifungal agents

Several new options are now available for treating serious fungal infections. All three echinocandin agents currently available have been shown in randomized, blinded clinical trials to be efficacious in treating candidemia and invasive candidiasis. By contrast, the demonstrated efficacy of the echinocandins for the treatment of invasive aspergillosis has been based on historically controlled salvage treatment trials in patients failing or intolerant of other therapies. The new triazole agents, voriconazole and posaconazole, have a broad spectrum of antifungal activity. Voriconazole has become the agent of choice for invasive aspergillosis. On the basis of compassionate treatment data, posaconazole appears to be effective for treatment of zygomycosis. These agents have also been shown to be effective in the treatment of non-Aspergillus mould infections, several of the endemic mycoses and serious Candida infections.     

Cutaneous zygomycosis caused byAbsidia corymbifera in a leukemic patient

A case of cutaneous zygomycosis caused byAbsidia coryabifera in a leukemic patient submitted to chemotherapy is reported. The lesion was located on the little finger of the right hand and probably resulted from a latent osteomyelitis. It progressed to form extensive necrotic area. No systemic infection was detected and the lesion did not appear to be associated with any trauma.     

Current indications for voriconazole in onco-hematological patients

Invasive fungal infections (IFI) are the main cause of infectious death in cancer patients, especially in hematological malignancies and hematopoietic transplant recipients. Current epidemiology is characterized by a predominance of IFI caused by molds, mainly aspergillosis, along with a emergence of hard-to-treat fungi such are Zygomicetes, Fusarium and Scedosporium. Voriconazole is a broad spectrum antifungal agent with oral and intravenous formulations, approved by the EMEA for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, IFI caused by fluconazole-resistant species of Candida as well as Scedosporium and Fusarium infections. However, its use in clinical practice is broader, as empirical antifungal treatment and as secondary prophylaxis. It should be kept in mind the possibility of breakthrough IFI, particularly zygomycosis, in patients treated with voriconazole for long periods.     

Heterogeneous virulence potential and high antibiotic resistance of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> strains isolated from Korean pneumonia patients

Pseudomonas aeruginosa is an opportunistic human pathogen of clinical importance that causes airway infections in immunocompromised patients. Here, we report the virulence-associated characteristics of strains of P. aeruginosa, isolated from the sputa of 25 Korean pneumonia patients. A high degree of genomic plasticity was observed by random amplified polymorphic DNA genotype analysis, suggesting that the infections were caused by strains with diverse genomic backgrounds. Biofilm formation of each isolate was heterogeneous in terms of their relative motilities. In addition, 48% of isolates were defective in the production of 3-oxo-C₁₂-HSL (PAI-1), a quorum sensing signal molecule. In these strains, PAI-1-dependent elastase production was correspondingly decreased, suggesting that a large number of strains were presumed to be quorum sensing deficient. Multidrug resistance (MDR) was seen in 56% of the isolates tested, and 44% of the MDR strains were resistant to five or more antibiotics. Taken together, our results provide additional insights into the virulence traits of P. aeruginosa clinical isolates, which will aid in treating P. aeruginosa infections in pneumonia patients.     

Review of animal mycoses in Australia

This review covers the available literature on the mycoses of animals in Australia since the last review published in 1967. Of the cutaneous infections, dermatophytoses have been recorded in a wide range of animals: cattle, horses, goats, pigs, sheep, cats, dogs, mice, guinea-pigs, rabbits, a lion, kangaroos, a camel, koalas and wallabies. These infections were caused by several species and varieties of the genera,Microsporum andTrichophyton. Eight agents of ringworms have been recorded in the horse. Two subcutaneous mycoses, phaeohyphomycosis and sporotrichosis have been reported. Phaeohyphomycosis is becoming more common but sporotrichosis is rare having been recorded only once in a cat.The following systemic mycoses have been recorded: adiaspiromycosis, aspergillosis, candidiasis, cryptococcosis, dactylariosis, fusariomycosis, histoplasmosis, miscellaneous mycoses, mycotic abortion and related conditions, zygomycosis, pythiosis, protothecosis and green algal infections. Cryptococcosis has affected 11 different animal species. Mycotic abortion is a serious disease in Victoria. Pythiosis of horses has been extensively studied in northern Australia.     

Breakthrough Hormographiella aspergillata Infection in a Patient with Acute Myeloid Leukemia Receiving Posaconazole Prophylaxis: A Case Report and Review

Breakthrough invasive infections occur in immunosuppressed patients while they are receiving antifungal agents for both prophylaxis and therapy. Under such conditions, unusual fungal infections emerge. Hormographiella aspergillata is considered an uncommon human pathogen and causes devastating infections. Here, we present a case report of necrotizing pneumonia caused by H. aspergillata as a breakthrough infection in a neutropenic patient and review all previous cases of H. aspergillata infection reported in the literature.

     

Zygomycosis: A report of eleven cases and a review of the Brazilian literature

Eleven cases of zygomycosis (mucormycosis) observed throughout an eighteen year period (1982-2000) have been reviewed. The most important demographic and clinical data of seven patients were tabulated. The remaining four are related as illustrative cases. Seven patients presented with the pulmonary form of the disease; two patients presented with the pulmonary manifestation associated with sinusitis; and two patients presented with the rhinocerebral form. Predisposing conditions, in decreasing order of frequency, were diabetes mellitus (6), renal transplantation (2), associated with pancreas-kidney transplantation and diabetes (1), bone marrow aplasia (1), and chronic obstructive lung disease treated with corticosteroids (1). The diagnoses were based on the detection of characteristic zygomycetous hyphae in tissue. The causative organim was isolated and identified in only four cases; three were due to Rhizopus arrhizus, and one to Absidia corymbifera. In addition the Brazilian literature on zygomycosis is reviewed.     

植入性真菌病

植入性真菌病或称皮下组织真菌病,常见于热带和亚热带地区。此类感染有许多共同特征,包括相似的流行病学和感染方式等,有些还有明显的地域性。其临床表现形态各异,治疗困难,如不及时治疗常会导致畸形甚至致残,严重影响患者的生活质量。本文旨在对临床上重要的植入性真菌病,如孢子丝菌病、足菌肿、着色芽生菌病、暗色丝孢霉病和接合菌病的流行病学特征、临床表现、诊断和治疗进展做一复习。     

Iron gathering of opportunistic pathogenic fungi. A mini review

Iron is an essential nutrient for most organisms because it serves as a catalytic cofactor in oxidation-reduction reactions. Iron is rather unavailable because it occurs in its insoluble ferric form in oxides and hydroxides, while in serum of mammalian hosts is highly bound to carrier proteins such as transferrin, so the free iron concentration is extremely low insufficient for microbial growth. Therefore, many organisms have developed different iron-scavenging systems for solubilizing ferric iron and transporting it into cells across the fungal membrane. There are three major mechanisms by which fungi can obtain iron from the host: (a) utilization of a high affinity iron permease to transport iron intracellularly, (b) production and secretion of low molecular weight iron-specific chelators (siderophores), (c) utilization of a hem oxygenase to acquire iron from hemin. Patients with elevated levels of available serum iron treated with iron chelator, deferoxamine to remedy iron overload conditions have an increased susceptibility of invasive zygomycosis. Presumably deferoxamine predisposes patients to Zygomycetes infections by acting as a siderophore]. The frequency of zygomycosis is increasing in recent years and these infections respond very poorly to currently available antifungal agents, so new approaches to develop strategies to prevent and treat zygomycosis are urgently needed. Siderophores and iron-transport proteins have been suggested to function as virulence factors because the acquisition of iron is a crucial pathogenetic event. Biosynthesis and uptake of siderophores represent possible targets for antifungal therapy.     

Occurrence of subcutaneous zygomycosis caused by Basidiobolus haptosporus in Brazil

There were described the first three South American cases of subcutaneous zygomycosis caused by B. haptosporus. The patients were children from nearby towns lying just north of 13 ° latitude S. The diagnosis was based on histopathological aspects plus cultural isolation of the fungus.     

<Emphasis Type="Italic">Acr</Emphasis><Emphasis Type="Italic">emonium</Emphasis> Species: A Review of the Etiological Agents of Emerging Hyalohyphomycosis

Unusual fungal agents that exist environmentally as saprophytes can often lead to opportunistic infections. Hyalohyphomycosis is a group of fungal infections caused by fungi characterized by hyaline septate hyphae and can infect both immunocompetent as well as immunocompromised patients. Many a times it becomes difficult to distinguish a pathogenic and a contaminant fungus, because many such agents can assume clinical significance depending on circumstances. Subcutaneous and invasive fungal infection due to the emerging hyalohyphomycotic fungus, Acremonium, has drawn the attention of clinicians and microbiologists, as a potential pathogen in patients with and without underlying risk factors. Generally considered to be minimally invasive in the past, genus Acremonium has been responsible for eumycotic mycetomas and focal infections in otherwise healthy individuals. It has also been increasingly implicated in systemic fungal diseases. The management with different antifungals in various clinical situations has been very conflicting and hence needs to be carefully evaluated. This overview is an endeavor to consolidate the available clinical infections due to Acremonium and the recommendations on treatment.     

Treatment of deep mycoses with itraconazole

Four patients with deep mycoses were treated with itraconazole. Two patients had chromoblastomycosis, one patient each had aspergillosis and Rhinofacial zygomycosis. These patients were either resistant to or showed poor response to Amphotericin B and/or ketoconazole. After the initial clinical and mycological evaluation, itraconazole was given in a daily dose of 200 mg orally. All patients responded to the drug very well. No adverse effects attributable to itraconazole were detected.