Antifungals in a case of basidiobolomycosis: role and limitations.

A 10-year-old Saudi boy was diagnosed to have basidiobolomycosis after a stormy course of his ailment. Therapy was initiated with intravenous antifungal, voriconazole, which was well tolerated for 6 weeks except for local excoriation at the site of ileostomy. He developed drug-induced hepatitis on oral voriconazole, therefore, switched to oral itraconazole following which he experienced severe chest pain. Alternatively, co-trimoxazole (bactrim) an antibacterial with antifungal activity was prescribed but he had the intolerance to it as well. Unfortunately, posaconazole as an alternative antifungal was not available in our centre. We report here a Saudi boy who developed an intolerance to most common antifungals used clinically 6 weeks after the therapy was initiated.

A Rhinofacial Conidiobolus coronatus Fungal Infection Presenting as an Intranasal Tumour.

Conidiobolomycosis is a rare fungal infection that affects adults in tropical regions. We report a 42-year-old male patient who was referred to the Sulaiman Al Habib Hospital, Dubai, United Arab Emirates (UAE), in 2013 with excessive nasal bleeding and a suspected nasal tumour. He reported having briefly visited central India nine months previously. Computed tomography and magnetic resonance imaging showed a highly vascularised mass in the nasal cavity. However, after surgical excision, initial treatment with amphotericin B deoxycholate was unsuccessful and the disease progressed, leading to external and internal nasal deformation and necessitating further excision and facial reconstruction. Histopathological analysis of the second biopsy revealed Splendore-Hoeppli changes consistent with a fungal infection. Microbiological findings subsequently confirmed Conidiobolus coronatus. Subsequently, the patient was successfully treated with a combination of itraconazole and fluconazole. To the best of the authors' knowledge, this is the first report of a case of rhinofacial conidiobolomycosis from the UAE.

A case of pediatric gastrointestinal basidiobolomycosis mimicking Crohn`s disease. A review of pediatric literature.

Basidiobolomycosis is a rare fungal infection caused by basidiobolus ranarum. The vast majority of gastrointestinal basidiobolomycosis cases were reported from tropical and subtropical regions. We report a Saudi pediatric patient with ileal basidiobolomycosis and initial clinical presentation mimicking acute appendicitis before being misdiagnosed as Crohn's disease. Our case is the first to report effective treatment of pediatric gastrointestinal basidiobolomycosis using voriconazole mono-therapy. In addition, we present extensive review of pediatric gastrointestinal basidiobolomycosis in medical literature.

Fascitis necrotizante por Saksenaea vasiformis en una paciente inmunocompetente tras un accidente de tráfico / Necrotising fasciitis caused by Saksenaea vasiformis in an immunocompetent patient after a car accident

Antecedentes. La mucormicosis (zigomicosis) cutánea con extensión subcutánea y diseminación en pacientes inmunocompetentes es una patología infrecuente causada por especies de los géneros Apophysomyces, Rhizopus y Saksenaea, entre otros. Caso clínico. Se describe un caso de fascitis necrotizante por Saksenaea vasiformis en una mujer inmunocompetente, que sufrió politraumatismo y herida en brazo derecho a consecuencia de un accidente de tráfico. Tras la reducción quirúrgica de las fracturas, la lesión cutánea fue empeorando y derivó en necrosis y fascitis necrotizante grave con cultivos inicialmente negativos. A pesar de la amplia resección quirúrgica y el tratamiento antifúngico agresivo, el desenlace fue la muerte de la paciente. El estudio histopatológico puso en evidencia una infección por un hongo del orden Mucorales, confirmada mediante aislamiento primario en agar Sabouraud y posterior identificación de la especie mediante cultivo en agar Czapek-Dox y secuenciación de la región ITS del ADN ribosomal. Conclusiones. El presente caso confirma la presencia de este hongo en nuestro país, además de la utilidad del estudio histopatológico para el diagnóstico de la mucormicosis, y de los medios de cultivo especiales y las técnicas moleculares para la identificación de la especie(AU)

Background. Cutaneous mucormycosis (zygomycosis), with subcutaneous spreading and dissemination, in immunocompetent patients is an uncommon disease caused by species belonging to the fungal genera Apophysomyces, Rhizopus and Saksenaea, among others. Case report. A case of necrotising fasciitis by Saksenaea vasiformis in an immunocompetent woman is described. The infection was acquired through a car accident resulting in multiple injuries affecting mainly her right arm. After the surgical reduction of fractures, skin lesions worsened and led to necrosis. The patient quickly developed a severe necrotising fasciitis with negative cultures at first. Despite the extensive surgical debridement and the aggressive antifungal treatment, the patient died. The histopathological study showed a fungal infection due to a fungus belonging to the Mucorales order, which was confirmed by culturing the clinical sample on Sabouraud agar, and identifying the species by cultures on Czapek-Dox agar, and sequencing of the ITS region of the ribosomal DNA. Conclusions. This case confirm the presence of this fungus in Spain, the value of histopathology for the mucormycosis diagnosis, as well as the need to perform special cultures to facilitate their isolation and identification to the species level by the combined use of Czapek-Dox agar and sequencing of the ITS region(AU)

Cost of invasive fungal infections in the era of new diagnostics and expanded treatment options.

STUDY OBJECTIVE: To determine the true institutional cost of treating invasive fungal infections in light of recent advances in diagnostic techniques and antifungal therapies for both treatment and prophylaxis of these infections. DESIGN: Economic analysis. SETTING: Academic medical center. PATIENTS: A total of 200 patients discharged from the hospital during 2004-2005 with a diagnosis of proven, probable, or possible aspergillosis, cryptococcosis, invasive candidiasis, or zygomycosis (cases). Patients were matched in a 1:1 fashion with patients having similar underlying disease states but no invasive fungal infections (controls). MEASUREMENTS AND MAIN RESULTS: Data on demographic and clinical characteristics were collected from patients' medical records. In addition, information concerning each patient's hospitalization was recorded. Resource utilization data for a patient's entire hospitalization were collected from the hospital's charge databases and converted to costs. These data were compared between the cases and the controls. After adjusting for race-ethnicity, sex, age, and comorbid illnesses, mean total hospital cost for cases was $32,196 more than for controls (p<0.0001). Nonpharmacy costs accounted for the majority (63%) of this difference, and an additional $3996 was attributed to systemic antifungal drugs. The mean length of hospital stay was longer for cases than controls (25.8 vs 18.4 days). CONCLUSION: Treatment of patients with invasive fungal infections was associated with a significantly higher inpatient hospital cost compared with controls. However, due to new diagnostic techniques and effective antifungal therapy, the relative cost of these infections appears to be at least stable compared with the previous decade. These findings can help assess the utility of cost-avoidance strategies such as antifungal prophylaxis and application of appropriate treatment.

Pneumonia and lung infections due to emerging and unusual fungal pathogens.

Invasive mold infections affecting the lungs are increasing in incidence and diversity. Severely immunocompromised patients are particularly vulnerable to infection from unusual, normally nonpathogenic fungi that are found naturally in the environment. Certain fungi such as Scedosporium and the dematiaceous fungi also cause lung disease in hosts without overt immune compromise. The impacts of these emerging pathogens range from airway colonization to locally invasive lung, and disseminated, disease. Diagnosis requires isolation and identification of the etiologic agent by either or both phenotypic and molecular biology methods. Evidence of tissue invasion on histopathology is often required to distinguish infection from colonization. Diagnostic imaging techniques are nonspecific, and there are no reliable serological biomarkers of infection. Many rare molds and yeasts demonstrate reduced in vitro susceptibility to antifungal agents. Although amphotericin B formulations remain clinically useful for many of these infections, voriconazole and posaconazole are more effective for some of these difficult-to-treat pathogens. Surgical resection of diseased tissue and support of the host immune system are often required to optimize outcomes.

Forty-one recent cases of invasive zygomycosis from a global clinical registry.

BACKGROUND: Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited. PATIENTS AND METHODS: Fungiscope-A Global Rare Fungal Infection Registry is an international university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. RESULTS: Forty-one patients with invasive zygomycosis from central Europe and Asia were registered. The most common underlying conditions were malignancies (n = 26; 63.4%), diabetes mellitus (n = 7; 17.1%) and solid organ transplantation (n = 4; 9.8%). Diagnosis was made by culture in 28 patients (68.3%) and by histology in 26 patients (63.4%). The main sites of infection were the lungs (n = 24; 58.5%), soft tissues (n = 8; 19.5%), rhino-sinu-orbital region (n = 8; 19.5%) and brain (n = 6; 14.6%). Disseminated infection of more than one non-contiguous site was seen in six patients (14.6%). Mycocladus corymbifer was the most frequently identified species (n = 10, 24.4%). A favourable response was observed in 23 patients (56.1%). Overall survival was 51.2% (n = 21). At diagnosis, four patients (9.8%) were on continuous antifungal prophylaxis with itraconazole (n = 1; 2.4%) or posaconazole (n = 3; 7.3%). Initial targeted treatment with activity against zygomycetes was administered to 34 patients (82.9%). Liposomal amphotericin B was associated with improved response (P = 0.012) and survival rates (P = 0.004). CONCLUSIONS: Pathogen distribution and, consequently, drug susceptibility seem to vary across different geographic regions. Furthermore, protection from invasive zygomycosis for patients on posaconazole prophylaxis is not absolute. Our findings indicate that the use of liposomal amphotericin B as first-line treatment for patients diagnosed with zygomycoses merits further investigation, preferably in the form of a clinical trial.

Clinical presentation of zygomycosis.

Zygomycetes are filamentous fungi with a worldwide distribution. This class of fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales. Members of the latter are associated with chronic cutaneous and subcutaneous infections that are limited to the tropics and rarely disseminate to internal organs. The order Mucorales includes several species involved in rhinocerebral, pulmonary, cutaneous, gastrointestinal and other less frequent infections in immunocompetent and immunocompromised individuals, and is characterized by a tendency to disseminate. Portals of entry of zygomycetes are usually the lungs, skin, and gastrointestinal tract. A characteristic property of zygomycetes is their tendency to invade blood vessels and to cause thrombosis-processes that result in subsequent necrosis of involved tissues. Risk factors associated with zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes of age, and intravenous drug abuse. Recently, the widespread use of voriconazole for prophylaxis or treatment of aspergillosis in patients with haematological malignancies has been linked with a rise in the numbers of cases of invasive zygomycosis. As the symptoms, clinical signs and imaging findings of these infections are non-specific, a high index of suspicion is required for timely diagnosis. Early diagnosis, correction of the underlying predisposing factors, aggressive surgical debridement of all infected tissues and lengthy administration of antifungals are the only potentially curative options for this rare but emerging invasive fungal infection.

Increased virulence of Zygomycetes organisms following exposure to voriconazole: a study involving fly and murine models of zygomycosis.

BACKGROUND: Breakthrough zygomycosis is increasingly observed among patients at high risk for fungal infection who are receiving voriconazole, reflecting either selective pressure or voriconazole-associated alterations in Zygomycetes virulence. We tested the latter hypothesis, using 2 phylogenetically disparate zygomycosis models. METHODS: Three Zygomycetes strains were exposed to voriconazole by serial passages on voriconazole-containing medium. The virulence of voriconazole-exposed Zygomycetes strains was compared with that of voriconazole-nonexposed strains in Drosophila and murine models of zygomycosis by assessment of survival curves, pulmonary fungal burdens, and expression of inflammation-associated genes. RESULTS: Among Toll-deficient (Tl(-/-)) and wild-type fruit flies, infection with Zygomycetes isolates that had been exposed to voriconazole yielded significantly lower survival rates than infection with Zygomycetes strains grown in drug-free media. In contrast, exposure of Rhizopus oryzae to itraconazole, amphotericin B, or caspofungin and exposure of Aspergillus fumigatus to voriconazole did not alter the virulence of these isolates in fruit flies. In the murine model, infection with a R. oryzae strain preexposed to voriconazole was associated with decreased survival rates and increased pulmonary fungal burdens, compared with infection with a voriconazole-nonexposed R. oryzae strain. In addition, enhanced angioinvasion, inflammation, and expression of genes involved in stress response and tissue repair were found in mouse lungs infected with voriconazole-exposed R. oryzae. CONCLUSIONS: Exposure of Zygomycetes organisms to voriconazole selectively enhanced their virulence. The mechanisms underlying these phenotypic changes should be studied further.

Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.

Mucocutaneous entomophthoramycosis acquired by conjunctival inoculation of the fungus.

Entomophthoramycoses are classified into subcutaneous, mucocutaneous, and primary visceral forms. The mucocutaneous form, also known as rhinoentomophthoramycosis, involves the mucosa and subcutaneous tissues of the nose and is caused by Conidiobolus coronatus (Entomophthora coronata). In this report, we describe the first case of mucocutaneous entomophthoramycosis acquired by introduction of the fungus through the conjunctival mucosa as a consequence of trauma involving contamination with soil. The patient was a 37-year-old man with no other complaints. The lesion was tumoral and extended into the ethmoidal and maxillary sinuses. The histopathologic appearance of the lesion was characteristic of this infection with a granulomatous process rich in eosinophils and with hyphae surrounded by an eosinophilic, periodic acid-Schiff stain-positive halo (Splendore-Hoeppli phenomenon). To the best of our knowledge, this case constitutes the first report of mucocutaneous entomophthoramycosis acquired by ocular contamination.

Efecto de los nuevos antifúngicos en la etiología de las micosis invasoras: emergencia, resistencia e infección de brecha / Effect of new antifungal on the etiology of invasive fungal infections: emergence, resistance and breakthrough infection

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The influence of Conidiobolus coronatus on phagocytic activity of insect hemocytes.

An essential component of the insect cellular response is phagocytosis. Analyses of the in vitro phagocytosis could be useful for the studies of the relationship between insects and their pathogens. Fungal metabolites are known to inhibit phagocytosis whereas components of the fungal cell wall stimulate phagocytosis. To achieve a better understanding of fungal pathogenesis in insects, haemocyte populations of two insect species susceptible to Conidiobolus coronatus infection (Galleria mellonella, Dendrolimus pini ) were compared with haemocytes of the resistant species (Calliphora erythrocephala ). Fungal infection increased phagocytic activity of G. mellonella plasmatocytes 3.3 times and this of D. pini plasmatocytes 2.1 times. Analysis of infected C. erythrocephala larvae did not reveal any influence of C. coronatus upon phagocytic activity.

Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer.

BACKGROUND: Pulmonary zygomycosis (PZ), an emerging mycosis among patients with cancer, has a clinical manifestation similar to that of invasive pulmonary aspergillosis (IPA). Most cases of PZ in such patients develop as breakthrough infections if treatment with antifungal agents effective against Aspergillus species is administered. However, clinical criteria to differentiate PZ from IPA are lacking. METHODS: We retrospectively reviewed the clinical characteristics and computed tomography (CT) findings for 16 patients with cancer and PZ and for 29 contemporaneous patients with cancer and IPA at the time of infection onset (2002-2004). Patients with mixed infections were excluded. Parameters predictive of PZ by univariate analysis were included in a logistic regression model. RESULTS: Almost all patients with PZ (15 of 16) and IPA (28 of 29) had underlying hematological malignancies and typical risk factors for invasive mold infections. In logistic regression analysis of clinical characteristics, concomitant sinusitis (odds ratio [OR], 25.7; 95% confidence interval [CI], 1.47-448.15; P = .026) and voriconazole prophylaxis (OR, 7.76; 95% CI, 1.32-45.53; P = .023) were significantly associated with PZ. The presence of multiple (> or = 10) nodules (OR, 19.8; 95% CI, 1.94-202.29; P = .012) and pleural effusion (OR, 5.07; 95% CI, 1.06-24.23; P = .042) at the time that the patient underwent the initial CT were both independent predictors of PZ in the logistic regression analysis of radiological parameters. No difference occurred in the frequency of other CT findings suggestive of pulmonary mold infections (e.g., masses, cavities, halo sign, or air-crescent sign) between the 2 patient groups. CONCLUSIONS: PZ in immunocompromised patients with cancer could potentially be distinguished from IPA on the basis of clinical and radiological parameters; prospective validation is needed.

Entomophthora leyteensis Villacarlos & Keller sp. nov. (Entomophthorales: Zygomycetes) infecting Tetraleurodes acaciae (Quaintance) (Insecta, Hemiptera: Aleyrodidae), a recently introduced whitefly on Gliricidia sepium (Jaq.) Walp. (Fabaceae) in the Philippines.

Entomophthora leyteensis Villacarlos & Keller sp. nov., a species of Entomophthorales infecting the whitefly Tetraleurodes acaciae on Gliricidia sepium in the Philippines is described. Disease prevalence monitored weekly for 8 weeks indicated that the fungus could cause 8-31% infection within the whitefly population. Epizootics due to this fungus occurred in Inopacan, Leyte. Sampling live whitefly adults and dissecting them on glass slides for microscopic examination of fungal structures was found to give a better measure of prevalence than actual counts of infected insect cadavers. E. leyteensis is an important mortality factor for T. acaciae. Some speculations on the origin of the fungus are discussed here.