Gastrointestinal Zygomycosis in a Preterm Neonate Associated With Contaminated Probiotics.

A neonate of 29 weeks' gestation who received probiotics developed clinical signs suggesting surgical necrotizing enterocolitis. A specimen of resected ileum revealed fungal forms within the bowel wall. Rhizopus oryzae was detected via DNA sequencing from probiotic powder and tissue specimens from the infant. To our knowledge, this is the first report linking gastrointestinal zygomycosis to the administration of contaminated probiotics.

Zigomicosis y síndrome hemofagocítico en un paciente inmunocompetente: informe de caso / Zygomycosis and hemophagocytic lymphohistiocytosis in an immunocompetent patient: a case report

Introducción: la zigomicosis es una infección fúngica poco frecuente, con alta tasa de mortalidad y de mal pronóstico. Afecta principalmente a pacientes inmunocomprometidos. La asociación con el síndrome hemofagocítico es extremadamente inusual, más aún en pacientes inmunocompetentes, con pocos ejemplos registrados en la literatura. Caso clínico: se presenta el caso de un paciente masculino inmunocompetente de 40 años con diagnóstico de mucormicosis y síndrome hemofagocítico que evoluciona desfavorablemente, con fallo multiorgánico, a pesar de los esfuerzos médicos. Conclusión: la asociación de mucormicosis con síndrome hemofagocítico en un paciente inmunocompetente es extremadamente rara; existen pocos casos informados en Latinoamérica. Debemos tener presente esta asociación, ya que requiere un tratamiento agresivo y soporte vital avanzado. (AU)

Introduction: zygomycosis is a rare fungal infection that carries with high mortality rates. This poor prognosis, rapidly progressive infection mainly affects immunocompromised patients. The association with hemophagocytic lymphohistiocytosis is extremely unusual, even more in immunocompetent patients, with few cases reported. Case: we present the case of an immunocompetent male patient who was diagnosed with zygomycosis and hemophagocytic lymphohistiocytosis. Despite medical efforts he developed multiorganic failure. Conclusion: the association of mucormycosis with hemophagocytic lymphohistiocytosis in an immunocompetent patient is exceptional with few cases reported in Latin America. We must always suspect this association considering they require aggressive treatment and advanced life support. (AU)

Fulminant zygomycosis of graft liver following liver transplantation.

A 44-year-old man with hepatitis B virus (HBV)-related cirrhosis underwent living donor liver transplantation at our institute. Induction of immunosuppression was achieved with basiliximab, due to deranged renal function, and maintained with prednisolone, tacrolimus and mycophenolate mofetil. The intraoperative and immediate postoperative periods were fairly uneventful. A duplex scan, taken during the third week post-transplantation due to sudden rise in liver enzymes, revealed multifocal hypoechoic lesions in the graft liver with normal Doppler parameters. Multidetecor computed tomography (MDCT) showed multiple hypodense vessel-sparing lesions in the graft liver. Cultures from the aspirate grew filamentous fungi identified as Basidiobolus ranarum species. Despite multiple broad spectrum antifungal infusions including liposomal amphotericin, itraconazole, caspofungin and posaconazole, serial sonography showed the hepatic lesions increasing in size, and involving segments V, VI and VII. The patient developed severe liver dysfunction ultimately progressing to sepsis, multiorgan dysfunction and death.

[Fatal zygomycosis caused by Mucor indicus after haplo-identical stem cell transplantation].

A 62-year-old woman with acute lymphoblastic leukemia in first complete remission was treated with unrelated cord blood transplantation, but exhibited primary graft failure. She then underwent HLA-haploidentical peripheral blood stem cell transplantation from her daughter. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days, intravenous busulfan 3.2 mg/kg/day for 2 days, and thymoglobulin 1 mg/kg/day for 2 days. Voriconazole was administered to prevent fungal infections. The patient achieved prompt hematopoietic recovery. Fever was observed 21 days after the second transplant, followed by sigmoid colon perforation and a liver space occupying lesion (SOL). A filamentous fungus was detected in a percutaneous biopsy of the liver SOL. In spite of changing the antifungal drug from voriconazole to liposomal amphotericin B, the patient died on day 41. The fungus was identified as Mucor indicus, a type of zygomycete. Although Mucor indicus inhabits soil, an infectious disease is extremely rare, and breakthrough infection after voriconazole prophylaxis had not been reported until now. It is mandatory to consider preventive antifungal treatment for drug-resistant fungal infectious diseases in patients after neutrophilic recovery with a strongly immunocompromised state after a HLA-haploidentical transplant.

Disseminated zygomycosis due to Mycocladus corymbifera with cutaneous and cerebral involvement.

Fungal infections caused by zygomycetes are important and potentially life threatening infections. These opportunistic moulds have been increasingly implicated in human disease and are most frequently seen in immune compromised patients. We report a case of disseminated infection with Mycocladus corymbifera involving the brain, lungs, kidneys and skin in a 16-year-old patient with acute lymphoblastic leukaemia. The skin lesions played a significant role in the diagnosis of mucormycosis. These infections have an exceedingly high mortality rate and early recognition of cutaneous lesions is essential to successful management.

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)

Zigomicosis en ni˜nos: infección diseminada por Cunninghamella bertholletiae / Zygomycosis in Children: Disseminated Infection Caused by Cunninghamella bertholletiae

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Procalcitonin serum concentration in lung transplant recipients during mold colonization or infection.

BACKGROUND: This publication attempted to evaluate the frequency of mold colonization and infection and the procalcitonin serum concentrations (PCT) among lung transplant recipients. METHODS AND MATERIALS: We included 49 patients (36 males and 13 females) of mean age at transplantation of 47.1±13.6 years. Molds were isolated using routine microbiologic methods. PCT (ng/mL) was measured using an immunoluminescence assay with values below 0.5 showing no probability of infection, 0.5 to 2.0, a moderate infection risk; 2.0 to 10, a high infection risk; and above 10 high sepsis risk. RESULTS: Twenty-four (49%) patients revealed the presence of molds in material from the lower respiratory tract (sputum, tracheal, or tracheobronchial aspirate), mini-bronchoalveolar lavage. Aspergillus species was isolated in 14 (28.6%) patients, Penicillium in 7 (14.3%) patients, and Zygomycetes fungi in 9 (18.4%) patients. The average PCT value from 61 examinations of PCT during fungal isolation was 0.5±0.7 ng/mL. However, when the studied group was categorized according to the PCT range, the rates for the groups were no infection (n=30; 49.2%), moderate (n=20; 32.8%), high (n=9; 14.8%) and high sepsis risk (n=2; 3.3%). CONCLUSIONS: The mold colonization of transplanted lung is a frequent complication and should be considered even in the case of proper prophylaxis. Procalcitonin might be the marker helpful in mold infection diagnosis.

[Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia].

A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics.

Rhino-cerebral zygomycosis after allogeneic transplant: case report and literature review.

The proportion of patients with hematological malignancies (HM) who develop rare invasive fungal infections (IFI) has increased worldwide over the past few decades. Zygomycosis is an opportunistic fungal infection, which begins in the nose and paranasal sinuses due to inhalation of fungal spores. Rhino-cerebral zygomycosis is the most common form of the disease, it typically develops in diabetic or immunocompromised patients and presents as an acute fulminate infection, which is often lethal. We report a case of rhino-cerebral zygomycosis in an allotransplanted patient to emphasize early diagnosis and treatment of this potentially fatal fungal infection. We discuss different risk factors, specific diagnosis procedures and review the current concepts in management of zygomycosis.

[Multiple myeloma complicated with disseminated zygomycosis after bortezomib therapy].

A 67-year-old man was diagnosed with multiple myeloma IgA-lambda type, Durie-Salmon classification stage IIIA in October 2001. He received five courses of induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone and then underwent high dose chemotherapy followed by autologous stem cell transplantation in March 2003. He achieved partial response, but then relapsed after treatment with thalidomide and was admitted to our hospital in June 2007. The patient was complicated by tumor lysis syndrome (TLS) after receiving bortezomib therapy twice. Computed tomography after bortezomib therapy showed the rapid appearance of tumors in the right upper lobe of the lung, tail of the pancreas and the spleen. Though he was treated with antifungal agents, micafungin and voriconazole, he died eighty-five days after admission. Autopsy specimen showed fungal clumps and hemorrhagic infarction in the lung and spleen, and vegetation at the mitral valve was the same fungus as found in the lung. We diagnosed disseminated zygomycosis based on the pathological fungal morphology. This case suggested that metabolic acidosis was caused by TLS, while poorly controlled diabetes, secondary hemochromatosis due to transfusion, and breakthrough zygomycosis during antifungal therapy were thought to be factors contributing to the development of zygomycosis.

Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients.

BACKGROUND: Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. METHODS: SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. RESULTS: Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. CONCLUSIONS: Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.

Primary cutaneous zygomycosis from a tertiary care centre in north-west India.

BACKGROUND & OBJECTIVES: Zygomycosis is highly invasive fungal infection, with high mortality rate. In most of patients, diabetes mellitus is an underlying factor but in primary cutaneous zygomycosis, presentation may be different. Here we present the description of clinical presentation, fungi isolated and management of cases with cutaneous zygomycosis seen in a tertiary care hospital in north India during 2001-2007. METHODS: All patients diagnosed with primary cutaneous zygomycosis between November 2001 and September 2007 presenting with clinical diagnosis of necrotizing fasciitis were included. Detailed history of each patient was taken, clinical presentation, site of involvement, underlying illness and risk factor, if any were noted. The diagnosis was established by direct microscopic evidence of broad, aseptate or sparsely septate ribbon-like hyphae with right angle branching in KOH wet mount and histopathological examination of stained sections. Cultures were put up for fungal isolation and species identification. Outcome of the therapy was analysed. RESULTS: Of the nine patients reviewed, only one had diabetes mellitus. Commonest risk factor was injection abscess (33.3%). Apophysomyces elegans was isolated in four cases, Saksenaea vasiformis and Absidia corymbifera in one each. The fungal culture was sterile in three cases. Mortality rate was high with only four patients responded well to surgical and/or medical therapy. INTERPRETATION & CONCLUSION: Primary cutaneous zygomycosis appears to be on rise in India that calls for high index of clinical suspicion and an early biopsy of the affected area for timely diagnosis. The standard treatment is a combination of amphotericin B therapy, surgical debridement, and reversal of the underlying disease or immunosuppression.

Zygomycotic invasion of the central nervous system.

Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion.

Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors.

OBJECTIVES: Invasive zygomycosis is a rare fungal opportunistic disease with a high morbidity and mortality rate, predominantly affecting immunosuppressed patients. Presented herein is our investigation of the epidemiological factors associated with an increasing incidence of the disease at the University of Geneva Hospitals, Geneva, Switzerland, over the past five years. METHODS: This was a retrospective study of the clinical charts and microbiology records of patients with a positive culture for zygomycetes, to evaluate predisposing factors and epidemiological characteristics. RESULTS: Three of 19 proven/probable invasive infections were diagnosed during 1989-2003, and 16 during 2003-2008. While the number of positive isolates for zygomycetes remained mainly stable, the ratio between invasive infections and colonized patients increased after the introduction of voriconazole and caspofungin in 2003 at our institution (p<0.001). All cases were unrelated and no nosocomial source of exposure or seasonal aggregation was identified. The increase in cases was coincident with an incremented use of voriconazole and caspofungin, and with an increased number of immunosuppressed patients, especially allogeneic bone marrow transplant recipients. CONCLUSIONS: Invasive zygomycosis is an emerging infection at our center and is probably related to an increase in immunosuppressed patients and the wide use of newer antifungals. Changes in antifungal drug prophylaxis and treatment prescription may help to control this emergence.

Organising pneumonia mimicking invasive fungal disease in patients with leukaemia.

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.