Outbreaks of Mucorales and the Species Involved.

The order Mucorales is an ancient group of fungi classified in the subphylum Mucoromycotina. Mucorales are mainly fast-growing saprotrophs that belong to the first colonizers of diverse organic materials and represent a permanent part of the human environment. Several species are able to cause human infections (mucormycoses) predominantly in patients with impaired immune system, diabetes, or deep trauma. In this review, we compiled 32 reports on community- and hospital-acquired outbreaks caused by Mucorales. The most common source of mucoralean outbreaks was contaminated medical devices that are responsible for 40.7% of the outbreaks followed by contaminated air (31.3%), traumatic inoculation of soil or foreign bodies (9.4%), and the contact (6.2%) or the ingestion (6.2%) of contaminated plant material. The most prevalent species were Rhizopus arrhizus and R. microsporus causing 57% of the outbreaks. The genus Rhizomucor was dominating in outbreaks related to contaminated air while outbreaks of Lichtheimia species and Mucor circinelloides were transmitted by direct contact. Outbreaks with the involvement of several species are reported. Subtyping of strains revealed clonality in two outbreaks and no close relation in two other outbreaks. Based on the existing data, outbreaks of Mucorales can be caused by heterogeneous sources consisting of different strains or different species. Person-to-person transmission cannot be excluded because Mucorales can sporulate on wounds. For a better understanding and prevention of outbreaks, we need to increase our knowledge on the physiology, ecology, and population structure of outbreak causing species and more subtyping data.

Mucormicosis pulmonar en un paciente con trasplante renal y hemoptisis incoercible / Pulmonary mucormycosis in a patient with kidney transplant and uncontrolled haemoptysis

Antecedentes. La mucormicosis pulmonar es una infección oportunista rara con alta mortalidad causada por hongos Mucorales. Los más frecuentes son Rhizopus, Mucor, Lichtheimia y Rhizomucor. Caso clínico. Se presenta el caso de una mujer de 56 años con diabetes mellitus tipo 2 y enfermedad renal crónica, receptora de un trasplante de riñón cadavérico dos años antes de su ingreso. Por este motivo recibió tratamiento inmunomodulador con timoglobulina, micofenolato de mofetilo, tacrolimus y prednisona. La paciente ingresó por un cuadro neumónico con tos, expectoración y disnea; una tomografía computarizada mostró una lesión cavitada en el lóbulo superior derecho. Con la sospecha de una aspergilosis pulmonar invasiva se comenzó un tratamiento antifúngico con voriconazol, sin mejoría. Se realizó una biopsia por aspiración con aguja fina, y en el cultivo de la misma creció Rhizomucor pusillus. La identificación se confirmó por PCR. A pesar del tratamiento con anfotericina B, la paciente presentó hemoptisis masiva incoercible, que provocó su fallecimiento. Conclusiones. La mucormicosis pulmonar es una infección rara que suele ser fatal en receptores de trasplante renal con terapia antirrechazo. Los mucorales producen fenómenos trombóticos, necrosis y destrucción tisular, que provocaron en nuestra paciente una hemoptisis incoercible. Es importante un diagnóstico preciso que permita instaurar un tratamiento quirúrgico adecuado y la administración de anfotericina B (AU)

Background. Pulmonary mucormycosis is a rare opportunistic infection with high mortality that is caused by species of Mucorales. The most common species involved are Rhizopus, Mucor, Lichtheimia, and Rhizomucor. Case report. A 56 year-old woman presented with a clinical history of diabetes mellitus type 2 and chronic renal disease. She underwent a cadaveric kidney transplantation two years before her admission, for which immunomodulating therapy with thymoglobulin, tacrolimus, mofetil-microphenolate and prednisone was established. The patient suffered a pneumonic process with cough, expectoration, and dyspnoea. The computed tomography scan showed a cavitation in the right upper lobe. With all these findings an invasive broncopulmonary aspergillosis was suspected and the patient began an antifungal treatment with voriconazole without improvement. Rhizomucor pusillus was isolated from a clinical specimen obtained by fine needle aspiration, and its identification was confirmed by PCR. After this finding amphotericin B was administered, but the patient had an uncontrolled haemoptysis and died. Conclusions. Pulmonary mucormycosis is a rare infection, usually fatal in kidney transplant recipients with anti-rejection therapy. Mucorales species usually produce thrombotic phenomena, associated with necrosis and parenchymal destruction that caused a fatal uncontrolled haemoptysis in our patient. Early diagnosis is important in order to perform any surgical treatment and to administer amphotericin B (AU)

Mucormicosis diseminadas en pacientes sin inmunodeficiencias: una enfermedad que también existe / Disseminated mucormycosis in immunocompetent patients: A disease that also exists

Las mucormicosis son infecciones generalmente agudas, angioinvasivas, que provocan necrosis difusas no supurantes y gran destrucción tisular. Representan el 1,6% de todas las infecciones fúngicas invasivas, y predominan en pacientes inmunodeprimidos con factores de riesgo. Su incidencia se ha incrementado de forma significativa, incluso en pacientes sin inmunodeficiencias. A propósito de un caso de mucormicosis diseminada producida por Rhizomucor pusillus en un paciente joven sin inmunodeficiencias conocidas, hemos realizado una revisión bibliográfica de los casos de mucormicosis en pacientes adultos sin inmunodeficiencias reportados en PubMed, según sus principales localizaciones anatómicas y con referencia especial a los casos de mucormicosis diseminadas. Se revisan los principales factores de riesgo y la patogenia de la enfermedad, las formas clínicas de presentación y sus posibilidades diagnósticas, incidiendo en las técnicas de diagnóstico precoz, y la terapia actual disponible, discutiendo la indicación del tratamiento de combinación de antifúngicos y el pronóstico. Además, se revisa la taxonomía actual del género Mucor y su clasificación (AU)

Mucormycosis is usually an acute angioinvasive infections, which leads to non-suppurative necrosis and significant tissue damage. It represents 1.6% of all the invasive fungal infections and predominates in immunosuppressed patients with risk factors. Incidence has been significantly increased even in immunocompetent patients. Due to finding a case of disseminated mucormycosis caused by Rhizomucor pusillus in a young immunocompetent patient, a systematic review was carried out of reported cases in PubMed of mucormycosis in immunocompetent adults according to the main anatomic locations, and especially in disseminated cases. A review of the main risk factors and pathogenicity, clinical manifestations, techniques of early diagnosis, current treatment options, and prognosis is presented. Taxonomy and classification of the genus Mucorhas also been reviewed (AU)

Infección fúngica invasiva mixta por Rhizomucor pusillus y Aspergillus niger en un paciente inmunocompetente / Mixed invasive fungal infection due to Rhizomucor pusillus and Aspergillus niger in an immunocompetent patient

Antecedentes. Las mucormicosis son infecciones poco frecuentes en pacientes inmunocompetentes, y se han descrito muy pocos casos de mucormicosis asociadas a aspergilosis en pacientes no hematológicos. Caso clínico. Un varón de 17 años, inmunocompetente y sin factores de riesgo previamente conocidos, ingresó en el hospital tras presentar crisis convulsivas 11 días después de sufrir un accidente de moto. Presentó un curso clínico tórpido por infección fúngica invasiva mixta, con afectación pulmonar por Aspergillus niger y mucormicosis diseminada por Rhizomucor pusillus (diagnóstico histopatológico y microbiológico en varios lugares no contiguos). Fue tratado con anfotericina B liposomal durante 7 semanas (dosis total acumulada > 10 g) y precisó múltiples reintervenciones quirúrgicas. El paciente sobrevivió y fue dado de alta de UCI tras 5 meses de evolución y múltiples complicaciones. Conclusiones. El tratamiento con anfotericina B liposomal y el manejo quirúrgico agresivo consiguió la erradicación de la infección fúngica invasiva mixta, pero alertamos de la necesidad de mantener un mayor grado de sospecha clínica y de realizar técnicas de diagnóstico precoz de infecciones fúngicas invasivas en pacientes no inmunodeprimidos para evitar la diseminación de la enfermedad y el mal pronóstico asociado (AU)

Background. Mucormycosis infections are rare in immunocompetent patients, and very few cases of mucormycosis associated with aspergillosis in non-haematological patients have been reported. Case report. A 17-year-old male, immunocompetent and without any previously known risk factors, was admitted to hospital due to a seizure episode 11 days after a motorcycle accident. He had a complicated clinical course as he had a mixed invasive fungal infection with pulmonary involvement due to Aspergillus niger and disseminated mucormycosis due to Rhizomucor pusillus (histopathological and microbiological diagnosis in several non-contiguous sites). He was treated with liposomal amphotericin B for 7 weeks (total cumulative dose > 10 g) and required several surgical operations. The patient survived and was discharged from ICU after 5 months and multiple complications. Conclusions. Treatment with liposomal amphotericin B and aggressive surgical management achieved the eradication of a mixed invasive fungal infection. However, we emphasise the need to maintain a higher level of clinical suspicion and to perform microbiological techniques for early diagnosis of invasive fungal infections in non-immunocompromised patients, in order to prevent spread of the disease and the poor prognosis associated with it (AU)

Serial monitoring of Mucorales DNA load in serum samples of a patient with disseminated mucormycosis after allogeneic bone marrow transplantation.

Mucormycosis is a fatal complication in immunocompromised patients, and is additionally difficult to diagnose due to the lack of useful serum biomarkers. Using a quantitative PCR approach, we retrospectively analyzed Mucorales DNA load in sera collected serially from a 3-year-old patient with chronic granulomatous disease, who died of multi-organ failure probably due to dissemination of Rhizomucor pusillus, which was detected from necropsy specimens. Mucorales DNA load was below the detection limit on days 9, 2, and 4 after unrelated bone marrow transplantation. Rhizomucor DNA was first detected on day 14 (1.6 × 10(3) copies/mL), and subsequently fluctuated between 1.3 × 10(3) and 37.2 × 10(3) copies/mL until day 43. Rhizomucor achieved a peak value of 940.0 × 10(3) copies/mL on day 48 the day before death. The detection or fluctuation of Rhizomucor DNA appeared to be associated with corticosteroid dosages or C-reactive protein levels. This specific, noninvasive, and highly quantitative assay may be useful for the early diagnosis of mucormycosis and prediction of disease progression.

Pulmonary mucormycosis.

Mucormycosis (formerly zygomycosis) is a life-threatening opportunistic mycosis that infects a broad range of hosts with qualitative or quantitative defects in innate immunity, including patients with severe neutropenia, recipients of corticosteroids or other immunosuppressive medications, poorly controlled diabetes mellitus, and those with iron overload states. Mucormycosis has recently emerged as breakthrough sinopulmonary infection in hematologic patients and recipients of transplantation being on antifungal prophylaxis with Aspergillus-active antifungals that lack activity against Mucorales. Unlike pulmonary aspergillosis, the prognosis and outcome of pulmonary mucormycosis have not improved significantly over the last decade, mainly because of difficulties in early diagnosis and the limited activity of current antifungal agents against Mucorales. Recent evidence suggests a critical role for iron metabolism and fungal-endothelial cell interactions in pathogenesis of mucormycosis, and holds promise for development of novel therapeutic strategies. Currently, prompt initiation of antifungal therapy with a lipid amphotericin B-based regimen, reversal of underlying host factors, and aggressive surgical approach offers the best chances for survival of patients infected with this devastating mycosis.

Antifungal activity of statins and their interaction with amphotericin B against clinically important Zygomycetes.

The in vitro antifungal activity of different statins and the combinations of the two most effective ones (fluvastatin and rosuvastatin) with amphotericin B were investigated in this study on 6 fungal isolates representing 4 clinically important genera, namely Absidia, Rhizomucor, Rhizopus and Syncephalastrum . The antifungal effects of statins revealed substantial differences. The synthetic statins proved to be more effective than the fungal metabolites. All investigated strains proved to be sensitive to fluvastatin. Fluvastatin and rosuvastatin acted synergistically and additively with amphotericin B in inhibiting the fungal growth in clinically available concentration ranges. Results suggest that statins combined with amphotericin B have a therapeutic potential against fungal infections caused by Zygomycetes species.

Systemic zygomycosis in farmed tilapia fish.

Decreased feed intake and persistent low-level mortality in a production tank of hybrid tilapia (Oreochromis niloticus x Oreochromis mossambicus x Oreochromis aureus) prompted the submission of three affected fish for diagnosis. Consistent macrosopical findings included multifocal dermal haemorrhage, excess abdominal fluid and an enlarged friable liver. On microscopical examination, broad non-septate fungal hyphae and chlamydospores were identified within numerous internal organs, often within and adjacent to blood vessels. The fungal hyphae were readily seen by silver staining (GMS) and the chlamydospores were stained deep magenta by the periodic acid-Schiff reaction. In addition to several species of Gram-negative bacteria, moderate growths of woolly white fungal colonies were obtained from the posterior part of the kidney in two of the three tilapia. These colonies were identified as a Rhizomucor sp. on the basis of the morphological characteristics of the sporulating fungi in culture. This represents the first reported episode of zygomycosis in fish.