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As the battle against the deadly Covid-19 pandemic is still continuing worldwide, several complications are being reported in patients who have recovered post-covid. One such lethal complication being reported in patients in India in recent times, who have tested positive for Covid-19 and are gradually recovering, is a fungal disease called Mucormycosis or the black fungus. With several hundreds of cases being reported all over the country, it has triggered an additional wave of panic among the general public. Post-Covid-19 patients who are more vulnerable to Mucormycosis are those with a history of poorly controlled diabetes mellitus and also those who are immuno-compromised and have been treated with steroids and other drugs for Covid-19. The aim of this short review is to briefly cover the epidemiology of mucormycosis, its possible pathophysiology in Post Covid scenario, the clinical presentation and its diagnosis and management. [ABSTRACT FROM AUTHOR]

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought. • Pulmonary mucormycosis has been rarely reported in critically ill COVID-19 patients. • R. microsporus and L. corymbifera were identified in two COVID-19 patients. • Clinical characteristics included fever, septic shock and refractory hypoxemia. • Typical radiologic findings (halo, reverse halo, vessel occlusion) were absent. • Further research is needed to understand the role of Mucorales in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Pulmonary mucormycosis (PM) is increasingly being reported in immunocompromised patients and has a high mortality. Our aim was to assess the mortality of PM and its trend over time. We also evaluated the role of combined medical–surgical therapy in PM. We performed a systematic review of Pubmed, Embase, and Cochrane central databases. Studies were eligible if they described at least five confirmed cases of PM and reported mortality. We also assessed the effect of combined medical–surgical therapy versus medical treatment alone on PM mortality. We used a random-effects model to estimate the pooled mortality of PM and compared it across three time periods. The factors influencing mortality were assessed using meta-regression. We evaluated the risk difference (RD) of death in the following: subjects undergoing combined medical–surgical therapy versus medical therapy alone, subjects with isolated PM versus disseminated disease, and PM in diabetes mellitus (DM) versus non-DM as a risk factor. We included 79 studies (1544 subjects). The pooled mortality of PM was 57.1% (95% confidence interval [CI] 51.7–62.6%). Mortality improved significantly over time (72.1% versus 58.3% versus 49.8% for studies before 2000, 2000–2009, and 2010–2020, respectively, p 0.00001). This improved survival was confirmed in meta-regression after adjusting for the study design, the country's income level, and the sample size. Combined medical–surgical therapy was associated with a significantly lower RD (95%CI) of death: –0.32 (–0.49 to –0.16). The disseminated disease had a higher risk of death than isolated PM, but DM was not associated with a higher risk of death than other risk factors. While PM is still associated with high mortality, we noted improved survival over time. Combined medical–surgical therapy improved survival compared to medical treatment alone. [ABSTRACT FROM AUTHOR]

• Mucormycosis is a rare disease and is often fatal in the immunocompromised. • We present a series of 3 patients with poorly controlled diabetes and mucormycosis. • Diagnosing mucormycosis requires microbiologic and microscopic evidence. • Combined medical and surgical management yields better outcomes for mucormycosis. Mucormycosis is a rare, aggressive, and invasive disease with a fatal outcome. It most commonly affects patients with compromised immunity, particularly those with poorly controlled diabetes. We present a case series of patients with uncontrolled diabetes and mucormycosis. We present a series of three patients with uncontrolled diabetes, with main symptoms of paranasal sinusitis, nasal discharge, ophthalmic changes, and facial nerve involvement. Diagnoses of mucormycosis were made via microbiological testing and computed tomography. These cases were managed by combination therapy of tight glycemic control, urgent endoscopic sinus debridement, and antifungal therapy. Diagnosing rhino-orbito-cerebral mucormycosis requires a high degree of suspicion and both microbiologic and microscopic evidence. Better clinical outcomes can be obtained by combining medical and surgical management. We describe our experience in handling three cases of poorly controlled diabetes with rhino-orbito-cerebral mucormycosis. [ABSTRACT FROM AUTHOR]

Mucormycosis is a frequently lethal fungal infection that most commonly affects patients with poorly controlled diabetes or other immunosuppressed states. We report the case of a suspected disseminated Rhizopus infection in a patient who was pursuing naturopathic treatment including mud baths for metastatic adrenocortical carcinoma. He was empirically treated with liposomal amphotericin B but opted to stop treatment following multiorgan failure. The patient passed away on the tenth day of his hospital admission. [ABSTRACT FROM AUTHOR]

We describe two cases of mucormycosis with systemic and gastrohepatic involvement in two male poodles. Respiratory, neurological and gastrointestinal signs progressed to death within 3 and 19 days of the onset of clinical signs, respectively. In case 1, there was systemic disease affecting the lungs, heart and brain. The lesions were characterized by yellow or red, raised, irregular areas that extended into deeper tissue from the surface. In case 2, there was gastric rupture; the margins of the rupture and the gastric mucosa were covered by a thick, white, friable material. In the liver, there were multiple yellow–white cavitated nodules. Histologically, pyogranulomas occurred in the affected organs and were associated with vasculitis, thrombosis and fungal hyphae. The diagnosis of mucormycosis was based on the characteristic microscopical lesions together with the morphology and staining features of the fungus. The hyphae were strongly labelled by monoclonal antibody specific for Rhizopus arrhizus on immunohistochemistry. Underlying immunosuppression was suspected in both cases. [ABSTRACT FROM AUTHOR]

Mucormycosis is a rare but potentially mortal opportunistic infection caused by Mucorales. We present a case of rhinoorbital mucormycosis in an 11-year old male with neuroblastoma successfully treated with aggressive surgical debridement and antifungal combination of liposomal amphotericin B and posaconazole. Our patient developed signs of paranasal sinus infection and culture of fine needle biopsy grew Rhizopus arrhizus. Prompt treatment and drastic surgical resection led to complete clinical and radiological recovery without evidence of mucormycosis relapse. [ABSTRACT FROM AUTHOR]

Highlights • Retrospective analysis of patients with non- Aspergillus invasive mould infections (IMIs) at a US university medical centre. • IMIs occurred in patients with a variety of underlying diseases and at diverse sites. • Most Fusarium and Lomentospora isolates had MICs > 16 µg/mL for voriconazole and/or posaconazole. • Overall 180-day mortality was significantly lower among those receiving combination therapy vs. single-agent therapy. ABSTRACT Non- Aspergillus invasive mould infections (IMIs) are associated with devastating morbidity and mortality rates and are increasingly diagnosed in immunocompromised hosts. The aim of this study was to describe the epidemiology and outcomes of non- Aspergillus IMIs at a university hospital in San Diego, California, USA. A retrospective chart review of the medical records of all patients with cultures growing non- Aspergillus moulds at the microbiology laboratory in the Center for Academic Laboratory Medicine, Department of Pathology, University of California, San Diego (UCSD) Health between mid-2014 and mid-2017 (3-year period) was performed. A total of 23 cases of non- Aspergillus IMI were identified, including 10 cases of mucormycosis, 8 cases of lomentosporiosis and 5 cases of fusariosis. Antifungal susceptibility testing was performed for 14 isolates, and 10/11 Fusarium and Lomentospora isolates had minimum inhibitory concentrations (MICs) of >16 µg/mL for voriconazole and/or posaconazole. Overall 180-day mortality was significantly lower among those who received combination antifungal therapy than among those who received single-agent therapy [3/13 (23%) vs. 9/10 (90%); P = 0.003]. In conclusion, Lomentospora prolificans (35% of non- Aspergillus IMIs) and Fusarium spp. (22%) accounted for high proportions of non- Aspergillus IMIs during the study period. Non- Aspergillus IMIs were detected in patients with various underlying diseases and were associated with high mortality rates, which was significantly lower in those who received antifungal combination therapy. [ABSTRACT FROM AUTHOR]

Summary In spring 2014, several wild passeriform garden birds were found severely ill or dead, all with severe periocular swellings. A blue tit (Cyanistes caeruleus) showing severe depression was humanely destroyed and sent for necropsy examination. In this bird, the lower eyelids were sagging, red and oedematous. Microscopical examination revealed marked infiltration of the eyelid tissue with fungal hyphae (stained by periodic acid–Schiff) without any inflammatory reaction. Polymerase chain reaction followed by sequencing identified Mucor racemosus and a so far unknown circovirus. The circovirus infection in this bird might have induced immunosuppression and thus facilitated the fungal infection. To our knowledge this is the first report of ocular M. racemosus infection associated with circovirus infection in a bird. [ABSTRACT FROM AUTHOR]

Resumen Las infecciones por cigomicetos, producidas tanto por hongos mucorales como entomoftorales, se caracterizan por la invasión de los vasos sanguíneos y de otros órganos o estructuras adyacentes. Los mucorales suelen producir infección orbitorrinocerebral, pulmonar, cutánea, digestiva o diseminada y su desarrollo se ve favorecido por ciertas enfermedades de base (diabetes, insuficiencia renal) o factores de riesgo (neutropenia, inmunosupresión, sobrecarga de hierro). Se asocian a una elevada mortalidad y la clave del éxito reside en el diagnóstico y el tratamiento antifúngico precoz asociado, en la mayoría de los casos, a un desbridamiento quirúrgico amplio. En la actualidad, el isavuconazol representa una alternativa en el tratamiento de la mucormicosis refractaria o intolerante a la anfotericina B liposomal, y dadas sus características farmacocinéticas y farmacodinámicas, así como su escasa toxicidad, constituye la mejor opción para el tratamiento de mantenimiento de estas infecciones fúngicas invasivas. Abstract Infections due to zygomycetes, caused by mucorales and entomophthorales, are characterized by angioinvasion and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous or disseminated infection and its spread is favored by several diseases (such as diabetes or chronic kidney disease) and risk factors (neutropenia, immunosuppression, iron overload). They have a high mortality rate, and the key to success in their treatment are early diagnosis, prompt administration of antifungal treatment, and extensive surgical debridement. Currently, isavuconazole constitutes an option for the treatment of those mucormycosis refractory to liposomal amphotericin B. Due to its pharmacokinetic and pharmacodynamic characteristics and its low toxicity, it is also the best choice for maintenance therapy. [ABSTRACT FROM AUTHOR]

Abstract The patients with hematologic malignancies and hematopoietic stem cell transplantation (HSCT) recipients are at high risk for invasive fungal diseases (IFDs) mainly due to the severe and prolonged neutropenia related to high-dose chemotherapy. Voriconazole prophylaxis is recommended for possible IFDs. Mucormycosis is a fulminant infection, which may occur after voriconazole prophylaxis for invasive aspergillosis in immunocompromised hosts. Here, we report mucormycosis after 4 months of voriconazole prophylaxis in a young patient with relapsed acute lymphoblastic leukemia and hematopoietic stem cell transplant failure and discuss the clinical manifestation, imaging, laboratory findings and therapeutic regimens. Clinician's awareness of this entity and timely diagnosis using conventional and molecular methods are the promising approach for the management of this devastating infection. [ABSTRACT FROM AUTHOR]

A 54-year-old woman with acute myeloid leukemia (AML) achieved complete remission by induction chemotherapy, but developed zygomycosis after consolidation therapy. As zygomycosis could not be cured by liposomal amphotericin B and micafungin, left lower lobectomy was performed. As AML relapsed 7 months after onset, she received haploidentical stem cell transplantation under administration of liposomal amphotericin B. Despite experiencing severe acute graft-versus-host disease, she remains alive with no relapse of either zygomycosis or AML. [ABSTRACT FROM AUTHOR]

Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved for various hematological malignancies. Invasive aspergillosis is a known complication of ibrutinib, but mucormycosis is rare. We describe the case of a 70-year-old man with mantle cell lymphoma infiltrating the trachea, managed with a tracheobronchial stent and ibrutinib. He had improved one month after treatment, and we removed the airway stent. Four months later, he developed tracheal nodules confirmed to be tracheal mucormycosis and responded to liposomal amphotericin B (3.5 g) followed by posaconazole. After transient improvement, the tracheal lesions recurred, the biopsy showed lymphoma (with no evidence of mucormycosis), and he died. A systematic review of the literature identified 20 additional cases of ibrutinib-associated mucormycosis. Most of the 21 patients included were men (95%), and ibrutinib was the only risk factor in 15.7%. The reported mortality was 31.6% (6/19), attributable to mucormycosis in half the cases. [ABSTRACT FROM AUTHOR]

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004–2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non- Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1–42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2–481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3–25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3–13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome. [ABSTRACT FROM AUTHOR]

Given increased international travel, immigration, changing climate conditions, and the increased incidence of iatrogenic immunosuppression, fungal, protozoan, helminthic, and ectoparasitic infections that were once uncommon are being seeing more frequently in the Western hemisphere. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. In addition, delays in the diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. We review the epidemiology, cutaneous manifestations, diagnostic modalities, and treatment options for emerging fungal, protozoan, helminthic, and ectoparasitic infections. It should be noted, however, that throughout this review we cite statistics documenting their increased incidence to back-up these infections as emerging, and although some of the diagnoses are clinical, others rely on newer laboratory tests, and the possibility exists that the increased incidence could be caused by better detection methods. [ABSTRACT FROM AUTHOR]

Summary Cutaneous zygomycosis is the third most common form of zygomycosis. However, scalp involvement is rare for this disease. In this study, we present a case of acute zygomycosis in a diabetic patient who was effectively treated with local debridement, amphotericin B lipid complex and posaconazole. [ABSTRACT FROM AUTHOR]

Aim Subcutaneous entomophthoromycosis (EM) is an uncommon fungal infection of childhood. This article is intended to draw the attention of pediatric surgeons to the fact that EM can mimic soft-tissue tumor. Methods It is a retrospective review of 16 children treated for subcutaneous EM between 2000 and 2013. Results The median age of patients was 3.5 years. The typical lesion was a discoid subcutaneous mass that can be easily lifted from deeper tissues (the doughnut lifting sign). Lesions were mostly distributed in the lower half of body. All the patients were immunocompetent. Correct clinical diagnosis was made only in 4 cases while others were mistaken for a tumor. All the 8 children who underwent wide excision of the pseudotumor had local recurrence. Supersaturated solution of potassium iodide was curative in 11 cases while addition of itraconazole was needed in one case. One child died of muti-drug resistant infection. The mean treatment duration was 4.7 months (range 2–8 months). Conclusion Subcutaneous EM can mimic soft-tissue tumor. High index of suspicion is essential to avoid misdiagnosis and inappropriate treatment. A newly described “doughnut-lifting sign’ may be helpful in clinical diagnosis. Emergence of multi-drug resistant infection is a source of concern. [ABSTRACT FROM AUTHOR]

Mucormycosis, also known as Zygomycosis and Phycomycosis, is a rare opportunistic fungal infection with a fulminant course and high mortality rate. Its Rhinocerebral variant is an acute invasive fungal infection which normally affects immunocompromised patients with uncontrolled diabetes, organ transplant and hematological malignancies. It may pose a therapeutic challenge considering the fact that its onset may be followed by rapid progress, extensive involvement and rapid clinical deterioration which may even be fatal. With due regard to such nature of the disease, early diagnosis and aggressive treatment become the cornerstone for better prognosis and survival. Vigilance on the part of the clinician to include Rhinocerebral Mucormycosis as part of the differential diagnosis in susceptible hosts with sino-orbital involvement holds the key. A multimodal treatment strategy comprising of early diagnosis, reversal or stabilization of underlying medical condition, systemic antifungals and surgical debridement has shown best results. This paper reviews the literature on Rhinocerebral Mucormycosis and presents a series of seven cases with their varying predisposing conditions, clinical manifestations and treatment outcome, thus adding to the bank of knowledge on this emerging threat. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Mycology / Journal de Mycologie Médicale is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement. [ABSTRACT FROM AUTHOR]

Zygomycosis (mucormycosis) is being increasingly recognized as causing infection in recent years. National and multinational European surveys attempting to analyse the epidemiological parameters of this potentially devastating infection are very few. Although the exact incidence could not be defined due to the different methodologies used in these studies and the absence of a denominator, there were some useful observations made regarding the clinical presentation, sites of infection and diagnostic practices. Moreover, the importance for a prompt and accurate diagnosis has been stressed. As early diagnosis can significantly affect the initiation of treatment and decrease mortality, future research should focus on the development of an epidemiological risk assessment tool and novel diagnostic methods. [ABSTRACT FROM AUTHOR]

Although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. Despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. Successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents. However, mucormycosis is not always amenable to cure. There are challenging obstacles that lead to difficulties in management of amphotericin B. These include unique host-based risk factors for mucormycosis, the fungus' resistance to innate host defences and distinctive features of its immunopathogenesis, such as extensive angioinvasion, increased virulence and use of chelators by the fungus as siderophores. In addition to these obstacles, the difficulties in early diagnosis, including nonspecific clinical manifestations, lack of serological methods, as well limitations of culture and molecular methods, lead to delay in initiation of antifungal therapy. Finally, the variability of susceptibility to amphotericin B and resistance to most other conventional antifungal agents leads to major limitations in successful treatment of this devastating infection. [ABSTRACT FROM AUTHOR]

These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4 × 200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors. [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Basidiobolomycosis is a rare chronic subcutaneous infection caused by Basidiobolus ranarum. The disease usually occurs in children, less often in adolescent and rarely in adults. Males are more frequently affected than females. We report a case of subcutaneous zygomycosis of head and neck region caused by B. ranaram, in an immunocompetent adult female presenting with nontender firm swelling over the nape of neck and temporo-parietal region. The diagnosis was confirmed by histopathology, microbiology (culture) and DNA sequencing of molecular technique (sequencing). The patient was successfully treated with amphotericin B and potassium iodide [Copyright &y& Elsevier]

Abstract: Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to randomly selected controls matched on underlying disease and hospital discharge date using conditional logistic regression. Environmental assessments, including collection of samples for fungal cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous leukemia and 3 (27%) were allogeneic HSCT recipients. Five case-patients (45%) died. In univariate analysis, case-patients were more likely than controls to have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence interval [CI], 1.31–689); neutropenia >14 days (OR, 11.50; 95% CI, 1.27–558) or to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11–infinity). A point source was not identified. Factors such as underlying disease state and antifungal prophylaxis type may identify hematology patients at highest risk for mucormycosis. Our investigation highlighted critical knowledge gaps, including strain typing methods, the role of the hospital environment in mucormycosis outbreaks, and hospital environmental infection control measures most likely to reduce exposure of immunosuppressed persons to mucormycetes. [Copyright &y& Elsevier]

Copyright of Journal of Medical Mycology / Journal de Mycologie Médicale is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Mucormycosis (zygomycosis) is an emerging fungal disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. A 30-year-old woman diagnosed with acute myelomonocytic leukemia and needing allo-HSCT presented pulmonary and cerebral infection due to Rhizomucor pusillus. This fungal infection was treated with surgical treatment and posaconazole delayed-release tablets. This strategy allowed reaching high drug levels that could not be obtained with the posaconazole solution. [ABSTRACT FROM AUTHOR]

Abstract: A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P >0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections. [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: First-aid education for the management of burns advocates cool running water over burnt skin to limit soft tissue damage. However, the water used may itself constitute a risk. We report three cases of severe invasive and necrotizing infection in patients who used or immersed themselves in contaminated water in an attempt to extinguish the fire following acute major burns. Wound cultures from all patients yielded Aeromonas hydrophila and two yielded Bacillus cereus. One patient had a complex polymicrobial infection, including zygomycosis with Rhizomucor variabilis. All patients were treated aggressively with wound débridement, including one patient who required bilateral lower limb amputations to control progressive infection. All infections were successfully treated and all patients survived their burn injuries. We review the management of burns complicated by exposure to contaminated water leading to burn wound infections. We describe commonly reported organisms from various water sources, the appropriate initial empirical antimicrobial chemotherapy and present the clinician with a proposed algorithm for managing these serious infections. [Copyright &y& Elsevier]

Mucormycosis (zygomycosis) is an uncommon infection that afflicts severely immunocompromised patients and those with poorly controlled diabetes mellitus. A recent increase in the incidence of mucormycosis at many transplant centres has been linked to the introduction and widespread use of voriconazole prophylaxis in these high-risk populations. However, it is not known if this association reflects a true epidemiological link or represents a marker of changing immunosuppression occurring in parallel with the evolution of transplant practices and immunosuppression strategies. [ABSTRACT FROM AUTHOR]

Zygomycetes are increasingly reported as a cause of life-threatening invasive fungal infections in profoundly immunocompromised patients and in those with diabetic ketoacidosis. Zygomycosis, typically presents as soft tissue, rhino-orbitocerebral, pulmonary or disseminated disease and is characterized by rapid clinical progression and high mortality rates. Treatment with amphotericin B lipid formulations in combination with surgery and, perhaps, the addition of caspofungin offers the best chance for survival; posaconazole, a new antifungal triazole, is increasingly used for consolidation or maintenance therapy. Because of the poor prognosis of zygomycosis, particularly in immunocompromised cancer patients, adjunctive treatments such as hyperbaric oxygen therapy, use of immunomodulatory cytokines, and in vivo iron starvation continue to be explored. However, although each of these modalities is based on a plausible scientific rationale and has been helpful in the management of individual patients, there is no clinical evidence for their general effectiveness as adjunctive treatments in patients with zygomycosis. Further experimental and clinical investigations are necessary to determine whether and how these treatments can impact on outcome and to determine which patients and which types of infection may benefit from them. [ABSTRACT FROM AUTHOR]

Zygomycosis is a difficult to treat and frequently fatal infection affecting immunocompromised and, rarely, immunocompetent patients. The early diagnosis and immediate initiation of treatment with an antifungal agent in combination with surgical intervention has proved critical for the favourable outcome of the disease. Few antifungal agents are available for treatment. Amphotericin B (AmB) deoxycholate has been the drug of choice for many years and is usually given at high daily doses which can result in renal toxicity. Currently, lipid formulations of AmB (liposomal AmB (L-AmB), AmB lipid complex (ABLC), AmB colloidal dispersion (ABCD)), mainly L-AmB, rather than conventional AmB have become the standard therapy. The rationale behind the use of lipid formulations is that they decrease the nephrotoxicity associated with longterm AmB use. Although there is a developing consensus that high doses of lipid formulations of AmB should be the antifungal therapy of choice for all patients with zygomycosis, until now there have been no data available with which to define the appropriate dose. The duration of therapy remains an unresolved issue, regarding both lipid formulations of AmB as well as sequential or combination treatments consisting of lipid formulations of AmB with posaconazole, a drug which has now emerged as a new therapeutic option. [ABSTRACT FROM AUTHOR]

Zygomycetes are unique among filamentous fungi in their great ability to infect a broader, more heterogeneous population of human hosts than other opportunistic moulds. Various members of the Zygomycetes have been implicated in zygomycosis, although those belonging to the family Mucoraceae are isolated more frequently than those of any other family. The environmental microbiology literature provides limited insights into how common zygomycetes are in the environment, and provides a few clues about which ecological niches these fungi are found in. Mucorales are thermotolerant moulds that are supposedly ubiquitous in nature and widely found on organic substrates, including bread, decaying fruits, vegetable matter, crop debris, soil between growing seasons, compost piles, and animal excreta. The scientific and medical literature does not support this generalization. Sporangiospores released by mucorales range from 3 to 11 μm in diameter, are easily aerosolized, and are readily dispersed throughout the environment. This is the major mode of transmission. However, there are very few data concerning the levels of zygomycete sporangiospores in outdoor and indoor air, especially in geographical areas where zygomycosis is particularly prevalent. Airborne fungal spores are almost ubiquitous and can be found on all human surfaces in contact with air, especially on the upper and lower airway mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly, members of the Mucorales are very rarely found in nasal mucus, suggesting that spores in the mucus of airway mucosa are cleared by mucociliary transport or that there is a low level of airborne contamination. Zygomycetes are found occasionally in water-damaged buildings, as demonstrated by air-sampling, and analysis of settled dust by quantitative PCR. Moreover, inhalation of sporangiospores in dust has been linked to outbreaks of rhinocerebral or pulmonary zygomycosis due to excavation, construction, or contaminated air-conditioning filters. Whereas most zygomycete infections are community-acquired, nosocomial acquisition due to percutaneous routes of exposure is very important. Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages and adhesive dressings, needles, and tongue depressors used to construct splints for intravenous and arterial cannulation sites in preterm infants. Insect bites or stings have been implicated in disease transmission in cases of cutaneous and subcutaneous zygomycosis, e.g. diseases caused by the Entomophthorales. Traumatic implantation of spores in dirt or in contaminated water, e.g. as occurred during the Asian tsunami, has led to infection in multiple patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Zygomycoses are severe angio-invasive fungal infections that develop in immunocompromised and diabetic patients. Any episode of sinusitis not responding to short-term antibacterial therapy should evoke the diagnosis of zygomycosis in the latter population, especially in cases of a surrounding necrotic area. Appropriate diagnosis is obtained after careful direct examination of the sample and culture. Current therapy underscores the need to control glycaemia and acidosis in addition to the need for urgent administration of high-dose liposomal amphotericin B in combination with extensive surgery. [ABSTRACT FROM AUTHOR]

Iron is an essential element for cell growth and development, contributing to DNA synthesis and regulating the G1-phase to S-phase transition. Moreover, iron is important for the virulence of the majority of microorganisms, and the function of the genes regulating iron uptake is coupled with the manifestations of the virulence phenotype. All fungi elaborate specific uptake mechanisms to sequester iron, and most commonly produce small molecules with high affinity for iron, the siderophores. The importance of iron appears to be particularly high for Zygomycetes, which grow abundantly in iron-rich media, and all the known predisposing factors for zygomycosis have, as a common feature, the increased availability of free iron. Among the known iron chelators, deferoxamine supports the growth of Zygomycetes because it acts as xenosiderophore, delivering iron to iron-uptaking molecules of these species. Conversely, the newer iron chelators deferiprone and deferasirox do not exhibit similar activity, apparently because they share higher affinity constants for iron and, as a result, deprive the fungi of iron, inhibiting their growth. This activity has been documented in various culture systems and in many animal models of zygomycosis, and therefore suggests that these drugs might be used as adjuvant treatment for systemic zygomycosis. There are few case reports in which the newer iron chelators have been used as antifungals, and their possible benefit must be verified in a prospective randomized trial. [ABSTRACT FROM AUTHOR]

The prevalence of cutaneous and soft tissue zygomycosis appears to have increased in recent years. We reviewed 78 case reports of cutaneous zygomycosis published from 2004 through 2008. Most patients with cutaneous zygomycosis have underlying conditions such as haematological malignancies, diabetes mellitus or solid organ transplantation, but a large proportion of them are immunocompetent. Trauma is the most common predisposing factor leading to zygomycosis in immunocompetent patients. If the patient is immunocompromised, the infection may disseminate. Cutaneous zygomycosis may be localized, may extend to deep underlying tissues, or may be disseminated. The most common clinical presentation is induration of the skin with surrounding erythema, rapidly progressing to necrosis. Histological examination and culture of soft tissue are important for the diagnosis of cutaneous zygomycosis. Treatment consists of surgical debridement, administration of antifungal agents (amphotericin B formulations and/or posaconazole) and, occasionally, hyperbaric oxygen. Mortality rates are approximately 30%. [ABSTRACT FROM AUTHOR]

Zygomycosis of the central nervous system (CNS) can manifest in three distinct clinical forms, as rhinocerebral zygomycosis, as disseminated zygomycosis with CNS involvement, and as isolated cerebral zygomycosis. We present a case of a 2-year-old boy with leukaemia and disseminated zygomycosis, caused by Absidia corymbifera, involving the brain, spinal cord, lung and liver. The child received treatment with liposomal amphotericin B and posaconazole for 6 months. Although the lesions of the lungs and liver resolved, those of the CNS persisted and the child is in a vegetative state. A review of the literature after 2004 identified ten additional cases of disseminated zygomycosis with cerebral involvement, all but one of which had concurrent lung infection. The most common underlying disease in these cases was haematological malignancy and the mortality rate was 70%. Disseminated zygomycosis with cerebral involvement is a fatal disease. Early recognition and prompt intervention with combined medical and surgical treatment may improve the outcome. [ABSTRACT FROM AUTHOR]

Zygomycosis refers to a group of uncommon and frequently fatal mycoses caused by fungi of the class Zygomycetes, the organisms of which are usually found in decaying organic matter. Disease can be transmitted by the inhalation of spores or by direct inoculation on disrupted skin or mucosa. For rare diseases such as zygomycosis, two or more cases occurring in a short time should be investigated as a probable epidemic. Twelve hospital outbreaks and two pseudoepidemics caused by Zygomycetes have been cited in the English literature. The first epidemic was recorded in 1977 and the last in 2008. Outbreaks have been reported in the USA, the UK and elsewhere in Europe. Cases have included cutaneous, disseminated, pulmonary and rhinocerebral disease. Species identified have included Rhizopus arrhizus, Rhizopus rhizopodiformis, Rhizopus microsporus, Rhizopus spp., Absidia corymbifera and Rhizomucor pusillius. Sources of infection have included Elastoplast adhesive bandage rolls, ventilation systems, wooden tongue depressors, karaya (plant-derived adhesive) ostomy bags, and water damage to a linen store and patient shower room. Patients have included cardiosurgery patients, renal transplant recipients, orthopaedic patients, adult leukaemia patients, intensive care unit neonates, immunocompromised haematology patients, and burn unit patients. Although zygomycosis outbreaks in the hospital environment are infrequent, a high index of suspicion should exist if necrotic lesions appear in proximity to a postoperative wound. Direct tissue examination and tissue culture and histopathology must be routinely performed. [ABSTRACT FROM AUTHOR]

The identification of Zygomycetes and diagnosis of zygomycosis are notoriously difficult. However, there have been recent advances, particularly in the availability and evaluation of new molecular approaches. Two main issues are of importance: the identification to species level of a strain isolated in culture, and the identification of a zygomycete in tissues. By using several molecular targets and by increasing the number of available DNA sequences in international databases, several studies have shown that accurate molecular identification of Zygomycetes to species level is feasible. The internal transcribed spacer (ITS) region may be used as a first-line molecular target for the identification of Zygomycetes in pure culture. However, cultures from infected tissues are often negative and the different Zygomycetes share similar morphology according to histopathology. Furthermore, differentiation of a zygomycete from another hyalohyphomycete can sometimes be difficult in histopathology. Thus, alternative methods for the diagnosis of zygomycosis and for species identification directly from tissues are needed. For this purpose, molecular methods have been recently evaluated, both on unfixed fresh/frozen material and on formalin-fixed, paraffin-embedded biopsies. This review discusses the molecular approaches currently available for the identification of Zygomycetes and the diagnosis of zygomycosis. [ABSTRACT FROM AUTHOR]

The treatment of zygomycosis has two cornerstones, namely, surgery and antifungal drugs. In many patients, both need to be applied to achieve treatment success; without treatment, the mortality rate of zygomycosis approaches 100%. Because treatment options are limited, no well-designed randomized clinical trial has been conducted and data are predominantly derived from compassionate-use programmes or case reports. Amphotericin B (AmB) lipid complex (ABLC) was clinically evaluated for efficacy against zygomycosis in a single series and resulted in cure or improvement in 52% and in the stabilizing of disease in 20% of patients. Liposomal AmB (L-AmB) is frequently used, but no large series have yet been published. Posaconazole has demonstrated in vitro and in vivo activity against Zygomycetes. Two series demonstrated salvage treatment response rates of 60% and 79%, respectively. Antifungal combinations have not been evaluated thoroughly enough to warrant recommendations outside of clinical trials. Survival is usually associated with surgical debridement and improvement in underlying diseases. Currently, surgical debridement should be performed. Antifungal treatment should consist of either ABLC ≥5 mg/kg once per day or L-AmB ≥3 mg/kg once per day. When toxicity occurs or stable fungal disease is achieved, treatment can be switched to oral posaconazole 200 mg four times per day. If impaired kidney function is overt or expected on the grounds of, for example, uncontrolled diabetes, primary treatment of zygomycosis with posaconazole is an option. [ABSTRACT FROM AUTHOR]

Rhinocerebral or rhino-orbitocerebral (mucormycosis) zygomycosis (ROCZ) usually occurs among patients with poorly controlled diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload or extensive burns, in patients undergoing treatment with glucocorticosteroid agents, or in patients with neutropenia related to haematologic malignancies. The disease process starts with inhalation of the fungus into the paranasal sinuses. The fungus may spread to invade the palate, sphenoid sinus, cavernous sinus, orbits or cranially to invade the brain. Pain and swelling precede oral ulceration and the resulting tissue necrosis can result in palatal perforation. Infection can sometimes extend from the sinuses into the mouth and produce painful, necrotic ulcerations of the hard palate. If untreated, infection usually spreads from the ethmoid sinus to the orbit, resulting in the loss of extraocular muscle function and proptosis. Surgical treatment includes the resection of involved tissues of the face, including skin and muscle, any skin of the nose that is involved, maxillary and ethmoid sinuses, necrotic tissue of the temporal area and infratemporal fossa, and orbital exenteration. The keys to successful therapy include suspicion of the diagnosis and early recognition of the signs and symptoms, correction of underlying medical disorders such as ketoacidosis, and aggressive medical and surgical intervention. [ABSTRACT FROM AUTHOR]

A definitive diagnosis of zygomycosis caused by Mucorales can be made by histopathological examination with or without isolation of the fungus from the same site. Histopathological examination of the tissues affected typically shows characteristic broad, hyaline, ribbon-like, irregular fungal hyphae with wide-angle branching, accompanied by tissue necrosis and angioinvasion of the fungi. Tissue invasion by the fungal hyphae as seen by microscopy is essential to establish the diagnosis. Fungal elements can be stained with Gomori methenamine-silver, periodic acid-Schiff or Calcoflour white stain. All Mucorales grow rapidly on most fungal media such as Sabouraud dextrose agar incubated at 25–30 °C. Mucorales from a sterile site or repeated positive cultures of the fungi from a non-sterile site are considered significant in a high-risk patient with predisposing factors for acquisition of zygomycosis. Positive cultures from non-sterile specimens should be interpreted with caution and will require correlation between the finding and the clinical situation. [ABSTRACT FROM AUTHOR]

Summary: Asia, the largest continent in the world, is heterogeneous in the ethnic, socioeconomic, and developmental status of its populations. A vast majority of it is poor with no adequate access to modern health care, making an accurate estimation of the nature and extent of acute kidney injury (AKI) difficult. Community-acquired AKI in otherwise healthy individuals is common, and the population developing AKI is younger compared with its counterparts in Europe or North America. The etiologic spectrum varies in different geographic regions of Asia depending on environmental, cultural, and socioeconomic factors. Some of the etiologic factors include AKI in relation to infectious diseases, intravascular hemolysis caused by glucose 6-phosphate dehydrogenase deficiency, poisonings caused by industrial chemicals or copper sulphate, animal venoms, natural medicines, heat stroke, and after complications of pregnancy. Preventive opportunities are missed because of failure to recognize the risk factors and early signs of AKI. Patients often present late for treatment, leading to multi-organ involvement and increased mortality. The exact etiologic diagnosis cannot be established in many instances because of a lack of appropriate laboratory support. Modern methods of renal replacement therapy are not universally available; and intermittent peritoneal dialysis is still widely practiced in many areas. [Copyright &y& Elsevier]

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Abstract: Background: Cerebral mucormycosis without rhino-orbital or systemic involvement is an extremely rare condition mostly associated with parenteral drug abuse. Case description: We report the case of a 42-year-old woman who presented with hemiparesis of the left side and altered mental status. Neuroradiologic workup demonstrated an inflammatory lesion involving the right basal ganglia. Proton magnetic resonance spectroscopy demonstrated features consistent with a pyogenic abscess. Computed tomography–guided stereotactic biopsy led to the diagnosis of cerebral mucormycosis. Parenteral AMB-L treatment was conducted, but the patient worsened clinically, presenting with a complete hemiplegia, and cerebral magnetic resonance imaging (MRI) scans demonstrated a voluminous abscess formation. Then, under stereotactic guidance, a surgical endoscopic debridement of the abscess cavity associated with the placement of an Ommaya reservoir was performed. Systemic and intralesional treatment with AmB associated with an adjunctive immune therapy was conducted. At 3-year follow-up, the patient had recovered partially from her left hemiplegia, allowing her to walk without help, and cerebral MRI scans showed complete resorption of the abscess. Conclusion: Our good results suggest that surgical endoscopic debridement associated with intravenous and intracavitary antifungal therapy might be valuable in treating voluminous deep-seated mucormycotic lesions. [Copyright &y& Elsevier]

The clinical importance of zygomycosis, an emerging and frequently fatal mycotic disease, has increased during recent years. This report describes an identification method based on PCR amplification and sequencing of the high-affinity iron permease 1 gene ( FTR1). Primers and amplification protocols were established and tested for the identification of Rhizopus oryzae, Rhizopus microsporus var. rhizopodiformis, R. microsporus var. oligosporus, Rhizopus schipperae, Rhizopus niveus and Rhizopus stolonifer. Rhizomucor and Syncephalastrum could be identified at the genus level. PCR–restriction fragment length polymorphism analysis of the amplified gene fragment using AluI digestion distinguished three subgroups among the R. oryzae isolates. [ABSTRACT FROM AUTHOR]