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Rhino-orbital infection caused by Syncephalastrum racemosum in a 64-year-old woman with relapsed acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation (unpublished case). (a and b) Nasal endoscopy showing hemorrhagic and necrotic lesions with white cottony growth. (c) Contrast-enhanced CT scan demonstrating ethmoid sinusitis. (d) Lactophenol cotton blue mount preparation showing cylindrical or finger-like projections (arrow) surrounding a swollen vesicle typical of merosporangia of S. racemosum . (Courtesy of George M. Viola, reproduced with permission.) 

Rhino-orbital infection caused by Syncephalastrum racemosum in a 64-year-old woman with relapsed acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation (unpublished case). (a and b) Nasal endoscopy showing hemorrhagic and necrotic lesions with white cottony growth. (c) Contrast-enhanced CT scan demonstrating ethmoid sinusitis. (d) Lactophenol cotton blue mount preparation showing cylindrical or finger-like projections (arrow) surrounding a swollen vesicle typical of merosporangia of S. racemosum . (Courtesy of George M. Viola, reproduced with permission.) 

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Rhizopus, Mucor, and Lichtheimia (formerly Absidia) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all cases. In contrast, Cunninghamella, Apophysomyces, Saksenaea, Rhizomucor, Cokeromyces, Actinomucor, and Syncephalastrum species individually are responsible for fewer than 1 to 5% of...

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... As with treatment of other Mucormycetes infections, its significant nephrotoxicity often limits its duration and dosage when administered for severe infections (319, 334). Information on the efficacy of posaconazole in treating these infections is scant. Posaconazole has been used as an alternative to AmB in treatment of S. vasiformis infections because of the toxicity of AmB (319, 334) or in combination with other antifungals (Table 4) (162). Posaconazole’s safety profile for children under the age of 13 years is limited (174, 334). Prognosis. Not surprisingly, underlying immunosuppression is associated with poor prognosis for S. vasiformis infections. About one-third (6/17 patients [35%]) of patients who died of this infection in reported studies were immunocompromised (48, 58, 90, 104, 107, 113, 329), whereas only 12% (3/25 patients) of those who survived had underlying immunocompromised conditions (29, 37, 326). Except for one patient who had renal involvement that required bilateral nephrectomy (1) and another who had osteomyelitis that required amputation, all patients with nonlocalized soft tissue infections (disseminated or rhinocerebral) caused by S. vasiformis described thus far died of their infections (27, 48, 104, 113, 127, 150, 316, 329). Taxonomy and reported cases. S. racemosum is considered the only pathogenic species of the genus Syncephalastrum , although three additional taxa have been described (http: //Zygomycetes.org/index.php?id ϭ 49). Until recently, it has been debated whether this fungus is a true pathogen (301) or merely a contaminant or transient colonizer of the human upper respiratory tract (272, 279). The first documented Syncephalastrum infection was described as a cutaneous infection that progressed to arteritis in the dermal vessels and contiguous osteomyelitis in a 50-year-old diabetic man who worked in a tea plantation in India, where Syncephalastrum spp. had been found in soil (147). The ability of Syncephalastrum species to cause ear infections and mycotic keratitis and isolation of these organisms in wound culture are not clear, as reports have not provided details about such cases (238, 324, 345). Also, re- searchers identified a cluster of eight patients with clinical specimens yielding Syncephalastrum isolates after natural di- sasters (272). All of these patients appeared to have transient colonization of Syncephalastrum spp. without evidence of infection, even those who were immunosuppressed (272). S. racemosum caused onychomycosis in a 45-year-old man who had injured the nail 7 months before (256) and intra-abdominal infection with a large abdominal wound in a previously healthy 23-year-old man who fell and was impaled on a steel reinforced rod (301). Additionally, two otherwise healthy boys in India were reported to have proven or probable chronic subcutaneous S. racemosum infections related to trauma that occurred while they were playing in their gardens (Table 2) (271). Epidemiology. S. racemosum is widely distributed in the environment (2, 138, 233, 269, 279, 301). It can be found in both tropical and subtropical areas, particularly at sites rich in decaying organic matter (279). Syncephalastrum spp. have been isolated from outdoor air samples collected in Nigeria (233), indoor air samples collected in Austria (269) and England (228), and both outdoor and indoor air samples collected in the United States (273, 310). Like the case for Cunninghamella spp., regional and climatic factors have influenced the detection of Syncephalastrum species from air (310), and probably the risk of exposure to them. Syncephalastrum spp. were the only thermotolerant Mucormycetes detected in 47% of indoor air samples from heavily damaged houses and in none of the mildly damaged houses in the flooded areas of New Orleans after Hurricanes Katrina and Rita (272, 273). Workers in farm operations, particularly those who handle, harvest, and process food and feed after harvest, may be particularly predisposed to exposure to airborne S. racemosum (2). Specifically, S. racemosum was detected in sorghum dust and wheat hay sites at low frequencies (2) and in water of swimming pools (202) in Egypt and soil in India (147). It was also isolated from settled dust samples in houses free of water damage in the United States (138). Low levels of S. racemosum were isolated from air in a bone marrow transplant unit in Austria over a 6-month period (269). The low degree of fungal air contamination may be more important for the risk of infection in profoundly immunocompromised patients than in otherwise healthy individuals (280). Despite the ubiquitous airborne characteristics of S. racemosum , percutaneous inoculation after trauma has been the only likely mode of infection in proven and probable reported cases of infection with this species (256, 271, 301). This suggests low pathogenicity of this fungus or erroneous interpretation of its isolation (considered a contaminant) or no report of cases. Figure 5 shows an unpublished case of rhino-orbital S. racemosum infection in a 64-year-old woman with relapsed ALL after allogeneic hematopoietic stem cell transplantation. This patient recovered with extensive debridement, L-AmB treatment, granulocyte transfusions, and G-CSF. Pathogenesis and clinical presentation. Although Syncephalastrum appears to have low pathogenicity (279), it has been shown to colonize immunocompetent individuals after heavy exposure to mold and immunocompromised individuals with minimal or no history of mold exposure after hurricanes (272). Specifically, S. racemosum causes chronic infections (a few months to 3 years) following minor trauma (256, 271) and acute infection when inoculated after major trauma (301) in immunocompetent hosts. Eight days after surgical repair of several visceral lacerations caused by trauma, splenectomy, and the use of temporary mesh interposed in the abdominal wall, the abdomen of a previously healthy 23-year-old man became distended and affected with necrotic skin (301). Later, S. racemosum was found to have invaded the abdominal wall, intra-abdominal fluids, and omen- tal and retroperitoneal tissues (301). Histopathological stains of normal tissue sections also showed invasion of this organism (301). Diagnosis. In culture, S. racemosum grows rapidly, and sporulation occurs readily on routine media at room temperature and temperatures above 37°C (279, 301). Regarding identification of S. racemosum , confusion with members of the genus Aspergillus , especially Aspergillus niger , is common (279). Specifically, fruiting bodies of S. racemosum and A. niger appear to be similar in direct KOH mounts, but the hyphal morphology (aseptate, ribbon-like mycelium) and merosporangial sack surrounding sporangiospores in Syncephalastrum cultures are cru- cial for distinguishing the two fungi (Fig. 3) (279). No molecular biology methods have been used for the diagnosis of Syncephalastrum species infections in reported cases (147, 256, 271, 272, 301), although a method based on PCR amplification and sequencing of the high-affinity iron permease 1 gene ( FTR1 ) has been used for identification of the genus Syncephalastrum (229). Management. Documented S. racemosum infection has been treated successfully using wide debridement of necrotic tissue in the abdominal wall, omentum, and retroperitoneum and with AmB lipid complex for 29 days, including 19 days after the last debridement and 15 days after the last identification of a specimen positive for S. racemosum (301). Repeated debridement may be necessary to remove necrotic tissue, and the duration of antifungal therapy depends on the clinical response of the infection (166, 301). The onychomycosis case responded to surgical extirpation and nystatin ointment applied twice daily (b.i.d.) to the exposed nail bed for 2 weeks (256). Chronic subcutaneous cases of S. racemosum infection have been treated with topical potassium iodide, and in one case, this was administered in combination with itraconazole (271). MICs of AmB (four strains), itraconazole (three strains), and nystatin (three strains) have been relatively low ( Յ 1 ␮ g/ ml) for S. racemosum (101, 238, 312). Resistance to azoles (posaconazole was not tested), except for itraconazole (three isolates) (238, 279, 312), as well as to caspofungin (two isolates), ciclopiroxolamine (two isolates), amorolfine (two isolates), and naftifine (one isolate) (238, 312), has been reported. The combination of posaconazole and AmB was indifferent to both conidia and hyphae of two clinical S. racemosum isolates in testing using a checkerboard method (258). Taxonomy and reported cases. C. recurvatus is a dimorphic Mucormycetes organism of the order Mucorales and family Thamnidiaceae that has been isolated only in North America (23, 293, 309), where it can be found in soils and the feces of lizards, certain rodents (23, 226, 279, 293), and occasionally humans (151, 284, 293). C. recurvatus has been recovered from peritoneal fluid after viscus perforation secondary to intestinal lymphosarcoma in a cat (226). Only eight cases of human C. recurvatus infection (293), probable (23, 270) or possible (15, 210, 219, 335) disease, or colonization (151, 284) have been reported in the literature. The species was first isolated by Shanor et al. (309) in 1950. This fungus has been isolated from vaginal secretions (151, 210, 284), stool (15, 335), urine (23), sputum (293), pleural and peritoneal fluids (219), and fluid from intra-abdominal abscesses (270). Also, yeast-like cells were observed in secretions from six of the patients with possible or probable infection or colonization (15, 23, 151, 270, 284, 335) and from tissue sections in three cases (15, 293, 335). However, histological evidence of C. recurvatus infection with invasion of lung tissue by yeast-like cells and pseudohyphae has been described in only one case (293). One possible case of a C. recurvatus infection was in a 14- ...

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... Mucorales species are usually saprophytic but a considerable number are found to cause severe infections commonly termed as mucormycosis. Earlier the term zygomycosis was commonly used [1][2][3]. The disease commonly affects patients with diabetes mellitus, organ or haematopoietic stem cell transplantation, blood disorders such as neutropenia or malignancy [4,5]. ...
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... More recently, Dimitrios has authored a number of useful reviews on more unusual presentations of mucormycosis, including breakthrough infections in patients with hematological malignancies and hyperglycemia [29], osteoarticular infections [30,31], gastrointestinal infections [32], CNS infections [33,34], infection risk after hurricanes and flooding [35], healthcare-associated mucormycosis [36], cutaneous mucormycosis associated with insect bites [37], combat injuries and trauma [38], infections caused by unusual Mucorales [39], and reviews of mucormycosis infections associated with the COVID-19 pandemic [40][41][42]. ...
... Numerous taxa, including Mucor, Rhizopus, Lichtheimia (formerly Absidia), Rhizomucor, Cunninghamella, Apophysomyces, and Saksenaea, are members of the order Mucorales. Mucor, Lichtheimia, and Rhizopus are the three genera most commonly associated with Mucormycosis 16 . Other genera are typically less prevalent. ...
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... Worldwide, the majority of infections is attributed to the genera Rhizopus, Lichtheimia and Mucor ( Figure 1A). Depending on geography and/or underlying disease, the species distribution varies and other genera such as Apophysomyces, Saksenaeaboth often associated with cutaneous mucormycosis (Al-Zaydani et al., 2015;Sigera et al., 2018;Chander et al., 2021;Gupta et al., 2022;Planegger et al., 2022) -Cunninghamella or Rhizomucor are reported (Gomes et al., 2011;Raju et al., 2020;Hallur et al., 2021;Schober et al., 2021). Mucorales are ubiquitously found in the environment and share common features like the coenocytic thallus and a cell wall containing chitosan. ...
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... These are generally seen as clinical contaminants with a low pathogenicity and are rarely known to cause human diseases [5,6]. However, in recent years, case reports of human infections due to the Syncephalastrum genus have increased significantly, especially in immunocompromised hosts with diabetes [7,8], chronic hepatorenal disease [9], corneal infections, or those who have been the recipients of organ transplantations [4,10]. These human infections are usually related to the skin, nails, lungs, and central nervous system [11] and can have fatal outcomes, resulting in highly invasive diseases [12,13]. ...
... All the strains did not grow ≥40 °C. In contrast to our observations, some authors have described S. racemosum and S. monosporum as hydrophilic and thermotolerant moulds [12] or have declared that Syncephalastrum species were able to grow above 40 °C [6,10]. ...
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... Co morbidities like COPD, diabetes and factors like prolonged ventilation, Corticosteroid therapy, and ICU stays without proper infection control measures can predispose to IFI. Among Mucorales Rhizopus spp., Cunninghamella spp., Saksenaena vasiformis etc. Have higher angio-invasiveness and can lead to disseminated fungal infections as compared to other species which are mainly observed in immunocompromised and neutropenic patients [6,7]. Invasive Zygomycete infections manifest as multiple cutaneous lesions, intracranial lesions, and pulmonary, or bloodstream infections because of the rapid progression of infection with angio-invasion, early prompt diagnosis and timely initiation of treatment are critical in these cases, which help in bringing down the mortality and complications associated with the disease. ...
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... All Mucorales fungi were detected, including the most common causes of mucoromycosis worldwide, namely Lichtheimia spp., Mucor circinelloides, Rhizopus arrhizus, and Rhizopus microsporus var. rhizopodiformis (Roden et al., 2005;Gomes et al., 2011;Skiada et al., 2011;Laternier et al., 2012;Zaki et al., 2014;Prakash and Chakrabarti, 2019;Skiada et al., 2020;Radotra and Challa, 2022;Özbek et al., 2023;Pham et al., 2023;Yang et al., 2023), and also rarer, emerging, or more regionally-prevalent causes of the disease (Gomes et al., 2011;Skiada et al., 2020) including Actinomucor (Tully et al., 2009), Apophysomyces (Chander et al., 2015), Cunninghamella (Mita et al., 2022), other Mucor spp. (Deja et al., 2006;Álvarez et al., 2011;Lu et al., 2013;Chander et al., 2018), Rhizomucor (Chander et al., 2018;Schober et al., 2021), other Rhizopus spp. ...
... All Mucorales fungi were detected, including the most common causes of mucoromycosis worldwide, namely Lichtheimia spp., Mucor circinelloides, Rhizopus arrhizus, and Rhizopus microsporus var. rhizopodiformis (Roden et al., 2005;Gomes et al., 2011;Skiada et al., 2011;Laternier et al., 2012;Zaki et al., 2014;Prakash and Chakrabarti, 2019;Skiada et al., 2020;Radotra and Challa, 2022;Özbek et al., 2023;Pham et al., 2023;Yang et al., 2023), and also rarer, emerging, or more regionally-prevalent causes of the disease (Gomes et al., 2011;Skiada et al., 2020) including Actinomucor (Tully et al., 2009), Apophysomyces (Chander et al., 2015), Cunninghamella (Mita et al., 2022), other Mucor spp. (Deja et al., 2006;Álvarez et al., 2011;Lu et al., 2013;Chander et al., 2018), Rhizomucor (Chander et al., 2018;Schober et al., 2021), other Rhizopus spp. ...
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Mucoromycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. While Rhizopus arrhizus is the principal agent of mucoromycosis, other Mucorales fungi including Apophysomyces, Cunninghamella, Lichtheimia, Mucor, Rhizomucor and Syncephalastrum are able to cause life-threatening rhino-orbital-cerebral, pulmonary, gastro-intestinal and necrotising cutaneous infections in humans. Diagnosis of the disease currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Mucorales-specific biomarkers of infection, and which allow point-of-care diagnosis of mucoromycosis. Here, we report the development of an IgG2b monoclonal antibody (mAb), TG11, which binds to extracellular polysaccharide (EPS) antigens of between 20 kDa and 250 kDa secreted during hyphal growth of Mucorales fungi. The mAb is Mucorales-specific and does not cross-react with other yeasts and molds of clinical importance including Aspergillus, Candida, Cryptococcus, Fusarium, Lomentospora and Scedosporium species. Using the mAb, we have developed a Competitive lateral-flow device that allows rapid (30 min) detection of the EPS biomarker in human serum and bronchoalveolar lavage (BAL), with a limit of detection (LOD) in human serum of ~100 ng/mL serum (~224.7 pmol/L serum). The LFD therefore provides a potential novel opportunity for detection of mucoromycosis caused by different Mucorales species.
... Though mucormycosis cases caused by Apophysomyces spp. have a global distribution, the highest incidence rates have been reported in the Southern United States and India [24,25]. Reportedly, India contributes to ∼60% of the global cases of Apophysomyces infections [5]. ...
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Mucormycosis is a severe and potentially life-threatening infection caused by a group of fungi classified as mucormycetes within the scientific order Mucorales. These infections are characterized by rapid and invasive fungal growth, presenting significant treatment challenges. Here we present five cases encountered from 2018 to 2022 at the University of Texas Medical Branch in Galveston, TX, including a novel Apophysomyces species, illustrating the diverse clinical manifestations of mucormycosis, including pulmonary, rhino-cerebral, gastrointestinal, and soft tissue involvement. Our investigation incorporates information provided by a multidisciplinary team of clinical collaborators, emphasizing the findings from radiology, histopathology, and microbiology. Given the escalating global incidence of mucormycosis, it is crucial for clinicians to become familiar with associated clinical findings, comorbidities, and risk factors, to facilitate prompt recognition, appropriate diagnostic testing, and timely initiation of treatment.
... Mucormycosis is a deep invasive mycotic infection caused by a group of molds referred to as mucormycetes, the most common being Rhizopus species. 1 While the infection was already more prevalent in India as compared to the Western countries, its incidence increased markedly in the wake of the COVID-19 pandemic. The disease served to 'add fuel to the fire' for patients suffering from already infected by the SARS-CoV-2 virus. ...
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Mucormycosis is a deep invasive mycotic infection caused by a group of molds referred to as mucormycetes. The incidence of mucormycosis increased markedly in the wake of the COVID-19 pandemic. The disease can be fatal in a very high percentage of individuals and in others, its effects can drastically affect the quality of life. The prognosis depends on the early diagnosis and treatment in which dental professionals play a major role, particularly in cases of rhinomaxillary mucormycosis. The present report describes the prosthetic management of a case of rhinomaxillary mucormycosis for functional restoration.