Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.

Evolutionary novelty in gravity sensing through horizontal gene transfer and high-order protein assembly.

Horizontal gene transfer (HGT) can promote evolutionary adaptation by transforming a species' relationship to the environment. In most well-understood cases of HGT, acquired and donor functions appear to remain closely related. Thus, the degree to which HGT can lead to evolutionary novelties remains unclear. Mucorales fungi sense gravity through the sedimentation of vacuolar protein crystals. Here, we identify the octahedral crystal matrix protein (OCTIN). Phylogenetic analysis strongly supports acquisition of octin by HGT from bacteria. A bacterial OCTIN forms high-order periplasmic oligomers, and inter-molecular disulphide bonds are formed by both fungal and bacterial OCTINs, suggesting that they share elements of a conserved assembly mechanism. However, estimated sedimentation velocities preclude a gravity-sensing function for the bacterial structures. Together, our data suggest that HGT from bacteria into the Mucorales allowed a dramatic increase in assembly scale and emergence of the gravity-sensing function. We conclude that HGT can lead to evolutionary novelties that emerge depending on the physiological and cellular context of protein assembly.

Molecular phylogeny, identification and pathogenicity of Rhizopus oryzae associated with root rot of mulberry in India.

AIMS: Root rot caused by a group of fungi is a serious disease in mulberry. This study aims to identify and characterize Rhizopus oryzae and other fungal species associated with root rot of mulberry in India. METHODS AND RESULTS: Rotted root samples were collected from the mulberry gardens from four states of Southern India. The majority of the isolates identified were R. oryzae, and others were saprophytic fungi, less abundant to occasional. Two methods of inoculations were tested to confirm the pathogenicity of the selected isolates and R. oryzae was found to be pathogenic on susceptible mulberry genotypes RC2 and SRDC-1. Multi gene phylogenetic analyses using the internal transcribed spacer region (ITS), actin (ACT) and translation elongation factor 1-α (TEF), identified the isolates as R. oryzae. Additionally, Ovatospora brasiliensis, Amesia nigricolor, Gongronella butleri, Myrmecridium schulzeri, Scedosporium boydii, Graphium euwallacea, Clonostachys rosea andTalaromyces spp. were also identified. CONCLUSION: This study revealed the existence of eleven species of fungi including the first report of R. oryzae and the occurrence of weak pathogens or saprophytes that are associated with the root rot of mulberry in India. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of R. oryzae causing Rhizopus rot of mulberry in India. Moreover, the occurrence of saprophytes associated with root rot of mulberry was identified. Further studies should focus more on the ability of these species to generate secondary metabolites and extracellular lytic enzymes as they are beneficial for the management of root rot disease.

Gongronella eborensis sp. nov., from vineyard soil of Alentejo (Portugal).

This study describes a novel fungal species belonging to the genus Gongronella. During a previous work focusing on metalaxyl degradation by Mucorales strains, two isolates from vineyard soil samples collected in the Alentejo region, south Portugal, were identified as a putative novel species based on combined molecular and MALDI-TOF MS data. This new species is described here using a polyphasic approach that combines morphology, internal transcribed spacer of ribosomal DNA (ITS) and 28S ribosomal DNA (LSU) sequence data analysis and proteomic profiling by MALDI-TOF MS. Phenotypic and molecular data enabled this novel species to be clearly distinguished from other Gongronella species with results of combined ITS+LSU analysis showing that the Gongronella species is related to Gongronella butleri and Gongronella brasiliensis. Therefore, from the results of morphological and molecular analyses, isolates MUM 10.262 and MUM 10.263 seem to represent a new Gongronella species and the name Gongronella eborensis sp. nov. is proposed, with the ex-type strain MUM 10.262 (=CCMI 1100=CBS 128763).

An aero mycological analysis of Mucormycetes in indoor and outdoor environments of northern India.

Mucormycosis is an angio-invasive infection, predominantly acquired by inhalation of sporangiospores from the environment. However, the burden of Mucormycetes sporangiospores in the air is not well studied. We aimed to estimate the burden of Mucormycetes spores in the outdoor and indoor (hospital) environment across different seasons in north India. A total of 380 air samples from outdoor (n = 180) and indoor (n = 200) environment were included in the study. Air samples were suctioned using air sampler (100 l/min) and cultured on Dichloran Rose Bengal Chloramphenicol (DRBC) with benomyl for selective isolation of Mucormycetes. The isolates were identified by phenotypic and genotypic methods. The mean spore count (±SD) of Mucormycetes (cfu/m3) in outdoor samples varied from 0.73 (±0.96) to 8.60 (±5.70) across different seasons. In hospital, the mean spore count varied from 0.68 (±1.07) to 1.12 (±1.07) and 0.88 (±1.01) to 1.72 (±2.17) for air-conditioned wards and non-air-conditioned wards, respectively. Rhizopus arrhizus was the predominant agent isolated from both indoor and outdoor environment followed by Cunninghamella species. We also report a single isolate of the rare mucormycete agent, Apophysomyces variabilis from outdoor environment. The present study highlights the presence of low spore burden of Mucormycetes in outdoor and hospital settings in north India. This study also reports the first isolation of A. variabilis from air samples in the Indian subcontinent.

Mucormycosis due to Apophysomyces species complex- 25 years' experience at a tertiary care hospital in southern India.

Apophysomyces elegans species complex is an important cause of cutaneous mucormycosis in India. However, majority of those cases are reported as case reports only. We desired to analyze our patients with Apophysomyces infection reported over 25 years (1992-2017) to understand the epidemiology, management, and outcome of the disease. During the study period 24 cases were reported, and the majority (95.8%) of them presented with necrotizing fasciitis following accidental/surgical/iatrogenic trauma. One patient presented with continuous ambulatory peritoneal dialysis (CAPD) related peritonitis. Healthcare related Apophysomyces infection was noted in 29.2% patients. In addition to trauma, comorbidities were noted in 37.5% patients (type 2diabetes mellitus-6, chronic alcoholism-2, and chronic kidney disease-1). Of the 24 isolates, 11 isolates starting from year 2014 were identified as Apophysomyces variabilis by molecular methods. Majority (95.8%) of the patients were managed surgically with or without amphotericin B deoxycholate therapy, while one patient was treated with amphotericin B deoxycholate alone. Among 24 patients, seven (29.1%) recovered, six (25%) patients could not afford antifungal management and left the hospital against medical advice, and 11 (45.9%) patients died.The present case series highlights that necrotizing fasciitis caused by A. variabilis is prevalent in India, and the disease may be healthcare related. Although diagnosis is not difficult, awareness among surgeons is still limited about the infection, leading to a delay in sending samples to the mycology laboratory. Apophysomyces infection must be considered in the differential diagnosis in apatient with progressive necrosis of a wound who is not responding to antibacterial therapy.

First Case of Rhinocerebral Mucormycosis Caused by Lichtheimia ornata, with a Review of Lichtheimia Infections.

BACKGROUND: Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents are Lichtheimia corymbifera and L. ramosa, while L. ornata is a novel agent. Available data on a species-specific analysis of Lichtheimia infections are limited. METHODS: The first case of a fatal rhino-orbital-cerebral infection in a hematopoietic stem cell transplantation recipient caused by L. ornata is reported; the agent was identified by sequencing the ITS ribosomal region. We reviewed the literature on mucormycosis due to Lichtheimia species between 2009 and 2018, with an analysis of risk factors and epidemiological and clinical data. RESULTS: In addition to our Lichtheimia ornata case, 44 cases of human Lichtheimia were analyzed. Lichtheimia predominated in Europe (68.2%), followed by Asia (16%), and Africa (9%). The most common underlying condition was hematological malignancy (36.3%), followed by trauma/major surgery (27.3%), while diabetes mellitus was rare (11.4%). Site of infection was mostly skin and soft tissues (45.5%) and lung (25%), while relatively few cases were disseminated (13.6%) or rhinocerebral (11.4%). Mortality (36.4%) was mainly due to disseminated and rhinocerebral infections. CONCLUSION: In contrast to Rhizopus, the most common agent of mucormycosis recorded in patients with diabetes mellitus, Lichtheimia infections were primarily associated with hematological malignancies and major skin barrier damage. Given the fact that classical rhinocerebral mucormycosis remains difficult to treat, independent of causative species, timely application of amphotericin B accessory to debridement may be required for patient survival.

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.

The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains.

Mucormycoses are life-threatening infections that affect patients suffering from immune deficiencies. We performed phagocytosis assays confronting various strains of Lichtheimia species with alveolar macrophages, which form the first line of defence of the innate immune system. To investigate 17 strains from four different continents in a comparative fashion, transmitted light and confocal fluorescence microscopy was applied in combination with automated image analysis. This interdisciplinary approach enabled the objective and quantitative processing of the big volume of image data. Applying machine-learning supported methods, a spontaneous clustering of the strains was revealed in the space of phagocytic measures. This clustering was not driven by measures of fungal morphology but rather by the geographical origin of the fungal strains. Our study illustrates the crucial contribution of machine-learning supported automated image analysis to the qualitative discovery and quantitative comparison of major factors affecting host-pathogen interactions. We found that the phagocytic vulnerability of Lichtheimia species depends on their geographical origin, where strains within each geographic region behaved similarly, but strongly differed amongst the regions. Based on this clustering, we were able to also classify clinical isolates with regard to their potential geographical origin.

Occurrence and species diversity of human-pathogenic Mucorales in commercial food-stuffs purchased in Paris area.

Mucormycoses are life-threatening fungal diseases that affect a variety of patients including those with diabetes mellitus or hematological malignancies. The responsible agents, the Mucorales, are opportunistic pathogens originating from the environment such as soil or decaying organic matter. The aim of the present study was to assess the prevalence and diversity of human-pathogenic species of Mucorales in commercially available foodstuffs in France. All food samples were purchased from January 2014 to May 2015 in France. A total of 159 dried food samples including spices and herbs (n = 68), herbal tea (n = 19), cereals (n = 19), vegetables (n = 14), and other foodstuffs (n = 39) were analyzed. Each strain of Mucorales was identified phenotypically, and molecular identification was performed by ITS sequencing. From the 28 (17.6%) samples that were culture-positive for Mucorales, 30 isolates were recovered. Among the isolates, 13 were identified as Rhizopus arrhizus var. arrhizus, 10 R. arrhizus var. delemar, two Rhizopus microsporus, one Lichtheimia corymbifera, three Lichtheimia ramosa, and one Syncephalastrum racemosum. Culture-positive samples originated from different countries (Europe, Asia) and brands. The samples most frequently contaminated by Mucorales were spices and herbs (19/68, 27.9%), followed by herbal tea (2/19, 10.5%), cereals (2/19, 10.5%), other food products (5/39, 12.8%). The present study showed that human-pathogenic Mucorales were frequently recovered from commercially available foodstuffs in France with a large diversity of species. The potential danger represented by Mucorales present in food for immunocompromised patients should be further analyzed.

A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment.

Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.

The use of genome sequencing to investigate an outbreak of hospital-acquired mucormycosis in transplant patients.

We report three cases of hospital-acquired mucormycosis in heart and lung transplant patients over a 6-month period. Traditional epidemiological investigation tools were used to look for a common link between patients to explain the outbreak. Genome sequencing of each fungal strain was used to supplement the investigation. By disproving a close genetic link between infecting strains of mucormycosis, we were able to conclude the outbreak investigation. Genome sequencing is a novel tool that can be used in addition to traditional epidemiologic investigations to help determine linkage of patients during outbreak investigations.

Mucormycosis-A clinicoepidemiological review of cases over 10 years.

BACKGROUND: Limited data exist for epidemiology and outcomes of various agents causing mucormycosis in various clinical settings from developing countries like India. OBJECTIVES: To study the epidemiology and outcomes of various agents causing mucormycosis in different clinical settings in a tertiary care hospital from South India. PATIENTS AND METHODS: We reviewed details of 184 consecutive patients with culture-proven mucormycosis with consistent clinical syndrome and supporting features from September 2005 to September 2015. RESULTS: The mean age of patients was 50.42 years; 70.97% were male. Unlike developed countries, R microsporus (29/184; 15.7%) and Apophysomyces elegans (20/184; 10.8%) also evolved as important pathogens in addition to R arrhizus in our setting. Paranasal sinuses (136/184; 73.9%) followed by musculoskeletal system (28/184; 15.2%) were the common areas of involvement. Apophysomyces elegans typically produced skin and musculoskeletal disease in immune-competent individuals with trauma (12/20; 60%) and caused significantly lower mortality (P = 0.03). R microsporus was more common in patients with haematological conditions (25% vs 15.7%) and was less frequently a cause for sinusitis than R arrhizus (27.58% vs 10.9%). The overall mortality was 30.97%. Combination therapy with surgery and antifungals offered the best chance for cure. CONCLUSIONS: Agents causing mucormycosis may have unique clinical and epidemiological characteristics.

Invasive mucormycosis in children with cancer: A retrospective study from the Infection Working Group of Italian Pediatric Hematology Oncology Association.

BACKGROUND: Invasive mucormycosis is a rare but frequently fatal fungal disease. The acute and rapidly progressive evolution causes unfavourable outcome in 22%-59% of patients and its treatment represents a clinical challenge, especially in immunocompromised patients. Current data in paediatric oncological patients are limited. OBJECTIVES: The infection Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) analysed the episodes of invasive mucormycosis occurred between 2009 and 2016. PATIENTS: Fifteen cases of proven mucormycosis (male/female 8/7; median age 14.1 years, range 7.7-18.6) were reported after chemotherapy for acute leukaemia and lymphoma (12) and allogeneic stem cell transplantation (3). The aetiology was Rhizopus oryzae 4, Lichtheimia corymbifera 3 and Mucor spp. 8. RESULTS: Paranasal sinus was the primary site of infection in 14/15 patients combined with orbital involvement (9), central nervous system (8), lung (4), thyroid gland and kidney (1). All patients received liposomal Amphotericin B (L-AmB) (3-10 mg/kg), with surgical debridement in 14/15 cases. Eleven patients received maintenance treatment with posaconazole (9) or isavuconazole (2). Eight out of fifteen patients (53.3%) died, after 3-6 months. CONCLUSIONS: Mucormycosis involved mainly the sinu-orbital site and affected children >10 years. Despite aggressive treatment with high-dose L-AmB and timely surgical debridement, the mortality rate remains still high.

Internal transcribed spacer (ITS) sequence-based characterization of fungal isolates from multiple yogurt facilities-A case study.

Fungal spoilage remains a significant issue in dairy product quality, especially for cultured dairy products such as yogurt formulated without preservatives such as potassium sorbate. Fungal contamination can occur throughout the processing continuum, from the dairy farm environment to the finished product processing environment. As molecular characterization of fungal isolates is used more frequently, we obtained fungal isolates obtained in 2 yogurt processing facilities as part of routine fungal testing of raw materials (e.g., fruit preparations, added ingredients), in-process product samples, environmental samples (e.g., air plates, equipment surfaces such as valves, face plates, air nozzles), and finished product samples, to determine whether internal transcribed spacer (ITS) barcoding data would be helpful to support source tracking of fungal contamination issues. Internal transcribed spacer PCR amplification and sequencing allowed us to classify the 852 isolates from these 2 facilities into 200 unique ITS allelic types (AT), representing the phyla Ascomycota (743 isolates), Basidiomycota (97 isolates), and Mucoromycota (12 isolates). Thirty ITS AT were isolated from both facilities; 62 and 108 ITS AT were isolated from only facility A or only facility B, respectively. Nine ITS AT were each represented by more than 20 isolates; these AT comprised 53% of the 852 isolates. The considerable diversity of fungal isolates even within a single facility illustrates the challenge associated with controlling fungal contamination of dairy products. The ITS barcoding technique, however, did show promise for facilitating the source tracking of fungal contamination, particularly for ITS AT over-represented in a given facility. For example, we found evidence for equipment-specific reservoirs for 2 AT (14 and 219) in facility B. Our data suggest that despite its limited discriminatory power, ITS sequencing can provide initial information that can help trace fungal contamination along the processing continuum. However, development and implementation of discriminatory subtyping methods will be needed to further improve the ability to identify sources of fungal contamination in dairy facilities. Developing and implementing sampling plans that comprehensively capture yeast and mold diversity in a given processing facility remain a considerable challenge.

Widespread Lichtheimia Infection in a Patient with Extensive Burns: Opportunities for Novel Antifungal Agents.

The Mucorales fungi-formerly classified as the zygomycetes-are environmentally ubiquitous fungi, but generally rare causes of clinical infections. In the immunocompromised host, however, they can cause invasive, rapidly spreading infections that confer a high risk of morbidity and mortality, often despite surgical and antifungal therapy. Patients with extensive burn injuries are particularly susceptible to skin and soft-tissue infections with these organisms. Here, we present a case of Lichtheimia infection in a patient with extensive full-thickness burns that required significant and repeated surgical debridement successfully treated with isavuconazole and adjunctive topical amphotericin B washes. We also review the available literature on contemporary antifungal treatment for Lichtheimia species and related Mucorales fungi.

Species Identification and Delineation of Pathogenic Mucorales by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

This study aimed to validate the effectiveness of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based identification of filamentous fungi of the order Mucorales. A total of 111 isolates covering six genera preserved at the Research Center for Medical Mycology of Peking University were selected for MALDI-TOF MS analysis. We emphasized the study of 23 strains of Mucor irregularis predominantly isolated from patients in China. We first used the Bruker Filamentous Fungi library (v1.0) to identify all 111 isolates. To increase the identification rate, we created a compensatory in-house database, the Beijing Medical University (BMU) database, using 13 reference strains covering 6 species, including M. irregularis, Mucor hiemalis, Mucor racemosus, Cunninghamella bertholletiae, Cunninghamella phaeospora, and Cunninghamella echinulata All 111 isolates were then identified by MALDI-TOF MS using a combination of the Bruker library and BMU database. MALDI-TOF MS identified 55 (49.5%) and 74 (66.7%) isolates at the species and genus levels, respectively, using the Bruker Filamentous Fungi library v1.0 alone. A combination of the Bruker library and BMU database allowed MALDI-TOF MS to identify 90 (81.1%) and 111 (100%) isolates at the species and genus levels, respectively, with a significantly increased accuracy rate. MALDI-TOF MS poorly identified Mucorales when the Bruker library was used alone due to its lack of some fungal species. In contrast, this technique perfectly identified M. irregularis after main spectrum profiles (MSPs) of relevant reference strains were added to the Bruker library. With an expanded Bruker library, MALDI-TOF MS is an effective tool for the identification of pathogenic Mucorales.

Occurrence and species distribution of pathogenic Mucorales in unselected soil samples from France.

Mucormycosis is a life-threatening invasive fungal disease that affects a variety of patient groups. Although Mucorales are mostly opportunistic pathogens originating from soil or decaying vegetation, there are currently few data on prevalence of this group of fungi in the environment. The aim of the present study was to assess the prevalence and diversity of species of Mucorales from soil samples collected in France. Two grams of soil were homogenized in sterile saline and plated on Sabouraud dextrose agar and RPMI agar supplemented with itraconazole or voriconazole. Both media contained chloramphenicol and gentamicin. The plates were incubated at 35 ± 2 °C and checked daily for fungal growth for a maximum of 7 d. Mucorales were subcultured for purity. Each isolate was identified phenotypically and molecular identification was performed by ITS sequencing. A total of 170 soil samples were analyzed. Forty-one isolates of Mucorales were retrieved from 38 culture-positive samples. Among the recovered isolates, 27 Rhizopus arrhizus, 11 Mucor circinelloides, one Lichtheimia corymbifera, one Rhizopus microsporus and one Cunninghamella bertholletiae were found. Positive soil samples came from cultivated fields but also from other types of soil such as flower beds. Mucorales were retrieved from samples obtained in different geographical regions of France. Voriconazole-containing medium improved the recovery of Mucorales compared with other media. The present study showed that pathogenic Mucorales are frequently recovered from soil samples in France. Species diversity should be further analyzed on a larger number of soil samples from different geographic areas in France and in other countries.

Diabetes mellitus as the major risk factor for mucormycosis in Mexico: Epidemiology, diagnosis, and outcomes of reported cases.

Mucormycosis is an emerging infectious disease with high rates of associated mortality and morbidity. Little is known about the characteristics of mucormycosis or entomophthoromycosis occurring in Mexico. A search strategy was performed of literature published in journals found in available databases and theses published online at Universidad Nacional Autónoma de México (UNAM) library website reporting clinical cases or clinical case series of mucormycosis and entomophthoromycosis occurring in Mexico between 1982 and 2016. Among the 418 cases identified, 72% were diabetic patients, and sinusitis accounted for 75% of the reported cases. Diabetes mellitus was not a risk factor for entomophthoromycosis. Mortality rate was 51% (125/244). Rhizopus species were the most frequent isolates (59%, 148/250). Amphotericin B deoxycholate was used in 89% of cases (204/227), while surgery and antifungal management as combined treatment was used in 90% (172/191). In diabetic individuals, this combined treatment approach was associated with a higher probability of survival (95% vs 66%, OR = 0.1, 95% CI, 0.02-0.43' P = .002). The most common complications were associated with nephrotoxicity and prolonged hospitalization due to IV antifungal therapy. An algorithm is proposed to establish an early diagnosis of rhino-orbital cerebral (ROC) mucormycosis based on standardized identification of warning signs and symptoms and performing an early direct microbiological exam and histopathological identification through a multidisciplinary medical and surgical team. In summary, diabetes mellitus was the most common risk factor for mucormycosis in Mexico; combined antifungal therapy and surgery in ROC mucormycosis significantly improved survival.

Gastrointestinal mucormycosis in apparently immunocompetent hosts-A review.

The diagnosis of gastrointestinal (GI) mucormycosis is always a challenge due to its non-specific clinical presentations and often diagnosed at autopsy. Recently increased number of GI mucormycosis has been reported in immunocompetent hosts and during 1948 through 2017, 200 cases of GI mucormycosis are available in literature. We could review 176 cases where case details were available. Majority (50.6%) of the cases were reported from Asia. The disease is nearly equally recorded in adults and paediatric population. The infection commonly affected the intestine (64.2%) followed by stomach (33%). A significant improvement in antemortem diagnosis was noted since 2001. Rhizopus species were the predominant (67.5%) aetiological agents. Amphotericin B was the most commonly used drug (93.4%). Despite improvement of antemortem diagnosis and therapy, the mortality was 60.5% and 67.5% in adults and children respectively. Combined medical and surgical therapy (reported in 47.8% patients) had significantly better survival rate than those receiving either of them. Analysing the clinical presentations, we propose to suspect GI mucormycosis in a malnourished/ dehydrated child (especially premature neonate) with history of exposure to broad-spectrum antibiotics or formula/spoon feeding and presenting with mass in abdomen, abdominal distension or bilious vomiting; and an adult presenting with abdominal distension, fever or GI bleed with underlying risk factors for mucormycosis.