Mucormycosis In Patient Research Articles

1172. Mucormycosis Treated with Isavuconazole: A matched-Pair Analysis from the FungiScope® Registry

BackgroundIsavuconazole (ISAV) is a novel, broad-spectrum triazole antifungal, available in both intravenous and oral formulations, for the treatment of adult patients with invasive aspergillosis or mucormycosis. In this retrospective case collection study, we compared outcomes for patients with invasive mucormycosis treated with ISAV versus other systemic antifungal therapies, in order to evaluate the real-world effectiveness of ISAV.MethodsProven and probable invasive mucormycosis cases treated with ISAV for a minimum of four consecutive days between 2016 and 2019 were identified from the FungiScope® registry. Matched controls were defined as patients treated with lipid formulations of amphotericin B (lipid-AMB), posaconazole, or a combination of both, as first-line therapy between 2011 and 2019. Case-matching criteria included disease severity, presence of hematological malignancy or allogeneic stem cell transplantation, and surgery for fungal disease. Baseline patient characteristics and clinical outcomes were compared descriptively.ResultsEach of 30 ISAV cases was matched to 1–3 controls, including 25 ISAV cases each matched to 2 or 3 controls, which resulted in a total of 69 control cases. In 70.0% of ISAV cases (n=21), ISAV was administered as a treatment for invasive mucormycosis in patients who had received prior lipid-AMB. In the remaining cases, ISAV was administered after prior voriconazole treatment (n=3) or as first-line therapy (n=6). All control patients received either lipid-AMB, posaconazole, or a combination of both.Baseline demographic and clinical characteristics and causative pathogens were similar between ISAV cases and controls (Table). Overall response rates (defined as achieving a complete or partial response) at the final assessment were 50.0% (15/30) for ISAV cases and 50.7% (35/69) for controls. All-cause mortality was 43.3% (13/30) in ISAV cases as compared to 46.4% (32/69) in controls (Figure).Table. Demographic and clinical characteristics of 30 isavuconazole cases and 69 control cases Figure. Clinical response at final assessment and all cause mortality for 30 isavuconazole cases and 69 control cases ConclusionIn this retrospective analysis of cases from the FungiScope® registry, patients with invasive mucormycosis showed similar overall treatment response and all-cause mortality rates with ISAV compared to treatment with lipid-AMB and/or posaconazole. These data support the effectiveness of isavuconazole in clinical practice.Disclosures Danila Seidel, PhD, Basilea (Other Financial or Material Support, travel grant) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Philipp Koehler, MD, Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker’s Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker’s Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees) Nikolay Klimko, n/a, Astellas (Speaker’s Bureau)Gilead (Speaker’s Bureau)Merck/MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Farima Barmaki-Rad, n/a, Basilea Pharmaceutica International Ltd. (Employee) Mikael Saulay, n/a, Basilea Pharmaceutica International Ltd. (Employee) Marc Engelhardt, n/a, Basilea Pharmaceutica International Ltd. (Board Member, Consultant, Employee, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Shareholder, Speaker’s Bureau, Independent Contractor, Other Financial or Material Support)Basilea Pharmaceutica International Ltd. (Employee) Kamal Hamed, n/a, Basilea Pharmaceutica International Ltd. (Employee)

Mucormycosis with cutaneous involvement. A retrospective study of 115 cases at a tertiary care hospital in Mexico.

Cutaneous mucormycosis is an emerging opportunistic mycosis caused by Mucorales. It can be divided into primary caused by trauma and secondary by extension of rhino-cerebral and disseminated cases. The objective is to present a retrospective study of cases of mucormycosis with cutaneous involvement. A retrospective and descriptive study was carried out. Mucormycosis patients were included and divided into two groups: a) Primary Cutaneous and b) Secondary Cutaneous. Mycological tests were performed; the agents were identified by morphology and molecular studies (PCR and sequencing); some cases underwent histopathology. Clinical data and response to treatment were collected. 115 cases were included, 18 of primary, and 97 of secondary cutaneous mucormycosis. Primary cutaneous mucormycosis was most associated with adhesive bands (44.4%) and trauma from traffic accidents (33.3%). The principal clinical form was extensive and deep necrotic ulcers. Secondary cutaneous mucormycosis cases were rhino-cerebral with uncontrolled diabetes (81.4%) The most frequent clinical presentation was necrosis of the eyelid and the nose (65.9%). In both groups, the principal agent was Rhizopus arrhizus, 38.8% and 74.2% respectively. The most effective treatment was the combination of amphotericin B with surgical debridement. The clinical and mycological cure was achieved in 31.0% of primary cases, and 44.4% for secondary cases. Primary cutaneous mucormycosis is caused by implantation of the Mucorales due to trauma or rupture of the cutaneous barrier-breach, and secondary cutaneous mucormycosis develops as part of the rhino-cerebral process. The response to treatment depends on the extension and depth, as well as the predisposing factors.

Detection of Rhizopus-specific antigen in human and murine serum and bronchoalveolar lavage.

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1ng/ml) than that in invasive pulmonary aspergillosis patients (0.53ng/ml) and the negative control (0.49ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.

Rhino-orbito-cerebral mucormycosis in patients with uncontrolled diabetes: A case series

IntroductionMucormycosis 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. Presentation of caseWe 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. DiscussionDiagnosing 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. ConclusionWe describe our experience in handling three cases of poorly controlled diabetes with rhino-orbito-cerebral mucormycosis.

The clinical pattern of orbital mucormycosis in a tertiary eye care hospital

This study aimed to report the clinical profile of patients with rhino-orbital mucormycosis at a tertiary eye care center in Tamil Nadu. This was a single-center, retrospective case series of patients who were diagnosed as rhino-orbital mucormycosis between January and December 2018. The study included nine patients of rhino-orbital mucormycosis with a mean age of 53.33 ± 8.3 years (range: 35–61 years), comprising five males and four females. All the cases were unilateral in presentation. Uncontrolled diabetes mellitus was the most common underlying predisposing factor. Four patients presented with proptosis, two patients complained of headache, and five patients had defective vision. Computed tomography scan showed pansinusitis in six patients. Total ophthalmoplegia was noted in four patients. All patients received parenteral therapy with amphotericin B. Rhino-orbital mucormycosis is a rare, life-threatening, and insidious fungal infection. Uncontrolled diabetes mellitus and immunosuppression are the most important risk factors. The orbital findings may range from orbital pain to ophthalmoplegia and blindness. We present this case series to emphasize the importance of early diagnosis and treatment of rhino-orbital mucormycosis.

Pulmonary mucormycosis in a patient with acute liver failure: A case report and systematic review of the literature

PurposePulmonary mucormycosis is a highly lethal invasive fungal infection usually found in immunocompromised patients. We report herein the case of an adult woman who developed pulmonary mucormycosis with possible systemic dissemination after recovering from acute liver failure secondary to acetaminophen overdose. ResultsOur case developed an invasive pulmonary mucormycosis with probable systemic dissemination. She did not suffer from any immunocompromising disease other than severe acute liver failure. She did not survive the disease, although she received appropriate antifungal treatment. We also performed a systematic review of the literature on pulmonary mucormycosis, with or without dissemination, in immunocompetent patients. We found 16 cases of pulmonary or disseminated mucormycosis in immunocompetent patients. Fifty-seven percent of them died and none occurred after an acute liver failure episode. ConclusionThis case report is the first one to present an invasive pulmonary mucormycosis infection after acute liver failure in an adult patient. The clinical course of this disease is highly lethal, even in immunocompetent adults.

Clinical features of pulmonary mucormycosis in patients with different immune status.

Pulmonary mucormycosis (PM) is a relatively rare but often fatal and rapidly progressive disease. Most studies of PM are case reports or case series with limited numbers of patients, and focus on immunocompromised patients. We investigated the clinical manifestations, imaging features, treatment, and outcomes of patients with PM with a focus on the difference in clinical manifestations between patients with different immune status. Clinical records, laboratory results, and computed tomography scans of 24 patients with proven or probable PM from January 2005 to December 2018 in Peking Union Medical College Hospital were retrospectively analyzed. Ten female and 14 male patients were included (median age, 43.5 years; range, 13-64 years). Common presenting symptoms were fever (70.8%), cough (70.8%), sputum production (54.2%), and hemoptysis (41.7%). Radiological findings included consolidation (83.3%), ground-glass opacities (58.3%), nodules (50.0%), masses (37.5%), cavities (33.3%), mediastinal lymphadenopathy (29.2%), and halo sign (12.5%); one patient had a reversed halo sign. Seven patients (29.2%) had no obvious predisposing risk factors, and 17 (70.8%) had underlying diseases including diabetes, hematological malignancy, and use of immunosuppressants. Compared with immunocompromised patients, immunocompetent patients with PM were younger {23 [13-46] vs. 48 [17-64] years, P=0.023}, comprised a higher proportion of men (100.0% vs. 41.2%, P=0.019), had a longer disease course {34 [8-47] vs. 9 [2-102] weeks, P=0.033}, had a higher eosinophil count [0.66 (0.07-2.00) ×109/L vs. 0.04 (0.00-0.23) ×109/L, P=0.001], and had a lower erythrocyte sedimentation rate {12 [1-88] vs. 74 [9-140] mm/h, P=0.032}. PM can occur in heterogeneous patients with different immune status, and the clinical phenotype differs between immunocompetent and immunocompromised patients. Because of the lack of specific clinic and imaging manifestations, aggressive performance of invasive procedures to obtain histopathological and microbial evidence is crucial for a definitive diagnosis.

Mucormycosis in patients with hematological diseases: seven cases reports and literature review

目的探讨血液病合并毛霉菌病患者的临床特征、诊治与转归，提高对该病的认识。方法回顾性分析2012年9月至2018年9月7例血液病合并毛霉菌病患者的临床资料，分析其临床特征、治疗过程和转归。结果7例血液病合并毛霉菌病患者中，男4例，女3例，中位年龄36（19~79）岁。基础疾病：急性髓系白血病2例，急性B淋巴细胞白血病、外周T细胞淋巴瘤、慢性髓性白血病急髓变、骨髓增殖性肿瘤及重型再生障碍性贫血（移植后）各1例。毛霉菌病临床类型：4例为肺型，1例为鼻眶脑型，1例为皮肤型，1例为播散型。7例患者均通过活检组织病理确诊。治疗药物为两性霉素B、两性霉素B脂质体及泊沙康唑。手术治疗4例，其中3例术中彻底清除病变组织，1例仅行局限性清除。治愈2例，好转1例，死亡4例。结论血液病合并毛霉菌病患者临床表现及影像学表现多样，死亡率高，确诊主要依赖于组织病理学。早期诊断、控制基础疾病、改善免疫抑制状态、尽早行有效的抗真菌药物治疗及彻底的手术清创治疗是提高血液病合并毛霉菌病患者生存率的关键。

2465. Healthcare-Associated Pediatric Cutaneous Mucormycosis at Texas Children’s Hospital, 2012–2019

BackgroundCutaneous mucormycosis in children is a rare fungal infection which primarily occurs in patients with underlying medical conditions and is associated with significant morbidity. We describe characteristics of pediatric patients with healthcare-associated (HCA) cutaneous mucormycosis at Texas Children’s Hospital (TCH) and results of an outbreak investigation.MethodsPatients at TCH were identified retrospectively through review of the TCH Microbiology Laboratory mycology culture reports from 1/1/2012–2/18/2019. Pediatric patients <21 years of age with cutaneous mucormycosis that developed during a hospitalization or was associated with a medical device were included. Demographic information was collected through review of the electronic medical record. Randomly amplified polymorphic DNA (RAPD) analysis were performed by the Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio. This study was approved through the Baylor College of Medicine Institutional Review Board.ResultsWe identified 12 patients with HCA cutaneous mucormycosis. The characteristics of these patients are detailed in the table. Six cases of Rhizopus infection occurred over a narrow 7 month period from March through September of 2017 prompting an outbreak investigation. Genotyping results revealed 4 molecular types from 5 available isolates suggesting that the isolates were not clonally related. Adhesive products were suspected as a potential source. Infection Control activities included site visits to the hospital supply warehouse and linen facility. Tape practices throughout the hospital were assessed through a nursing survey. Samples of adhesive products were cultured at an environmental microbiology laboratory and no Rhizopus spp. were isolated. A source was not identified.ConclusionMucormycosis is a life-threatening infection in children. Providers should have a low threshold of suspicion for cutaneous mucormycosis in patients with underlying medical conditions (malignancies and extreme prematurity) that develop skin lesions near medical device dressings or securement sites. Disclosures All authors: No reported disclosures.

LUNG MASS: PULMONARY MUCORMYCOSIS IN AN IMMUNOCOMPETENT ADULT DIABETIC

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Mucormycosis is an invasive fungal infection for which the most common manifestation is rhino-orbital-cerebral infection, seen as the presenting feature of diabetes in one fourth of patients.Pulmonary infection is the most common form of mucormycosis in patients with hematologic malignancies and remains the second most common presentation after rhinocerebral infection in diabetics.Upon literature review, there are very few cases reported of isolated pulmonary mucormycosis in a diabetic but otherwise immunocompetent. Here, we present a case of pulmonary mucormycosis in a diabetic without any rhino-orbital involvement or immunocompromise. CASE PRESENTATION: A 76-year-old female with multiple medical comorbidities including diabetes presented for intermittent cough with yellow sputum production, dyspnea, and eight pound unintentional weight loss in six months.She denied any hemoptysis, fevers, chills, recent travel or sick contacts.Social history was significant for poor living conditions at home with dust and mold exposure.Upon presentation, vitals were stable.On exam, she had coarse bibasilar breath sounds with rhonchi in left posterior mid-lower lung fields.She had neutrophilic predominant leukocytosis and chest x-ray which showed new round densities over left lower lung field for which she was started on antibiotics for presumed pneumonia.CT chest without contrast showed 2.9cm spiculated left upper lung mass and 2.5cm cavitary mass in left upper lung.She underwent Bronchoscopy during which a firm, stone-like mass was seen at the orifice of the upper segment of the left upper lobe.Endobronchial biopsy results were negative for malignancy, but consistent with pulmonary mucormycosis, showing acute inflammatory exudate and fibrin with accumulation of large, non-septate hyphae with ninety degree angle branching.Staining with Grocott’s methenamine silver was positive for fungal elements. She was started on Posaconazole and discharged from the hospital one week later. DISCUSSION: Mucormycosis is an opportunistic and fulminating fungal infection that presents as rhinocerebral mucormycosis in 30 to 50% of infected patients.In this case, our diabetic patient presented with isolated pulmonary mucormycosis without rhinocerebral involvement.In a literature review of 212 patients with various forms of mucormycosis, 3.3% (7 patients) of immunocompetent patients from 1978 to 2009 had pulmonary mucormycosis. CONCLUSIONS: A review of 929 cases of Mucormycosis reported malignancy as the most common risk factor, found in about 36% of cases with decreasing incidence of isolated pulmonary involvement in diabetics.It is rare to see persistent nodular opacities along with endobronchial involvement that our patient presented with.Antifungals remain the initial treatment of choice in these patients with surgical options pursued when there are signs of angioinvasion including extensive thrombosis and tissue necrosis. Reference #1: Greenerg RN, Scott LJ, Vaughn HH, Ribes JA. Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis 2004; 17:517. Reference #2: Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41:634 Reference #3: Mallis A, Mastronikolis S, Naxakis S, Papadas a. Rhinocerebral mucormycosis: an update. European Review for Medical and Pharmacological Sciences. 2010:14:987-992 Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. DISCLOSURES: No relevant relationships by Hemal Mehta, source=Web Response No relevant relationships by Sylvana Salama, source=Web Response No relevant relationships by Salama Salama, source=Web Response

Adverse outcome of mucormycosis in patients with non-Hodgkin’s lymphoma (clinical observation)

Over the past two decades, mucormycosis has firmly taken 3rd place among invasive mycoses after candidiasis and aspergillosis in patients with oncohematological diseases. The article presents a clinical case of disseminated mucormycosis that developed in a child with nonHodgkin’s lymphoma on the background of deep immunosuppression.

Treatment of Cutaneous Mucormycosis in Patients with Corticosteroid Treatment After Trauma

Amac: Mukormikozis, invaziv yumusak doku nekrozu yapabilen ve agresif seyirli nadir bir firsatci mantar enfeksiyonudur. Genellikle immun sistem yetersizligi olan hastalarda gorulurken, nadiren immunkompetan hastalarda da karsilasilabilir. Bu yazida, travma sonrasi kisa sureli kortikosteroid tedavisi alan ve ardindan fasiyal kutanoz mukormikoz gelisen 4 immunkompetan olgunun prognoz ve tedavisi bildirilmektedir. Gerec ve Yontemler: Calismaya 2016 – 2018 yillari arasinda Manisa Celal Bayar Universitesi Hastanesi’ne travma sonrasinda basvuran, intrakranial veya spinal patolojileri nedeniyle kisa sureli kortikosteroid tedavisi alarak immun sistemi baskilanmis olan ve fasiyal kutanoz mukormikoz tanisi alan dort adet hasta dahil edildi. Prognoz, medikal ve cerrahi tedavi sonuclari degerlendirildi. Bulgular: Malar ve maksiller bolge tutulumu olan bir hastada seri debridmanlar ve medikal tedavilerle kur saglandi. Serbest fleplerle rekonstruksiyon yapilan hastada estetik ve fonksiyonel olarak kabul edilebilir sonuclara ulasildi. 2 hastanin tedavisi tamamlandiktan sonra lokal fleplerle onarimi yapildi. Bir hastaya, fungal osteomiyelit ve intrakraniyal inflamatuar degisiklikleri bulunmasi nedeniyle onarim operasyonu yapilamadi. Bu hastanin takiplerinde MR goruntulemelerinde regresyon saptandi. Sonuc: Multitravma sonrasinda, kontamine yara enfeksiyonu meydana gelen ve kisa donem icin bile olsa kortikosteroid tedavisi alan hastalarda mukormikozisin akilda tutulmasi gerekmektedir. Seri, tekrarlayan ve agresif debridmanlar yapilmali, rekonstruksiyon plani enfeksiyonda kur saglandiktan sonra yapilmalidir.

Analysis of the Clinical Features of Tracheobronchial Fungal Infections with Tumor-Like Lesions

Background: Tracheobronchial fungal infections (TBFI) cause life-threatening complications in immunocompromised hosts but are rarely reported. Misdiagnosis and delayed antifungal treatment are associated with the high mortality rate of patients with TBFI. Objectives: This study analyzed the bronchoscopic features of TBFI and their roles in the early diagnosis of TBFI. Methods: The demographic, clinical, radiologic, and bronchoscopic data of 53 patients diagnosed with TBFI in our department during a 15-year period were retrospectively analyzed. Results: Most of the TBFI patients were male, and mass was the most common radiologic abnormality. Obvious predilection in primary bronchus distributions was observed. 41.9% of the 43 Aspergillus tracheobronchitis (AT) patients, 70% of the 10 tracheobronchial mucormycosis (TM) patients, and 100% of the 3 endobronchial cryptococcosis patients had been misdiagnosed as having cancer on bronchoscopy because of the presence of tumor-like lesions. The most common features of AT were bronchial occlusion with a mass or mucosal necrosis, bronchial stenosis with mucosal hyperplasia, or uneven mucosa. The main descriptions of TM were bronchial stenosis or obstruction due to mucosal necrosis, uneven mucosa, or a mass. The endoscopic characteristics of endobronchial cryptococcosis included occlusion due to uneven mucosa or mass, or external compressive stricture. Conclusion: Immunocompromised patients and immunocompetent patients with underlying disease displaying tumor-like lesions on bronchoscopy should be differentially diagnosed with cancer. Bronchial biopsy is indispensable for the early diagnosis of TBFI.

Global Epidemiology of Mucormycosis.

Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but it is very high in the Asian continent. Though diabetes mellitus overshadow all other risk factors in Asia, post-tuberculosis and chronic renal failure have emerged as new risk groups. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas, pulmonary mucormycosis in patients with haematological malignancy and transplant recipients. In immunocompetent hosts, cutaneous mucormycosis is commonly seen following trauma. The intriguing clinical entity, isolated renal mucormycosis in immunocompetent patients is only reported from China and India. A new clinical entity, indolent mucormycosis in nasal sinuses, is recently recognized. The causative agents of mucormycosis vary across different geographic locations. Though Rhizopus arrhizus is the most common agent isolated worldwide, Apophysomyces variabilis is predominant in Asia and Lichtheimia species in Europe. The new causative agents, Rhizopus homothallicus, Mucor irregularis, and Thamnostylum lucknowense are reported from Asia. In conclusion, with the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents.

Contrasts between mucormycosis and aspergillosis in oncohematological patients.

In retrospective multicenter study from years 2007-2017, we evaluated 59 oncohematological patients with mucormycosis and 541 with invasive aspergillosis (IA). Mucormycosis developed more often in children and adolescents (P = .001), as well as after the emergence of graft versus host disease (P = .0001). Patients with mucormycosis had more severe neutropenia (88%vs 82%), the median duration was 30 versus 14 days (P = .0001) and lymphocytopenia (77%vs 65%), with a median duration (25vs 14 days, P = .001) as compared to patients with IA. The lung infection was less frequent in patients with mucormycosis than in IA patients (73%vs 97%, P = .02), but more frequent was involvement of 2 or more organs (42%vs 8%, P = .001) and involvement of paranasal sinuses (15%vs 6%, P = .04). Typical clinical features of mucormycosis were localized pain syndrome (53%vs 5%, P = .0001), hemoptysis (32%vs 6%, P = .001), pleural effusion on lung CT scan (53%vs 7%, P = .003), lesions with destruction (38%vs 8%, P = .0001), and a "reverse halo" sign (17%vs 3%). The overall 12-week survival was significantly lower in patients with mucormycosis than for IA patients (49%vs 81%, P = .0001). In both groups unfavorable prognosis factors were ≥2 organs involvement (P = .0009), and concomitant bacterial or viral infection (P = .001, P = .008, respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (P = .006).

Preexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection Model.

Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. In contrast to A. fumigatus, a hypervirulent phenotype was found in all tested Mucorales upon preexposure to either voriconazole or isavuconazole. These findings may contribute to the explanation of breakthrough mucormycosis in isavuconazole-treated patients.

Pulmonary Mucormycosis (Zygomycosis) Presenting as an Infective Exacerbation of Chronic Obstructive Pulmonary Disease.

Mucormycosis is a life-threatening fungal infection whose incidence has been rising recently, mainly due to the increasing use of immunosuppressive and corticosteroid treatment. In previous decades, mucormycosis was associated with a very poor prognosis as mortality was approximately 100%. Mortality rates reported in recent literature have only slightly improved despite the availability of targeted therapy with amphotericin B. Pulmonary mucormycosis is characteristically encountered in severely immunocompromised hosts, while rhino-orbital disease is often seen in individuals with diabetes mellitus. We report a rare case of fulminant pulmonary mucormycosis as an exceptionally rare complication of corticosteroid treatment in a 76-year-old patient with chronic obstructive pulmonary disease (COPD) and diabetes. The patient had presented with typical symptoms of an infective COPD exacerbation. The interesting aspects of our case were the absence of malignancy or immunosuppression, the isolation of Rhizomucor species, and the fungal invasion of the pleura and pericardium. Unfortunately, our patient died on the 49th day of hospitalisation, despite appropriate treatment.LEARNING POINTSPulmonary mucormycosis in patients with known respiratory disease may mimic an exacerbation of their lung disease, thus delaying diagnosis.Pulmonary mucormycosis can complicate corticosteroid treatment in elderly individuals with other predisposing factors, which is an emerging clinical concern.Pulmonary mucormycosis remains a potentially fatal disease, although early diagnosis and appropriate medical and surgical management can improve outcomes.

400. The Frequency and Clinical Characteristics of Positive Galactomannan Assay Results in Patients With Mucormycosis

BackgroundDiscrepancies between histomorphologic finding and indirect test results such as galactomannan (GM) assay make diagnosis of invasive fungal infection difficult. We investigated the frequency and clinical characterisitics of positive GM assay results in patients with mucormycosis.MethodsPatients who met the modified criteria for proven or probable mucormycosis and had serum and/or bronchoalveolar lavage (BAL) fluid GM assay result were enrolled at a tertiary hospital from July 2009 to October 2017. Proven mucormycosis was defined as histologic evidence of tissue invasion of hyphae with positive mucormycosis immunohistochemistry (IHC) test result and the recovery of agents of mucormycosis (Rhizopus spp., Cunninghamella spp., Apophysomyces spp., Saksenaea spp., Absidia spp., Mucor spp.) by culture from sterile specimens. Probable mucormycosis was defined as histologic evidence of tissue invasion of hyphae with positive mucormycosis IHC test result with or without recovery of agents of mucormycosis by culture from nonsterile specimens.ResultsAmong 50 patients of proven or probable mucormycosis, 20 (40%) patients were positive for serum and/or BAL fluid GM assay results; 13 of 20 (65.0%) were positive in serum, nine of 12 (75.0%) were positive in BAL fluid, and two of 12 (16.7%) were positive in both. There were more patients with gastrointestinal infections (4 of 20 [20%] vs. 0 of 30 [0%], P = 0.021) and diagnosed as histomorphologically aspergillosis (6 of 20 [30%] vs. 1 of 30 [3%], P = 0.012) in GM positive group than GM negative group.ConclusionThese results suggest that positive GM assay results are not uncommon in mucormycosis. GM assay results from the patients with mucormycosis appear to be related with gastrointestinal infections and histomorphologic diagnosis of aspergillosis. Further studies are needed on the mechanism of positive GM results in patients with mucormycosis and possible coinfection with other fungi such as Aspergillus species in these patients.Disclosures S. H. Kim, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI): Investigator, Grant recipient

399. Multi-centre Observational Study on Epidemiology, Treatment, and Outcome of Mucormycosis in India

BackgroundThough the rise in number of mucormycosis cases has been reported globally, the rise in India is alarming especially in uncontrolled diabetics. However, multiple gaps exist in the understanding of the disease in this country.MethodsTo describe the epidemiology, diagnosis, treatment practices, and outcome of mucormycosis in India. A single-arm prospective observational study was conducted in the network of 17 tertiary care centres across India during April 2016 through September 2017. All consecutive proven mucormycosis patients were enrolled in this study. Clinical data including risk factors, investigations, and treatment were collected. All isolates and histopathological specimens were sent to Mycology Reference Laboratory at Chandigarh for final identification (phenotypic and sequencing) and drug susceptibility testing.ResultsA total of 474 cases were enrolled between the study period. Rhino-orbito-cerebral mucormycosis was common (42.7%) presentation with 22.8% patients had brain involvement, followed by pulmonary (14.6%), cutaneous (11.8%), isolated renal (3.9%), and intra-abdominal (2.8%) mucormycosis. The underlying disease or predisposing factors were noted in 79.7% cases (84.9% diabetes mellitus, 12.9% steroids, 10.3% trauma or history of surgery, 9.7% malignancy, and 9.2% transplant). The most common agents isolated were Rhizopus species (75.9%, R. arrhizus [74.3%] and R. homothallicus [6.7%]) followed by Apophysomyces variabilis (7.4%), Mucor species (6%), and Lichtheimia corymbifera (4%). The patients were managed by medical therapy in 82.8%, surgery in 56.8% while 51.7% received combined medical and surgical management. Amphotericin B (96.8%) either lipid formulations (65.7%) or conventional form (39.1%) was the common antifungal used. The mortality of patients was 30.4%; of which, 80.3% patients died within 6 weeks of their diagnosis. 24.3% patients left hospital against medical advice while 50.1% survived.ConclusionRhino-orbital-cerebral mucormysosis in uncontrolled diabetics is common presentation in India. R. arrhizus followed by A. variabilis are common species isolated from those patients. Survival was noted only in half of the patients despite increased awareness and diagnosis.Disclosures All authors: No reported disclosures.

INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001).