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      Mucor in a Viral Land: A Tale of Two Pathogens

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          Abstract

          Purpose:

          COVID-19 infection, its treatment, resultant immunosuppression, and pre-existing comorbidities have made patients vulnerable to secondary infections including mucormycosis. It is important to understand the presentation, temporal sequence, risk factors, and outcomes to undertake measures for prevention and treatment.

          Methods:

          We conducted a retrospective, interventional study on six consecutive patients with COVID-19 who developed rhino-orbital mucormycosis and were managed at two tertiary ophthalmic referral centers in India between August 1 and December 15, 2020. Diagnosis of mucormycosis was based on clinical features, culture, and histopathology from sinus biopsy. Patients were treated with intravenous liposomal amphotericin B with addition of posaconazole and surgical debridement of necrotic tissue.

          Results:

          All patients were male, mean age 60.5 ± 12 (46.2–73.9) years, type 2 diabetics with mean blood glucose level of 222.5 ± 144.4 (86–404) mg/dL. Except for one patient who was diagnosed with mucormycosis concurrently with COVID-19, all patients received systemic corticosteroids for the treatment of COVID-19. The mean duration between diagnosis of COVID-19 and development of symptoms of mucor was 15.6 ± 9.6 (3–42) days. All patients underwent endoscopic sinus debridement, whereas two patients required orbital exenteration. At the last follow-up, all six patients were alive, on antifungal therapy.

          Conclusion:

          Mucormycosis is a life-threatening, opportunistic infection, and patients with moderate to severe COVID-19 are more susceptible to it. Uncontrolled diabetes mellitus and use of corticosteroids increase the risk of invasive fungal infection with mucormycosis which can develop during the course of the illness or as a sequelae. High index of suspicion, early diagnosis, and appropriate management can improve survival.

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          Most cited references20

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          Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

          Abstract Background To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. Methods MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. Results 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. Conclusions Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.
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            Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

            Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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              Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

              Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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                Author and article information

                Journal
                Indian J Ophthalmol
                Indian J Ophthalmol
                IJO
                Indian Journal of Ophthalmology
                Wolters Kluwer - Medknow (India )
                0301-4738
                1998-3689
                February 2021
                18 January 2021
                : 69
                : 2
                : 244-252
                Affiliations
                [1]Ophthalmic and Facial Plastic Surgery and Ocular Oncology Services, Centre for Sight, Hyderabad, India
                [1 ]Department of Ophthalmology, Sir JJ Group of Hospitals, Mumbai, Maharashtra, India
                Author notes
                Correspondence to: Dr. Santosh G Honavar, Centre for Sight, Ashoka Capitol, Road Number 2, Banjara Hills, Hyderabad, Telangana, India. E-mail: santosh.honavar@ 123456gmail.com
                Article
                IJO-69-244
                10.4103/ijo.IJO_3774_20
                7933891
                33463566
                d0b1e9d1-0338-4db6-b574-04ecc828e9b7
                Copyright: © 2021 Indian Journal of Ophthalmology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 28 December 2020
                : 06 January 2021
                : 07 January 2021
                Categories
                Original Article

                Ophthalmology & Optometry
                corticosteroids,covid-19,diabetes mellitus,mucormycosis
                Ophthalmology & Optometry
                corticosteroids, covid-19, diabetes mellitus, mucormycosis

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