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Kumar R, Singh A, Srivastava A. Xenosiderophores: bridging the gap in microbial iron acquisition strategies. World J Microbiol Biotechnol 2025; 41:69. [PMID: 39939429 DOI: 10.1007/s11274-025-04287-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/04/2025] [Indexed: 02/14/2025]
Abstract
Microorganisms acquire iron from surrounding environment through specific iron chelators known as siderophores that can be of self-origin or synthesized by neighboring microbes. The latter are termed as xenosiderophores. The acquired iron supports their growth, survival, and pathogenesis. Various microorganisms possess the ability to utilize xenosiderophores, a mechanism popularly termed as 'siderophore piracy' besides synthesizing their own siderophores. This adaptability allows microorganisms to conserve energy by reducing the load of siderogenesis. Owing to the presence of xenosiderophore transport machinery, these microbial systems can be used for targeting antibiotics-siderophore conjugates to control pathogenesis and combat antimicrobial resistance. This review outlines the significance of xenosiderophore utilization for growth, stress management and virulence. Siderogenesis and the molecular mechanism of its uptake by related organisms have been discussed vividly. It focuses on potential applications like disease diagnostics, drug delivery, and combating antibiotic resistance. In brief, this review highlights the importance of xenosiderophores projecting them beyond their role as mere iron chelators.
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Affiliation(s)
- Ravinsh Kumar
- Department of Life Science, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar, India
| | - Ashutosh Singh
- Department of Life Science, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar, India
| | - Amrita Srivastava
- Department of Life Science, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar, India.
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2
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Mahapatra C, Jadhav S, Kumar P, Roy DN, Kumar A, Paul MK. Potential activity of nanomaterials to combat SARS-CoV-2 and mucormycosis coinfection. Expert Rev Anti Infect Ther 2024; 22:1143-1155. [PMID: 39466600 DOI: 10.1080/14787210.2024.2423359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/26/2024] [Accepted: 10/27/2024] [Indexed: 10/30/2024]
Abstract
INTRODUCTION Mucormycosis, popularly known as the black fungus, has become a worldwide concern in the continuing COVID-19 pandemic, causing increased morbidity and death in immunocompromised people. Due to multi-drug resistance and the limited number of antifungals, surgical interventions, including the excision of infected tissue, remain a standard treatment option. Surgical treatment usually results in the loss of organs or their function, long-term intensive care, and a significant risk of reinfection during the procedure. A comprehensive approach is needed to treat the disease, and nanomaterials can be a powerful alternative therapeutic approach. AREAS COVERED We searched PubMed, Scopus, and Google Scholar with the keywords 'emerging role of nanomaterials,' and 'combating COVID-19-related mucormycosis,' and reviewed the related research paper. Antifungal nanomaterials and their delivery can significantly impact the treatment of COVID-19-related fungal infections like mucormycosis. However, the therapeutic options for mucormycosis are limited and drug resistance is also reported. EXPERT OPINION The current review encompasses a detailed overview of the recent developments in antifungal/antiviral nanomaterials and the properties of these therapeutic nanomaterials that may contribute to formulating an efficient strategy against invasive mucormycosis. Further extensive research is needed to develop nano-based therapeutics for the management of mucormycosis-viral coinfection with a definitive end-point.
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Affiliation(s)
- Chinmaya Mahapatra
- Department of Biotechnology, National Institute of Technology (NIT), Raipur, India
| | - Sakshi Jadhav
- Department of Biotechnology and Medical Engineering, National Institute of Technology (NIT), Rourkela, India
| | - Prasoon Kumar
- Department of Biotechnology and Medical Engineering, National Institute of Technology (NIT), Rourkela, India
| | - Dijendra Nath Roy
- Department of Biotechnology, National Institute of Technology (NIT), Raipur, India
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology (NIT), Raipur, India
| | - Manash K Paul
- Department of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
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Panda S, Sahu MC, Turuk J, Pati S. Mucormycosis: A Rare disease to Notifiable Disease. Braz J Microbiol 2024; 55:1065-1081. [PMID: 38561499 PMCID: PMC11153412 DOI: 10.1007/s42770-024-01315-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 03/21/2024] [Indexed: 04/04/2024] Open
Abstract
Mucormycosis is the third most frequent invasive mycosis, following candidiasis and aspergillosis. It is frequently neglected due to its rare occurrence; but recently attend the status of notifiable disease due to its higher incidence in both developed and developing nations. India has received global notice since its estimated instances were greater than the global estimated figures. Mucormycosis has several clinical manifestations, including rhino-orbital-cerebral (ROCM), pulmonary, gastrointestinal, cutaneous, renal, and diffuse Mucormycosis. ROCM is the most frequent clinical manifestation in India, although pulmonary mucormycosis is prevalent worldwide. This review also discusses host defenses, pre disposing risk factors and fungal virulence factors that impair host's ability to prevent fungus invasion and disease establishment. The diagnosis of the disease depends on clinical interventions, histological or microbiological procedures along with molecular methods to obtain timely results. But there are still unmet challenges for rapid diagnosis of the disease. Treatment of the disease is achieved by multimodal approaches such as reversal of underlying predisposing factors, rapid administration of antifungals in optimal doses and surgical procedures to remove infected tissues. Liposomal Amphotericin B, Posaconazole and Isavuconazoles are preferred as the first line of treatment procedures. clinical trials. Different studies have improved the existing drug and under clinical trials while several studies predicted the new potential targets as CotH and Ftr1 as shown in infection and in vitro models. Therefore, current scenario demands a multidisciplinary approach is needed to investigate the prevalence, pathogenesis which is highly important for the advancement of rapid diagnosis and effective treatment.
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Affiliation(s)
- Sunita Panda
- Regional Medical Research Center, Bhubaneswar, Odisha, 751023, India
| | | | - Jyotirmayee Turuk
- Regional Medical Research Center, Bhubaneswar, Odisha, 751023, India.
| | - Sanghamitra Pati
- Regional Medical Research Center, Bhubaneswar, Odisha, 751023, India.
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Faiyazuddin M, Sophia A, Ashique S, Gholap AD, Gowri S, Mohanto S, Karthikeyan C, Nag S, Hussain A, Akhtar MS, Bakht MA, Ahmed MG, Rustagi S, Rodriguez-Morales AJ, Salas-Matta LA, Mohanty A, Bonilla-Aldana DK, Sah R. Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review. Front Immunol 2023; 14:1264502. [PMID: 37818370 PMCID: PMC10561264 DOI: 10.3389/fimmu.2023.1264502] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 09/11/2023] [Indexed: 10/12/2023] Open
Abstract
The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.
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Affiliation(s)
- Md. Faiyazuddin
- School of Pharmacy, Al – Karim University, Katihar, Bihar, India
- Nano Drug Delivery®, Raleigh-Durham, NC, United States
| | - A. Sophia
- PG & Research Department of Physics, Cauvery College for Women (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Sumel Ashique
- Department of Pharmaceutics, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal, India
| | - Amol D. Gholap
- Department of Pharmaceutics, St. John Institute of Pharmacy and Research, Palghar, Maharashtra, India
| | - S. Gowri
- PG & Research Department of Physics, Cauvery College for Women (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - C. Karthikeyan
- Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| | - Sagnik Nag
- Department of Bio-Sciences, School of Biosciences & Technology (SBST), Vellore Institute of Technology (VIT), Tamil Nadu, India
| | - Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
| | - Mohammad Shabib Akhtar
- Department of Clinical Pharmacy, College of Pharmacy, Najran University, Najran, Saudi Arabia
| | - Md. Afroz Bakht
- Chemistry Department, College of Science and Humanity Studies, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Mohammed Gulzar Ahmed
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Alfonso J. Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas—Institución Universitaria Visión de las Américas, Pereira, Colombia
- Faculties of Health Sciences and Environmental Sciences, Universidad Científica del Sur, Lima, Peru
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Luis Andres Salas-Matta
- Faculties of Health Sciences and Environmental Sciences, Universidad Científica del Sur, Lima, Peru
| | - Aroop Mohanty
- Department of Clinical Microbiology, All India Institute of Medical Sciences, Gorakhpur, India
| | | | - Ranjit Sah
- Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
- Department of Clinical Microbiology, DY Patil Medical College, Hospital and Research Centre, DY Patil Vidyapeeth, Pune, Maharashtra, India
- Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, India
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Gupta I, Baranwal P, Singh G, Gupta V. Mucormycosis, past and present: a comprehensive review. Future Microbiol 2023; 18:217-234. [PMID: 36970978 DOI: 10.2217/fmb-2022-0141] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023] Open
Abstract
Mucormycosis is an emerging opportunistic angioinvasive fungal infection. Predisposing factors such as diabetes, neutropenia, long-term corticosteroid therapy, solid organ transplantation and immunosuppression contribute to its occurrence. This disease was not of significant concern prior to the COVID-19 pandemic, but gained prominence due to infections in COVID-19 patients. Mucormycosis needs special attention and coordinated efforts of the scientific community and medical professionals to reduce morbidity and mortality. Here we present an overview of the epidemiology and prevalence of mucormycosis in the pre- and post-COVID-19 eras, the factors that contributed to the abrupt increase in COVID-19-associated mucormycosis (CAM), the actions taken by the regulatory agencies (including Code Mucor and CAM registry), the existing diagnostic tools and CAM management strategies.
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Shah NN, Khan Z, Ahad H, Elderdery AY, Alomary MN, Atwah B, Alhindi Z, Alsugoor MH, Elkhalifa AME, Nabi S, Bashir SM, Yaqub T, Rather GA, Ansari MA. Mucormycosis an added burden to Covid-19 Patients: An in-depth systematic review. J Infect Public Health 2022; 15:1299-1314. [PMID: 36279686 PMCID: PMC9562622 DOI: 10.1016/j.jiph.2022.10.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 10/01/2022] [Accepted: 10/10/2022] [Indexed: 01/08/2023] Open
Abstract
As of 25th July, 2022, global Disease burden of 575,430,244 confirmed cases and over 6,403,511 deaths have been attributed to coronavirus disease 2019 (COVID-19). Co-infections/secondary infections continue to plague patients around the world as result of the co-morbidities like diabetes mellitus, biochemical changes caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) especially significant elevation in free iron levels, immune suppression caused by SARS-CoV-2, and indiscriminate use of systemic corticosteroids for the treatment of severe COVID-19 disease. In such circumstances, opportunistic fungal infections pose significant challenge for COVID-19 disease therapy in patients with other co-morbidities. Although COVID-19-associated Mucormycosis (CAM) has been widely recognized, currently extensive research is being conducted on mucormycosis. It has been widely agreed that patients undergoing corticosteroid therapy are highly susceptible for CAM, henceforth high index of screening and intensive care and management is need of an hour in order to have favorable outcomes in these patients. Diagnosis in such cases is often delayed and eventually the disease progresses quickly which poses added burden to clinician and increases patient load in critical care units of hospitals. A vast perusal of literature indicated that patients with diabetes mellitus and those with other co-morbidities might be highly vulnerable to develop mucormycosis. In the present work, the case series of three patients presented at Chest Disease Hospital Srinagar, Jammu and Kashmir infected with CAM has been described with their epidemiological data in supplementary section. All these cases were found to be affected with co-morbidity of Diabetes Mellitus (DM) and were under corticosteroid therapy. Furthermore, given the significant death rate linked with mucormycosis and the growing understanding of the diseases significance, systematic review of the literature on CAM has been discussed and we have attempted to discuss emerging CAM and related aspects of the disease.
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Affiliation(s)
- Naveed Nazir Shah
- Department of Chest Medicine, Govt. Medical College Srinagar, Jammu & Kashmir, India
| | - Zaid Khan
- Department of Chest Medicine, Govt. Medical College Srinagar, Jammu & Kashmir, India
| | - Hashim Ahad
- Government Dental College, Srinagar, Jammu & Kashmir, India
| | - Abozer Y Elderdery
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Saudi Arabia
| | - Mohammad N Alomary
- National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia
| | - Banan Atwah
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Zain Alhindi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Mahdi H Alsugoor
- Department of Emergency Medical Services, faculty of Health Sciences, AlQunfudah, Umm Al-Qura University, Makkah 21912, Saudi Arabia
| | - Ahmed M E Elkhalifa
- Department of Public Health, College of Health Sciences, Saudi Electronic University, Riyadh, Saudi Arabia & Department of Haematology, Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Kosti 1158, Sudan
| | - Showket Nabi
- Large Animal Diagnostic Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama Alusteng, Srinagar, Jammu & Kashmir 190006, India
| | - Showkeen Muzamil Bashir
- Molecular biology Laboratory, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama Alusteng, Srinagar, Jammu & Kashmir 190006, India.
| | - Tahir Yaqub
- Institute of Microbiology University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Gulzar Ahmed Rather
- Department of Biomedical Engineering, Sathyabama Institute of Science & Technology, Deemed to be University, Chennai, Tamil Nadu, India
| | - Mohammad Azam Ansari
- Department of Epidemic Disease Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
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7
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Trevijano-Contador N, Torres-Cano A, Carballo-González C, Puig-Asensio M, Martín-Gómez MT, Jiménez-Martínez E, Romero D, Nuvials FX, Olmos-Arenas R, Moretó-Castellsagué MC, Fernández-Delgado L, Rodríguez-Sevilla G, Aguilar-Sánchez MM, Ayats-Ardite J, Ardanuy-Tisaire C, Sanchez-Romero I, Muñoz-Algarra M, Merino-Amador P, González-Romo F, Megías-Lobón G, García-Campos JA, Mantecón-Vallejo MÁ, Alcoceba E, Escribano P, Guinea J, Durán-Valle MT, Fraile-Torres AM, Roiz-Mesones MP, Lara-Plaza I, de Ayala AP, Simón-Sacristán M, Collazos-Blanco A, Nebreda-Mayoral T, March-Roselló G, Alcázar-Fuoli L, Zaragoza O. Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic. Open Forum Infect Dis 2022; 9:ofac605. [PMID: 36467290 PMCID: PMC9709632 DOI: 10.1093/ofid/ofac605] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 11/03/2022] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. METHODS Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. RESULTS We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). CONCLUSIONS Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.
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Affiliation(s)
- Nuria Trevijano-Contador
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo, Madrid, Spain
| | - Alba Torres-Cano
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo, Madrid, Spain
| | - Cristina Carballo-González
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo, Madrid, Spain
| | - Mireia Puig-Asensio
- Department of Infectious Diseases, Hospital Universitari de Bellvitge-Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain
- Center for Biomedical Research in Network in Infectious Diseases (CIBERINFEC, CB21/13/00009), Instituto de Salud Carlos III, Madrid, Spain
| | - María Teresa Martín-Gómez
- Department of Microbiology, Vall D'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Emilio Jiménez-Martínez
- Department of Infectious Diseases, Hospital Universitari de Bellvitge-Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain
| | - Daniel Romero
- Department of Microbiology, Vall D'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Francesc Xavier Nuvials
- Intensive Care Unit, Vall D'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Roberto Olmos-Arenas
- Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | | | | | | | | | - Josefina Ayats-Ardite
- Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | - Carmen Ardanuy-Tisaire
- Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
- Center for Biomedical Research Network in Respiratory Diseases (CIBERES-CB06/06/0037), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Sanchez-Romero
- Microbiology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - María Muñoz-Algarra
- Microbiology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Paloma Merino-Amador
- Microbiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Department of Medicine, Universidad Complutense School of Medicine, Madrid, Spain
| | - Fernando González-Romo
- Microbiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Department of Medicine, Universidad Complutense School of Medicine, Madrid, Spain
| | - Gregoria Megías-Lobón
- Department of Clinical Microbiology, Hospital Universitario de Burgos, Burgos, Castilla y León, Spain
| | - Jose Angel García-Campos
- Department of Clinical Microbiology, Hospital Universitario de Burgos, Burgos, Castilla y León, Spain
| | | | - Eva Alcoceba
- Clinical Microbiology Department, Hospital Universitari Son Espases, Mallorca, Spain
| | - Pilar Escribano
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Jesús Guinea
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- Center for Biomedical Research Network in Respiratory Diseases (CIBERES-CB06/06/0058), Madrid, Spain
| | | | | | - María Pía Roiz-Mesones
- Microbiology Department, Marqués de Valdecilla Universitary Hospital and Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria,Spain
| | - Isabel Lara-Plaza
- Microbiology Department, Marqués de Valdecilla Universitary Hospital and Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria,Spain
| | | | - María Simón-Sacristán
- Microbiology and Parasitology Department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain
| | - Ana Collazos-Blanco
- Microbiology and Parasitology Department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain
| | - Teresa Nebreda-Mayoral
- Microbiology and Immunology Unit, Universitary Clinic Hospital of Valladolid, Valladolid, Spain
| | - Gabriel March-Roselló
- Microbiology and Immunology Unit, Universitary Clinic Hospital of Valladolid, Valladolid, Spain
| | - Laura Alcázar-Fuoli
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo, Madrid, Spain
- Center for Biomedical Research in Network in Infectious Diseases (CIBERINFEC-CB21/13/00105), Instituto de Salud Carlos III, Madrid, Spain
| | - Oscar Zaragoza
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III. Carretera Majadahonda-Pozuelo, Madrid, Spain
- Center for Biomedical Research in Network in Infectious Diseases (CIBERINFEC-CB21/13/00105), Instituto de Salud Carlos III, Madrid, Spain
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8
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Al-Ani RM. Rhino-orbital-cerebral mucormycosis as a complication of coronavirus disease 2019. World J Virol 2022; 11:293-299. [PMID: 36188746 PMCID: PMC9523325 DOI: 10.5501/wjv.v11.i5.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 05/13/2022] [Accepted: 08/12/2022] [Indexed: 02/05/2023] Open
Abstract
Coronavirus disease 2019 is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. This disease as well as its various treatments like steroids, antivirals, and antibacterials can alter the immune state of the affected individuals and result in secondary infections such as mucormycosis. Mucormycosis is a well-known opportunistic fungal infection that affects immunocompromised subjects, particularly those with diabetes mellitus, prolonged antibiotic or steroid use, and patients with organ trans-plantation, neutropenia, and hematological malignancies. Rhino-orbital-cerebral mucormycosis is an aggressive disease owing to its ability to invade the blood vessels by fungal hyphae, leading to necrosis of the involved structures. Large cases were reported from India, indicating that this clinical entity shows a geographical variation. The affected patients are suffering on a clinical spectrum depending on the stage of the disease. Radiological assessment, including computerized tomography and magnetic resonance imaging, is necessary to evaluate the stage of the disease and choose the appropriate surgical treatment. A multidisciplinary approach is required to treat rhino-orbital-cerebral mucor-mycosis and includes local or intravenous antifungal drugs, debridement of the dead tissues, and appropriate management of any predisposing conditions. The disease has a very poor prognosis with a death rate of 50%. This review aimed to sum-marize the demographic and clinical risk factors, investigations, treatments, and outcomes of coronavirus disease 2019 patients with rhino-orbital-cerebral mucormycosis.
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Affiliation(s)
- Raid M Al-Ani
- Department of Surgery/Otolaryngology, University of Anbar, College of Medicine, Ramadi 31001, Anbar, Iraq
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9
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Arjmand P, Bahrami M, Mohammadie ZE, Taherynejad M, Khorasani NY, Mehrad‐Majd H, Roshanzamir I, Bakhshaee M. Mucormycosis in pre-COVID-19 and COVID-19 era: A study of prevalence, risk factors and clinical features. Laryngoscope Investig Otolaryngol 2022; 7:1343-1350. [PMID: 36249085 PMCID: PMC9539365 DOI: 10.1002/lio2.899] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/01/2022] [Accepted: 08/08/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Mucormycosis is a rare yet devastating fungal disease with a frequently fatal outcome. The purpose of this study was to compare the prevalence of mucormycosis, evaluate its risk factors, and assess the patients' outcomes in pre-COVID-19 and COVID-19 era. METHODS In this retrospective observational study, clinical data of 158 patients with confirmed histopathological diagnosis of mucormycosis were collected from the medical records departments of Imam Reza and Ghaem hospitals, Mashhad, Iran during 2018-2021. The collected data were risk factors associated with mucormycosis including age, gender, underlying diseases, details of corticosteroid administration, and complications such as blindness and mortality. RESULTS Of 158 studied patients, 48 patients were diagnosed in the pre-pandemic period whereas 110 cases were admitted during the pandemic era. COVID-19 associated mucormycosis (CAM) was observed in 58.1% of the pandemic cases. In the pre-pandemic period, cancer (89.5% vs. 39%, p < .001) was significantly more prevalent while during the pandemic era, the prevalence of diabetes mellitus (16.7% vs. 51%, p < .001) was remarkably higher. Moreover, the mortality rate of mucormycosis was considerably reduced after the pandemic (64.6%-45.4%), especially in CAM patients (35.9%). CONCLUSION The COVID-19 pandemic has led to an increased prevalence of mucormycosis, due to the convergence of interlinked risk factors such as diabetes mellitus, corticosteroid therapy, and COVID-19. Therefore, clinicians must be aware of the probable occurrence of mucormycosis in the first or second week of COVID-19 infection in vulnerable patients and use the steroids cautiously. LEVEL OF EVIDENCE 4 Laryngoscope Investigative Otolaryngology, 2022.
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Affiliation(s)
- Parisa Arjmand
- Department of Otorhinolaryngology, Ghaem HospitalMashhad University of Medical SciencesMashhadIran
| | - Milad Bahrami
- Department of Laboratory Sciences, Faculty of Paramedical SciencesMashhad University of Medical SciencesMashhadIran
| | | | | | | | - Hassan Mehrad‐Majd
- Cancer Molecular Pathology Research CenterMashhad University of Medical SciencesMashhadIran
| | - Imaneh Roshanzamir
- Sinus and Surgical Endoscopic Research Center, Department of OtorhinolaryngologyMashhad University of Medical SciencesMashhadIran
| | - Mehdi Bakhshaee
- Sinus and Surgical Endoscopic Research Center, Department of OtorhinolaryngologyMashhad University of Medical SciencesMashhadIran
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Arjmand G, Askari E, Kazemi A, Zarei E, Haseli S, Sadraei N. Bronchial wall necrosis secondary to mucormycosis following SARS-Cov2 infection: A case report. Radiol Case Rep 2022; 17:2956-2959. [PMID: 35747739 PMCID: PMC9212854 DOI: 10.1016/j.radcr.2022.05.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 11/27/2022] Open
Abstract
Coronavirus 2019 infection (COVID-19) has a broad spectrum of clinical complications, some unrecognized. Herein, a case of a diabetic patient with multiple episodes of hemoptysis 2 months following her recovery from SARS-CoV-2 infection is reported. The initial computed tomography (CT scan) revealed the left lower lobe collapsed secondary to bronchial narrowing and obliteration. Bronchoscopy was performed, indicating necrotic endobronchial tissue, which was confirmed histopathologically as invasive mucormycosis. Bronchial necrosis due to mucormycosis is an unusual presentation of COVID-19-associated pulmonary mucormycosis. The accurate diagnosis could be challenging as it can resemble other pathologies such as malignancies. Therefore, it is crucial to identify this fatal complication in patients with prolonged COVID-19 and lung collapse.
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Affiliation(s)
- Ghazal Arjmand
- Medical student at Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elham Askari
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arya Kazemi
- Medical student at Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Zarei
- Department of Radiology, Shohada-E-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Haseli
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nazanin Sadraei
- Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Corresponding author.
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COVID-19-Associated Mucormycosis: A Matter of Concern Amid the SARS-CoV-2 Pandemic. Vaccines (Basel) 2022; 10:vaccines10081266. [PMID: 36016154 PMCID: PMC9415927 DOI: 10.3390/vaccines10081266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 08/04/2022] [Accepted: 08/05/2022] [Indexed: 12/16/2022] Open
Abstract
Mucormycosis is an invasive fungal infection caused by fungi belonging to order Mucorales. Recently, with the increase in COVID-19 infections, mucormycosis infections have become a matter of concern globally, because of the high morbidity and mortality rates associated with them. Due to the association of mucormycosis with COVID-19 disease, it has been termed COVID-19-associated mucormycosis (CAM). In the present review, we focus on mucormycosis incidence, pathophysiology, risk factors, immune dysfunction, interactions of Mucorales with endothelial cells, and the possible role of iron in Mucorales growth. We review the limitations associated with current diagnostic procedures and the requirement for more specific, cost-effective, convenient, and sensitive assays, such as PCR-based assays and monoclonal antibody-based assays for the effective diagnosis of mucormycosis. We discuss the current treatment options involving antifungal drug therapies, adjunctive therapy, surgical treatment, and their limitations. We also review the importance of nutraceuticals-based therapy for the prevention as well as treatment of mucormycosis. Our review also highlights the need to explore the potential of novel immunotherapeutics, which include antibody-based therapy, cytokine-based therapy, and combination/synergistic antifungal therapy, as treatment options for mucormycosis. In summary, this review provides a complete overview of COVID-19-associated mucormycosis, addressing the current research gaps and future developments required in the field.
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García-Carnero LC, Mora-Montes HM. Mucormycosis and COVID-19-Associated Mucormycosis: Insights of a Deadly but Neglected Mycosis. J Fungi (Basel) 2022; 8:445. [PMID: 35628701 PMCID: PMC9144279 DOI: 10.3390/jof8050445] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/22/2022] [Accepted: 04/22/2022] [Indexed: 02/04/2023] Open
Abstract
The ongoing COVID-19 pandemic has quickly become a health threat worldwide, with high mortality and morbidity among patients with comorbidities. This viral infection promotes the perfect setting in patients for the development of opportunistic infections, such as those caused by fungi. Mucormycosis, a rare but deadly fungal infection, has recently increased its incidence, especially in endemic areas, since the onset of the pandemic. COVID-19-associated mucormycosis is an important complication of the pandemic because it is a mycosis hard to diagnose and treat, causing concern among COVID-19-infected patients and even in the already recovered population. The risk factors for the development of mucormycosis in these patients are related to the damage caused by the SARS-CoV-2 itself, the patient's overstimulated immune response, and the therapy used to treat COVID-19, causing alterations such as hyperglycemia, acidosis, endothelial and lung damage, and immunosuppression. In this review, the molecular aspects of mucormycosis and the main risk factors for the development of COVID-19-associated mucormycosis are explained to understand this virus-fungi-host interaction and highlight the importance of this neglected mycosis.
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Affiliation(s)
- Laura C. García-Carnero
- Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato 36050, Mexico
| | - Héctor M. Mora-Montes
- Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato 36050, Mexico
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Singh A, Agrawal P, Kumar V. An analysis of proposed etiological factors for sudden spike in mucormycosis infection during COVID-19 pandemic at a tertiary hospital of North India. INDIAN JOURNAL OF MEDICAL SPECIALITIES 2022. [DOI: 10.4103/injms.injms_15_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Anand S, Ahmad A, Singh A, Megha V, Maharaj A. Management of coronavirus disease (Covid-19) associated mucormycosis with palatal ulcer, dental pain and anterior maxillary teeth mobility- A clinical dilemma of Covid 19 pandemic in India. J Family Med Prim Care 2022; 11:1539-1541. [PMID: 35516697 PMCID: PMC9067228 DOI: 10.4103/jfmpc.jfmpc_1236_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 10/11/2021] [Accepted: 10/20/2021] [Indexed: 11/08/2022] Open
Abstract
Mucormycosis represents a group of life-threatening infections caused by fungi of the order mucorales of subphylum mucormycotina. Due to high vascularity, the maxilla rarely undergoes necrosis. Mucormycosis is an opportunistic fulminant fungal infection, which mainly infects immune-compromised patients. Due to the inhalation of fungal spores, the infection may begin in the nose and paranasal sinuses. Necrosis of hard and soft tissues is due to thrombosis of arteries, which is caused by the inhalation of fungal spores. We report a case of maxillary necrosis by mucormycosis in a COVID-19-recovered patient to emphasize the early diagnosis of this potentially fatal fungal infection. We reviewed the current concepts in the management of mucormycosis and different diseases that can lead to maxillary necrosis. The mortality and morbidity of this lethal fungal infection can be successfully reduced by early diagnosis and quick treatment by the general primary care provider, family physicians, and dentists.
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