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1
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Czech MM, Cuellar-Rodriguez J. Mucormycosis. Infect Dis Clin North Am 2025; 39:121-144. [PMID: 39638718 PMCID: PMC11786989 DOI: 10.1016/j.idc.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Mucormycosis is an aggressive and frequently lethal disease. Most patients with mucormycosis have poorly controlled diabetes mellitus and rhino-orbito-cerebral disease. Patients with hematologic malignancy and transplant recipients mostly present with rhino-orbito-cerebral or pulmonary disease. Prompt recognition of clinical symptoms and radiographic features of mucormycosis is required to establish timely diagnosis and initiate targeted therapy. Diagnosis is, historically, made by direct microscopy, culture, and pathology of biopsy tissue, but molecular methods are increasingly playing a role in establishing an earlier diagnosis. Treatment is multidisciplinary, involving early surgical intervention, antifungal therapy, and correction of underlying immune compromising risk factors when possible.
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Affiliation(s)
- Mary M Czech
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Building 10 2C146B, Bethesda, MD 20892, USA
| | - Jennifer Cuellar-Rodriguez
- Transplant Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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2
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Liang M, Xu J, Luo Y, Qu J. Epidemiology, pathogenesis, clinical characteristics, and treatment of mucormycosis: a review. Ann Med 2024; 56:2396570. [PMID: 39221718 PMCID: PMC11370679 DOI: 10.1080/07853890.2024.2396570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/25/2024] [Accepted: 07/16/2024] [Indexed: 09/04/2024] Open
Abstract
AIM This review aims to summarize the epidemiology, etiology, pathogenesis, clinical manifestations, and current diagnostic and therapeutic approaches for mucormycosis. The goal is to improve understanding of mucormycosis and promote early diagnosis and treatment to reduce mortality. METHODS A comprehensive literature review was conducted, focusing on recent studies and data on mucormycosis. The review includes an analysis of the disease's epidemiology, etiology, and pathogenesis, as well as current diagnostic techniques and therapeutic strategies. RESULTS Mucormycosis is increasingly prevalent due to the growing immunocompromised population, the COVID-19 pandemic, and advances in detection methods. The pathogenesis is closely associated with the host immune status, serum-free iron levels, and the virulence of Mucorales. However, the absence of typical clinical manifestations complicates diagnosis, leading to missed or delayed diagnoses and higher mortality. CONCLUSION An enhanced understanding of the epidemiology, pathogenesis, and clinical presentation of mucormycosis, along with the adoption of improved diagnostic and therapeutic approaches, is essential for reducing mortality rates associated with this opportunistic fungal infection. Early diagnosis and prompt treatment are critical to improving patient outcomes.
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Affiliation(s)
- Mei Liang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian Xu
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yanan Luo
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Junyan Qu
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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3
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Tariq M, Wei B. To Cut (Minimally Invasively) Is to Cure: Robotic Lobectomy for Pulmonary Mucormycosis. ANNALS OF THORACIC SURGERY SHORT REPORTS 2024; 2:629-632. [PMID: 39790618 PMCID: PMC11708524 DOI: 10.1016/j.atssr.2024.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 06/04/2024] [Indexed: 01/12/2025]
Abstract
Pulmonary mucormycosis is a rapidly progressive and highly morbid disease commonly found in immunosuppressed patients. Rapid diagnosis and treatment are essential, with thoracotomy and video-assisted thoracoscopic surgery techniques previously described for surgical resection of infected lobes. Here we present the case of a patient with acute myeloid leukemia and nonresolving Mucor pneumonia treated with robotic left upper lobectomy. The patient had an uneventful postoperative course and significant clinical improvement, thereby demonstrating the feasibility of the robotic approach in treating patients with invasive fungal infections of the lung.
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Affiliation(s)
- Marvi Tariq
- Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | - Benjamin Wei
- Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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4
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Ogawa L, Multani A, Beaird OE, Gaynor P, Carlson M, Garner OB, Schiller G, Schaenman JM. Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients. Transplant Proc 2024; 56:1683-1690. [PMID: 39174391 DOI: 10.1016/j.transproceed.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 07/29/2024] [Indexed: 08/24/2024]
Abstract
BACKGROUND Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. METHODS This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. RESULTS Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. CONCLUSION Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.
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Affiliation(s)
- Lauren Ogawa
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
| | - Ashrit Multani
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Omer E Beaird
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Pryce Gaynor
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Margrit Carlson
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Omai B Garner
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Gary Schiller
- Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Joanna M Schaenman
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
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5
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Seto K, Nohara R, Sugita Y, Ishibashi H, Okubo K. Pulmonary Mucormycosis Involving the Left Main Bronchus and the Pulmonary Artery. Ann Thorac Cardiovasc Surg 2023; 29:315-318. [PMID: 35387926 PMCID: PMC10767655 DOI: 10.5761/atcs.cr.22-00035] [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: 02/15/2022] [Accepted: 03/27/2022] [Indexed: 11/16/2022] Open
Abstract
Pulmonary mucormycosis is an extremely rare disease. It often occurs in immunocompromised patients, such as patients with diabetes and those on long-term steroid use. The prognosis of the disease is poor despite the administration of antifungal agents and removal of the necrotic tissue. Herein, we present a successfully treated case of pulmonary mucormycosis in a patient with type 2 diabetes who underwent left pneumonectomy because of the involvement of the left main pulmonary artery and the left main bronchus. Irrespective of the infected organ, complete debridement of the infected tissue and treatment with antifungal agents are essential for treating mucormycosis.
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Affiliation(s)
- Katsutoshi Seto
- Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Rika Nohara
- Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yusuke Sugita
- Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hironori Ishibashi
- Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kenichi Okubo
- Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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6
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Zhou Y, Hu Y, Liu S, Yao H. Clinical diagnosis and treatment of invasive pulmonary mucormycosis: A case report and technical precautions. Asian J Surg 2023; 46:5939-5941. [PMID: 37690896 DOI: 10.1016/j.asjsur.2023.08.219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 08/30/2023] [Indexed: 09/12/2023] Open
Affiliation(s)
- Yue Zhou
- Zunyi Medical University, China; Department of Respiratory Medicine, Guizhou Provincial People's Hospital, Guizhou Province, China
| | - Yunxiang Hu
- Dalian Medical University, China; Department of Orthopedics, Central Hospital of Dalian University of Technology, Dalian City, Liaoning Province, China
| | - Sanmao Liu
- Dalian Medical University, China; Department of Orthopedics, Central Hospital of Dalian University of Technology, Dalian City, Liaoning Province, China
| | - Hongmei Yao
- Department of Respiratory Medicine, Guizhou Provincial People's Hospital, Guizhou Province, China.
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7
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Lynch JP, Zhanel GG. Part 2: Mucormycosis: Focus on Therapy. Expert Rev Anti Infect Ther 2023. [PMID: 37300820 DOI: 10.1080/14787210.2023.2224564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023]
Abstract
INTRODUCTION Mucormycosis (MCR) a rare but life-threatening infection occurs primarily in immunocompromised hosts. Mortality rates with invasive MCR are high (>30-50%), up to 90% with disseminated disease, but lower (10-30%) with localized cutaneous disease. Due to the rarity of MCR, randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy or in MCR cases refractory to or intolerant of LFAB. Early surgical debridement or excision play important adjunctive roles in localized invasive disease. Control of hyperglycemia in diabetic patients, correction of neutropenia and reduction of immunosuppressive therapy is critical for optimal survival. AREAS COVERED The authors discuss various therapeutic options for mucormycosis. A literature search of mucormycosis therapies was performed via PubMed (up to December 2022), using the key words: invasive fungal infections; mold; mucormycosis; Mucorales; amphotericin B; isavuconazole; posaconazole. EXPERT OPINION Randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy, in MCR cases refractory to or intolerant of LFAB. We encourage early surgical debridement or excision as adjunctive measures.
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Affiliation(s)
- Joseph P Lynch
- Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, the David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - George G Zhanel
- Department of Medical Microbiology/Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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Guo XZ, Gong LH, Wang WX, Yang DS, Zhang BH, Zhou ZT, Yu XH. Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult: A case report. World J Clin Cases 2023; 11:3295-3303. [PMID: 37274035 PMCID: PMC10237139 DOI: 10.12998/wjcc.v11.i14.3295] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 04/02/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.
CASE SUMMARY A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up.
CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.
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Affiliation(s)
- Xing-Zi Guo
- Department of Gynecologic Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Liang-Hui Gong
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Wen-Xiang Wang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - De-Song Yang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Bai-Hua Zhang
- The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
| | - Ze-Tao Zhou
- GZMU-GIBH School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, Guangdong Province, China
| | - Xiao-Hui Yu
- Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410031, Hunan Province, China
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9
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What Is New in Pulmonary Mucormycosis? J Fungi (Basel) 2023; 9:jof9030307. [PMID: 36983475 PMCID: PMC10057210 DOI: 10.3390/jof9030307] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 03/06/2023] Open
Abstract
Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral (ROC) areas and the skin. The main risk factors for PM include hematological malignancies and solid organ transplantation, whereas ROC infections are classically favored by diabetes mellitus. The differences between the ROC and pulmonary locations are possibly explained by the activation of different mammalian receptors—GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells—in response to Mucorales. Alveolar macrophages and neutrophils play a key role in the host defense against Mucorales. The diagnosis of PM relies on CT scans, cultures, PCR tests, and histology. The reversed halo sign is an early, but very suggestive, sign of PM in neutropenic patients. Recently, the serum PCR test showed a very encouraging performance for the diagnosis and follow-up of mucormycosis. Liposomal amphotericin B is the drug of choice for first-line therapy, together with correction of underlying disease and surgery when feasible. After a stable or partial response, the step-down treatment includes oral isavuconazole or posaconazole delayed release tablets until a complete response is achieved. Secondary prophylaxis should be discussed when there is any risk of relapse, such as the persistence of neutropenia or the prolonged use of high-dose immunosuppressive therapy. Despite these novelties, the mortality rate from PM remains higher than 50%. Therefore, future research must define the place for combination therapy and adjunctive treatments, while the development of new treatments is necessary.
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10
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Motamedi M, Golmohammadi Z, Yazdanpanah S, Saneian SM, Shafiekhani M. Epidemiology, clinical features, therapeutic interventions and outcomes of mucormycosis in Shiraz: an 8-year retrospective case study with comparison between children and adults. Sci Rep 2022; 12:17174. [PMID: 36229497 PMCID: PMC9561111 DOI: 10.1038/s41598-022-21611-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 09/29/2022] [Indexed: 01/04/2023] Open
Abstract
Mucormycosis is an invasive fungal infection with high morbidity and mortality rate despite the early diagnosis and proper therapeutic interventions. Given the importance of epidemiological data in reviewing the attitude toward infectious diseases in developing countries, the current retrospective case study aimed to compare the epidemiological aspects, risk factors, clinical characteristics, therapeutic interventions, and outcomes of mucormycosis between adults and children during eight years (2013-2021) in the main infectious disease referral centers in the southwest of Iran. The median age of 164 patients included in this study was 47 years (IQR 22-59). The median length of hospitalization was 33 days.The annual incidence of mucormycosis-related hospitalizations was estimated 1.76 per 10,000 admissions during the study period. Moreover, the incidence of infection was 2.4 times higher in males than females in children. Diabetes mellitus was the most frequent predisposing factor in adults (46.0%). The main risk factor in children was hematologic malignancy (52.6%), but a considerable proportion of them (28.9%) were immunocompetent.The most frequent antifungal agent used was liposomal amphotericin B (82.3%) as monotherapy. The combination therapy was used more in adults (15.8%) than children (7.9%). In addition, surgical intervention with antifungal therapy was considered the most effective therapeutic approach. The in-hospital mortality rate was 14.6% for adults, whereas it was zero for children. Our findings provide a recent epidemiologic analysis of mucormycosis among hospitalized patients in both children and adults. Mucormycosis mainly affects individuals with diabetes mellitus or hematological malignancies and presents as rhino-orbito-cerebral form. Proven diagnosis of mucormycosis according to clinical manifestations and histopathology observations accompanied by proper antifungal treatments may improve survival rates.
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Affiliation(s)
- Marjan Motamedi
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Golmohammadi
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Somayeh Yazdanpanah
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - S Mojtaba Saneian
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mojtaba Shafiekhani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
- Shiraz Organ Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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11
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Muthu V, Agarwal R, Patel A, Kathirvel S, Abraham OC, Aggarwal AN, Bal A, Bhalla AS, Chhajed PN, Chaudhry D, Garg M, Guleria R, Krishnan RG, Kumar A, Maheshwari U, Mehta R, Mohan A, Nath A, Patel D, Rudramurthy SM, Saxena P, Sethuraman N, Singhal T, Soman R, Thangakunam B, Varghese GM, Chakrabarti A. Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India. THE LANCET. INFECTIOUS DISEASES 2022; 22:e240-e253. [PMID: 35390293 PMCID: PMC8979562 DOI: 10.1016/s1473-3099(22)00124-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/03/2022] [Accepted: 02/03/2022] [Indexed: 12/16/2022]
Abstract
COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.
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Affiliation(s)
- Valliappan Muthu
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ritesh Agarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Atul Patel
- Department of Infectious Diseases, Sterling Hospital, Ahmedabad, India
| | - Soundappan Kathirvel
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Ashutosh Nath Aggarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Amanjit Bal
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashu Seith Bhalla
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Prashant N Chhajed
- Department of Pulmonary Medicine, Institute of Pulmonology, Medical Research and Development, Mumbai, India
| | - Dhruva Chaudhry
- Department of Pulmonary Medicine, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, India
| | - Mandeep Garg
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Randeep Guleria
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
| | | | - Arvind Kumar
- Department of Thoracic Surgery, Medanta Hospital, Gurgaon, India
| | - Uma Maheshwari
- Department of Pulmonary Medicine, St John's Hospital, Bengaluru, India
| | - Ravindra Mehta
- Department of Pulmonary Medicine, Apollo Hospitals, Bengaluru, India
| | - Anant Mohan
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Alok Nath
- Department of Pulmonary Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Dharmesh Patel
- Department of Pulmonary Medicine, City Clinic and Bhailal Amin General Hospital, Vadodara, India
| | | | - Puneet Saxena
- Department of Pulmonary Medicine, Army Hospital Research and Referral, New Delhi, India
| | | | - Tanu Singhal
- Department of Infectious Diseases, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India
| | - Rajeev Soman
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | | | - George M Varghese
- Department of Internal Medicine, Christian Medical College, Vellore, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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12
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COVID-19-Associated Pulmonary Mucormycosis. J Fungi (Basel) 2022; 8:jof8070711. [PMID: 35887466 PMCID: PMC9315775 DOI: 10.3390/jof8070711] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/30/2022] [Accepted: 07/01/2022] [Indexed: 12/21/2022] Open
Abstract
COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino–orbital mucormycosis was well reported during the pandemic, in the absence of routine diagnostic facilities including lower airway sampling, pulmonary mucormycosis was probably under-recognized. In this review, we have focused on the epidemiology and management of COVID-19-associated pulmonary mucormycosis (CAPM). CAPM is a deadly disease and mortality can be as high as 80% in the absence of early clinical suspicion and treatment. While histopathological examination of tissue for angio-invasion and cultures have remained gold standard for diagnosis, there is an increasing interest in molecular and serological methods to facilitate diagnosis in critically ill patients and often, immune-suppressed hosts who cannot readily undergo invasive sampling. Combined medical and surgical treatment offers more promise than standalone medical therapy. Maintaining adequate glycemic control and prudent use of steroids which can be a double-edged sword in COVID-19 patients are the key preventative measures. We would like to emphasize the urgent need for the development and validation of reliable biomarkers and molecular diagnostics to facilitate early diagnosis.
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13
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Byrd CT, Vyas D, Guo HH, Lui NS. 3-D printed model of surgically resectable angioinvasive pulmonary mucormycosis. JTCVS Tech 2022; 13:244-246. [PMID: 35711220 PMCID: PMC9197082 DOI: 10.1016/j.xjtc.2022.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/14/2022] [Accepted: 04/11/2022] [Indexed: 12/03/2022] Open
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14
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Merritt RE. Commentary: Pneumonectomy for resection of pulmonary mucormycosis: Enough is never too much. JTCVS Tech 2022; 11:87-88. [PMID: 35169750 PMCID: PMC8828789 DOI: 10.1016/j.xjtc.2021.10.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 10/11/2021] [Accepted: 10/22/2021] [Indexed: 10/26/2022] Open
Affiliation(s)
- Robert E. Merritt
- Division of Thoracic Surgery, The Ohio State University-Wexner Medical Center, Columbus, Ohio
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15
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The Reverse Halo Sign in an Immunocompromised Host. J Gen Intern Med 2021; 36:2452-2453. [PMID: 33904050 PMCID: PMC8342741 DOI: 10.1007/s11606-021-06795-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 04/01/2021] [Indexed: 10/21/2022]
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16
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Yousaf M, Salameh S, Haq IU, Alhyassat S, Thomas M, Hussain A, Wani M, Massad E, Hadi HA, Sattar HA, Hameed M. Challenges in the diagnosis of pulmonary mucormycosis in a diabetic with a review of literature. Respir Med Case Rep 2021; 33:101474. [PMID: 34401308 PMCID: PMC8349084 DOI: 10.1016/j.rmcr.2021.101474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/23/2021] [Accepted: 07/06/2021] [Indexed: 11/28/2022] Open
Abstract
Diabetes Mellitus appears to be the most common underlying condition associated with mucormycosis; a rare opportunistic fungal infection associated with high morbidity and mortality. Pulmonary mucormycosis may mimic pneumonia and thus pose challenges in achieving a timely diagnosis critical to successful outcomes. We present a case of a 65-year-old diabetic who presented with fever and haemoptysis that was managed as pneumonia. A bronchial alveolar lavage grew Rhizopus mould that was thought to be a contaminant as he responded well to antibiotics. He required another admission in 4 weeks due to worsening symptoms. Failure to respond to antibiotics and ongoing clinical and radiological deterioration led to a lobectomy that confirmed a diagnosis of pulmonary mucormycosis. He responded well to surgical resection and antifungal therapy with a complete recovery. Elusive clinical presentation and insensitive conventional diagnostic techniques may make the diagnosis of mucormycosis challenging. Our case reports highlight the issues involved in the diagnosis and management of pulmonary Mucormycosis mimicking as pneumonia.
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Affiliation(s)
- Muhammad Yousaf
- Hazm Mebaireek Hospital, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar
| | - Sarah Salameh
- Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar.,Communicable Diseases Centre, Hamad Medical Corporation, Qatar
| | - Irfan Ul Haq
- Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar
| | - Samir Alhyassat
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Qatar
| | - Merlin Thomas
- Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar
| | - Aisha Hussain
- Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Mohd Wani
- Department of Cardiothoracic Surgery, Hamad Medical Corporation, Qatar
| | - Ehab Massad
- Department of Cardiothoracic Surgery, Hamad Medical Corporation, Qatar
| | | | | | - Mansoor Hameed
- Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar
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17
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Larcher R, Platon L, Amalric M, Brunot V, Besnard N, Benomar R, Daubin D, Ceballos P, Rispail P, Lachaud L, Bourgeois N, Klouche K. Emerging Invasive Fungal Infections in Critically Ill Patients: Incidence, Outcomes and Prognosis Factors, a Case-Control Study. J Fungi (Basel) 2021; 7:330. [PMID: 33923333 PMCID: PMC8146331 DOI: 10.3390/jof7050330] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/12/2021] [Accepted: 04/23/2021] [Indexed: 12/29/2022] Open
Abstract
Comprehensive data on emerging invasive fungal infections (EIFIs) in the critically ill are scarce. We conducted a case-control study to characterize EIFIs in patients admitted to a French medical ICU teaching hospital from 2006 to 2019. Among 6900 patients, 26 (4 per 1000) had an EIFI: Mucorales accounted for half, and other isolates were mainly Saprochaete, Fusarium and Scedosporium. EIFIs occurred mostly in patients with immunosuppression and severe critical illness. Antifungal treatments (mainly amphotericin B) were administered to almost all patients, whereas only 19% had surgery. In-ICU, mortality was high (77%) and associated with previous conditions such as hematological malignancy or cancer, malnutrition, chronic kidney disease and occurrence of acute respiratory distress syndrome and/or hepatic dysfunction. Day-90 survival rates, calculated by the Kaplan-Meier method, were similar between patients with EIFIs and a control group of patients with aspergillosis: 20%, 95% CI (9- 45) versus 18%, 95% CI (8- 45) (log-rank: p > 0.99). ICU management of such patients should be assessed on the basis of underlying conditions, reversibility and acute event severity rather than the mold species.
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Affiliation(s)
- Romaric Larcher
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
- PhyMedExp, INSERM (French Institute of Health and Medical Research), CNRS (French National Centre for Scientific Research), University of Montpellier, 34090 Montpellier, France
| | - Laura Platon
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Matthieu Amalric
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Vincent Brunot
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Noemie Besnard
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Racim Benomar
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Delphine Daubin
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
| | - Patrice Ceballos
- Hematology Department, Saint Eloi Hospital, Montpellier University Hospital, 34090 Montpellier, France;
| | - Philippe Rispail
- Mycology and Parasitology Laboratory, Lapeyronie Hospital, Montpellier University Hospital, 34090 Montpellier, France; (P.R.); (L.L.); (N.B.)
| | - Laurence Lachaud
- Mycology and Parasitology Laboratory, Lapeyronie Hospital, Montpellier University Hospital, 34090 Montpellier, France; (P.R.); (L.L.); (N.B.)
- MiVEGEC (Infectious Diseases and Vectors: Ecology, Genetic, Evolution and Control), IRD (Research and Development Institute), CNRS, University of Montpellier, 911 Avenue Agropolis, 34394 Montpellier, France
| | - Nathalie Bourgeois
- Mycology and Parasitology Laboratory, Lapeyronie Hospital, Montpellier University Hospital, 34090 Montpellier, France; (P.R.); (L.L.); (N.B.)
- MiVEGEC (Infectious Diseases and Vectors: Ecology, Genetic, Evolution and Control), IRD (Research and Development Institute), CNRS, University of Montpellier, 911 Avenue Agropolis, 34394 Montpellier, France
| | - Kada Klouche
- Intensive Care Medicine Department, Lapeyronie Hospital, Montpellier University Hospital, 371, Avenue du Doyen Gaston Giraud, 34090 Montpellier, France; (L.P.); (M.A.); (V.B.); (N.B.); (R.B.); (D.D.); (K.K.)
- PhyMedExp, INSERM (French Institute of Health and Medical Research), CNRS (French National Centre for Scientific Research), University of Montpellier, 34090 Montpellier, France
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18
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Muthu V, Agarwal R, Dhooria S, Sehgal IS, Prasad KT, Aggarwal AN, Chakrabarti A. Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis. Clin Microbiol Infect 2021; 27:538-549. [PMID: 33418022 DOI: 10.1016/j.cmi.2020.12.035] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/25/2020] [Accepted: 12/31/2020] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Pulmonary mucormycosis (PM) is increasingly being reported in immunocompromised patients and has a high mortality. Our aim was to assess the mortality of PM and its trend over time. We also evaluated the role of combined medical-surgical therapy in PM. METHODS We performed a systematic review of Pubmed, Embase, and Cochrane central databases. Studies were eligible if they described at least five confirmed cases of PM and reported mortality. We also assessed the effect of combined medical-surgical therapy versus medical treatment alone on PM mortality. We used a random-effects model to estimate the pooled mortality of PM and compared it across three time periods. The factors influencing mortality were assessed using meta-regression. We evaluated the risk difference (RD) of death in the following: subjects undergoing combined medical-surgical therapy versus medical therapy alone, subjects with isolated PM versus disseminated disease, and PM in diabetes mellitus (DM) versus non-DM as a risk factor. RESULTS We included 79 studies (1544 subjects). The pooled mortality of PM was 57.1% (95% confidence interval [CI] 51.7-62.6%). Mortality improved significantly over time (72.1% versus 58.3% versus 49.8% for studies before 2000, 2000-2009, and 2010-2020, respectively, p 0.00001). This improved survival was confirmed in meta-regression after adjusting for the study design, the country's income level, and the sample size. Combined medical-surgical therapy was associated with a significantly lower RD (95%CI) of death: -0.32 (-0.49 to -0.16). The disseminated disease had a higher risk of death than isolated PM, but DM was not associated with a higher risk of death than other risk factors. CONCLUSIONS While PM is still associated with high mortality, we noted improved survival over time. Combined medical-surgical therapy improved survival compared to medical treatment alone.
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Affiliation(s)
- Valliappan Muthu
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
| | - Ritesh Agarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sahajal Dhooria
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Inderpaul Singh Sehgal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Kuruswamy Thurai Prasad
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ashutosh N Aggarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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19
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Shao W, Zhang Z, Feng H, Liang C, Liu D. Pulmonary mucormycosis: a case of pulmonary arterial hypertension, Westermark sign, and bronchopleural fistula. J Int Med Res 2020; 48:300060520971450. [PMID: 33249953 PMCID: PMC7708708 DOI: 10.1177/0300060520971450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
We herein describe a patient with pulmonary mucormycosis and acute myelogenous leukemia. Computed tomography showed a widened pulmonary artery, a bronchopleural fistula, and the Westermark sign. Despite worsening hemoptysis, the operation was delayed for 6 months. The operation was very complicated and difficult. A thorough preoperative examination, adequate preoperative preparation, appropriate surgical timing, and rich clinical and surgical experience were the keys to successful surgery in this case.
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Affiliation(s)
- Weipeng Shao
- Department of General Thoracic Surgery, Peking University China-Japan Friendship School of Clinical Medicine and China-Japan Friendship Hospital, Beijing, China
| | - Zhenrong Zhang
- Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Hongxiang Feng
- Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Chaoyang Liang
- Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Deruo Liu
- Department of General Thoracic Surgery, Peking University China-Japan Friendship School of Clinical Medicine and China-Japan Friendship Hospital, Beijing, China
- Deruo Liu, Department of General Thoracic Surgery, Peking University China-Japan Friendship School of Clinical Medicine and China-Japan Friendship Hospital, No. 2 Yinghua East Road, Beijing 100029, China.
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20
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Chen Q, Chen K, Qian S, Wu S, Xu L, Huang X, Shi P, Wang K, Wang M, Wang X. Disseminated mucormycosis with cerebellum involvement due to Rhizomucor pusillus in a patient with multiple myeloma and secondary myelodysplastic syndrome: A case report. Exp Ther Med 2019; 18:4076-4080. [PMID: 31656543 PMCID: PMC6812476 DOI: 10.3892/etm.2019.8065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 09/04/2019] [Indexed: 12/15/2022] Open
Abstract
Mucormycosis is an angioinvasive fungal infection with a high mortality rate. Patients with hematological malignancies following voriconazole therapy are at high risk from mucormycosis. Here, the present study reports on a 68-year-old man diagnosed with multiple myeloma and secondary myelodysplastic syndrome, who was infected with disseminated mucormycosis with cerebellum involvement confirmed by mycological culture and histopathological examination. For patients with hematological malignancies who are receiving antifungal therapy, an opportunistic infection of mucormycosis should be considered if a ‘breakthrough’ infection occurs in the predilection sites (such as the sinuses, lungs, skin, brain and gastrointestinal tract). It is difficult to diagnose mucormycosis because of the limited reliable detection methods, and because mucormycosis often presents with an acute onset and progresses rapidly, particularly in immunocompromised patients. Antifungal therapy with amphotericin B or posaconazole should be started as soon as possible considering the empirical diagnosis.
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Affiliation(s)
- Qiong Chen
- Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Kuang Chen
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Shenxian Qian
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Shenghai Wu
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Lihui Xu
- Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Xilian Huang
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Pengfei Shi
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Kaile Wang
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Minmin Wang
- Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Xianjun Wang
- Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
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21
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Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients. Antimicrob Agents Chemother 2019; 63:AAC.01244-19. [PMID: 31481441 DOI: 10.1128/aac.01244-19] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
While Aspergillus spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as Mucorales, Fusarium, and Scedosporium spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-Aspergillus invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between in vitro susceptibility and in vivo responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.
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