Management of Pulmonary Mucormycosis: A Systematic Review

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This systematic review focuses on the management of PM. Although the mortality from PM has improved over the last few decades, it is still high, at 49.8%. Objective The objective is to identify and map the management of pulmonary mucormycosis. Design This review is designed for knowledge synthesis, with a systematic approach to identifying, synthesizing, and mapping treatment protocols for the management of PM. Methods This systematic review is reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Inclusion criteria were defined: peer-reviewed journal articles published in English from 2018 to 2023 relating to treatment protocols for PM, where the full text of the article was available. Exclusion criteria were also defined - articles that focus on limited treatment regimens, or topics not relevant to the research question. Results The results span six years, from 2018 to 2023, with 355 articles identified. After removing duplicates, 227 papers remained. Inclusion and exclusion criteria were applied, with 202 articles excluded as a result. The remaining 19 articles were deemed relevant. In addition, seven relevant articles were identified via citation tracking and two articles identified by hand search. Thus, a total of 28 articles thus reviewed. The management of PM was mapped in tabular and diagrammatic form. Conclusion The results indicate that early diagnosis, early and aggressive surgery, and effective antifungals may improve survival. There is a shift away from using Am-B and a clear preference for L-AmB as a first-line antifungal. Posaconazole and Isavuconazole are the drugs of choice for stepdown, maintenance, and salvage therapy, and as alternative therapies. The control of co-morbidities is a crucial aspect of treatment. Cytokines and hyperbaric oxygen may be beneficial. The therapeutic value of iron chelators, zinc, and nebulized amphotericin B (NAB) merit further study. 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F1000Research 2025, 13 :1165 ( https://doi.org/10.12688/f1000research.151564.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Revised Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] Tarig Fadelelmoula 1 , Navas Ayyalil 1 , Nandini Doreswamy 2 Tarig Fadelelmoula 1 , Navas Ayyalil 1 , Nandini Doreswamy 2 PUBLISHED 28 Jul 2025 Author details Author details 1 Department of Medicine, College of Medicine and Health Sciences, National University of Science and Technology, Sohar, North AlBatina, Oman 2 National Coalition of Independent Scholars, Suite 465, 48, Dickson Place, Dickson, ACT 2602, Australia Tarig Fadelelmoula Roles: Conceptualization, Methodology, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing Navas Ayyalil Roles: Conceptualization, Data Curation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Nandini Doreswamy Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Global Public Health gateway. This article is included in the Pathogens gateway. Abstract Background Pulmonary mucormycosis is a life-threatening fungal infection. This systematic review focuses on the management of PM. Although the mortality from PM has improved over the last few decades, it is still high, at 49.8%. Objective The objective is to identify and map the management of pulmonary mucormycosis. Design This review is designed for knowledge synthesis, with a systematic approach to identifying, synthesizing, and mapping treatment protocols for the management of PM. Methods This systematic review is reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Inclusion criteria were defined: peer-reviewed journal articles published in English from 2018 to 2023 relating to treatment protocols for PM, where the full text of the article was available. Exclusion criteria were also defined - articles that focus on limited treatment regimens, or topics not relevant to the research question. Results The results span six years, from 2018 to 2023, with 355 articles identified. After removing duplicates, 227 papers remained. Inclusion and exclusion criteria were applied, with 202 articles excluded as a result. The remaining 19 articles were deemed relevant. In addition, seven relevant articles were identified via citation tracking and two articles identified by hand search. Thus, a total of 28 articles thus reviewed. The management of PM was mapped in tabular and diagrammatic form. Conclusion The results indicate that early diagnosis, early and aggressive surgery, and effective antifungals may improve survival. There is a shift away from using Am-B and a clear preference for L-AmB as a first-line antifungal. Posaconazole and Isavuconazole are the drugs of choice for stepdown, maintenance, and salvage therapy, and as alternative therapies. The control of co-morbidities is a crucial aspect of treatment. Cytokines and hyperbaric oxygen may be beneficial. The therapeutic value of iron chelators, zinc, and nebulized amphotericin B (NAB) merit further study. READ ALL READ LESS Keywords pulmonary mucormycosis, pulmonary fungal infections, COVID-19 associated pulmonary mucormycosis, CAPM; management of pulmonary mucormycosis, management of pulmonary mucormycosis; mucormycosis, Mucorales. Corresponding Author(s) Tarig Fadelelmoula ( [email protected] ) Close Corresponding author: Tarig Fadelelmoula Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Fadelelmoula T et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Fadelelmoula T, Ayyalil N and Doreswamy N. Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.12688/f1000research.151564.2 ) First published: 08 Oct 2024, 13 :1165 ( https://doi.org/10.12688/f1000research.151564.1 ) Latest published: 28 Jul 2025, 13 :1165 ( https://doi.org/10.12688/f1000research.151564.2 ) Revised Amendments from Version 1 Points from the first reviewer were carefully addressed regarding the confining the introduction to pulmonary Mucormycosis and balancing the management part with regards to cheating agents in the treatment of Mucormycosis. Points from the first reviewer were carefully addressed regarding the confining the introduction to pulmonary Mucormycosis and balancing the management part with regards to cheating agents in the treatment of Mucormycosis. See the authors' detailed response to the review by Eric Dannaoui READ REVIEWER RESPONSES Introduction Etiology Humans usually contract mucormycosis by inhaling sporangiospores of Mucorales species leading to pulmonary mucormycosis ( Ribes et al., 2000 ; Richardson, 2009 ). Mucorales species have significant angio-invasive characteristics, which results in rapid local progression and substantial morbidity ( Lee et al., 1999 ; Moreira et al., 2016 ; Prakash et al., 2019 ). Epidemiology The most common clinical presentations of mucormycosis are rhino-orbito-cerebral (34%) and pulmonary (21%), the lungs being the second most common site of involvement in patients with mucormycosis ( Jeong et al., 2019 ; Prakash et al., 2019 ). The incidence of mucormycosis is rising globally ( Ambrosioni et al., 2010 ; Bitar et al., 2009 ; Pana et al., 2016 ; Torres-Narbona et al., 2007 ). Significant risk factors include uncontrolled diabetes mellitus in ketoacidosis, other forms of metabolic acidosis, treatment with glucocorticoids, organ or bone marrow transplantation, neutropenia, trauma and burns, malignant hematologic disorders, and deferoxamine therapy in patients receiving hemodialysis ( Ibrahim et al., 2003 ; Spellberg et al., 2005 ; Sugar, 1990 ). For PM, haematological malignancy is the major risk factor (32–40%), followed by diabetes mellitus (32–56%), haematopoietic stem cell transplant (1–9.8%) and solid organ transplant (6.5–9%), and renal disease (13–18%) ( Feng & Sun, 2018 ; Tedder et al., 1994 ). There are recent changes in the epidemiology of the disease, especially in Asia, where tuberculosis and chronic renal failure are emerging risks ( Prakash & Chakrabarti, 2019 ). Clinical presentation Symptoms of PM include dyspnea, cough, chest pain, and fever is present in most reported cases ( Tedder et al., 1994 ). Angioinvasion leads to the necrosis of the pulmonary parenchyma, which may lead to cavitation and hemoptysis. This can be fatal if a major blood vessel is involved ( Harada et al., 1992 ; Watts, 1983 ). Although most patients with PM present with a fulminant and rapidly progressive disease, some patients only present with chronic symptoms ( Agarwal et al., 2006 ). Screening and diagnosis Early diagnosis is a cornerstone of successful management ( Fernandez et al., 2013 ). Clinical diagnostic methods have low sensitivity and specificity, which makes the diagnosis of PM challenging ( Skiada et al., 2018 ). Therefore, diagnosis requires a high index of suspicion, recognition of host factors, and analysis of the clinical presentation. The prompt use of imaging, as well as histology, microbiology, and advanced molecular methods underpin successful diagnosis and management ( Skiada et al., 2018 ). Molecular diagnosis In 2014, Gebremariam et al. investigated host immune responses to Mucorales. They discovered the genes for proteins that encode spore coatings – the CotH genes, which are only found in Mucorales ( Gebremariam et al., 2014 ). A 2018 study by Baldin et al. showed that CotH could be used as a target for the early diagnosis of mucormycosis ( Baldin et al., 2018 ). In this study, mice infected with Rhizopus delemar , Lichtheimia corymbifera , Cunninghamella bertholettiae , and Mucor circinelloides , were positive for CotH , detected through polymerase chain reaction (PCR), in 3/3, 1/3, 2/2, and 3/3 urine samples, respectively ( Baldin et al., 2018 ). Real-time qualitative polymerase chain reaction (qPCR) can now be used to detect Mucorales DNA in blood samples. qPCR is non-invasive and allows mucormycosis to be diagnosed up to eight days before mycological diagnosis ( Bourcier et al., 2017 ; Millon et al., 2013 , 2016 ; Springer et al., 2016 ). In 2022, Alinaghi et al. (2022) found that when mucormycosis occurred as a co-infection alongside COVID-19, the mortality rate was 33.6%. Furthermore, mucormycosis was diagnosed between 3 and 45 days after the diagnosis of COVID-19, and other co-infections such as aspregillosis occasionally occurred ( Alinaghi et al., 2022 ). Chest X-ray Radiology may only show peribronchial ground-glass opacity in the early stages, but later, pulmonary nodules, isolated masses, lobar consolidation, or cavitation may be found ( Kawakami et al., 2004 ; Lin et al., 2017 ; McAdams et al., 1997 ). Wedge-shaped pulmonary infarcts may also be found. These infarcts are usually seen when there is thrombosis of the pulmonary vessels, following fungal angioinvasion ( Marchevsky et al., 1980 ). Chest CT scan High-resolution chest CT scans are the preferred method to detect the extent of PM. These scans may show evidence of a Mucorales infection earlier than a chest X-ray. If an expanding mass is found, or a consolidation across tissue planes, especially towards the great vessels of the mediastinum, it is highly suggestive of mucormycosis ( Reimund & Ramos, 1994 ). Other suggestive findings include 10 or more nodules with pleural effusion ( Skiada et al., 2018 ). When a reverse halo sign is found on CT, it is more suggestive of PM than IPA ( Agrawal et al., 2020 ). Bronchoscopy The use of bronchoscopy in obtaining tissue biopsy for microscopic histological examination and culture seems to be safe in capitating lung lesions, despite its potential risk factors (e.g., pneumothorax) ( Smith & Kauffman, 2012 ). Bronchoscopic guided Trans-Bronchial Lung Biopsy (TBLB) is the most common modality used to obtain lung tissue for diagnosis ( Krishna et al., 2022 ). As far back as 1999, Lee, Mossad, and Adal undertook a 30-year review of patients with mucormycosis – of the 35 patients reviewed, bronchoscopy was required in more than 70% for a definitive diagnosis ( Lee et al., 1999 ). Bronchoscopy remains a mainstay of diagnosis even today. In 2022, the Delphi panel recommended early bronchoscopy in all suspected cases of this life-threatening disease ( Muthu et al., 2022 ). Histology, Molecular Tests, and Biopsy The diagnosis of mucormycosis is based on both histopathological findings of tissue invasion by hyphae and cultures isolating pathogens of the order Mucorales, most commonly Rhizopus, Mucor, and Rhizomucor species ( Smith & Lee, 2022 ). Many molecular based tests can be used either for detection or identification of mucorales, these tests include polymerase chain reaction (PCR) ( Hsiao et al., 2005 ), restriction fragment length polymorphism analyses (RFLP) ( Kumar et al., 2022 ; Page et al., 2021 ), DNA sequencing of defined gene regions ( Nyilasi et al., 2008 ; Springer et al., 2016 ), and melt curve analysis of PCR products ( Kasai et al., 2008 ). While transbronchial lung biopsy (TBLB) is the most common method of obtaining lung tissue for diagnosis, specimen tissue can also be obtained by video-assisted thoracoscopic surgery (VATS) and open lung biopsy in patients undergoing surgical treatment ( Krishna et al., 2022 ). In patients with haematologic disease, it can be a challenge to perform a diagnostic biopsy early. In a study of 28 haematologic patients, Potenza et al. (2011) demonstrated that Mucorales-specific T cells were only detected in patients with proven invasive mucormycosis – these cells neither detected before the onset of infection nor after the infection was fully resolved. Therefore, when early diagnostic biopsy is a challenge, Mucorales-specific T cells can be an effective surrogate diagnostic marker. Artificial intelligence (AI) Syed-Abdul et al. (2022) showed that Artificial Intelligence-based models may be able to predict the risk of mucormycosis after COVID-19. AI models may be able to identify high-risk patients and flag predisposing factors such as obesity, anosmia, de novo diabetes, myalgia, and nasal discharge. Such models may enable protocols during and after COVID-19 that prevent co-infection with Mucorales ( Agrawal et al., 2020 ). Despite treatment with antifungal therapy and surgical debridement, the mortality rate is around 50% ( Muthu, Singh, et al., 2021 ). The incidence of mucormycosis is rising globally ( Ambrosioni et al., 2010 ; Bitar et al., 2009 ; Pana et al., 2016 ; Torres-Narbona et al., 2007 ). Although the mortality rate of this disease has improved over time, it is still high ( Muthu, Agarwal, et al., 2021 ). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. This systematic review focuses on the pulmonary form of the disease, seeking to identify and map recent treatment protocols for PM. For PM, haematological malignancy is the major risk factor (32–40%), followed by diabetes mellitus (32–56%), haematopoietic stem cell transplant (1–9.8%) and solid organ transplant (6.5–9%), and renal disease (13–18%) ( Feng & Sun, 2018 ; Tedder et al., 1994 ). The clinical presentation, radiological presentation, and risk factors of PM are often very similar to acute Invasive Pulmonary Aspergillosis (IPA) ( Agrawal et al., 2020 ). One of the most remarkable signs of PM is tissue necrosis, which is often a result of vascular thrombosis. In immunocompromised hosts, the primary route of infection is the inhalation of sporangiospores, which leads to pulmonary infection ( Roden et al., 2005 ). PM tends to occur in patients with high neutropenia ( Roden et al., 2005 ). A definitive diagnosis of PM relies on histopathology of pulmonary tissue, culture of sputum secretions, bronchoalveolar lavage, fine needle aspiration, or a combination of these diagnostic methods ( Mir et al., 2018 ). The incidence of PM increased dramatically during the COVID-19 pandemic, with most cases seen in India. Uncontrolled diabetes and the use of glucocorticoids in India, and ICU stays elsewhere, are the main factors associated with this increase ( Hoenigl et al., 2022 ). COVID-19-associated PM (CAPM) is difficult to diagnose because its clinical presentation is often the same as COVID-19 itself ( Hoenigl et al., 2022 ). It is diagnosed at the same time as COVID-19 or within 3 months of virologically confirmed infection ( Muthu et al., 2022 ). Any patient with COVID-19 who has haemoptysis, or expectorates brownish or black sputum, should be investigated for CAPM ( Pruthi et al., 2022 ). Before the advent of the antifungal amphotericin B deoxycholate (Am-B) in 1959, mucormycosis in all its forms carried a mortality of 84%, but the use of Am-B led to a dramatic improvement – by the 1990s, the mortality rate fell to 47% ( Roden et al., 2005 ). A review conducted in 2021 shows how mortality from PM, specifically, has improved over time – before the year 2000, it was as high as 72.1%, dropping to 58.3% between 2000 and 2009, and decreasing even further, to 49.8%, between 2010 and 2020 ( Muthu, Agarwal, et al., 2021 ). While Am-B has been the mainstay of antifungal treatment for decades, its use has often been limited by a high degree of dose-dependent toxicity. It has now largely been replaced by liposomal amphotericin B, a lipid-based form of the drug, which has a significantly better toxicity profile. Other drugs, such as triazoles, have been found to be effective – posaconazole, introduced in 2006 ( Brigmon et al., 2021 ), and isuvaconazole, approved for use in 2015 ( Greenberg et al., 2006 ; van Burik et al., 2006 ) have not only been deployed as primary therapies, usually in combination with L-AmB, but also as stepdown, maintenance, and salvage therapies. Adjunctive immune therapies have also looked promising in recent years – granulocyte transfusions, cytokines such as interferon-gamma (IFN-γ), and recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) ( Spellberg & Ibrahim, 2010 ). Hyperbaric oxygen may also be a useful adjunct ( John et al., 2021 ). In addition, there has been some debate about whether iron chelators and zinc have a role to play in the treatment of mucormycosis. During the pandemic, there was a surge in mucormycosis in patients with COVID-19 and in those who recovered from COVID-19 ( Ghazi et al., 2021 ). COVID-19-associated PM (CAPM) has been described in patients infected with SARS-CoV-2. Several factors have been implicated in the development of CAPM, including the use of glucocorticoids, poor glycaemic control, and viral-induced lymphopenia ( Pal et al., 2021 ). Thromboembolic events are also seen in COVID-19, including pulmonary embolism, deep vein thrombosis (DVT), cerebrovascular accidents (CVA), and myocardial infarction ( Abbas et al., 2021 ). The resultant hyper-coagulability and distal ischemia may well contribute to mucormycosis, although definitive proof for this remains elusive. The prime site of infection depends on the type of Mucorales and the comorbidity of the affected individual ( Jeong et al., 2019 ; Lanternier et al., 2012 ; Skiada et al., 2011 ). Bone and joint infections, peritonitis, and nephritis are rare forms of mucormycosis ( Serris et al., 2019 ). Endocarditis is also rare and is usually only seen in intravenous drug users ( Serris et al., 2019 ). Climate change Climate change plays a role in the emergence of diseases ( El-Sayed & Kamel, 2020 ). It may result in a surge in known fungal diseases and the emergence of new fungal diseases as well ( Garcia-Solache & Casadevall, 2010 ). Climate change is defined by the United Nations Framework Convention on Climate Change (FCCC) as “a change of climate which is attributed directly or indirectly to human activity that alters the composition of the global atmosphere and which is in addition to natural climate variability observed over comparable time periods” ( Pielke, 2004 ). The geographic range of fungal pathogens is expanding because of the increase in temperature at higher latitudes ( Gadre et al., 2022 ). Many fungal species are capable of developing thermotolerance and, as a result, fungi previously harmless to humans may become pathogenic ( Gadre et al., 2022 ). Sivagnanam et al. (2017) reported patient clusters with sino-pulmonary mucormycosis associated with changes in climatic conditions, such as changes in precipitation and temperature. Extreme climate events may also exacerbate the incidence of fungal disease - for instance, there are reports of necrotizing fasciitis caused by mucormycosis after the Indian Ocean tsunami of 2004 ( Andresen et al., 2005 ) and the Missouri tornado of 2011 ( Neblett Fanfair et al., 2012 ). The incidence of mucormycosis in India and Pakistan is a hundred times higher than the rest of the world combined ( van Rhijn & Bromley, 2021 ). The higher incidence of co-morbidities such as diabetes mellitus accounts for some proportion of this significant difference in incidence ( Ghazi et al., 2021 ). However, even before the advent of Covid-19, there was an increase in the number of cases of mucormycosis in these South Asian countries, and the higher incidence of diabetes mellitus alone does not account for the increase ( van Rhijn & Bromley, 2021 ). Climate change in South Asia could be a contributing factor because fungi thrive at higher temperatures and in conditions of increasing humidity ( Pörtner et al., 2022 ; Safdar et al., 2019 ; van Rhijn & Bromley, 2021 ). Management The effective management of depends on early suspicion or recognition of PM. Early diagnosis is critical to effective treatment. The essential components of the management of this disease include the reversal of underlying risk factors, such as correcting hyperglycemia or tapering glucocorticoids; early and aggressive surgical resection, if possible; and optimal anti-fungal therapy ( Pandey et al., 2020 ; Patel et al., 2020 ). Amphotericin B is a reliable antifungal that is used for primary anti-fungal therapy, with L-AmB widely in use as a less toxic form of the drug. The triazoles posaconazole and isuvaconazole are also effective against mucormycosis, and are used as primary therapies and in stepdown, maintenance, and salvage therapies ( Smith & Lee, 2022 ). Surgical treatment PM usually progresses rapidly. Surgery is often a necessity because of the massive amount of tissue necrosis that occurs during the disease. Treating the disease and killing these highly virulent fungi may not prevent or reverse the tissue necrosis ( Ibrahim et al., 2005 ). While surgery and anti-fungal therapies are the primary modalities of treatment, clear-cut guidelines regarding the extent and timing of surgical resection are yet to be defined. However, a successful attempt at methodological management of PM was made by the authors in the previously reported surgical series ( Pulle et al., 2021 ). Aggressive surgical resection with clear margins should be offered whenever feasible, as anti-fungal therapy alone may have sub-optimal outcomes. Surgical resection should be synergised with peri-operative anti-fungal therapy to improve long-term survival ( Kumar et al., 2022 ). Antifungal therapy Amphotericin B (Am-B) has been in use from 1959, as a reliable antifungal that is effective in treating progressive and potentially fatal fungal infections ( Cavassin et al., 2021 ). It is still an important option in the treatment of mucormycosis. However, Am-B has a high dose-dependent toxicity that can manifest as nephrotoxicity ( Deray, 2002 ) or reactions to infusions ( Cavassin et al., 2021 ). Am-B is only recommended now in settings where resources are limited, or it is the only treatment option available ( Cornely et al., 2019 ). There is sufficient evidence in the literature to merit the early initiation of the lipid-based amphotericin B formulation, liposomal amphotericin-B (L-AmB), instead of Am-B, as the first line of treatment, in doses of 5 to 10 mg per kilogram per day ( Kontoyiannis & Lewis, 2006 ; Lewis & Wiederhold, 2003 ). Nephrotoxicity and infusion-related reactions are significantly less with L-AmB ( Hamill, 2013 ). Its peak plasma level is much higher than Am-B and the area under the concentration-time curve is larger ( Hamill, 2013 ). It is smaller in size and carries a negative charge, so it avoids substantial recognition and uptake by the mononuclear phagocyte system ( Hamill, 2013 ). Recently, posaconazole and isuvaconazole have been used as primary therapies, usually in conjunction with L-AmB. Intravenous isuvaconazole, intravenous posaconazole, or delayed release posaconazole tablets are also recommended as salvage treatments, in moderate doses ( Cornely et al., 2019 ; Kohno et al., 2023 ). They are also used as stepdown or maintenance therapies, or as alternative therapies in patients who are unable to tolerate amphotericin B in any form ( Smith & Lee, 2022 ). It is worth noting that fluconazole, voriconazole and itraconazole have no activity on Mucorales ( Sun et al., 2002 ). Iron chelating agents Rhizoferrin is the most specific siderophore that Mucorales produce ( Tahiri et al., 2023 ). A recent experimental study in a murine model showed that rhizoferrin may increase fungal virulence ( Alejandre-Castañeda et al., 2022 ). Mucorales also produce permeases that have a high affinity for iron and make it available to the fungus ( Stearman et al., 1996 ). Therefore, iron chelators may have a role to play in the management of mucormycosis ( Boelaert et al., 1994 ; Symeonidis, 2009 ). Mucorales species have a very high affinity for iron. Therefore, iron chelators that do not capture and bind iron as efficiently as the pathogen, may “donate” iron to the fungus, thereby increasing a patient’s susceptibility to mucormycosis. Indeed, haemodialysis patients treated with the iron chelator deferoxamine (DFO) are more susceptible to mucormycosis ( Mahalmani et al., 2021 ). However, there are new iron chelators, deferiprone and deferasirox, are even more efficient at binding iron than Mucorales fungi ( Divakar Jose et al., 2021 ; Neufeld, 2006 ). Deferiprone and deferasirox also have a stable chemical structure and low molecular mass – these properties render them impervious to fungal iron uptake systems ( Boelaert et al., 1994 ; Symeonidis, 2009 ). There is anecdotal support as well – a case report in 2006 showed that salvage treatment with deferasirox had clear therapeutic benefits in rhino-cerebral mucormycosis ( Reed et al., 2006 ). Further study is warranted to evaluate the role of iron chelators in the management of mucormycosis. Cytokines, Granulocyte Transfusions and Hyperbaric Oxygen Cytokines, granulocyte transfusions, and hyperbaric oxygen are promising new therapies. Cytokines such as IFN-γ, G-CSF, and GM-CSF enhance host immunity by activating granulocytes that damage fungal cells ( Spellberg et al., 2009 ). IFN-gamma and GM-CSF are also known to enhance the activity of polymorphonuclear leukocytes to augment the damage to fungal hyphae ( Gil-Lamaignere et al., 2005 ). In neutropenic hosts, granulocyte transfusions can help, as they can deliver polymorphonuclear leukocytes to the site of the infection ( Spellberg et al., 2009 ). L-AmB acts synergistically with polymorphonuclear leukocytes to damage the hyphae of some Rhizopus species ( Simitsopoulou et al., 2008 ). Hyperbaric oxygen (HBO) enhances the oxidative action of amphotericin B by correcting lactic acidosis, at pressures over 10 atmospheres absolute (ATA) ( Gebremariam et al., 2014 ; Siddiqui et al., 1997 ). HBO may enhance leukocyte-mediated phagocytoses and tissue repair ( Chakrabarti & Singh, 2020 ). However, there is a paucity of data on the use of HBO in PM ( Grigull et al., 2006 ; John et al., 2021 ; Spellberg et al., 2009 ). It has been used as adjunctive therapy for rhino-orbital-cerebral mucormycosis and soft tissue infections, but it is much less commonly used for PM and other manifestations of the disease ( John et al., 2021 ). The recommended dose of hyperbaric oxygen therapy consists of two sessions of 90–120-min each, at 2–3 ATA, per day ( Chakrabarti & Singh, 2020 ). HBO reportedly benefits patients with diabetes or in trauma, but is less effective in stem cell transplantation and in patients with haematological malignancies ( Chakrabarti & Singh, 2020 ). Randomized controlled trials may prove the efficacy of HBO in mucormycosis ( Brunet & Rammaert, 2020 ). Methods This systematic review identifies and maps recent treatment protocols for PM. It provides a clear, reproducible methodology ( Sucharew & Macaluso, 2019 ) and is reported in accordance with the framework and recommendations by Peters et al. (2015) . Although the mortality rate of this disease has improved over time, it is still high ( Muthu, Agarwal, et al., 2021 ). The objective of this review is to systematically identify and map the management of pulmonary mucormycosis. Therefore, a systematic review is appropriate here. Review question This systematic review was designed to answer the following research question: ○ What recent treatment protocols have been reported in the literature that can be deployed in the management of pulmonary mucormycosis? Inclusion criteria All articles relating to treatment protocols for PM were included. The concept is treatment protocols in the context of PM. The population of interest is the human population. The following inclusion criteria were applied: • Articles published in English. • Peer-reviewed journal articles. • Articles where the full text was available. • Publications from 2018 to 2023. Exclusion criteria Articles that focus on limited treatment regimens or topics that are not relevant to the research question, were excluded. For example, articles focusing on the following topics were excluded: • Articles that only mention limited treatment regimens for PM, such as the use of amphotericin B only. • Fungal infections other than mucormycosis. • Covid-19 treatments and sequelae unrelated to mucormycosis. • Pulmonary disease unrelated to mucormycosis. Search strategy Four electronic search systems were identified: Scopus, PubMed, ScienceDirect, and Web of Science. Scopus offers excellent coverage ( Falagas et al., 2008 ; Kulkarni et al., 2009 ) and is the most effective search engine for the overview of a topic ( Tober, 2011 ). ScienceDirect is also a highly effective, second only to Scopus as a search engine ( Tober, 2011 ). PubMed, a subset of Scopus, is the optimal search system for biomedical topics - it is the most frequently updated and includes early releases of articles ( Falagas et al., 2008 ; Kulkarni et al., 2009 ; Samadzadeh et al., 2013 ). PubMed was included for this reason, to ensure a more precise and in-depth search. Science Direct is second only to PubMed in terms of precision, recall, and relevance of search results ( Samadzadeh et al., 2013 ). Therefore, ScienceDirect was also selected as an appropriate search engine for this systematic review. Web of Science has a well-documented performance in tracking citation counts ( Falagas et al., 2008 ; Kulkarni et al., 2009 ) and was therefore selected as a suitable search engine for this review. While Google Scholar is also effective in terms of recall and relevance, the search results it provides are inconsistent, and citation information is often inadequate or not updated ( Falagas et al., 2008 ; Kulkarni et al., 2009 ). Therefore, Google Scholar was not selected for this systematic review. For each of the four search systems selected, search strategy/search terms were defined ( Table 1 ). Within these search systems, all databases were included in the search. After the search results were assessed and articles relevant to the research question identified, citation tracking (snowball search) was also undertaken – a search of references within the relevant articles identified. Data extraction The second and third authors reviewed this. The extracted data was cross-checked by all authors to minimise personal bias ( Page et al., 2021 ). Any disagreements on data extraction and the categorisation of articles were resolved through detailed discussions, leading to a consensus between the authors. All three authors developed the concept and idea for this systematic review. The first author provided expert guidance on this review and verified the methods and results. The second and third authors conducted the search, identified, and removed duplicates from search results, and read the abstract and titles of the remaining articles, reading the full text of those articles where abstracts were unavailable. The second and third authors then applied the exclusion and inclusion criteria to the remaining articles, to ensure that only relevant articles were selected. Data analysis The selected articles were analysed to identify broad qualitative themes. A descriptive analysis was also undertaken to: • identify recent treatment protocols mentioned in the literature reviewed; and • map the results in tabular form. Transparency and openness The authors confirm that this paper is an accurate and transparent account of the systematic review conducted. The review’s design and analysis were not preregistered. Results The selected articles were reviewed in detail, with a focus on identifying and mapping treatment protocols for PM. The results span six years, from 2018 through 2023. Overall, 355 articles were identified in the four electronic search systems. 128 duplicates were removed. The titles and abstracts of the remaining 227 articles were screened and exclusion criteria applied. This process resulted in the exclusion of 202 articles. All the authors read the full text of the remaining 25 articles, applying the inclusion criteria. 19 articles were found to be relevant to the research question. Citation tracking was then undertaken – a snowball search of all references within these 19 articles. This process identified seven more relevant articles. Two more articles were identified by hand search. Thus, a total of 28 relevant articles were included. Table 1 lists the search systems, databases and search terms used to identify relevant articles. Figure 1 ( Fadelelmoula et al., 2024a ) shows the PRISMA flow diagram of article screening and selection. Supplementary Table 1 ( Fadelelmoula et al., 2024d ) lists the key features of selected articles, listed by date of publication. Figure 2 ( Fadelelmoula et al., 2024b ) shows the treatment modalities for PM in diagrammatic form. Supplementary Table 2 ( Fadelelmoula et al., 2024e ) lists the co-morbidities mentioned in the articles selected and Figure 3 ( Fadelelmoula et al., 2024c ) illustrates these co-morbidities. Supplementary Table 3 ( Fadelelmoula et al., 2024f ) sets out the PRISMA checklist for this review. Table 1. Search systems, databases and search terms used to identify relevant articles. Search conducted on 1 December 2023. Database Search terms Number of articles Scopus (All available databases) Limiters: TITLE-ABS (“pulmonary mucormycosis”) AND TITLE-ABS (mucormycosis) AND TITLE-ABS (treatment) AND NOT TITLE-ABS (COPD) AND NOT TITLE-ABS (cardiovascular) AND NOT TITLE-ABS (virus) AND NOT TITLE-ABS (bacteria) Expansion of abbreviations: ABS=Abstract Article type: Peer-reviewed journal articles. Languages: English only. Year of publication: 2018 to 2023 186 PubMed (All available databases) Limiters: (((((pulmonary mucormycosis [Title/Abstract]) AND (treatment [Title/Abstract])) NOT (COPD [Title/Abstract])) NOT (cardiovascular [Title/Abstract])) NOT (virus [Title/Abstract])) NOT (bacteria [Title/Abstract]) Article type: Peer-reviewed journal articles. Languages: English only. Species: Human only. Year of publication: 2018 to 2023 108 ScienceDirect (All available databases) Limiters: Title, abstract or author-specified keywords: pulmonary AND mucormycosis AND treatment NOT COPD NOT cardiovascular NOT virus NOT bacteria Article type: Peer-reviewed journal articles. Languages: English only. Year of publication: 2018 to 2023 51 Web of Science (All available databases) Limiters: ((((((TI=(pulmonary)) AND TI=(mucormycosis)) AND TI=(treatment)) NOT TS=(COPD)) NOT TS=(cardiovascular)) NOT TS=(virus)) NOT TS=(bacteria) Expansion of abbreviations: TI=Title TS=Topic Article type: Peer-reviewed journal articles. Languages: English only. Year of publication: 2018 to 2023 10 Total records identified by the database search 355 Total records after duplicates were removed 227 Figure 1. Flow diagram based on the PRISMA-ScR. Figure 2. Treatment modalities for PM. Figure 3. Comorbidities and underlying conditions. The key results relevant to the research question are presented below . • Of the primary therapies recommended for PM, liposomal amphotericin B (L-AmB) was recommended in 21 articles, surgery in 20, amphotericin B in eight, posaconazole in 10, Isavuconazole in three, bronchoscopy or BAL in two, and antibiotics in one. Three articles mention echinocandins, but these antifungals had no therapeutic benefit in the treatment of PM. • Stepdown, maintenance, or salvage therapy with posaconazole was mentioned in 10 articles, and isavuconazole in six articles. • Combination therapy was recommended in eight articles, but the authors of three other articles did not find combination therapy helpful. • Adjunctive therapies are recommended in four of the selected articles. • Alternative therapies are mentioned in 12 articles – Am-B and Digital Subtraction Angiography in one article each, posaconazole and isavuconazole in four articles each, and iron chelators in five. • Early diagnosis is underlined as the key to survival and low morbidity in 10 articles. • Eight articles recommend the effective control of predisposing factors and co-morbidities. • Multidisciplinary teams and a multimodal approach are recommended in four articles. • Four articles mention the use of glucocorticoids such as dexamethasone in patients with COVID-19 but stress the need for caution. • Two articles recommend checking for drug-drug interactions, particularly when triazoles are used for treatment. • One article stated that combination therapy with L-AmB and NAB is not useful but recommends that nebulized amphotericin B (NAB) merits further investigation, as other doses and formulations may be of use. • Two articles recommend against voriconazole. • One article stated that zinc therapy may be protective, but another states that zinc does not have any therapeutic use in the treatment of this disease. Discussion The incidence of PM is rising globally, particularly since the advent of COVID-19. Climate change could also be a contributing factor, as fungi thrive at higher temperatures and in conditions of increasing humidity. Although survival and recovery from PM has improved over time, this disease still carries a high mortality – around 50%. Till the end of the twentieth century, the three mainstays of managing PM were surgery, where feasible; Am-B, the preferred first-line antifungal; and the control of underlying factors such as hyperglycaemia, ketoacidosis, and neutropenia. However, there seems to be a gradual but noticeable shift in the management of PM – not only because more efficacious antifungals are now available, but also because there is a more considered approach to diagnosis and therapy. An analysis of the articles included in this review point to four broad themes: early diagnosis; first-line or primary therapy; stepdown, maintenance, or salvage therapies; and adjunctive therapies. Early diagnosis, early surgery, and a multidisciplinary approach: Early diagnosis may be the key to survival and low morbidity. However, as Wu states, early diagnosis may present a challenge – in many instances, patients with PM have nonspecific symptoms that may point to the possibility of COVID-19 or bacterial pneumonia, instead ( Wu et al., 2023 ). Today, the emphasis is on a high index of suspicion, recognition of predisposing factors, and analysis of the clinical presentation. For instance, pleuritic pain in a patient with neutropenia should arouse the suspicion of PM. Urgent and early imaging, histology, microbiology, and advanced molecular methods can confirm the diagnosis early, and make all the difference to survival. In terms of the approach, multidisciplinary teams and a multimodal approach are important pieces of the puzzle that improve the chances of achieving early diagnosis and instituting effective therapy ( Elgarten et al., 2018 ; Pruthi et al., 2022 ; Ramirez et al., 2018 ; Seifert et al., 2020 ). Primary therapies : Surgery and L-AmB are the mainstays of primary therapy. Posaconazole also seems to be gaining traction as a first-line antifungal, either on its own or in combination with L-AmB. Posaconazole and isuvaconazole are the keys to successful stepdown, maintenance, or salvage therapy. While surgery remains a recommended first-line treatment, there seems to be a shift in thinking on whether, and when, surgery is required in PM. There is a growing recognition that early and aggressive surgical resection may significantly reduce mortality ( Choi et al., 2019 ; Cornely et al., 2019 ; Dantis et al., 2021 ; Elgarten et al., 2018 ; Guo et al., 2019 ; Kanj et al., 2023 ; Liang et al., 2021 ; Mehta et al., 2022 ; Mills et al., 2018 ; Muthu et al., 2022 ; Muthu, Singh, et al., 2021 ; Pruthi et al., 2022 ; Pulle et al., 2021 ; Ramirez, 2018 ; Rana et al., 2021 ; Sipsas et al., 2018 ; Skiada et al., 2018 ; Yang et al., 2023 ). In addition, bronchoscopy and bronchoalveolar lavage (BAL) may be useful in removing retained secretions and necrotic tissue ( Liang et al., 2021 ; Seifert et al., 2020 ). Alongside early diagnosis, a multidisciplinary approach, and early and aggressive surgery, new antifungal drugs and formulations with a higher safety index are now preferred. The lipid-based L-AmB is the most widely used first-line antifungal, with the older and more toxic Am-B now reserved for use in settings where resources are limited. Posaconazole is being used in primary antifungal therapy as well, both in conjunction with L-AmB and as a monotherapy. Isuvaconazole is also being used as a primary therapy in clinical settings, but as it has only been available since 2015, it remains to be seen whether its clinical efficacy can be established more firmly, in time. Combination therapy with more than one antifungal was recommended by the authors of 11 articles ( Choi et al., 2019 ; Cornely et al., 2019 ; Ding et al., 2020 ; Guo et al., 2019 ; Hanks et al., 2023 ; Hoenigl et al., 2022 ; Manjunath et al., 2018 ; Meena et al., 2023 ; Rana et al., 2021 ; Seifert et al., 2020 ; Yang et al., 2023 ). However, Kanj et al. (2023) , Muthu et al. (2023) and Yuan et al. (2021) , did not find combination therapy useful in the treatment of PM. Stepdown, maintenance, salvage, and alternative therapies : For stepdown, maintenance, and salvage therapy, posaconazole is now the antifungal of choice ( Elgarten et al., 2018 ; van Burik et al., 2006 ). However, based on a 2006 review of 91 patients treated with posaconazole as salvage therapy, Elgarten et al. (2018) concluded that while posaconazole can be effective, treatment failures are not unknown. Isuvaconazole can also be used for salvage. Posaconazole and isuvaconazole are also preferred alternative therapies for patients who cannot tolerate L-AmB. Controlling co-morbidities and contributing factors: The control of co-morbidities continues to be a crucial aspect of effective treatment. Of the articles included, twenty-six mention co-morbidities – the details are listed in Supplementary Table 1 ( Fadelelmoula et al., 2024d ). Diabetes mellitus was the most common co-morbidity and is reported in fourteen articles, followed by COVID-19, which is stated in seven. Chronic kidney disease (CKD), hematological malignancies, immunosuppression, the use of glucocorticoids, hyperglycemia, and renal transplant are each mentioned in three or more articles. It is worth noting that in patients with COVID-19, glucocorticoids should be reserved for those with hypoxia, as these drugs can increase susceptibility to mucormycosis ( Rana et al., 2021 ). Prolonged Intensive Care Unit (ICU) stays, ketoacidosis, chronic liver disease, a history of tuberculosis, pulmonary artery pseudoaneurysm (PAP), pulmonary compromise, high sequential organ failure assessment (SOFA) scores, and hypoproteinemia are some of the other contributing factors mentioned in the articles included in this review. Kontoyiannis and Lewis mention many of the same contributing factors in their recommendations for the treatment of mucormycosis, and state that the relative contribution of each of these factors is unknown ( Kontoyiannis & Lewis, 2011 ). Adjunctive therapies: Selected articles also mention promising new adjunctive therapies that may well improve the prognosis of this disease. Hanks et al. (2023) suggest that ECMO may be useful as an adjunctive therapy, while Yuan et al. (2021) state that mucolytic agents such as ambroxol may be helpful adjuncts. Sipsas et al. (2018) recommends monoclonal antibodies, GM-CSF, IFN-γ, and white blood cell transfusions. Skiada et al. (2018) suggest that hyperbaric oxygen, GM-CSF, IFN-γ, and ergosterol synthesis inhibitor (VT-1161) may be useful. Sipsas et al. (2018) also postulate that emerging therapies may offer promise in improving survival rates and decreasing the morbidity currently associated with PM – these authors state argue that targeted immunotherapy, reversal of tissue hypoxia, and host-specific immunological and metabolic profiling, all merit further study. Potential therapies with insufficient or conflicting evidence : Five articles mention iron chelators, but there does not seem to be sufficient evidence or consensus, yet, of their efficacy in clinical practice. Meena et al. note that the DEFEAT Mucor study, a randomized trial, showed that combination therapy with the iron chelator, deferasirox, and L-AMB actually increased the 90-day mortality ( Meena et al., 2023 ; Spellberg et al., 2012 ). However, Meena et al. (2023) still recommend that iron chelators merit consideration – larger studies may be required for definitive proof of therapeutic benefit or harm. In their view, diabetic patients with COVID-19 may benefit more from iron chelators than neutropenic patients with haematological malignancies. Skiada et al. (2018) note that the DEFEAT Mucor study had several limitations; they state that there are many case reports to show that deferasirox may be a useful adjunctive therapy in patients with diabetes. However, they state that its therapeutic role is yet to be established through prospective, randomized clinical trials ( Skiada et al., 2018 ). Sipsas et al. (2018) state that the combination of deferasirox and L-AmB increases mortality in haematological malignancies, but may be beneficial in diabetic patients with mucormycosis, especially in ketoacidosis, where an acidic pH increases unbound tissue iron. Muthu et al. (2023) state that adjunctive therapy with zinc supplements is helpful. However, Rana et al. (2021) state that zinc does not have any therapeutic use in this disease. Muthu et al. (2023) also found that NAB was not helpful as an adjunctive therapy, but postulate that a different dose or formulation may prove beneficial and warrants further investigation. Therapies that are not recommended: Elgarten et al. (2018) and Manjunath et al. (2018) found no therapeutic benefit from echinocandins such as micafungin, used in combination with either L-AmB, or both L-AmB and posaconazole. Seifert et al. (2020) also used micafungin in combination with L-AmB to treat a patient with PM, but the patient did not survive. Yuan et al. (2021) does not recommend fluconazole or itraconazole because cultures from specimens obtained through bronchoscopy were not sensitive to these triazoles. There are clear recommendations against the use of voriconazole. Meena et al. (2023) , Hanks et al. (2023) , and Manjunath et al. (2018) state that PM does not respond to voriconazole. As early as 2007, a multicenter study ( Trifilio et al., 2007 ) found that voriconazole-associated mucormycosis carried a 73% mortality rate. Pongas et al. (2009) state that the prophylactic use of voriconazole leads to selection pressure, which increases the risk of Mucorales infections and contributes to poorer outcomes. It is an open question as to whether there is a direct link between the hypervirulence of Mucorales and the use of voriconazole, or if is this a causal association ( Meena et al., 2023 ). Promising new therapies: Mucorales species are developing resistance to amphotericin B, posaconazole, and isavuconazole ( Cornely et al., 2014 ; Dannaoui, 2017 ; Roden et al., 2005 ; Schwarz et al., 2019 ). There is an urgent need for new antifungal therapies that are effective and safe. There are innovative therapies emerging, currently, that hold great potential in the treatment of this disease. Among these novel therapies, the humanized clone VX01 may be the most promising. It is created by humanizing a mouse monoclonal antibody (C2 MAb). In the murine model, VX01 targets CotH3, a spore coat protein specific to Mucorales species. VX01 has an affinity for this protein and binds it, resulting in the loss of CotH3. Therefore, the fungus is rendered non-invasive, and its virulence is attenuated. Other promising therapies for PM include nanoemulsions such as NB-201, silver nanoparticles (AgNPs), and zirconium oxide nanoparticles (ZrO2NPs) ( León-Buitimea et al., 2021 ). These nanomaterials are currently in the experimental, in vitro phase of development ( George et al., 2011 ). Transparency: The authors of this systematic review have endeavoured to use transparent and robust methods. The framework described by Peters et al. (2015) guided this review. The authors undertook an initial exploration to identify appropriate search systems, which had disciplines and subjects relevant to the research question. Four electronic search systems were thus identified, and the search strategy consisted of searching all available databases within each of these four systems, as well as citation tracking (snowball search) and a hand search. Limitations: There are limitations to this review. It only includes peer-reviewed journal articles published between 2018 and 2023, in English. A search of other databases and systems may have provided additional results. But still relevant papers may have been missed because of these limitations. Conclusion The objective of this systematic review was to identify and map the management of pulmonary mucormycosis. Four broad themes were identified, that are not only critical to survival, but also to lowering the burden of morbidity associated with this disease. The four themes are: early diagnosis; first-line or primary therapy; stepdown, maintenance, or salvage therapies; and adjunctive therapies. Recommended approaches and modalities of treatment were identified and mapped within each of these themes. The results indicate that early diagnosis, and early and aggressive surgery, may hold the key to effective management. The results also indicate that a multidisciplinary, multimodal approach may improve the chances of achieving an early diagnosis and a prompt decision to operate. In addition, the results show that there has been a shift away from the use of Am-B as an antifungal, except in resource-limited settings. There is a clear preference for L-AmB as a first-line antifungal, with posaconazole used either in combination with L-AmB or as a first-line monotherapy. Posaconazole and isavuconazole are the drugs of choice for stepdown, maintenance, and salvage therapy, and as alternatives for patients who are unable to tolerate L-AmB. The control of co-morbidities such as diabetes continues to be a crucial aspect of effective management. The results highlight new adjunctive therapies that may well improve the chances of surviving this deadly disease – immunomodulators such as IFN-γ and GM-CSF, hyperbaric oxygen, and ergosterol synthesis inhibitor (VT-1161). The results also highlight potential therapies such as iron chelators, zinc, and NAB that do not, yet, have sufficient evidence for their use, or have conflicting evidence. The results indicate that there is considerable debate about the role of iron chelators such as deferasirox, but no broad consensus yet for their use in clinical settings. However, as many Mucorales species depend on iron for both growth and virulence, iron chelators seem to offer substantial promise as future therapies. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Author contributions All three authors were responsible for developing the concept of this systematic review. The first author provided expert guidance, provided critical revisions of intellectual content, and verified methods and results. The second and third authors conducted the search, extracted the data, performed the analysis, and drafted the manuscript. All the authors read and approved the final version of the manuscript for publication. Author note This review has not been published and is not under consideration for publication elsewhere. Correspondence concerning this article should be addressed to Tarig Fadelelmoula, Head of the Department of Internal Medicine, College of Medicine and Health sciences, National University of Science and Technology, Sohar, Sultanate of Oman. Email: [email protected] Registration This systematic review did not entail any preregistered protocols. Data availability Underlying data No data are associated with this article. Extended data Figshare: Management of Pulmonary Mucormycosis: A Systematic Review, DOI: https://doi.org/10.6084/m9.figshare.26362093.v1 , https://doi.org/10.6084/m9.figshare.26362099.v1 , https://doi.org/10.6084/m9.figshare.26362519.v2 , https://doi.org/10.6084/m9.figshare.26362600.v1 ( Fadelelmoula et al., 2024b , 2024c , 2024d , 2024e , 2024f ). This project contains the following underlying data: • Supplementary Table 1 lists the key features of selected articles, listed by date of publication. • Figure 2 shows the treatment modalities for PM in diagrammatic form. • Supplementary Table 2 lists the co-morbidities mentioned in the articles selected • Figure 3 illustrates Co-morbidities, underlying conditions, and contributing factors in pulmonary mucormycosis Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Reporting guidelines Figshare: Management of Pulmonary Mucormycosis: A Systematic Review, DOI https://doi.org/10.6084/m9.figshare.26362480.v2 , https://doi.org/10.6084/m9.figshare.26362585.v1 ( Fadelelmoula et al., 2024a , 2024f ). This project contains the following underlying data: • Supplementary Table 3 - PRISMA 2020 Checklist • FIGURE 1 - PRISMA Flow Diagram Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). This systematic review has been reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) ( Page et al., 2021 ). Acknowledgements Not applicable. References Abbas Z, Chaudhary A, Chaudhary MA: COVID-19 associated coagulopathy resulting in cerebral venous thrombosis and pulmonary embolism. Cureus. 2021; 13 (11). Publisher Full Text Agarwal R, Kumar V, Gupta D: Pulmonary mucormycosis: two of a kind. Eur. J. Intern. Med. 2006; 17 (1): 63–65. PubMed Abstract | Publisher Full Text Agrawal R, Yeldandi A, Savas H, et al. : Pulmonary mucormycosis: risk factors, radiologic findings, and pathologic correlation. Radiographics. 2020; 40 (3): 656–666. PubMed Abstract | Publisher Full Text Alejandre-Castañeda V, Patiño-Medina JA, Valle-Maldonado MI, et al. : Secretion of the siderophore rhizoferrin is regulated by the cAMP-PKA pathway and is involved in the virulence of Mucor lusitanicus. Sci. Rep. 2022; 12 (1): 10649. PubMed Abstract | Publisher Full Text | Free Full Text Alinaghi S, Karimi SA, Amirali B, et al. : Mucormycosis infection in patients with COVID-19: A systematic review. Health Sci. Rep. 2022; 5 (2): e529. PubMed Abstract | Publisher Full Text | Free Full Text Ambrosioni J, Bouchuiguir-Wafa K, Garbino J: Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors. Int. J. Infect. Dis. 2010; 14 : e100–e103. PubMed Abstract | Publisher Full Text Andresen D, Donaldson A, Choo L, et al. : Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. Lancet. 2005; 365 (9462): 876–878. Publisher Full Text Baldin C, Soliman SS, Jeon HH, et al. : PCR-based approach targeting mucorales-specific gene family for diagnosis of mucormycosis. J. Clin. Microbiol. 2018; 56 (10). 00746-00718. PubMed Abstract | Publisher Full Text | Free Full Text Bitar D, Van Cauteren D, Lanternier F, et al. : Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg. Infect. Dis. 2009; 15 (9): 1395–1401. PubMed Abstract | Publisher Full Text | Free Full Text Boelaert JR, Van Cutsem J, de Locht M , et al. : Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int. 1994; 45 (3): 667–671. PubMed Abstract | Publisher Full Text Bourcier J, Heudes PM, Morio F, et al. : Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: Data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016). Mycoses. 2017; 60 (8): 526–533. PubMed Abstract | Publisher Full Text Brigmon MM, Ochoa B, Brust K: Successful long-term therapy of mucormycosis with isavuconazole.Baylor University Medical Center Proceedings.2021. Brunet K, Rammaert B: Mucormycosis treatment: Recommendations, latest advances, and perspectives. J. Mycol. Médicale. 2020; 30 (3): 101007. PubMed Abstract | Publisher Full Text Cavassin FB, Baú-Carneiro JL, Vilas-Boas RR, et al. : Sixty years of amphotericin B: an overview of the main antifungal agent used to treat invasive fungal infections. Infect. Dis. Ther. 2021; 10 : 115–147. PubMed Abstract | Publisher Full Text | Free Full Text Chakrabarti A, Singh S: Management of Mucormycosis. Curr. Fungal Infect. Rep. 2020; 14 (4): 348–360. Publisher Full Text Choi H, Lee H, Jeon K, et al. : Factors affecting surgical resection and treatment outcomes in patients with pulmonary mucormycosis. J. Thorac. Dis. 2019; 11 (3): 892–900. PubMed Abstract | Publisher Full Text | Free Full Text Cornely O, Arikan-Akdagli S, Dannaoui E, et al. : ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin. Microbiol. Infect. 2014; 20 : 5–26. PubMed Abstract | Publisher Full Text Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. : Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect. Dis. 2019; 19 (12): e405–e421. PubMed Abstract | Publisher Full Text | Free Full Text Dannaoui E: Antifungal resistance in mucorales. Int. J. Antimicrob. Agents. 2017; 50 (5): 617–621. Publisher Full Text Dantis K, Rathore V, Kashyap NK, et al. : SARS-CoV-2 sequel: pulmonary mucormycosis with a mycotic aneurysm in a transplant recipient. Tuberc. Respir. Dis. 2021; 84 (4): 335–337. PubMed Abstract | Publisher Full Text | Free Full Text Deray G: Amphotericin B nephrotoxicity. J. Antimicrob. Chemother. 2002; 49 (suppl_1): 37–41. Publisher Full Text Ding X-L, Li H-M, Du J: Successful treatment of cutaneous mucormycosis disseminated from pulmonary mucormycosis with liposomal amphotericin B and posaconazole. Chin. Med. J. 2020; 133 (14): 1747–1748. PubMed Abstract | Publisher Full Text | Free Full Text Divakar Jose RR, Delhikumar C, Ram Kumar G: Efficacy and safety of combined oral chelation with deferiprone and deferasirox on iron overload in transfusion dependent children with thalassemia–A Prospective Observational Study. Indian J. Pediatr. 2021; 88 : 330–335. El-Sayed A, Kamel M: Climatic changes and their role in emergence and re-emergence of diseases. Environ. Sci. Pollut. Res. 2020; 27 : 22336–22352. PubMed Abstract | Publisher Full Text | Free Full Text Elgarten CW, Levy EM, Mattei P, et al. : Successful treatment of pulmonary mucormycosis in two pediatric hematopoietic stem cell transplant patients. Pediatr. Transplant. 2018; 22 (7): e13270. PubMed Abstract | Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Figure 1 - PRISMA flow diagram.2024a. Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Figure 2 - Treatment modalities for pulmonary mucormycosis.2024b. Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Figure 3 - Co-morbidities, underlying conditions, and contributing factors in pulmonary mucormycosis.2024c. Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Supplementary Table 1 - Key features of selected articles listed by date of publication.2024d. Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Supplementary Table 2 - Co-morbidities mentioned in the articles selected.2024e. Publisher Full Text Fadelelmoula T, Navas AA, Doreswamy N: Supplementary Table 3 - PRISMA 2020 Checklist.2024f. Publisher Full Text Falagas ME, Pitsouni EI, Malietzis GA, et al. : Comparison of PubMed, Scopus, web of science, and Google scholar: strengths and weaknesses. FASEB J. 2008; 22 (2): 338–342. PubMed Abstract | Publisher Full Text Feng J, Sun X: Characteristics of pulmonary mucormycosis and predictive risk factors for the outcome. Infection. 2018; 46 : 503–512. PubMed Abstract | Publisher Full Text Fernandez JF, Maselli DJ, Simpson T, et al. : Pulmonary mucormycosis: what is the best strategy for therapy? Respir. Care. 2013; 58 (5): e60–e63. PubMed Abstract | Publisher Full Text | Free Full Text Gadre A, Enbiale W, Andersen LK, et al. : The effects of climate change on fungal diseases with cutaneous manifestations: A report from the International Society of Dermatology Climate Change Committee. J. Climate Change Health. 2022; 6 : 100156. Publisher Full Text Garcia-Solache MA, Casadevall A: Global warming will bring new fungal diseases for mammals. MBio. 2010; 1 (1). 00061-00010. Publisher Full Text Gebremariam T, Liu M, Luo G, et al. : CotH3 mediates fungal invasion of host cells during mucormycosis. J. Clin. Invest. 2014; 124 (1): 237–250. PubMed Abstract | Publisher Full Text | Free Full Text George C, Kuriakose S, George S, et al. : Antifungal activity of silver nanoparticle-encapsulated β-cyclodextrin against human opportunistic pathogens. Supramol. Chem. 2011; 23 (8): 593–597. Publisher Full Text Ghazi BK, Rackimuthu S, Wara UU, et al. : Rampant increase in cases of mucormycosis in India and Pakistan: a serious cause for concern during the ongoing COVID-19 pandemic. Am. J. Trop. Med. Hyg. 2021; 105 (5): 1144–1147. PubMed Abstract | Publisher Full Text | Free Full Text Gil-Lamaignere C, Simitsopoulou M, Roilides E, et al. : Interferon- gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J. Infect. Dis. 2005; 191 (7): 1180–1187. PubMed Abstract | Publisher Full Text Greenberg R, Mullane K, Van Burik J-A, et al. : Posaconazole as salvage therapy for zygomycosis. Antimicrob. Agents Chemother. 2006; 50 (1): 126–133. PubMed Abstract | Publisher Full Text | Free Full Text Grigull L, Beilken A, Schmid H, et al. : Secondary prophylaxis of invasive fungal infections with combination antifungal therapy and G-CSF-mobilized granulocyte transfusions in three children with hematological malignancies. Support. Care Cancer. 2006; 14 : 783–786. PubMed Abstract | Publisher Full Text Guo S, Liu H, Tang X, et al. : Clinical characteristics and prognoses of pulmonary mucormycosis in four children. Pediatr. Investig. 2019; 3 (04): 223–227. PubMed Abstract | Publisher Full Text | Free Full Text Hamill RJ: Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs. 2013; 73 (9): 919–934. PubMed Abstract | Publisher Full Text Hanks J, Unai S, Bribriesco A, et al. : Successful treatment of pulmonary mucormycosis (Lichtheimia spp.) in a post-partum patient with COVID-19 ARDS requiring extra-corporeal membrane oxygenation using salvage therapy. Perfusion. 2023; 38 (6): 1315–1318. PubMed Abstract | Publisher Full Text | Free Full Text Harada M, Manabe T, Yamashita K, et al. : Pulmonary mucormycosis with fatal massive hemoptysis. Pathol. Int. 1992; 42 (1): 49–55. Publisher Full Text Hoenigl M, Seidel D, Carvalho A, et al. : The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe. 2022; 3 : e543–e552. PubMed Abstract | Publisher Full Text | Free Full Text Hsiao CR, Huang L, Bouchara J-P, et al. : Identification of medically important molds by an oligonucleotide array. J. Clin. Microbiol. 2005; 43 (8): 3760–3768. PubMed Abstract | Publisher Full Text | Free Full Text Ibrahim A, Edwards J, Filler S: Zygomycosis. Clinical mycology. New York, NY: Oxford University Press; 2003; 241–251. Publisher Full Text Ibrahim AS, Spellberg B, Avanessian V, et al. : Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro. Infect. Immun. 2005; 73 (2): 778–783. PubMed Abstract | Publisher Full Text | Free Full Text Ibrahim AS, Spellberg B, Walsh TJ, et al. : Pathogenesis of mucormycosis. Clin. Infect. Dis. 2012; 54 (suppl_1): S16–S22. PubMed Abstract | Publisher Full Text | Free Full Text Jeong W, Keighley C, Wolfe R, et al. : The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin. Microbiol. Infect. 2019; 25 (1): 26–34. PubMed Abstract | Publisher Full Text John TM, Jacob CN, Kontoyiannis DP: When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J. Fungi. 2021; 7 (4): 298. PubMed Abstract | Publisher Full Text | Free Full Text Kanj SS, Haddad SF, Meis JF, et al. : The battle against fungi: lessons in antifungal stewardship from COVID 19 times. Int. J. Antimicrob. Agents. 2023; 62 (1): 106846. PubMed Abstract | Publisher Full Text | Free Full Text Kasai M, Harrington SM, Francesconi A, et al. : Detection of a molecular biomarker for zygomycetes by quantitative PCR assays of plasma, bronchoalveolar lavage, and lung tissue in a rabbit model of experimental pulmonary zygomycosis. J. Clin. Microbiol. 2008; 46 (11): 3690–3702. PubMed Abstract | Publisher Full Text | Free Full Text Kawakami K, Watanabe Y, Kadowaki S: Early onset invasive pulmonary zygomycosis following allogeneic peripheral blood stem cell transplantation in a patient with therapy-related myelodysplastic syndrome. [Rinsho Ketsueki]. 2004; 45 (4): 319–321. PubMed Abstract Kohno S, Izumikawa K, Takazono T, et al. : Efficacy and safety of isavuconazole against deep-seated mycoses: A phase 3, randomized, open-label study in Japan. J. Infect. Chemother. 2023; 29 (2): 163–170. PubMed Abstract | Publisher Full Text Kontoyiannis DP, Lewis RE: Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management. Infect. Dis. Clin. 2006; 20 (3): 581–607, vi. PubMed Abstract | Publisher Full Text Kontoyiannis DP, Lewis RE: How I treat mucormycosis. Blood. 2011; 118 (5): 1216–1224. PubMed Abstract | Publisher Full Text | Free Full Text Krishna V, Bansal N, Morjaria J, et al. : COVID-19-associated pulmonary mucormycosis. J. Fungi. 2022; 8 (7): 711. PubMed Abstract | Publisher Full Text | Free Full Text Kulkarni AV, Aziz B, Shams I, et al. : Comparisons of citations in Web of Science, Scopus, and Google Scholar for articles published in general medical journals. JAMA. 2009; 302 (10): 1092–1096. PubMed Abstract | Publisher Full Text Kumar A, Pulle MV, Asaf BB, et al. : Covid-associated pulmonary mucormycosis. Lung India. 2022; 39 (2): 100–101. PubMed Abstract | Publisher Full Text | Free Full Text Lanternier F, Dannaoui E, Morizot G, et al. : A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin. Infect. Dis. 2012; 54 (suppl_1): S35–S43. PubMed Abstract | Publisher Full Text Lee FY, Mossad SB, Adal KA: Pulmonary mucormycosis: the last 30 years. Arch. Intern. Med. 1999; 159 (12): 1301–1309. Publisher Full Text León-Buitimea A, Garza-Cervantes JA, Gallegos-Alvarado DY, et al. : Nanomaterial-Based Antifungal Therapies to Combat Fungal Diseases Aspergillosis, Coccidioidomycosis, Mucormycosis, and Candidiasis. Pathogens. 2021; 10 (10). PubMed Abstract | Publisher Full Text | Free Full Text Lewis RE, Wiederhold NP: The solubility ceiling: a rationale for continuous infusion amphotericin B therapy?. Clin. Infect. Dis. 2003; 37 (6): 871–872. PubMed Abstract | Publisher Full Text Liang Y, Chen X, Wang J, et al. : Oral posaconazole and bronchoscopy as a treatment for pulmonary mucormycosis in pediatric acute lymphoblastic leukemia patient: A case report. Medicine. 2021; 100 (6): e24630. Publisher Full Text Lin E, Moua T, Limper AH: Pulmonary mucormycosis: clinical features and outcomes. Infection. 2017; 45 : 443–448. Publisher Full Text Mahalmani V, Sarma P, Prakash A, et al. : Role of Iron Chelators in Mucormycosis. Indian J. Pharm. 2021; 53 (4): 261–263. PubMed Abstract | Publisher Full Text | Free Full Text Manjunath M, Prajapat D, Sharma RK, et al. : Refractory bronchovascular pleuropulmonary mucormycosis: Case report and difficulties in management. Lung India. 2018; 35 (1): 70–72. PubMed Abstract | Publisher Full Text | Free Full Text Marchevsky AM, Bottone EJ, Geller SA, et al. : The changing spectrum of disease, etiology, and diagnosis of mucormycosis. Hum. Pathol. 1980; 11 (5): 457–464. PubMed Abstract McAdams HP, Rosado de Christenson M, Strollo DC, et al. : Pulmonary mucormycosis: radiologic findings in 32 cases. AJR Am. J. Roentgenol. 1997; 168 (6): 1541–1548. PubMed Abstract | Publisher Full Text Meena DS, Kumar D, Bohra GK: Combination therapy in Mucormycosis: Current evidence from the world literature, a mini review. J. Med. Mycol. 2023; 33 (1): 101332. PubMed Abstract | Publisher Full Text | Free Full Text Mehta RM, Bansal S, Kalpakkam H: Critical COVID-19-associated pulmonary mucormycosis: The underreported life-threatening spectrum of the mucormycosis epidemic. Lung India. 2022; 39 (2): 187–190. PubMed Abstract | Publisher Full Text | Free Full Text Millon L, Herbrecht R, Grenouillet F, et al. : Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clin. Microbiol. Infect. 2016; 22 (9): 810.e1–810.e8. PubMed Abstract | Publisher Full Text Millon L, Larosa F, Lepiller Q, et al. : Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin. Infect. Dis. 2013; 56 (10): e95–e101. PubMed Abstract | Publisher Full Text Mills SEA, Yeldandi AV, Odell DD: Surgical treatment of multifocal pulmonary mucormycosis. Ann. Thorac. Surg. 2018; 106 (2): e93–e95. PubMed Abstract | Publisher Full Text | Free Full Text Mir I, Basnet S, Ellsworth D, et al. : Pulmonary Mucormycosis in chronic lymphocytic leukemia and Neutropenia. Case Rep. Infect. Dis. 2018; 2018 : 1–4. PubMed Abstract | Publisher Full Text | Free Full Text Moreira J, Ridolfi F, Almeida-Paes R, et al. : Cutaneous mucormycosis in advanced HIV disease. Braz. J. Infect. Dis. 2016; 20 : 637–640. PubMed Abstract | Publisher Full Text | Free Full Text Muthu V, Agarwal R, Dhooria S, et al. : Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis. Clin. Microbiol. Infect. 2021; 27 (4): 538–549. PubMed Abstract | Publisher Full Text Muthu V, Agarwal R, Patel A, et al. : 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. Lancet Infect. Dis. 2022; 22 (9): e240–e253. PubMed Abstract | Publisher Full Text | Free Full Text Muthu V, Gogineni RR, Agarwal R, et al. : Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial. Mycoses. 2023; 66 : 688–696. PubMed Abstract | Publisher Full Text Muthu V, Singh H, Gorsi U, et al. : Large pulmonary artery pseudoaneurysm in mucormycosis: successfully managed with surgery and amphotericin. BMJ Case Rep. 2021; 14 (1). Publisher Full Text Neblett Fanfair R, Benedict K, Bos J, et al. : Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N. Engl. J. Med. 2012; 367 (23): 2214–2225. PubMed Abstract | Publisher Full Text Neufeld EJ: Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006; 107 (9): 3436–3441. Nyilasi I, Papp T, Csernetics Á, et al. : High-affinity iron permease (FTR1) gene sequence-based molecular identification of clinically important Zygomycetes. Clin. Microbiol. Infect. 2008; 14 (4): 393–397. PubMed Abstract | Publisher Full Text Page MJ, McKenzie JE, Bossuyt PM, et al. : The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int. J. Surg. 2021; 88 : 105906. PubMed Abstract | Publisher Full Text Pal R, Singh B, Bhadada SK, et al. : COVID-19-associated mucormycosis: an updated systematic review of literature. Mycoses. 2021; 64 (12): 1452–1459. PubMed Abstract | Publisher Full Text | Free Full Text Pana ZD, Seidel D, Skiada A, et al. : Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries. BMC Infect. Dis. 2016; 16 : 1–9. Publisher Full Text Pandey N, Kaushal V, Puri GD, et al. : Transforming a general hospital to an infectious disease hospital for COVID-19 over 2 weeks. Front. Public Health. 2020; 8 : 382. PubMed Abstract | Publisher Full Text | Free Full Text Patel A, Kaur H, Xess I, et al. : A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clin. Microbiol. Infect. 2020; 26 (7): 944.e9–944.e15. Publisher Full Text Peters MD, Godfrey CM, Khalil H, et al. : Guidance for conducting systematic scoping reviews. JBI Evidence Implementation. 2015; 13 (3): 141–146. Pielke RA: What is Climate Change? Energy Environ. 2004; 15 (3): 515–520. Publisher Full Text Pongas GN, Lewis RE, Samonis G, et al. : Voriconazole-associated zygomycosis: a significant consequence of evolving antifungal prophylaxis and immunosuppression practices? Clin. Microbiol. Infect. 2009; 15 (s5): 93–97. PubMed Abstract | Publisher Full Text Pörtner H, Roberts D, Tignor M, et al. , editors. Climate change 2022: Impacts, adaptation, and vulnerability. Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press; 2022. In Press. Reference Source Potenza L, Vallerini D, Barozzi P, et al. : Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients. Blood. 2011; 118 (20): 5416–5419. PubMed Abstract | Publisher Full Text Prakash H, Chakrabarti A: Global epidemiology of mucormycosis. J. Fungi. 2019; 5 (1): 26. PubMed Abstract | Publisher Full Text | Free Full Text Prakash H, Ghosh AK, Rudramurthy SM, et al. : A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Med. Mycol. 2019; 57 (4): 395–402. PubMed Abstract | Publisher Full Text Pruthi H, Muthu V, Bhujade H, et al. : Pulmonary artery pseudoaneurysm in COVID-19-associated pulmonary mucormycosis: case series and systematic review of the literature. Mycopathologia. 2022; 187 (1): 31–37. PubMed Abstract | Publisher Full Text | Free Full Text Pulle MV, Puri HV, Asaf BB, et al. : Outcomes of early anti-fungal therapy with aggressive surgical resection in pulmonary mucormycosis. Lung India. 2021; 38 (4): 314–320. PubMed Abstract | Publisher Full Text | Free Full Text Ramirez JL, Urisman A, Kukreja J, et al. : Surgical Management of Pulmonary Mucormycosis in Third-Trimester Pregnancy. Thorac. Cardiovasc. Surg. Rep. 2018; 07 : e27–e29. PubMed Abstract | Publisher Full Text | Free Full Text Rana G, Gautam S, Mawari G, et al. : Massive hemoptysis causing mortality in a post COVID-19 infected Asian male patient: Presenting as pulmonary mucormycosis, pulmonary tuberculosis and later sino-nasal mucormycosis. Respir. Med. Case. Rep. 2021; 34 : 101511. PubMed Abstract | Publisher Full Text | Free Full Text Reed C, Ibrahim A, Edwards JE Jr, et al. : Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob. Agents Chemother. 2006; 50 (11): 3968–3969. PubMed Abstract | Publisher Full Text | Free Full Text Reimund E, Ramos A: Disseminated neonatal gastrointestinal mucormycosis: a case report and review of the literature. Pediatr. Pathol. 1994; 14 (3): 385–389. PubMed Abstract Ribes JA, Vanover-Sams CL, Baker DJ: Zygomycetes in human disease. Clin. Microbiol. Rev. 2000; 13 (2): 236–301. Publisher Full Text Richardson M: The ecology of the Zygomycetes and its impact on environmental exposure. Clin. Microbiol. Infect. 2009; 15 : 2–9. PubMed Abstract | Publisher Full Text Roden MM, Zaoutis TE, Buchanan WL, et al. : Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis. 2005; 41 (5): 634–653. PubMed Abstract | Publisher Full Text Safdar F, Khokhar MF, Arshad M, et al. : Climate change indicators and spatiotemporal shift in monsoon patterns in Pakistan. Adv. Meteorol. 2019; 2019 : 1–14. Publisher Full Text Samadzadeh GR, Rigi T, Ganjali AR: Comparison of four search engines and their efficacy with emphasis on literature research in addiction (prevention and treatment). Int. J. High Risk Behav. Addict. 2013; 1 (4): 166–171. PubMed Abstract | Publisher Full Text Schwarz P, Cornely OA, Dannaoui E: Antifungal combinations in Mucorales: A microbiological perspective. Mycoses. 2019; 62 (9): 746–760. PubMed Abstract | Publisher Full Text Seifert S, Wiley J, Kirkham J, et al. : Pulmonary mucormycosis with extensive bronchial necrosis and bronchomediastinal fistula: a case report and review. Respir. Med. Case. Rep. 2020; 30 : 101082. PubMed Abstract | Publisher Full Text | Free Full Text Serris A, Danion F, Lanternier F: Disease entities in mucormycosis. J. Fungi. 2019; 5 (1): 23. PubMed Abstract | Publisher Full Text | Free Full Text Siddiqui A, Davidson JD, Mustoe TA: Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy: a new physiologic concept. Plast. Reconstr. Surg. 1997; 99 (1): 148–155. PubMed Abstract | Publisher Full Text Simitsopoulou M, Roilides E, Maloukou A, et al. : Interaction of amphotericin B lipid formulations and triazoles with human polymorphonuclear leucocytes for antifungal activity against Zygomycetes. Mycoses. 2008; 51 (2): 147–154. PubMed Abstract | Publisher Full Text Sipsas NV, Gamaletsou MN, Anastasopoulou A, et al. : Therapy of mucormycosis. J. Fungi. 2018; 4 (3): 90. PubMed Abstract | Publisher Full Text | Free Full Text Sivagnanam S, Sengupta DJ, Hoogestraat D, et al. : Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center. Antimicrob. Resist. Infect. Control. 2017; 6 : 1–11. Publisher Full Text Skiada A, Lass-Floerl C, Klimko N, et al. : Challenges in the diagnosis and treatment of mucormycosis. Med. Mycol. 2018; 56 (suppl_1): S93–S101. PubMed Abstract | Publisher Full Text | Free Full Text Skiada A, Pagano L, Groll A, et al. : Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin. Microbiol. Infect. 2011; 17 (12): 1859–1867. PubMed Abstract | Publisher Full Text Smith C, Lee SC: Current treatments against mucormycosis and future directions. PLoS Pathog. 2022; 18 (10): e1010858. PubMed Abstract | Publisher Full Text | Free Full Text Smith JA, Kauffman CA: Pulmonary fungal infections. Respirology. 2012; 17 (6): 913–926. Publisher Full Text Spellberg B, Edwards J Jr, Ibrahim A: Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin. Microbiol. Rev. 2005; 18 (3): 556–569. PubMed Abstract | Publisher Full Text | Free Full Text Spellberg B, Ibrahim AS: Recent Advances in the Treatment of Mucormycosis. Curr. Infect. Dis. Rep. 2010; 12 (6): 423–429. PubMed Abstract | Publisher Full Text | Free Full Text Spellberg B, Ibrahim AS, Chin-Hong PV, et al. : The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J. Antimicrob. Chemother. 2012; 67 (3): 715–722. PubMed Abstract | Publisher Full Text | Free Full Text Spellberg B, Walsh TJ, Kontoyiannis DP, et al. : Recent advances in the management of mucormycosis: from bench to bedside. Clin. Infect. Dis. 2009; 48 (12): 1743–1751. PubMed Abstract | Publisher Full Text | Free Full Text Springer J, Lackner M, Ensinger C, et al. : Clinical evaluation of a Mucorales-specific real-time PCR assay in tissue and serum samples. J. Med. Microbiol. 2016; 65 (12): 1414–1421. PubMed Abstract | Publisher Full Text Stearman R, Yuan DS, Yamaguchi-Iwai Y, et al. : A Permease-Oxidase Complex Involved in High-Affinity Iron Uptake in Yeast. Science. 1996; 271 (5255): 1552–1557. PubMed Abstract | Publisher Full Text Sucharew H, Macaluso M: Methods for research evidence synthesis: The scoping review approach. J. Hosp. Med. 2019; 14 (7): 416–418. Publisher Full Text Sugar A: Agents of mucormycosis and related species. Agents of mucormycosis and related species. 3rd ed.1990; 1962–1972. Sun QN, Fothergill AW, McCarthy DI, et al. : In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob. Agents Chemother. 2002; 46 (5): 1581–1582. PubMed Abstract | Publisher Full Text | Free Full Text Syed-Abdul S, Babu AS, Bellamkonda RS, et al. : Using artificial intelligence-based models to predict the risk of mucormycosis among COVID-19 survivors: An experience from a public hospital in India. J. Infect. 2022; 84 (3): 351–354. PubMed Abstract | Publisher Full Text | Free Full Text Symeonidis AS: The role of iron and iron chelators in zygomycosis. Clin. Microbiol. Infect. 2009; 15 : 26–32. PubMed Abstract | Publisher Full Text Tahiri G, Lax C, Cánovas-Márquez JT, et al. : Mucorales and Mucormycosis: Recent Insights and Future Prospects. J. Fungi. 2023; 9 (3). PubMed Abstract | Publisher Full Text | Free Full Text Tedder M, Spratt JA, Anstadt MP, et al. : Pulmonary mucormycosis: results of medical and surgical therapy. Ann. Thorac. Surg. 1994; 57 (4): 1044–1050. Publisher Full Text Tober M: PubMed, ScienceDirect, Scopus or Google Scholar–Which is the best search engine for an effective literature research in laser medicine? Med. Laser Appl. 2011; 26 (3): 139–144. Publisher Full Text Torres-Narbona M, Guinea J, Martínez-Alarcón J, et al. : Impact of zygomycosis on microbiology workload: a survey study in Spain. J. Clin. Microbiol. 2007; 45 (6): 2051–2053. PubMed Abstract | Publisher Full Text | Free Full Text Trifilio SM, Bennett CL, Yarnold PR, et al. : Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 2007; 39 (7): 425–429. Publisher Full Text van Burik J-AH , Hare RS, Solomon HF, et al. : Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin. Infect. Dis. 2006; 42 (7): e61–e65. PubMed Abstract | Publisher Full Text van Rhijn N , Bromley M: The consequences of our changing environment on life threatening and debilitating fungal diseases in humans. J. Fungi. 2021; 7 (5): 367. PubMed Abstract | Publisher Full Text | Free Full Text Watts WJ: Bronchopleural fistula followed by massive fatal hemoptysis in a patient with pulmonary mucormycosis: a case report. Arch. Intern. Med. 1983; 143 (5): 1029–1030. PubMed Abstract | Publisher Full Text Wu H-Y, Chang P-H, Huang Y-S, et al. : Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan. J. Microbiol. Immunol. Infect. 2023; 56 (2): 207–235. PubMed Abstract | Publisher Full Text | Free Full Text Yang N, Zhang L, Feng S: Clinical Features and Treatment Progress of Invasive Mucormycosis in Patients with Hematological Malignancies. J. Fungi. 2023; 9 (5): 592. PubMed Abstract | Publisher Full Text | Free Full Text Yuan F, Chen J, Liu F, et al. : Successful treatment of pulmonary mucormycosis caused by Rhizopus microsporus with posaconazole. Eur. J. Med. Res. 2021; 26 : 1–4. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 08 Oct 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Medicine, College of Medicine and Health Sciences, National University of Science and Technology, Sohar, North AlBatina, Oman 2 National Coalition of Independent Scholars, Suite 465, 48, Dickson Place, Dickson, ACT 2602, Australia Tarig Fadelelmoula Roles: Conceptualization, Methodology, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing Navas Ayyalil Roles: Conceptualization, Data Curation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Nandini Doreswamy Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 28 Jul 2025, 13:1165 https://doi.org/10.12688/f1000research.151564.2 version 1 Published: 08 Oct 2024, 13:1165 https://doi.org/10.12688/f1000research.151564.1 Copyright © 2025 Fadelelmoula T et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Fadelelmoula T, Ayyalil N and Doreswamy N. Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.12688/f1000research.151564.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 28 Jul 2025 Revised Views 0 Cite How to cite this report: RAJ K. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r437446 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-437446 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Dec 2025 KHEM RAJ , Panjab University, Chandigarh, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175240.r437446 1. The review gives a good summary of the available treatments for pulmonary mucormycosis. 2. The methods are not very strong for a systematic review, as there is no quality assessment of the included studies, making the reliability of ... Continue reading READ ALL 1. The review gives a good summary of the available treatments for pulmonary mucormycosis. 2. The methods are not very strong for a systematic review, as there is no quality assessment of the included studies, making the reliability of the findings uncertain. 3. At many points, the discussion shifts toward mucormycosis in general rather than focusing specifically on pulmonary disease, which slightly weakens the clarity and focus of the review. 4. Certain therapies with limited or conflicting evidence, such as iron chelators and zinc supplementation, are discussed without sufficient available data. 5. Focusing on how many papers mention a particular treatment can be misleading, as many of these studies are either case reports or small case series, which do not provide any reliable evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Partly If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Microbial genomics, transcriptomics, and fungal pathogenesis., microbial-host interactions and antimicrobial resistance, combining experimental biology with integrative omics approaches. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT RAJ K. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r437446 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-437446 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Drogari-Apiranthitou M. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r400950 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-400950 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 19 Aug 2025 Maria Drogari-Apiranthitou , Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, Attikon General University, National and Kapodistrian University of Athens, Athens, Greece Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.175240.r400950 I am afraid the issues I ... Continue reading READ ALL I am afraid the issues I raised in my initial review remain unaddressed. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Clinical Mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Drogari-Apiranthitou M. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r400950 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-400950 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 08 Oct 2024 Views 0 Cite How to cite this report: Drogari-Apiranthitou M. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334217 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334217 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Nov 2024 Maria Drogari-Apiranthitou , Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, Attikon General University, National and Kapodistrian University of Athens, Athens, Greece Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.166217.r334217 In the submitted manuscript titled “Management of Pulmonary Mucormycosis: A Systematic Review,” the authors state their objective as identifying and mapping the management of PM through a systematic review approach. While the study tackles an important subject, it exhibits several ... Continue reading READ ALL In the submitted manuscript titled “Management of Pulmonary Mucormycosis: A Systematic Review,” the authors state their objective as identifying and mapping the management of PM through a systematic review approach. While the study tackles an important subject, it exhibits several shortcomings. Major points Background. The introduction is overly lengthy, whereas it should rather focus on the main subject which is PM and the challenges associated with its treatment. The authors claim that “this systematic review aims to shed light on recent treatment protocols for PM”, and that “a systematic review is appropriate because many of these treatments are new or emerging”. It would be helpful to provide more specificity on how their systematic review will contribute to advancing current knowledge in this field. Methodology and Results While the PRISMA-ScR method used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) is a valid guideline designed to ensure transparency and comprehensiveness in the reporting of scoping reviews, it seems that the authors did not take full advantage of it. Rather than merely presenting numerical summaries (e.g., the number of papers reporting specific comorbidities or the use of L-AmB), it would be of more value to group patients by key underlying conditions (e.g., hematologic malignancies, diabetes) and tabulate these alongside the therapies they received and their outcomes. This would allow for a more insightful analysis of potential associations between treatments and outcomes. Result presentation. Table 1 appears redundant, as the search methodology could be more effectively described in the text. Fig. 2 seems to inaccurately represent the data. For instance, it suggests that L-AmB and surgery were used in equal numbers of studies, whereas in most cases, these interventions were applied simultaneously. A tabular format would better represent this information. Fig. 3 is not informative in its current form. Presenting patient numbers and their characteristics in a table would be more effective for conveying meaningful insights. Discussion and Conclusions The Discussion section is overly generic, which may be attributed to the absence of patient-specific results. For instance, conclusions such as “The results indicate that early diagnosis and early and aggressive surgery may hold the key to effective management” and “The control of co-morbidities such as diabetes continues to be a crucial aspect of effective management” do not appear to be directly supported by the data presented. Additionally, the study lacks detailed results regarding novel or adjunctive therapies, along with patient-specific data such as underlying diseases, risk factors, species of Mucorales involved, demographics, country of origin, etc, which would provide deeper insights. Other Points of Concern There are several inaccuracies, or outdated literature has been occasionally used. Some examples: In the Background, the statement that malignancies (63.4%), diabetes mellitus (17.1%), and solid organ transplantation (9.8%) are the most common underlying conditions is misleading. Globally, diabetes is the leading cause of mucormycosis, with hematologic malignancies ranking first only in Europe. There is more recent literature that reflects this trend and should be cited. Furthermore, under Epidemiology, some contradictory data are presented. The most common clinical presentations of mucormycosis are rhino-orbito-cerebral (ROC), pulmonary, cutaneous, and disseminated. Jeong et al. report corresponding rates of 34%, 21%, 20%, and 14%, while in the European study of the Working Group on Zygomycosis the corresponding numbers were 27%, 30%, 26%, and 15%. The data from Pana et al. (2016) specifically pertain to children, but this distinction is not made. It should be also mentioned that in India, during the COVID-19 pandemic, PM cases indeed increased, but the predominant form of mucormycosis was ROC [refer 1]. To summarize, the current study appears incomplete and does not achieve its objectives. It would be more valuable to include a detailed analysis of all patients from the retrieved articles, potentially using statistical methods to draw conclusions about the effectiveness of different treatment modalities and their association with patient outcomes. Are the rationale for, and objectives of, the Systematic Review clearly stated? No Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable References 1. Pasquier G: COVID-19-associated mucormycosis in India: Why such an outbreak?. J Mycol Med . 2023; 33 (3): 101393 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Clinical Mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Drogari-Apiranthitou M. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334217 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334217 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Dannaoui E. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334224 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334224 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 19 Nov 2024 Eric Dannaoui , Faculty of Medicine, Paris Cité University, Paris, France Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.166217.r334224 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review ... Continue reading READ ALL In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature The " Background " section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM. Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. Are the rationale for, and objectives of, the Systematic Review clearly stated? No Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Medical mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Dannaoui E. Reviewer Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334224 ) The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334224 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 10 Sep 2025 Tarig Fadelelmoula , Internal Medicine, National University of Science and Technology, Sohar, Oman 10 Sep 2025 Author Response VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The ... Continue reading VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature>>> thank you for kind observations The "Background" section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. Thank you for your critique, we have cross checked the references and found that they are UpToDate . The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM. >>> thank you we have made changes accordingly Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM.>>> Presentation of other forms of mucomycosis can overlap with pm in some instances especially in the early stages there for we believe its relevant Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies>>>>Thank you we believe that details of qpcr beyond the scope . however we are of its important that why we included it Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript.>>>> after the careful consideratoion we have balanced this section. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines.>>> Thank you we believe our question is stated clearly : To determine the recent treatment protocol for pm through a systamtic review of the literature. It’s not our aim to create a framework or guideline. We believe the value of this paper is to shed light on the recent literature on the treatment of pm. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. >>>>Thank you, we have provided Supplementary Table 1 and Supplementary Table 2; they list the key features of the selected articles: https://doi.org/10.6084/m9.figshare.26362093.v1 https://doi.org/10.6084/m9.figshare.26362099.v1 Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. >>> It is possible that you may not, perhaps, have viewed these tables. Are the rationale for, and objectives of, the Systematic Review clearly stated? No >> Thank you, we respectfully disagree. Are sufficient details of the methods and analysis provided to allow replication by others? No >>>> This review clearly states, and follows, accepted PRISMA guidelines. We have provided the method and analysis used for this review very clearly, including the search strategy, databases searched, etc., so that this review can be replicated. Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. >>Thank you , we have ensured that it is Are the conclusions drawn adequately supported by the results presented in the review? No >>> Thank you, we respectfully disagree. If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Yes this not a systematic review https://f1000research-files.f1000.com/linked/749694.151564-Fig.png The mortality rate of PM has improved over time, but it is still high (Muthu, Agarwal, et al., 2021). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. A systematic review is appropriate because many of these treatments are new or emerging. VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature>>> thank you for kind observations The "Background" section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. Thank you for your critique, we have cross checked the references and found that they are UpToDate . The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM. >>> thank you we have made changes accordingly Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM.>>> Presentation of other forms of mucomycosis can overlap with pm in some instances especially in the early stages there for we believe its relevant Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies>>>>Thank you we believe that details of qpcr beyond the scope . however we are of its important that why we included it Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript.>>>> after the careful consideratoion we have balanced this section. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines.>>> Thank you we believe our question is stated clearly : To determine the recent treatment protocol for pm through a systamtic review of the literature. It’s not our aim to create a framework or guideline. We believe the value of this paper is to shed light on the recent literature on the treatment of pm. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. >>>>Thank you, we have provided Supplementary Table 1 and Supplementary Table 2; they list the key features of the selected articles: https://doi.org/10.6084/m9.figshare.26362093.v1 https://doi.org/10.6084/m9.figshare.26362099.v1 Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. >>> It is possible that you may not, perhaps, have viewed these tables. Are the rationale for, and objectives of, the Systematic Review clearly stated? No >> Thank you, we respectfully disagree. Are sufficient details of the methods and analysis provided to allow replication by others? No >>>> This review clearly states, and follows, accepted PRISMA guidelines. We have provided the method and analysis used for this review very clearly, including the search strategy, databases searched, etc., so that this review can be replicated. Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. >>Thank you , we have ensured that it is Are the conclusions drawn adequately supported by the results presented in the review? No >>> Thank you, we respectfully disagree. If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Yes this not a systematic review https://f1000research-files.f1000.com/linked/749694.151564-Fig.png The mortality rate of PM has improved over time, but it is still high (Muthu, Agarwal, et al., 2021). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. A systematic review is appropriate because many of these treatments are new or emerging. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 10 Sep 2025 Tarig Fadelelmoula , Internal Medicine, National University of Science and Technology, Sohar, Oman 10 Sep 2025 Author Response VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The ... Continue reading VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature>>> thank you for kind observations The "Background" section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. Thank you for your critique, we have cross checked the references and found that they are UpToDate . The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM. >>> thank you we have made changes accordingly Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM.>>> Presentation of other forms of mucomycosis can overlap with pm in some instances especially in the early stages there for we believe its relevant Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies>>>>Thank you we believe that details of qpcr beyond the scope . however we are of its important that why we included it Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript.>>>> after the careful consideratoion we have balanced this section. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines.>>> Thank you we believe our question is stated clearly : To determine the recent treatment protocol for pm through a systamtic review of the literature. It’s not our aim to create a framework or guideline. We believe the value of this paper is to shed light on the recent literature on the treatment of pm. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. >>>>Thank you, we have provided Supplementary Table 1 and Supplementary Table 2; they list the key features of the selected articles: https://doi.org/10.6084/m9.figshare.26362093.v1 https://doi.org/10.6084/m9.figshare.26362099.v1 Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. >>> It is possible that you may not, perhaps, have viewed these tables. Are the rationale for, and objectives of, the Systematic Review clearly stated? No >> Thank you, we respectfully disagree. Are sufficient details of the methods and analysis provided to allow replication by others? No >>>> This review clearly states, and follows, accepted PRISMA guidelines. We have provided the method and analysis used for this review very clearly, including the search strategy, databases searched, etc., so that this review can be replicated. Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. >>Thank you , we have ensured that it is Are the conclusions drawn adequately supported by the results presented in the review? No >>> Thank you, we respectfully disagree. If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Yes this not a systematic review https://f1000research-files.f1000.com/linked/749694.151564-Fig.png The mortality rate of PM has improved over time, but it is still high (Muthu, Agarwal, et al., 2021). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. A systematic review is appropriate because many of these treatments are new or emerging. VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature>>> thank you for kind observations The "Background" section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. Thank you for your critique, we have cross checked the references and found that they are UpToDate . The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM. >>> thank you we have made changes accordingly Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM.>>> Presentation of other forms of mucomycosis can overlap with pm in some instances especially in the early stages there for we believe its relevant Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies>>>>Thank you we believe that details of qpcr beyond the scope . however we are of its important that why we included it Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript.>>>> after the careful consideratoion we have balanced this section. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines.>>> Thank you we believe our question is stated clearly : To determine the recent treatment protocol for pm through a systamtic review of the literature. It’s not our aim to create a framework or guideline. We believe the value of this paper is to shed light on the recent literature on the treatment of pm. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. >>>>Thank you, we have provided Supplementary Table 1 and Supplementary Table 2; they list the key features of the selected articles: https://doi.org/10.6084/m9.figshare.26362093.v1 https://doi.org/10.6084/m9.figshare.26362099.v1 Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. >>> It is possible that you may not, perhaps, have viewed these tables. Are the rationale for, and objectives of, the Systematic Review clearly stated? No >> Thank you, we respectfully disagree. Are sufficient details of the methods and analysis provided to allow replication by others? No >>>> This review clearly states, and follows, accepted PRISMA guidelines. We have provided the method and analysis used for this review very clearly, including the search strategy, databases searched, etc., so that this review can be replicated. Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. >>Thank you , we have ensured that it is Are the conclusions drawn adequately supported by the results presented in the review? No >>> Thank you, we respectfully disagree. If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Yes this not a systematic review https://f1000research-files.f1000.com/linked/749694.151564-Fig.png The mortality rate of PM has improved over time, but it is still high (Muthu, Agarwal, et al., 2021). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. A systematic review is appropriate because many of these treatments are new or emerging. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 08 Oct 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 28 Jul 25 read read Version 1 08 Oct 24 read read Eric Dannaoui , Paris Cité University, Paris, France Maria Drogari-Apiranthitou , National and Kapodistrian University of Athens, Athens, Greece KHEM RAJ , Panjab University, Chandigarh, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 RAJ K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Dec 2025 | for Version 2 KHEM RAJ , Panjab University, Chandigarh, India 0 Views copyright © 2026 RAJ K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. The review gives a good summary of the available treatments for pulmonary mucormycosis. 2. The methods are not very strong for a systematic review, as there is no quality assessment of the included studies, making the reliability of the findings uncertain. 3. At many points, the discussion shifts toward mucormycosis in general rather than focusing specifically on pulmonary disease, which slightly weakens the clarity and focus of the review. 4. Certain therapies with limited or conflicting evidence, such as iron chelators and zinc supplementation, are discussed without sufficient available data. 5. Focusing on how many papers mention a particular treatment can be misleading, as many of these studies are either case reports or small case series, which do not provide any reliable evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Partly If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Microbial genomics, transcriptomics, and fungal pathogenesis., microbial-host interactions and antimicrobial resistance, combining experimental biology with integrative omics approaches. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) RAJ K. Peer Review Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r437446) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-437446 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Drogari-Apiranthitou M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Aug 2025 | for Version 2 Maria Drogari-Apiranthitou , Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, Attikon General University, National and Kapodistrian University of Athens, Athens, Greece 0 Views copyright © 2025 Drogari-Apiranthitou M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I am afraid the issues I raised in my initial review remain unaddressed. Competing Interests No competing interests were disclosed. Reviewer Expertise Clinical Mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Drogari-Apiranthitou M. Peer Review Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.175240.r400950) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1165/v2#referee-response-400950 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Drogari-Apiranthitou M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 Nov 2024 | for Version 1 Maria Drogari-Apiranthitou , Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, Attikon General University, National and Kapodistrian University of Athens, Athens, Greece 0 Views copyright © 2024 Drogari-Apiranthitou M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In the submitted manuscript titled “Management of Pulmonary Mucormycosis: A Systematic Review,” the authors state their objective as identifying and mapping the management of PM through a systematic review approach. While the study tackles an important subject, it exhibits several shortcomings. Major points Background. The introduction is overly lengthy, whereas it should rather focus on the main subject which is PM and the challenges associated with its treatment. The authors claim that “this systematic review aims to shed light on recent treatment protocols for PM”, and that “a systematic review is appropriate because many of these treatments are new or emerging”. It would be helpful to provide more specificity on how their systematic review will contribute to advancing current knowledge in this field. Methodology and Results While the PRISMA-ScR method used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) is a valid guideline designed to ensure transparency and comprehensiveness in the reporting of scoping reviews, it seems that the authors did not take full advantage of it. Rather than merely presenting numerical summaries (e.g., the number of papers reporting specific comorbidities or the use of L-AmB), it would be of more value to group patients by key underlying conditions (e.g., hematologic malignancies, diabetes) and tabulate these alongside the therapies they received and their outcomes. This would allow for a more insightful analysis of potential associations between treatments and outcomes. Result presentation. Table 1 appears redundant, as the search methodology could be more effectively described in the text. Fig. 2 seems to inaccurately represent the data. For instance, it suggests that L-AmB and surgery were used in equal numbers of studies, whereas in most cases, these interventions were applied simultaneously. A tabular format would better represent this information. Fig. 3 is not informative in its current form. Presenting patient numbers and their characteristics in a table would be more effective for conveying meaningful insights. Discussion and Conclusions The Discussion section is overly generic, which may be attributed to the absence of patient-specific results. For instance, conclusions such as “The results indicate that early diagnosis and early and aggressive surgery may hold the key to effective management” and “The control of co-morbidities such as diabetes continues to be a crucial aspect of effective management” do not appear to be directly supported by the data presented. Additionally, the study lacks detailed results regarding novel or adjunctive therapies, along with patient-specific data such as underlying diseases, risk factors, species of Mucorales involved, demographics, country of origin, etc, which would provide deeper insights. Other Points of Concern There are several inaccuracies, or outdated literature has been occasionally used. Some examples: In the Background, the statement that malignancies (63.4%), diabetes mellitus (17.1%), and solid organ transplantation (9.8%) are the most common underlying conditions is misleading. Globally, diabetes is the leading cause of mucormycosis, with hematologic malignancies ranking first only in Europe. There is more recent literature that reflects this trend and should be cited. Furthermore, under Epidemiology, some contradictory data are presented. The most common clinical presentations of mucormycosis are rhino-orbito-cerebral (ROC), pulmonary, cutaneous, and disseminated. Jeong et al. report corresponding rates of 34%, 21%, 20%, and 14%, while in the European study of the Working Group on Zygomycosis the corresponding numbers were 27%, 30%, 26%, and 15%. The data from Pana et al. (2016) specifically pertain to children, but this distinction is not made. It should be also mentioned that in India, during the COVID-19 pandemic, PM cases indeed increased, but the predominant form of mucormycosis was ROC [refer 1]. To summarize, the current study appears incomplete and does not achieve its objectives. It would be more valuable to include a detailed analysis of all patients from the retrieved articles, potentially using statistical methods to draw conclusions about the effectiveness of different treatment modalities and their association with patient outcomes. Are the rationale for, and objectives of, the Systematic Review clearly stated? No Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable References 1. Pasquier G: COVID-19-associated mucormycosis in India: Why such an outbreak?. J Mycol Med . 2023; 33 (3): 101393 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Clinical Mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Drogari-Apiranthitou M. Peer Review Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334217) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334217 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Dannaoui E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Nov 2024 | for Version 1 Eric Dannaoui , Faculty of Medicine, Paris Cité University, Paris, France 0 Views copyright © 2024 Dannaoui E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature The " Background " section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM. Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. Are the rationale for, and objectives of, the Systematic Review clearly stated? No Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Medical mycology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 10 Sep 2025 Tarig Fadelelmoula, Internal Medicine, National University of Science and Technology, Sohar, Oman VIEWS 0 In this article, the authors present a systematic review of pulmonary mucormycosis. They start with an extended introduction that encompasses general information of all forms of mucormycosis. The methods section outlines the article selection process and specifies the main review question. The results show that 28 articles were analyzed, with key findings briefly summarized. Finally, the authors discuss the main points in relation to existing literature>>> thank you for kind observations The "Background" section covers various clinical forms of mucormycosis, which could benefit from a sharper focus on pulmonary mucormycosis (PM) as it is the primary topic of this review. Some references cited are not fully up-to-date. Thank you for your critique, we have cross checked the references and found that they are UpToDate . The inclusion of multiple mucormycosis forms sometimes makes the statements unclear; for example, the mortality rate is noted as around 50%, but it’s unclear if this figure applies to all mucormycosis types or is specific to PM. >>> thank you we have made changes accordingly Epidemiology: Including information on other forms of mucormycosis in this section introduces confusion. To improve clarity, it would be more effective to concentrate exclusively on PM.>>> Presentation of other forms of mucomycosis can overlap with pm in some instances especially in the early stages there for we believe its relevant Molecular Diagnosis: The role of qPCR in diagnosing mucormycosis is not emphasized enough. This technique has transformed mucormycosis diagnosis and warrants a more detailed discussion. Additionally, it’s important to note that qPCR is versatile and can be applied to a variety of samples beyond blood, including respiratory specimens and tissue biopsies>>>>Thank you we believe that details of qpcr beyond the scope . however we are of its important that why we included it Iron Chelating Agents: The information on iron-chelating agents as an adjunctive therapy appears disproportionately detailed relative to other sections. Reducing this section or balancing it with more information on alternative therapies could improve the overall focus and coherence of the manuscript.>>>> after the careful consideratoion we have balanced this section. Review Question: The review question would benefit from clarification. The current phrasing suggests an aim to establish treatment guidelines based on the literature. However, comprehensive, recent guidelines by international experts already address this topic. It would be helpful to specify how this review adds unique value or complements existing guidelines.>>> Thank you we believe our question is stated clearly : To determine the recent treatment protocol for pm through a systamtic review of the literature. It’s not our aim to create a framework or guideline. We believe the value of this paper is to shed light on the recent literature on the treatment of pm. Key Results: The presentation of key results could be improved for clarity. The distinction between studies that “recommend” versus those that “mention” a therapy is unclear and should be specified. For instance, of the 28 articles included, it is noted that two explicitly recommend against voriconazole use. Clarification is needed on for the remaining 26 articles, whether they support, oppose, or simply discuss its usage without recommendation. >>>>Thank you, we have provided Supplementary Table 1 and Supplementary Table 2; they list the key features of the selected articles: https://doi.org/10.6084/m9.figshare.26362093.v1 https://doi.org/10.6084/m9.figshare.26362099.v1 Discussion Primary Therapies: Please clarify whether posaconazole is suggested as a possible first-line treatment for PM. The text also mentions that 11 articles support combination therapy, yet no specific results are provided in the results section to demonstrate that combination therapy is more effective than monotherapy. Including relevant data or further explanation would enhance clarity. >>> It is possible that you may not, perhaps, have viewed these tables. Are the rationale for, and objectives of, the Systematic Review clearly stated? No >> Thank you, we respectfully disagree. Are sufficient details of the methods and analysis provided to allow replication by others? No >>>> This review clearly states, and follows, accepted PRISMA guidelines. We have provided the method and analysis used for this review very clearly, including the search strategy, databases searched, etc., so that this review can be replicated. Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. >>Thank you , we have ensured that it is Are the conclusions drawn adequately supported by the results presented in the review? No >>> Thank you, we respectfully disagree. If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Yes this not a systematic review https://f1000research-files.f1000.com/linked/749694.151564-Fig.png The mortality rate of PM has improved over time, but it is still high (Muthu, Agarwal, et al., 2021). Therefore, this systematic review aims to shed light on recent treatment protocols for PM. A systematic review is appropriate because many of these treatments are new or emerging. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Dannaoui E. Peer Review Report For: Management of Pulmonary Mucormycosis: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2025, 13 :1165 ( https://doi.org/10.5256/f1000research.166217.r334224) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1165/v1#referee-response-334224 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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