Journal of Fungi

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5 pages, 239 KiB

Open AccessEditorial

Special Issue “Diagnosis and Treatment of Invasive Pulmonary Fungal Infections”

by Joseph P. Lynch and Dimitrios P. Kontoyiannis

J. Fungi 2023, 9(7), 744; https://doi.org/10.3390/jof9070744 - 13 Jul 2023

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Abstract

The Guest Editors Dr [...] Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

Review

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12 pages, 317 KiB

Open AccessReview

Invasive Fungal Infections Associated with COVID-19

by Kyaw M. Hlaing, Lea M. Monday, Marcio Nucci, Simone A. Nouér and Sanjay G. Revankar

J. Fungi 2023, 9(6), 667; https://doi.org/10.3390/jof9060667 - 14 Jun 2023

Cited by 6 | Viewed by 1917

Abstract

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the [...] Read more.

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the most serious of these infections. Risk factors included alterations in immune defense mechanisms by COVID-19 itself, as well as immunosuppression due to various therapies utilized in severely ill patients. Diagnosis was often challenging due to lack of sensitivity of current testing. Outcomes were generally poor, due to significant co-morbidities and delayed diagnosis, with mortality rates >50% in some studies. High index of clinical suspicion is needed to facilitate early diagnosis and initiation of appropriate antifungal therapy. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

15 pages, 263 KiB

Open AccessReview

Clinical Uses of Inhaled Antifungals for Invasive Pulmonary Fungal Disease: Promises and Challenges

by Nancy N. Vuong, Danielle Hammond and Dimitrios P. Kontoyiannis

J. Fungi 2023, 9(4), 464; https://doi.org/10.3390/jof9040464 - 12 Apr 2023

Cited by 2 | Viewed by 2042

Abstract

The role of inhaled antifungals for prophylaxis and treatment of invasive fungal pneumonias remains undefined. Herein we summarize recent clinically relevant literature in high-risk groups such as neutropenic hematology patients, including those undergoing stem cell transplant, lung and other solid transplant recipients, and [...] Read more.

The role of inhaled antifungals for prophylaxis and treatment of invasive fungal pneumonias remains undefined. Herein we summarize recent clinically relevant literature in high-risk groups such as neutropenic hematology patients, including those undergoing stem cell transplant, lung and other solid transplant recipients, and those with sequential mold lung infections secondary to viral pneumonias. Although there are several limitations of the available data, inhaled liposomal amphotericin B administered 12.5 mg twice weekly could be an alternative method of prophylaxis in neutropenic populations at high risk for invasive fungal pneumonia where systemic triazoles are not tolerated. In addition, inhaled amphotericin B has been commonly used as prophylaxis, pre-emptive, or targeted therapy for lung transplant recipients but is considered as a secondary alternative for other solid organ transplant recipients. Inhaled amphotericin B seems promising as prophylaxis in fungal pneumonias secondary to viral pneumonias, influenza, and SARS CoV-2. Data remain limited for inhaled amphotericin for adjunct treatment, but the utility is feasible. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

22 pages, 3139 KiB

Open AccessReview

What Is New in Pulmonary Mucormycosis?

by François Danion, Anne Coste, Coralie Le Hyaric, Clea Melenotte, Frederic Lamoth, Thierry Calandra, Dea Garcia-Hermoso, Vishukumar Aimanianda, Fanny Lanternier and Olivier Lortholary

J. Fungi 2023, 9(3), 307; https://doi.org/10.3390/jof9030307 - 28 Feb 2023

Cited by 12 | Viewed by 4812

Abstract

Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral [...] Read more.

Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral (ROC) areas and the skin. The main risk factors for PM include hematological malignancies and solid organ transplantation, whereas ROC infections classically are classically favored by diabetes mellitus. The differences between the ROC and pulmonary locations are possibly explained by the activation of different mammalian receptors—GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells—in response to Mucorales. Alveolar macrophages and neutrophils play a key role in the host defense against Mucorales. The diagnosis of PM relies on CT scans, cultures, PCR tests, and histology. The reversed halo sign is an early, but very suggestive, sign of PM in neutropenic patients. Recently, the serum PCR test showed a very encouraging performance for the diagnosis and follow-up of mucormycosis. Liposomal amphotericin B is the drug of choice for first-line therapy, together with correction of underlying disease and surgery when feasible. After a stable or partial response, the step-down treatment includes oral isavuconazole or posaconazole delayed release tablets until a complete response is achieved. Secondary prophylaxis should be discussed when there is any risk of relapse, such as the persistence of neutropenia or the prolonged use of high-dose immunosuppressive therapy. Despite these novelties, the mortality rate from PM remains higher than 50%. Therefore, future research must define the place for combination therapy and adjunctive treatments, while the development of new treatments is necessary. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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21 pages, 2782 KiB

Open AccessReview

Pulmonary Histoplasmosis: A Clinical Update

by Nicolas Barros, Joseph L. Wheat and Chadi Hage

J. Fungi 2023, 9(2), 236; https://doi.org/10.3390/jof9020236 - 10 Feb 2023

Cited by 9 | Viewed by 7078

Abstract

Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America [...] Read more.

Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. The most common clinical presentations include pulmonary histoplasmosis, which can resemble community-acquired pneumonia, tuberculosis, sarcoidosis, or malignancy; however, certain patients can develop mediastinal involvement or progression to disseminated disease. Understanding the epidemiology, pathology, clinical presentation, and diagnostic testing performance is pivotal for a successful diagnosis. While most immunocompetent patients with mild acute or subacute pulmonary histoplasmosis should receive therapy, all immunocompromised patients and those with chronic pulmonary disease or progressive disseminated disease should also receive therapy. Liposomal amphotericin B is the agent of choice for severe or disseminated disease, and itraconazole is recommended in milder cases or as “step-down” therapy after initial improvement with amphotericin B. In this review, we discuss the current epidemiology, pathology, diagnosis, clinical presentations, and management of pulmonary histoplasmosis. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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25 pages, 4327 KiB

Open AccessReview

Diagnosis and Treatment of Pulmonary Coccidioidomycosis and Paracoccidioidomycosis

by Paula Massaroni Peçanha-Pietrobom, Andrés Tirado-Sánchez, Sarah Santos Gonçalves, Alexandro Bonifaz and Arnaldo Lopes Colombo

J. Fungi 2023, 9(2), 218; https://doi.org/10.3390/jof9020218 - 07 Feb 2023

Cited by 6 | Viewed by 3499

Abstract

Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with [...] Read more.

Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with peculiarities in their geographic distribution. The genus Paracoccidioides now includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which encompasses four phylogenetic species. In both diseases, pulmonary signs and symptoms are the main reasons for patients to seek medical assistance, and they are frequently misdiagnosed as tuberculosis. In this paper, we present a critical view of the strategies for diagnosis and clinical management of CM and PCM. Over the past few decades, there has been an increase in the number of reports of endemic fungal infections in areas previously thought to be “non-endemic” due to climate change and increased travel, among other factors. Learning to recognize their main epidemiological aspects and clinical manifestations is crucial so that clinicians can include them in the differential diagnosis of lung disease and avoid late diagnosis. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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30 pages, 490 KiB

Open AccessReview

Non-Aspergillus Hyaline Molds: A Host-Based Perspective of Emerging Pathogenic Fungi Causing Sinopulmonary Diseases

by Samantha E. Jacobs and Thomas J. Walsh

J. Fungi 2023, 9(2), 212; https://doi.org/10.3390/jof9020212 - 06 Feb 2023

Cited by 3 | Viewed by 2229

Abstract

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to [...] Read more.

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

24 pages, 424 KiB

Open AccessReview

Systemic Antifungal Therapy for Invasive Pulmonary Infections

by Ronen Ben-Ami

J. Fungi 2023, 9(2), 144; https://doi.org/10.3390/jof9020144 - 21 Jan 2023

Cited by 5 | Viewed by 3040

Abstract

Antifungal therapy for pulmonary fungal diseases is in a state of flux. Amphotericin B, the time-honored standard of care for many years, has been replaced by agents demonstrating superior efficacy and safety, including extended-spectrum triazoles and liposomal amphotericin B. Voriconazole, which became the [...] Read more.

Antifungal therapy for pulmonary fungal diseases is in a state of flux. Amphotericin B, the time-honored standard of care for many years, has been replaced by agents demonstrating superior efficacy and safety, including extended-spectrum triazoles and liposomal amphotericin B. Voriconazole, which became the treatment of choice for most pulmonary mold diseases, has been compared with posaconazole and itraconazole, both of which have shown clinical efficacy similar to that of voriconazole, with fewer adverse events. With the worldwide expansion of azole-resistant Aspergillus fumigatus and infections with intrinsically resistant non-Aspergillus molds, the need for newer antifungals with novel mechanisms of action becomes ever more pressing. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

24 pages, 4969 KiB

Open AccessReview

Invasive Pulmonary Aspergillosis

by Marie-Pierre Ledoux and Raoul Herbrecht

J. Fungi 2023, 9(2), 131; https://doi.org/10.3390/jof9020131 - 17 Jan 2023

Cited by 13 | Viewed by 8117

Abstract

Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific [...] Read more.

Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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13 pages, 902 KiB

Open AccessReview

Blastomycosis: A Review of Mycological and Clinical Aspects

by Kathleen A. Linder, Carol A. Kauffman and Marisa H. Miceli

J. Fungi 2023, 9(1), 117; https://doi.org/10.3390/jof9010117 - 14 Jan 2023

Cited by 8 | Viewed by 3939

Abstract

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several [...] Read more.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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13 pages, 2174 KiB

Open AccessReview

The Pathogenesis and Diagnosis of Pneumocystis jiroveci Pneumonia

by Anna Apostolopoulou and Jay A. Fishman

J. Fungi 2022, 8(11), 1167; https://doi.org/10.3390/jof8111167 - 05 Nov 2022

Cited by 27 | Viewed by 11134

Abstract

Pneumocystis jiroveci remains an important fungal pathogen in immunocompromised hosts. The environmental reservoir remains unknown. Pneumonia (PJP) results from airborne transmission, including in nosocomial clusters, or with reactivation after an inadequately treated infection. Pneumocystis pneumonia most often occurs within 6 months of organ [...] Read more.

Pneumocystis jiroveci remains an important fungal pathogen in immunocompromised hosts. The environmental reservoir remains unknown. Pneumonia (PJP) results from airborne transmission, including in nosocomial clusters, or with reactivation after an inadequately treated infection. Pneumocystis pneumonia most often occurs within 6 months of organ transplantation, with intensified or prolonged immunosuppression, notably with corticosteroids and following cytomegalovirus (CMV) infections. Infection may be recognized during recovery from neutropenia and lymphopenia. Invasive procedures may be required for early diagnosis and therapy. Despite being a well-established entity, aspects of the pathogenesis of PJP remain poorly understood. The goal of this review is to summarize the data on the pathogenesis of PJP, review the strengths and weaknesses of the pertinent diagnostic modalities, and discuss areas for future research. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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19 pages, 1720 KiB

Open AccessReview

Pulmonary Cryptococcosis

by Annaleise R. Howard-Jones, Rebecca Sparks, David Pham, Catriona Halliday, Justin Beardsley and Sharon C.-A. Chen

J. Fungi 2022, 8(11), 1156; https://doi.org/10.3390/jof8111156 - 31 Oct 2022

Cited by 20 | Viewed by 4121

Abstract

Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that [...] Read more.

Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Invasive Pulmonary Fungal Infections)

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