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Expert Review of Respiratory Medicine Jul 2020Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised... (Review)
Review
INTRODUCTION
Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised individuals. The diagnostic approach for many fungal pathogens continues to evolve. Herein, we outline available diagnostic tests for the most common fungal infections with a focus on recent advances and future directions.
AREAS COVERED
We discuss the diagnostic testing methods for angioinvasive molds ( spp. and spp.), invasive yeast ( spp. and ssp.), Pneumocystis, and endemic fungi ( sp., Coccidioides sp., and Hitoplasma sp.). The PubMed-NCBI database was searched within the past 5 years to identify the most recent available literature with dates extended in cases where literature was sparse. Diagnostic guidelines were utilized when available with references reviewed.
EXPERT OPINION
Historically, culture and/or direct visualization of fungal organisms were required for diagnosis of infection. Significant limitations included ability to collect specimens and delayed diagnosis associated with waiting for culture results. Antigen and antibody testing have made great strides in allowing quicker diagnosis of fungal infections but can be limited by low sensitivity/specificity, cross-reactivity with other fungi, and test availability. Molecular methods have a rich history in some fungal diseases, while others continue to be developed.
Topics: Aspergillus; Blastomyces; Candida; Coccidioides; Cryptococcus; Histoplasma; Humans; Lung Diseases, Fungal; Mucor; Pneumocystis; Pneumonia
PubMed: 32290725
DOI: 10.1080/17476348.2020.1753506 -
Revista Espanola de Quimioterapia :... Jun 2023The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any... (Review)
Review
The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.
Topics: Humans; Antifungal Agents; Voriconazole; Azoles; Antineoplastic Agents; Hematologic Neoplasms
PubMed: 37017117
DOI: 10.37201/req/013.2023 -
Journal of Fungi (Basel, Switzerland) Jul 2022COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino-orbital mucormycosis was... (Review)
Review
COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino-orbital mucormycosis was well reported during the pandemic, in the absence of routine diagnostic facilities including lower airway sampling, pulmonary mucormycosis was probably under-recognized. In this review, we have focused on the epidemiology and management of COVID-19-associated pulmonary mucormycosis (CAPM). CAPM is a deadly disease and mortality can be as high as 80% in the absence of early clinical suspicion and treatment. While histopathological examination of tissue for angio-invasion and cultures have remained gold standard for diagnosis, there is an increasing interest in molecular and serological methods to facilitate diagnosis in critically ill patients and often, immune-suppressed hosts who cannot readily undergo invasive sampling. Combined medical and surgical treatment offers more promise than standalone medical therapy. Maintaining adequate glycemic control and prudent use of steroids which can be a double-edged sword in COVID-19 patients are the key preventative measures. We would like to emphasize the urgent need for the development and validation of reliable biomarkers and molecular diagnostics to facilitate early diagnosis.
PubMed: 35887466
DOI: 10.3390/jof8070711 -
Journal of Fungi (Basel, Switzerland) Jun 2020Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven... (Review)
Review
Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven different genera that can infect humans. This heterogeneity is associated with species-specific invasion pathways and responses to the host defense mechanisms. The host innate immune system plays a major role in preventing Mucorales growth and host invasion. In this system, macrophages are the main immune effector cells in controlling these fungi by rapid and efficient phagocytosis of the spores. However, Mucorales have evolved mechanisms to block phagosomal maturation and species-specific mechanisms to either survive as dormant spores inside the macrophage, as species, or geminate and escape, as species. Classical fungal models of mucormycosis, mostly , have made important contributions to elucidate key aspects of the interaction between Mucorales and macrophages, but they lack robust tools for genetic manipulation. The recent introduction of the genetically tractable as a model of mucormycosis offers the possibility to analyze gene function. This has allowed the identification of regulatory pathways that control the fungal response to phagocytosis, including a non-canonical RNAi pathway (NCRIP) that regulates the expression of most genes regulated by phagocytosis.
PubMed: 32604972
DOI: 10.3390/jof6020094 -
Microorganisms Mar 2021Mucormycosis is an angioinvasive disease caused by saprophytic fungi of the order Mucorales. The exact incidence of mucormycosis in India is unknown due to the lack of... (Review)
Review
Mucormycosis is an angioinvasive disease caused by saprophytic fungi of the order Mucorales. The exact incidence of mucormycosis in India is unknown due to the lack of population-based studies. The estimated prevalence of mucormycosis is around 70 times higher in India than that in global data. Diabetes mellitus is the most common risk factor, followed by haematological malignancy and solid-organ transplant. Patients with postpulmonary tuberculosis and chronic kidney disease are at additional risk of developing mucormycosis in this country. Trauma is a risk factor for cutaneous mucormycosis. Isolated renal mucormycosis in an immunocompetent host is a unique entity in India. Though is the most common etiological agent of mucormycosis in this country, infections due to , , and are rising. Occasionally, , , and are isolated. Though awareness of the disease has increased among treating physicians, disease-associated morbidity and mortality are still high, as patients seek medical attention late in the disease process and given the low affordability for therapy. In conclusion, the rise in the number of cases, the emergence of new risk factors and causative agents, and the challenges in managing the disease are important concerns with mucormycosis in India.
PubMed: 33806386
DOI: 10.3390/microorganisms9030523 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Mucormycosis
PubMed: 37743863
DOI: 10.3389/fcimb.2023.1280784 -
Current Fungal Infection Reports May 2023Invasive mucormycosis (IM), caused by fungi of the order Mucorales, is one of the deadliest fungal infection among hematologic cancer patients. Its incidence is also... (Review)
Review
PURPOSE OF REVIEW
Invasive mucormycosis (IM), caused by fungi of the order Mucorales, is one of the deadliest fungal infection among hematologic cancer patients. Its incidence is also increasingly reported in immunocompetent individuals, notably with the COVID-19 pandemic. Therefore, there is an urgent need for novel diagnostic and therapeutic approaches of IM. This review discusses the current advances in this field.
RECENT FINDINGS
Early diagnosis of IM is crucial and can be improved by Mucorales-specific PCR and development of lateral-flow immunoassays for specific antigen detection. The spore coat proteins (CotH) are essential for virulence of the Mucorales and may represent a target for novel antifungal therapies. Adjuvant therapies boosting the immune response, such as interferon-γ, anti-PDR1 or fungal-specific chimeric antigen receptor (CAR) T-cells, are also considered.
SUMMARY
The most promising perspectives for improved management of IM consist of a multilayered approach targeting both the pathogen and the host immune system.
PubMed: 37360854
DOI: 10.1007/s12281-023-00463-3 -
Journal of Fungi (Basel, Switzerland) Nov 2020Mucormycosis is an angioinvasive fungal infection, due to fungi of the order Mucorales. Its incidence cannot be measured exactly, since there are few population-based... (Review)
Review
Mucormycosis is an angioinvasive fungal infection, due to fungi of the order Mucorales. Its incidence cannot be measured exactly, since there are few population-based studies, but multiple studies have shown that it is increasing. The prevalence of mucormycosis in India is about 80 times the prevalence in developed countries, being approximately 0.14 cases per 1000 population. Diabetes mellitus is the main underlying disease globally, especially in low and middle-income countries. In developed countries the most common underlying diseases are hematological malignancies and transplantation. Τhe epidemiology of mucormycosis is evolving as new immunomodulating agents are used in the treatment of cancer and autoimmune diseases, and as the modern diagnostic tools lead to the identification of previously uncommon genera/species such as or complex. In addition, new risk factors are reported from Asia, including post-pulmonary tuberculosis and chronic kidney disease. New emerging species include , , and . Diagnosis of mucormycosis remains challenging. Clinical approach to diagnosis has a low sensitivity and specificity, it helps however in raising suspicion and prompting the initiation of laboratory testing. Histopathology, direct examination and culture remain essential tools, although the molecular methods are improving. The internal transcribed spacer (ITS) region is the most widely sequenced DNA region for fungi and it is recommended as a first-line method for species identification of Mucorales. New molecular platforms are being investigated and new fungal genetic targets are being explored. Molecular-based methods have gained acceptance for confirmation of the infection when applied on tissues. Methods on the detection of Mucorales DNA in blood have shown promising results for earlier and rapid diagnosis and could be used as screening tests in high-risk patients, but have to be validated in clinical studies. More, much needed, rapid methods that do not require invasive procedures, such as serology-based point-of-care, or metabolomics-based breath tests, are being developed and hopefully will be evaluated in the near future.
PubMed: 33147877
DOI: 10.3390/jof6040265 -
Transplant International : Official... 2023Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against... (Review)
Review
Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.
Topics: Humans; Antifungal Agents; Aspergillosis; Nitriles; Organ Transplantation; Transplant Recipients; Voriconazole
PubMed: 38161768
DOI: 10.3389/ti.2023.11845 -
Microorganisms Jul 2023Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was... (Review)
Review
Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was (26.5%), followed by (20.7%) and (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.
PubMed: 37513000
DOI: 10.3390/microorganisms11071828