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Frontiers in Cellular and Infection... 2023Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in... (Review)
Review
Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.
Topics: Humans; Mucormycosis; Antifungal Agents; COVID-19; Mucorales; Diabetes Mellitus; Iron
PubMed: 37808914
DOI: 10.3389/fcimb.2023.1254919 -
The Journal of Infection Jul 2023We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies.
OBJECTIVES
We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies.
METHODS
BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions.
RESULTS
121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases.
CONCLUSIONS
BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.
Topics: Humans; Antifungal Agents; Prospective Studies; Invasive Fungal Infections; Fungi; Hematologic Neoplasms; Candidemia; Aspergillus
PubMed: 37201859
DOI: 10.1016/j.jinf.2023.05.005 -
Frontiers in Cellular and Infection... 2024
Topics: Mucormycosis; Mucorales; Humans; Antifungal Agents; Animals
PubMed: 38836052
DOI: 10.3389/fcimb.2024.1427252 -
Trends in Microbiology Sep 2023
Topics: Rhizopus oryzae; Rhizopus
PubMed: 37062623
DOI: 10.1016/j.tim.2023.03.013 -
Dermatology Online Journal Dec 2023A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous...
A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous plaques appeared on the upper extremities and anterior left hemithorax, which worsened and acquired a necrotic center. We performed a biopsy and histology showed a cutaneous infarction at the dermoepidermal and subcutaneous level. We observed abundant wide hyphae with right-angled branching and a culture isolated Rhizopus oryzae. A plastic surgery consultant performed a surgical debridement of the lesions and treatment was started with intravenous amphotericin B. The patient did well on treatment and after almost a month of hospitalization, he was discharged with oral posaconazole. Mucormycosis is an opportunistic fungal infection associated with immunosuppression, particularly involving prematurity and hematological diseases in the pediatric age group. Multiple lesions, as in our case, are infrequent. The clinical presentation is variable. Direct smear or histological observation is the quickest diagnostic technique whereas culture is the most definitive. The combination of surgical debridement and amphotericin B is the treatment with the highest survival rates.
Topics: Male; Humans; Child; Amphotericin B; Rhizopus; Mucormycosis; Skin; Necrosis; Antifungal Agents
PubMed: 38478665
DOI: 10.5070/D329662994 -
Expert Review of Anti-infective Therapy 2023Mucormycosis (MCR), a rare but life-threatening infection, occurs primarily in immunocompromised hosts. Mortality rates with invasive MCR are high (>30-50%), up to 90%... (Review)
Review
INTRODUCTION
Mucormycosis (MCR), a rare but life-threatening infection, occurs primarily in immunocompromised hosts. Mortality rates with invasive MCR are high (>30-50%), up to 90% with disseminated disease, but lower (10-30%) with localized cutaneous disease. Due to the rarity of MCR, randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy or in MCR cases refractory to or intolerant of LFAB. Early surgical debridement or excision plays important adjunctive roles in localized invasive disease. Control of hyperglycemia in diabetic patients, correction of neutropenia, and reduction of immunosuppressive therapy are critical for optimal survival.
AREAS COVERED
The authors discuss various therapeutic options for mucormycosis. A literature search of mucormycosis therapies was performed via PubMed (up to December 2022), using the following keywords: invasive fungal infections; mold; mucormycosis; Mucorales; amphotericin B; isavuconazole; and posaconazole.
EXPERT OPINION
Randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy, in MCR cases refractory to or intolerant of LFAB. We encourage early surgical debridement or excision as adjunctive measures.
Topics: Humans; Mucormycosis; Amphotericin B; Antifungal Agents; Triazoles; Mucorales; Lipids
PubMed: 37300820
DOI: 10.1080/14787210.2023.2224564 -
Journal of Fungi (Basel, Switzerland) Sep 2023Mucormycosis is a rare, opportunistic, and emerging fungal infection that can rapidly develop into a severe, highly fatal clinical picture. In most cases, it is caused... (Review)
Review
Mucormycosis is a rare, opportunistic, and emerging fungal infection that can rapidly develop into a severe, highly fatal clinical picture. In most cases, it is caused by fungi of the order Mucorales, which are usually avirulent but become pathogenic when the host's immune system is compromised. This systematic review was conducted according to PRISMA guidelines. The databases searched included PubMed, Scopus, and Web of Science. We chose articles that analyzed the oral manifestations of patients with mucormycosis, were published between 2018 and 2023, and met our search terms. The risk of bias in the articles was assessed using the CARE guideline for case reports and STROBE for a cross-sectional study. After the selection process, 20 articles were included in this review, all containing information about the different oral manifestations presented by people with mucormycosis. The most common oral manifestations are mainly bone exposures and oral ulcers, halitosis, pus discharge, gingival thickening, and periodontitis. However, despite the importance of recognizing these oral manifestations in the early stages of mucormycotic infection, providing early treatment, and reducing the high mortality rate of the infection, more studies are needed.
PubMed: 37755045
DOI: 10.3390/jof9090935 -
Current Opinion in Infectious Diseases Dec 2023Mucormycosis (MCR) is a common opportunistic mold infection, and Mucorales were recently designated by WHO as priority pathogens. The interest in this infection has... (Review)
Review
PURPOSE OF REVIEW
Mucormycosis (MCR) is a common opportunistic mold infection, and Mucorales were recently designated by WHO as priority pathogens. The interest in this infection has risen significantly since the major outbreak of MCR in the context of the COVID-19 pandemic, particularly in India. Herein, we summarize recently (last 24 months) published information regarding clinical aspects of MCR.
RECENT FINDINGS
The disease remains protean in its clinical presentation, difficult to diagnose, and challenging to treat. In 2021, cases of COVID-19-associated mucormycosis (CAM) exploded in India during COVID-19 and manifested primarily as sino-orbital or sino-cerebral disease. Its classic risk factors included the triad of COVID-19, uncontrolled diabetes mellitus and use of corticosteroids. Despite difficulties in the timely diagnosis of MCR, significant progress has been made with the use of molecular techniques in blood to assist with earlier diagnosis, which can facilitate earlier appropriate therapy and improve outcomes. In addition, advances have been made in the use of imaging to stage the disease, determining what types of multimodal therapy are required depending on staging, and tissue-based identification of Mucorales.
SUMMARY
Although the outlook for MCR has improved, effective new antifungals, risk stratification, and the optimal multimodality approaches remain an unmet need.
Topics: Humans; Mucormycosis; Pandemics; Combined Modality Therapy; Secondary Prevention; Mucorales; COVID-19; Opportunistic Infections; COVID-19 Testing
PubMed: 37732771
DOI: 10.1097/QCO.0000000000000976