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1.
J Assoc Physicians India ; 72(10): 24-31, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39390855

ABSTRACT

BACKGROUND AND OBJECTIVES: We studied the clinical presentation, risk factors, complications, and in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). MATERIALS AND METHODS: A retrospective study was done on 69 COVID-19 patients with microbiologically proven mucormycosis admitted over a period of seven months from March 2021 to September 2021. RESULTS: All 69 mucormycosis patients (46 males, 23 females) had reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection. Their mean age was 52.8 years, with mucormycosis developing in 51 patients (73.9%) within 30 days of COVID-19 infection; 7 (10.1%) were positive on admission. Rhino-orbital-cerebral mucormycosis (ROCM) was the most common (40.3%), followed by rhino-orbital (37.3%) and sinonasal (22.4%). Diabetes mellitus was present in 98.6% of patients. Common symptoms of mucormycosis were facial pain, headache, facial swelling, and vision loss. During COVID-19, 88.4 and 52.5% received immunosuppressive treatment and zinc sulfate, respectively; 34.7% needed intensive care unit (ICU) admission. The mortality rate was 26.1%. On multivariate logistic regression analysis, the presence of chronic kidney disease, leukocytosis, ophthalmoplegia, oral/palate ulceration, current need for invasive ventilation, and past duration of oxygen therapy and zinc supplementation were significantly associated with mortality. Patients with current COVID-19 infection had severe disease with increased need for intensive care (57.1 vs 14.5%) and higher mortality (57.1 vs 22.6%) compared to mucormycosis patients with previous COVID-19 infection. INTERPRETATION AND CONCLUSION: Rhino-orbital-cerebral, rhino-orbital, and sinonasal were the most common presentations in cases of mucormycosis, with a mortality rate of 26.1%. COVID-19 coinfection predisposes patients with mucormycosis to severe disease with higher mortality.


Subject(s)
COVID-19 , Mucormycosis , Humans , Mucormycosis/complications , Mucormycosis/epidemiology , Mucormycosis/diagnosis , COVID-19/complications , COVID-19/mortality , Male , Middle Aged , Female , Retrospective Studies , Adult , Risk Factors , Aged , SARS-CoV-2 , India/epidemiology , Antifungal Agents/therapeutic use
3.
Curr Microbiol ; 81(11): 400, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39384659

ABSTRACT

The COVID-19 pandemic caused death of 6 million lives globally, primarily from respiratory failure, but also a significant number from invasive fungal co-infections in these patients, owing to the immune dysfunction in hospitalized patients. Such complications occurred more often in critically ill, hospitalized patients particularly those admitted in intensive care units and were reported as the major reason associated with a high mortality rate worldwide. Fungal pathogens most commonly associated with COVID-19 patients comprise members of the Mucorales (such as Rhizopus, Mucor, and Lichtheimia), as well as genera Aspergillus and Candida. In India, the prevalence rate of mucormycosis is relatively high than aspergillosis and candidiasis, and the predisposing risk factors associated with such infections included uncontrolled diabetes, underlying lung disease, leukopenia, neutropenia, malignancies and prolonged steroid therapy. However, co-infection with other fungi, including Alternaria and Scedosporium was also sporadically reported. These devastating invasive fungal infections are associated with differential mortality (high-low) and morbidity rates even after active management. The diagnosis of such infections is often challenging due to lack of sensitivity in contemporary diagnostic methods and poses an enormous challenge to healthcare experts. Thus, the role of early and accurate diagnosis, and management of such fungal infections, is vital in preventing life-threatening situations. Hence, this review focusses primarily on the epidemiology, predisposing risk factors, host environment, diagnosis and treatment of the most common medically important invasive fungal infections in immunocompromised conditions associated with COVID-19.


Subject(s)
COVID-19 , Immunocompromised Host , Invasive Fungal Infections , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , COVID-19/immunology , Invasive Fungal Infections/epidemiology , SARS-CoV-2/immunology , Coinfection/epidemiology , Coinfection/microbiology , Risk Factors , Mucormycosis/epidemiology
4.
J Infect Public Health ; 17(10): 102523, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39217805

ABSTRACT

BACKGROUND: The emergence of mucormycosis as a life-threatening fungal infection after the coronavirus disease of 2019 (COVID-19) is a major concern and challenge, but there is limited information on the risk factors for mortality in patients. METHODS: We conducted a prospective cohort study from May 2021 to April 2022 to determine the in-hospital outcomes of post-COVID-19 mucormycosis during the intensive care unit (ICU) stay. The sample of the study was collected as consecutive sampling using all accessible patients in the study period. The Statistical Package for Social Sciences (SPSS), version 25 (IBM, Chicago, Illinois, USA) was used for statistical analysis. RESULTS: Among 150 patients with post-COVID-19 mucormycosis, the majority had a primary sinus infection (86.0 %), while 11.3 % had both sinus and ocular infections, and 2.7 % had sinus and cutaneous infections. Around 21 % (n = 31) of patients deceased after staying in the ICU for a median (range) of 45.0 (10.0-145.0) days. The majority of the patients who deceased had pneumonia patches on computed tomography (CT) (90.3 %) while none of the patients who were discharged had pneumonia patches (p < 0.001). The deceased group had higher rates of pulmonary embolism (93.5 %) compared to the surviving groups (21.8 %). In a multivariate Cox regression analysis, the risk of death was higher in older patients above 60 years old (hazard ratio (95 %CI): 6.7 (1.73-15.81)), increase among patient with history of steroid administration (hazard ratio (95 %CI): 5.70 (1.23-10.91)), who had facial cutaneous infection with mucormycosis (hazard ratio (95 %CI): 8.76 (1.78-25.18)), patients with uncontrolled diabetes (hazard ratio (95 %CI): 10.76 (1.78, 65.18)), and total leukocytic count (TLC>10 ×103 mcL) (hazard ratio (95 %CI): 10.03 (3.29-30.61)). CONCLUSIONS: Identifying high-risk patients especially old diabetic patients with corticosteroid administration and detecting their deterioration quickly is crucial in reducing post-COVID-19 mucormycosis mortality rates, and these factors must be considered when developing treatment and quarantine strategies.


Subject(s)
COVID-19 , Intensive Care Units , Mucormycosis , Tertiary Care Centers , Humans , COVID-19/mortality , COVID-19/complications , Male , Mucormycosis/mortality , Mucormycosis/epidemiology , Female , Prospective Studies , Middle Aged , Adult , Tertiary Care Centers/statistics & numerical data , Risk Factors , Intensive Care Units/statistics & numerical data , Egypt/epidemiology , Aged , SARS-CoV-2 , Critical Care/statistics & numerical data , Young Adult , Hospital Mortality
5.
Nat Commun ; 15(1): 8295, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39333566

ABSTRACT

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of ß-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some proteins are entrapped within this semi-crystalline chitin/chitosan layer, stabilized by the sidechains of hydrophobic amino acid residues, and situated distantly from ß-glucans. The mobile domain contains galactan- and mannan-based polysaccharides, along with polymeric α-fucoses. Treatment with the chitin synthase inhibitor nikkomycin removes the ß-glucan-chitin/chitosan complex, leaving the other chitin and chitosan allomorphs untouched while simultaneously thickening and rigidifying the cell wall. These findings shed light on the organization of Mucorales cell walls and emphasize the necessity for a deeper understanding of the diverse families of chitin synthases and deacetylases as potential targets for novel antifungal therapies.


Subject(s)
Cell Wall , Chitin , Chitosan , Magnetic Resonance Spectroscopy , Mucorales , Cell Wall/metabolism , Chitosan/chemistry , Chitosan/metabolism , Chitin/metabolism , Chitin/chemistry , Magnetic Resonance Spectroscopy/methods , Mucorales/metabolism , beta-Glucans/metabolism , beta-Glucans/chemistry , Mucormycosis/microbiology , Chitin Synthase/metabolism , Mucor/metabolism , Rhizopus/metabolism , Aminoglycosides
7.
Ear Nose Throat J ; 103(2_suppl): 7S-11S, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39305069

ABSTRACT

We present a novel case of acute invasive fungal rhinosinusitis (AIFRS) following a maxillary molar root canal in a 69-year-old diabetic female, who subsequently developed unilateral vision loss. The patient reported a 1-week history of progressive left facial pain, trismus, and numbness following the procedure. Initial evaluation was unremarkable, but her condition rapidly deteriorated, culminating in complete vision loss in the left eye. Imaging studies revealed opacification of the left-sided sinuses and a rim-enhancing collection in the left pterygopalatine fossa. Surgical debridement confirmed mucormycosis. The therapeutic approach included systemic and retrobulbar amphotericin B administration, along with multiple sinonasal debridements. The patient's poorly controlled diabetes mellitus significantly contributed to the rapid progression of the infection. Retrobulbar amphotericin B injections were effective in managing orbital involvement, thus avoiding the need for exenteration. Early diagnosis and aggressive treatment are paramount in improving outcomes for patients with AIFRS.


Subject(s)
Mucormycosis , Root Canal Therapy , Sinusitis , Humans , Female , Aged , Sinusitis/microbiology , Sinusitis/complications , Mucormycosis/complications , Root Canal Therapy/adverse effects , Root Canal Therapy/methods , Debridement/methods , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Invasive Fungal Infections/drug therapy , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Blindness/etiology , Rhinitis/microbiology , Rhinitis/complications
8.
Trop Doct ; 54(4): 389-391, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39300844

ABSTRACT

A 57-year old man with uncontrolled diabetes presented with features suggestive of chronic meningitis. Cerebrospinal fluid (CSF) analysis revealed a polymorphonuclear pleocytosis with low glucose and high protein levels in the CSF. Bacterial and fungal cultures and tests for M. tuberculosis were negative. MRI spine showed leptomeningeal enhancement. On ruling out other causes, fungal meningitis was considered. The patient developed paraparesis in the hospital. MRI showed peripherally enhancing subdural lesion with dorsal cord involvement at the level of D4 and D5 vertebrae. On laminectomy and exploration, an intradural extramedullary abscess and a granuloma were noticed at T4--T5 spinal levels causing compression of the cord below. Histopathological examination of the lesions revealed acute on chronic inflammatory infiltrates interspersed by broad, aseptate, ribbon-like fungal elements highlighted by PAS stain, diagnostic of mucormycosis. Intravenous amphotericin B and oral posaconazole were administered for more than 8 weeks. On follow-up, he had complete neurological recovery without sequelae.


Subject(s)
Amphotericin B , Antifungal Agents , Magnetic Resonance Imaging , Mucormycosis , Humans , Male , Middle Aged , Mucormycosis/diagnosis , Mucormycosis/complications , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Chronic Disease , Triazoles/therapeutic use , Triazoles/administration & dosage , Meningitis, Fungal/diagnosis , Meningitis, Fungal/drug therapy , Meningitis, Fungal/microbiology , Treatment Outcome , Laminectomy
9.
Indian J Ophthalmol ; 72(10): 1478-1482, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39331438

ABSTRACT

PURPOSE: Rhino-orbital-cerebral mucormycosis (ROCM) is the most common presentation of mucormycosis. Sinonasal-orbital debridement with exenteration is a life-saving procedure in ROCM patients in view of severe involvement of sinuses and the eyeball. Following the second wave of coronavirus disease 2019 (COVID-19), there was a massive surge in mucormycosis cases in India in post-COVID-19 patients. Of over 300 cases of mucormycosis admitted in our hospital, many underwent exenteration and these specimens were evaluated histopathologically, where fat necrosis was found to be a prominent finding. The spectrum of fat necrosis in ROCM in orbital fat has not been described in literature. Hence, we sought to evaluate the significance and spectrum of orbital fat necrosis in ROCM. METHODS: This 3-month retrospective study included 15 cases of ROCM which underwent exenteration. Clinical data, radiologic details, and histopathologic findings were tabulated. Sections were also subjected to Periodic acid Schiff (PAS) and Gomori's methenamine silver (GMS) stains for confirming the fungus. RESULTS: All 15 cases showed fat stranding on computed tomography (CT) scan. On histopathologic examination, various tissue reaction patterns observed included acute/chronic inflammatory infiltrate, suppurative granulomas with giant cells, coagulative and fat necrosis, broad aseptate fungal hyphae with or without angioinvasion, and neural invasion. Fungal hyphae were confirmed with PAS and GMS stains. The spectrum of fat necrosis observed in all the cases included 1) acute necrotizing fat necrosis, 2) ghost adipocytes with or without saponification, and 3) crystalline/gouty fat necrosis. CONCLUSION: Fat necrosis is a significant finding in ROCM, both on CT scan and histopathology. All three patterns of fat necrosis may be observed simultaneously in a case of ROCM.


Subject(s)
COVID-19 , Eye Infections, Fungal , Fat Necrosis , Mucormycosis , Orbital Diseases , SARS-CoV-2 , Tomography, X-Ray Computed , Humans , Mucormycosis/diagnosis , Mucormycosis/complications , Male , Retrospective Studies , Female , COVID-19/complications , Adult , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , Middle Aged , Orbital Diseases/diagnosis , Orbital Diseases/microbiology , Fat Necrosis/diagnosis , India/epidemiology , Orbit/diagnostic imaging , Orbit/pathology , Young Adult , Paranasal Sinus Diseases/diagnosis , Paranasal Sinus Diseases/microbiology , Debridement/methods , Aged
10.
Indian J Ophthalmol ; 72(10): 1488-1494, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39331440

ABSTRACT

INTRODUCTION: Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB). METHODS: We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease. RESULTS: Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4-6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12-15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12-15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75-80% cases. The degree of proptosis and resistance to retropulsion did not change significantly. CONCLUSION: In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease.


Subject(s)
Amphotericin B , Antifungal Agents , Eye Infections, Fungal , Mucormycosis , Orbital Diseases , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/therapy , Mucormycosis/epidemiology , Male , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/therapy , Prospective Studies , Female , Orbital Diseases/microbiology , Orbital Diseases/therapy , Orbital Diseases/diagnosis , Adult , Middle Aged , Antifungal Agents/therapeutic use , Amphotericin B/therapeutic use , COVID-19/epidemiology , COVID-19/complications , SARS-CoV-2 , Follow-Up Studies , Young Adult , Visual Acuity , Debridement/methods , Aged , Adolescent , Treatment Outcome , Orbit
12.
Mycoses ; 67(9): e13794, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39239767

ABSTRACT

BACKGROUND: Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US. OBJECTIVES: We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period. PATIENTS/METHODS: All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022. RESULTS: Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality. CONCLUSIONS: Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period.


Subject(s)
Antifungal Agents , Mucormycosis , Humans , Mucormycosis/epidemiology , Mucormycosis/mortality , Male , Female , Retrospective Studies , Middle Aged , United States/epidemiology , Aged , Longitudinal Studies , Incidence , Antifungal Agents/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , Adult , United States Department of Veterans Affairs , Comorbidity , Veterans Health/statistics & numerical data , SARS-CoV-2 , Hospitalization/statistics & numerical data , Nitriles , Pyridines , Triazoles
13.
Ann Med ; 56(1): 2396570, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39221718

ABSTRACT

AIM: This review aims to summarize the epidemiology, etiology, pathogenesis, clinical manifestations, and current diagnostic and therapeutic approaches for mucormycosis. The goal is to improve understanding of mucormycosis and promote early diagnosis and treatment to reduce mortality. METHODS: A comprehensive literature review was conducted, focusing on recent studies and data on mucormycosis. The review includes an analysis of the disease's epidemiology, etiology, and pathogenesis, as well as current diagnostic techniques and therapeutic strategies. RESULTS: Mucormycosis is increasingly prevalent due to the growing immunocompromised population, the COVID-19 pandemic, and advances in detection methods. The pathogenesis is closely associated with the host immune status, serum-free iron levels, and the virulence of Mucorales. However, the absence of typical clinical manifestations complicates diagnosis, leading to missed or delayed diagnoses and higher mortality. CONCLUSION: An enhanced understanding of the epidemiology, pathogenesis, and clinical presentation of mucormycosis, along with the adoption of improved diagnostic and therapeutic approaches, is essential for reducing mortality rates associated with this opportunistic fungal infection. Early diagnosis and prompt treatment are critical to improving patient outcomes.


The incidence of mucormycosis has increased following the COVID-19 pandemic.The presence of the halo sign and reverse halo sign may indicate the onset of pulmonary mucormycosis.Early implementation of molecular diagnostic methods, such as mNGS and qPCR, may improve the early diagnosis rate of mucormycosis.Isavuconazole and posaconazole can also be considered as first-line treatments for the initial management of mucormycosis.


Subject(s)
Antifungal Agents , COVID-19 , Mucormycosis , Mucormycosis/epidemiology , Mucormycosis/therapy , Mucormycosis/diagnosis , Humans , COVID-19/epidemiology , COVID-19/therapy , Antifungal Agents/therapeutic use , Mucorales/pathogenicity , Mucorales/isolation & purification , Immunocompromised Host , SARS-CoV-2 , Opportunistic Infections/epidemiology , Opportunistic Infections/microbiology , Opportunistic Infections/diagnosis , Opportunistic Infections/therapy
14.
BMC Pulm Med ; 24(1): 436, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232717

ABSTRACT

BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.


Subject(s)
Amphotericin B , Antifungal Agents , Bronchoscopy , Mucormycosis , Pulmonary Aspergillosis , Humans , Male , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Middle Aged , Mucormycosis/drug therapy , Mucormycosis/diagnosis , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/diagnosis , Coinfection/drug therapy , Mucor/isolation & purification , Tomography, X-Ray Computed
15.
Transplant Proc ; 56(7): 1683-1690, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39174391

ABSTRACT

BACKGROUND: Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. METHODS: This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. RESULTS: Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. CONCLUSION: Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.


Subject(s)
Antifungal Agents , Hematopoietic Stem Cell Transplantation , Mucorales , Mucormycosis , Organ Transplantation , Humans , Retrospective Studies , Risk Factors , Hematopoietic Stem Cell Transplantation/adverse effects , Middle Aged , Mucormycosis/epidemiology , Male , Female , Organ Transplantation/adverse effects , Adult , Antifungal Agents/therapeutic use , Receptors, Chimeric Antigen , Immunocompromised Host , Aged , Treatment Outcome
16.
Biomedica ; 44(2): 135-143, 2024 05 30.
Article in English, Spanish | MEDLINE | ID: mdl-39088531

ABSTRACT

Mucormycosis is a rare fungal infection caused by fungi of the Mucorales order that occurs in immunocompromised individuals or with loss of skin or mucosa barrier integrity. This report presents four cases of rhinocerebral mucormycosis attended at a third-level hospital in Cali (Colombia) during a period of three years. All patients had different case histories and times of evolution. All four had a previous or de novo diagnosis of type 2 diabetes mellitus, with glycated hemoglobin higher than 10% on admission. We ruled out other possible pathologies that could explain their immunocompromised condition. Mucormycosis diagnosis was made with direct visualization of hyaline coenocytic hyphae on biopsies. The basis of treatment was liposomal amphotericin B and surgical debridement. Two patients presented bacterial coinfection. One asked for voluntary discharge without having completed the treatment, and another one died. The remaining two have attended controls and had an adequate evolution.


La mucormicosis es una infección fúngica poco frecuente causada por hongos del orden Mucorales, la cual se presenta en individuos inmunocomprometidos o con pérdida de la integridad de la barrera de piel o mucosas. Se reportan cuatro casos de mucormicosis rinocerebral atendidos en un hospital de tercer nivel de Cali (Colombia) durante un periodo de tres años. Los cuatro pacientes presentaron diferentes cuadros clínicos y tiempos de evolución. Todos tenían diagnóstico de diabetes mellitus de tipo 2, de novo o previo, con una hemoglobina glucosilada de ingreso mayor del 10 % y en todos se descartaron otras enfermedades que explicaran su compromiso inmunitario. La mucormicosis se diagnosticó por la visualización directa de hifas hialinas sincitiales (coenocytic) en las biopsias tomadas. El pilar del tratamiento fue la anfotericina B liposómica junto con el desbridamiento quirúrgico. Dos pacientes presentaron coinfección bacteriana. De los cuatro, uno firmó su egreso voluntario sin completar el tratamiento y otro falleció. Los dos pacientes restantes han asistido a los controles y han mostrado una adecuada evolución.


Subject(s)
Amphotericin B , Mucormycosis , Humans , Mucormycosis/diagnosis , Male , Middle Aged , Amphotericin B/therapeutic use , Female , Antifungal Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Aged , Debridement , Immunocompromised Host
17.
Med Mycol ; 62(9)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39138063

ABSTRACT

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.


This article summarizes the epidemiology and risk factors for IFD, before focusing on the effectiveness and safety of the antifungal agent isavuconazole for treatment of invasive aspergillosis and mucormycosis, and its potential to prevent IFD in specific patient populations.


Subject(s)
Antifungal Agents , Invasive Fungal Infections , Nitriles , Pyridines , Triazoles , Humans , Nitriles/therapeutic use , Nitriles/pharmacology , Nitriles/adverse effects , Triazoles/therapeutic use , Pyridines/therapeutic use , Pyridines/adverse effects , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/prevention & control , Invasive Fungal Infections/epidemiology , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Global Health , Aspergillosis/drug therapy , Aspergillosis/epidemiology , Aspergillus/drug effects , Mucorales/drug effects
18.
Indian J Tuberc ; 71(3): 366-369, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111949

ABSTRACT

BACKGROUND: Pulmonary Mucormycosis (PM) is a relatively uncommon fungal disease, usually manifested in immunocompromised patients. It has an aggressive course, along with dilemmas in diagnosis and treatment. In view of the surge of Mucormycosis patients in COVID 19 pandemic, clinicians need to consider PM in suspected cases, and act in an expedited manner to avoid misdiagnosis and initiate prompt treatment. CASE PRESENTATION: In this case series, we present four cases of PM with varied presentation, clinical course and discuss management strategies. CONCLUSIONS: A strong suspicion of PM based on epidemiological and clinical findings should be considered, to ensure appropriate and timely treatment. It should be accompanied by judicious use of corticosteroids and aggressive control of comorbid conditions to decrease preventable morbidity and mortality.


Subject(s)
COVID-19 , Lung Diseases, Fungal , Mucormycosis , Humans , Antifungal Agents/therapeutic use , COVID-19/complications , COVID-19/diagnosis , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Mucormycosis/diagnosis , SARS-CoV-2 , Tomography, X-Ray Computed
19.
Microbiol Spectr ; 12(10): e0110324, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39189757

ABSTRACT

Survival factor 1 (Svf1) protein has been described in some ascomycetous fungi where it was found to be contributing to several essential physiological processes, such as response to osmotic, oxidative and cold stresses, sphingolipid biosynthesis, morphogenesis, sporulation, antifungal resistance, and pathogenicity. It was also suggested that it can be a novel central regulator affecting the expression of various genes. In the present study, function of this protein and the encoding genes is described for the first time in a fungus (i.e., in Mucor lusitanicus) belonging to the order Mucorales. M. lusitanicus has two putative svf1 genes named svf1a and svf1b. Expression of both genes was proven. Although the expression of svf1a was affected by several environmental stresses and knocking out the gene affected adaptation to low temperatures and the sporulation ability, the main survival factor functions, such as participation in the maintenance of the viability, the response to oxidative and cold stresses, and the sphingolipid biosynthesis, could be associated with Svf1b, suggesting a central regulatory role to this protein. Interestingly, knockout of both genes affected the pathogenicity of the fungus in a Drosophila model. IMPORTANCE: Mucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.


Subject(s)
Fungal Proteins , Gene Expression Regulation, Fungal , Mucor , Mucor/genetics , Mucor/metabolism , Animals , Fungal Proteins/genetics , Fungal Proteins/metabolism , Virulence/genetics , Mucormycosis/microbiology , Oxidative Stress , Stress, Physiological , Drosophila/microbiology , Drosophila/genetics , Spores, Fungal/genetics , Spores, Fungal/growth & development , Antifungal Agents/pharmacology
20.
Trop Doct ; 54(4): 365-368, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39135399

ABSTRACT

Dengue is a disease endemic to tropical countries such as India. In the past two years, cases of COVID-19 associated Mucormycosis have become a commonly encountered phenomenon. However, cases of dengue associated Mucormycosis have not found a significant mention in the literature yet. We, therefore, report two such cases in which Mucormycosis developed after recovery from Dengue fever and try to dig into the possible mechanism behind such an occurrence.


Subject(s)
COVID-19 , Dengue , Mucormycosis , SARS-CoV-2 , Humans , Mucormycosis/diagnosis , COVID-19/complications , Dengue/diagnosis , Dengue/complications , Male , Adult , India , Female , Antifungal Agents/therapeutic use , Middle Aged
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