Dynamics and prognostic value of plasma cell-free DNA PCR in patients with invasive aspergillosis and mucormycosis.

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.

Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study.

BACKGROUND: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients. METHODS: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage. RESULTS: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001). CONCLUSIONS: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Number of sinus procedures reduces inpatient mortality for invasive fungal rhinosinusitis.

OBJECTIVES: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. RESULTS: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. CONCLUSION: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.

Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

Invasive Fungal Sinusitis and Its Orbital Morbidity in Pediatric Population: A Strategic Treatment Algorithm and Outcomes.

BACKGROUND: Invasive fungal sinusitis, particularly mucormycosis, presents a significant clinical challenge, especially in pediatric populations. This retrospective epidemiologic study aimed to investigate the clinical characteristics, risk factors and outcomes associated with this rare but severe condition, with a focus on orbital morbidity. METHODS: Clinical data of 12 pediatric patients diagnosed with invasive fungal sinusitis between 2021 and 2023 were retrospectively analyzed. Diagnosis involved microbiological and histopathologic examinations, alongside radiologic imaging. Treatment comprised surgical intervention and antifungal therapy, with a detailed evaluation of orbital involvement. Statistical analysis included descriptive statistics and logistic regression. RESULTS: Predominantly affecting males, the median age of the patients was 8 years. Common symptoms included orbital swelling and impaired vision. Imaging revealed characteristic features of invasive fungal sinusitis, including fat stranding and bone erosions. Orbital involvement was extensive, with poor visual outcomes observed in several cases. Surgical debridement and antifungal therapy, including transcutaneous retrobulbar Amphotericin B, were administered. Risk factors associated with poor orbital outcomes included duration of diabetes and glycated hemoglobin levels. Mortality rate stood at 22.2%. CONCLUSIONS: Early diagnosis, aggressive surgical intervention and combined antifungal therapy are essential for improving outcomes. Timely intervention showed stabilization of the orbital disease and better outcomes in pediatric patients. Further research with larger sample sizes is warranted to better understand and address this serious condition.

Mucormicose:infecção oportunística grave em paciente imussuprimido.Relato de caso.

1. Mucormicose (zigomicose) é micose oportunística causada por fungos da ordem Mucorales, gêneros Rhizopus spp., Mucor spp., Rhizomucor spp. e Absidia spp., entre outros. 2. Mucormicose é enfermidade mais incidente em diabéticos em cetoacidose, pacientes com doenças linfoproliferativas, pós-transplantados e naqueles sob corticoterapia prolongada. 3. O subtipo clínico rinocerebral é o mais frequente e manifesta-se, em geral, por edema e dor periorbital, necrose cutâneo-mucosa e rápida evolução para comprometimento do sistema nervoso central. 4. O diagnóstico precoce é fundamental para que as chances de sobrevida sejam maiores. 5. Terapia antifúngica com anfotericina B, desbridamento cirúrgico precoce e reversão dos predisponentes sistêmicos são as condutas recomendadas.

Mucormicosis rino-orbito-cerebral: experiencia en doce años / Rhino-orbital-cerebral mucormycosis: a twelve-year experience

Introducción: La mucormicosis rino-órbito-cerebral (MROC) es una infección poco frecuente y de alta mortalidad, causada por hongos pertenecientes al orden Mucorales. Afecta excepcionalmente a individuos sanos, siendo mucho más frecuente que se produzca en sujetos inmunodeprimidos. Objetivo: Presentar la casuística de 12 años en mucormicosis del Hospital Barros Luco Trudeau. Material y método: El estudio incluye a 16 pacientes con MROC atendidos en el Hospital Barros Luco Trudeau, entre los años 1993 y 2004, detallando características clínicas de presentación de la enfermedad, procedimientos diagnósticos y terapéuticos realizados, efectos adversos de la terapia y mortalidad. Resultados: Sólo un paciente de la serie era inmunocompetente. El síntoma más frecuente fue dolor facial y el hallazgo más frecuente al examen físico, fue la presencia de una escara negra o grisácea en la mucosa nasal. El estudio micológico directo fue positivo en 11 casos, mientras que el cultivo de hongos resultó positivo sólo en 10 pacientes. Del total de pacientes, 15 recibieron tratamiento combinado de cirugía y terapia antifúngica intravenosa (anfotericina B). Once pacientes fueron debridados por medio de una cirugía abierta (8 maxilectomías parciales y 3 totales). Cuatro pacientes fueron debridados mediante una técnica endoscópicay todos ellos necesitaron mßs de un procedimiento. Discusión y Conclusión: Se discuten las causas y el hallazgo más consistente al examen físico y la conducta del hospital ante los casos sospechosos. También se comenta la importancia de las imágenes, el compromiso orbitario, la invasión cutánea y especialmente el tratamiento médico y quirúrgico. Se destaca la sobrevida general de la serie que fue de 62,5 por ciento

Introduction: Rhino-orbital-cerebral mucormycosis (MROC) is a rare, high mortality infection, produced by fungi belonging to the order Mucorales. It exceptionally affects healthy individuals, being much more prevalent in immunocompromised patients. Aim: To present the 12year experience in mucormycosis at the Barros Luco Trudeau Hospital. Material and Method: This study involves 16 MROC patients that were treatedatthe Barros Luco Trudeau Hospital between 1993 and 2004. We present detailed clinical characteristics of the disease, diagnostic and therapeutic procedures performed, adverse therapy effects and mortality. Results: Only one of the patients was immunocompetent. The most frequent symptom was facial pain and the most frequent finding at physical examination was a black or grayish scab on the nasal mucosa. Direct mycological study was positive in 11 cases, whereas fungal culture was positive in only 10 patients. Of all patients, 15 received combined surgical and intravenous antifungal therapy (amphotericin B). Eleven patients had debridement by open surgery (8 partial and 3 total maxillectomies). Four patients had endoscopic debridement; all of them required more than one procedure. Discussion and Conclusion: Possible causes are discussed as well as the more consistent findings at physical examination and the institution behavior when suspecting a case. In addition, imaging importance, orbital involvement, cutaneous invasion and medical and surgical treatments are discussed. The series survival rate of 62 percent is underscored

Mucormicosis: infección necrotizante como complicación de dermolipectomía abdominal / Mucormycosis: necrotizing infection as a complication of abdominal dermolipectomy

Las infecciones necrotizantes de los tejidos blandos varían en su presentación clínica, pero en general son de curso grave y alta mortalidad. El cuadro clínico incluye: fiebre, celulitis, edema, crepitación, necrosis y sepsis; con frecuencia existe un antecedente o traumático quirúrgico. Como hallazgo operatorio se encuentra necrosis de la piel y tejido subcutáneo, con o sin mionecrosis. El tratamiento es una inmediata y amplia debridación acompañada con antibioticoterapia de amplio espectro. Se presenta un caso clínico de infección necrotizante de tejidos blandos por mucor, en una mujer con antecedente de abdominoplastia y lipoescultura con progresión crítica y evolución fatal. La mucormicosis es una patología agresiva, cuyo diagnostico clínico no es fácil por lo cual debe ser considerada seriamente por el cirujano plástico.

Zigomicosis (mucormicosis) cutánea en paciente con leucemia / Cutaneous zygomycosis (mucormycosis) in a patient with leukemia

La zigomicosis (mucormicosis) cutánea es una enfermedad rara, causada por hongos Zygomycetes oportunistas, que se asocia en primer lugar a diabetes descompensada y en segundo lugar a padecimientos hematológicos como leucemias. Presentamos el caso de una paciente de 21 años con leucemia linfoblástica aguda tipo L2 que presentó en la nariz una lesión necrótica de color negroviolácea, indurada, que se extendía a la fosa nasal derecha y al paladar duro. El diagnóstico clínico fue de zigomicosis (mucormicosis) cutánea inicial con extensión posterior a senos paranasales y paladar. Se dio tratamiento con anfotericina B a dosis habituales, sin mejoría y con fallecimiento posterior de la paciente. Se discute si la zigomicosis fue cutánea primaria con extensión a estructuras adyacentes o cutánea secundaria, posterior a un cuadro rinocerebral (AU)

Mucormicosis rinocerebral. Reporte de un caso y revisión de la literatura / Rhinocerebral mucormycosis. A case report and review of the literature

La mucormicosis (MM) es una infección producida por el hongo, del género Rhizomucor, patógeno bajo condiciones de inmunocompromiso. Existen varias formas de presentación clínica: rinocerebral, pulmonar, mucocutánea, gastrointestinal y diseminada. La presentación rinocerebral es frecuentemente fatal, a pesar del uso de la anfotericina B, terapia hiperbárica y resección quirúrgica agresiva. Presentamos el caso de un paciente femenino de 61 años, diabética crónica con MM rinocerebral, enfermedad sumamente rara, que es descrita por primera vez en el Servicio de Neurocirugía del Centro Médico Nacional ®20 de Noviembre¼. El padecimiento fue de ocho meses de evolución y se caracterizó por: cefalea nasofrontal opresiva, crisis convulsivas tónico clónicas generalizadas, descargas nasales serohemáticas fétidas, disminución progresiva de la agudeza visual hasta la amaurosis bilateral, proptosis, oftalmoplejía de nervios oculomotores y pérdida ponderal de 15 Kg. La tomografía craneal demostró hiperdensidad nasoetmoidal con extensión frontal y orbitaria. Se realizó legrado de la lesión y toma de biopsia que corroboró la MM. Se administró anfotericina B tópica y sistémica, quedando la duda del efecto terapéutico del manejo hiperbárico en este padecimiento. Finalmente la paciente falleció 1.4 años después

Mucormicosis rinocerebral por Rhizopus sp / Cerebral mucormycosis by Rhizopus sp

Masculino de 24 años de edad con diabetes mellitus insulino-dependiente descompensada, cetoacidosis y mucormicosis rinocerebral por Rhizopus sp. Se trató en forma multidisciplinaria con control metabólico, anfotericina B y extensa debridación del área necrótica. El resultado fue satisfactorio; se planeó reconstrucción quirúrgica