Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review.

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.

Epidemiology, pathogenesis, clinical characteristics, and treatment of mucormycosis: a review.

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.

Spectrum of orbital fat necrosis in rhino-orbital-cerebral mucormycosis in post-COVID-19 patients.

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.

Targeted orbital intervention in the management of sino-orbital mucormycosis cases.

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.

Additional EBUS-guided intralesional amphotericin B injection combined systemic intravenous therapy in pulmonary mucormycosis: a case report.

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

A rare presentation of rhino-orbital-cutaneous mucormycosis in an immunocompetent patient: a case report.

Mucormycosis is a rare opportunistic infection caused by Mucorales fungi. Cutaneous mucormycosis typically present as chronic indolent infection, whereas rhino-orbital mucormycosis is rapidly progressive disease often invade the adjacent cerebral tissue associated with high mortality. This case represents the atypical clinical history of rhino-orbital-cutaneous mucormycosis. The patient was presented with a right orbital cellulitis associated with an extensive multiple suppurative deep cutaneous infection and worsening headache. The skin lesion was initiated from a localized abscess at the right periorbital area nine months before admission. Suspicion of fungal infection was raised after weeks of non-responsive antibiotics treatment. Aggressive treatment with exoneration of the right eye and surgical debridement was undertaken. Periodic acid Schiff staining from healthy periorbital tissue revealed ribbon-like hyphae with pauciseptate and 90° branching identified as Mucoraceaefamily. The resolution was seen after four weeks of antifungal treatment with Amphotericin B.

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.

Pulmonary mucormycosis eroding the chest wall: challenges in the management.

Pulmonary mucormycosis is a rare, life-threatening fungal infection usually seen in immunocompromised patients. Mortality in such patients is high due to underlying immunosuppression and poor general condition of the patients. Invasion of the adjacent structures is known but, to the best of our knowledge, pulmonary mucormycosis presenting with a full thickness chest wall erosion has not been reported. We report such a case with chest wall destruction with superadded bacterial infection. The use of prosthetic materials for chest wall reconstruction was not possible due to the presence of infection. In addition, there were other intra-operative and post-operative challenges which we managed using a multidisciplinary approach. This report highlights the successful outcome of this complex situation using pre-operative optimisation, adequate surgical debridement and effective management of post-operative complications with patience and perseverance.

A Case of Invasive Pulmonary Mycosis (Rhizopus microspores) secondary to Hematological Disease.

BACKGROUND: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer. METHODS: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed. RESULTS: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment. CONCLUSIONS: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.

Pulmonary mucormycosis as a presentation of COVID 19: Case series.

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.

Mucormycosis: A sweet enemy, case series / Mucormicosis: un dulce enemigo, serie de casos.

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.

Rhino-orbital-cerebral mucormycosis caused by Rhizopus arrhizus diagnosis via metagenomics next-generation sequencing: a case report.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease that is often easily misdiagnosed in the early stages due to the lack of specific clinical manifestations and adequate auxiliary examinations. Early diagnosis and timely therapy are essential for successful treatment. In this report, we presented a 46-year-old man with diabetes who experienced gradual vision loss, right ptosis, swelling, and headaches that progressively worsened to death within 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics next-generation sequencing (mNGS). Our report has proved that mNGS testing should be strongly recommended in highly suspected patients.

Diagnosis of mucormycosis from nasal swabs using commercial PCR platforms; a feasible alternative?

Rhino-orbital-cerebral mucormycosis (ROCM) is linked to uncontrolled diabetes, diabetic ketoacidosis, iron overload, corticosteroid therapy, and neutropenia. This study evaluated a commercial real-time PCR system's effectiveness in detecting Mucorales from nasal swabs in 50 high-risk patients. Nasal swab PCR showed 30% positivity, compared to 8% with KOH microscopy. Despite its improved sensitivity, nasal swab PCR has limitations, highlighting the importance of established sampling methods in mucormycosis diagnosis. Participants were predominantly male (64%), with diabetes (78%) and amphotericin B use (96%). Prior COVID-19 was 42%, with 30% positive for Mucorales by PCR, compared to 8% with KOH microscopy.

Exploring the feasibility of utilizing universal primers in detecting mucormycosis pathogens: An in-silico analysis.

This study aimed to design and evaluate a universal primer for Polymerase Chain Reaction (PCR)- based detection of mucormycosis-causing fungi by targeting their Internal Transcribed Spacer (ITS) sequences. In-silico analysis was conducted to assess primer suitability. Using Clustal Omega and Primer-BLAST, ITS sequences of 32 fungi species causing mucormycosis were aligned and subjected to primer design. Generated primers were sorted and in silico PCR simulations were performed to identify primers capable of amplifying all fungal species. Instead of identifying one pair of universal primer, in silico PCR analysis identified a panel of 14 primer pairs designed from full-length ITS sequences, and a panel of 12 primer pairs designed from conserved regions, that could detect 31 species. The study recommends a panel of 12 primers for multiplex-PCR to detect mucormycosis-causing fungi instead of a long list of PCR analyses for each fungus in diagnosing mucormycosis.

Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Cutaneous mucormycosis infection owing to Rhizomucor variabilis presenting as recurrent lower limb ulceration and cellulitis in a diabetic patient.

Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary.

Bilateral Rhino-Orbital-Cerebral Mucormycosis.

This case report discusses a diagnosis of rhino-orbital-cerebral mucormycosis in a man aged 61 years who presented with vision loss, ophthalmoplegia, and ptosis.