Progressive Fungal Infection Research Articles

Surgical treatment of invasive fungal infection in pediatric oncology.

Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome. From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days. Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy.

Transcriptomic landscape of the interaction between the entomopathogenic fungus Beauveria bassiana and its tolerant host Tribolium castaneum revealed by dual RNA-seq

Entomopathogenic fungi such as Beauveria bassiana are the only insect pathogens able to start the infection process by penetrating through the host cuticle. However, some insects try to avoid fungal infection by embedding their cuticle with antifungal compounds. This is the case of the red flour beetle Tribolium castaneum, which generates economical loss of great significance in stored product environments worldwide. In this study, T. castaneum adults were fed during different time periods (from 3 to 72 h) on B. bassiana conidia-covered corn kernels. The progression of fungal infection was monitored using the dual RNA-seq technique to reconstruct the temporal transcriptomic profile and to perform gene enrichment analyses in both interacting organisms. After mapping the total reads with the B. bassiana genome, 904 genes were identified during this process. The more expressed fungal genes were related to carbon catabolite repression, cation binding, peptidase inhibition, redox processes, and stress response. Several immune-related genes from Toll, IMD, and JNK pathways, as well as genes related to chitin modification, were found to be differentially expressed in fungus-exposed T. castaneum. This study represents the first dual transcriptomic approach to help understand the interaction between the entomopathogenic fungus B. bassiana and its tolerant host T. castaneum.

Risk Factors of Rhino Orbital Mucormycosis.

To determine the clinical presentation and risk factors associated with rhino orbital mucormycosis. Mucormycosis is a rapidly progressive fungal infection caused by filamentous fungi in the Mucoraceae family. In large numbers, they release spores into the air, and humans get exposed through inhalation. The spores inoculate in the paranasal sinuses and nasopharynx and subsequently spread to the orbit and intracranial cavity. The present COVID-19 pandemic has witnessed a resurgence of rhino-orbital mucormycosis cases, mainly seen in patients with immunocompromised status. Hence, our study evaluated the risk factors and clinical features of rhino orbital mucormycosis. This was a prospective, single-center, cross-sectional study. Patients attending tertiary care centers fulfilling the inclusion criteria were evaluated with a detailed history including sociodemographic profile, occupation, history of fever, COVID-19 infection, steroid or immunosuppressant use, organ transplants, diabetes mellitus and use of oxygen (O2). A complete ophthalmic evaluation was performed, including best-corrected visual acuity, anterior segment evaluation with slit lamp biomicroscopy, and posterior segment evaluation using indirect ophthalmoscopy. Computed Tomography (CT) scan of paranasal sinuses was done for all the patients, and Magnetic Resonance Imaging (MRI) for a few patients if indicated. Intraoperatively, samples were sent for Potassium Hydroxide (KOH) stain while debridement and patients with positive results were included in the study. Forty participants were included, out of which 34 (85%) were males and six (15%) were females. The mean age of the patients was 51.75 years. Out of 40 patients, 29 (72.5%) had h/o COVID-19 infection, 30 (75%) were known type 2 diabetes mellitus, 25 (62.5%) had a h/o steroid intake and 25 (62.5%) had a history of O2 use. 17 (42.5%) patients presented with low vision, out of which 15 had no light perception. 30 (75%) patients had ptosis, 22 (55%) patients presented with proptosis, 15 (37.5%) patients had limited ocular motility, 11 (27.5%) had complete ophthalmoplegia, and 11 (27.5%) patients had central retinal artery occlusion. Rhino orbital Mucormycosis is more prevalent in patients with COVID-19 infection, especially those who have used steroids and oxygen and with type 2 diabetes mellitus. Early presentation with treatment can prevent further ocular morbidity.

COVID-19-associated mucormycosis: an update of anesthetic management

BackgroundMucormycosis is uncommon, progressive fungal infection with mortality rate on higher side. The anesthetic management of surgical debridement in mucormycosis is challenging.We evaluated the anesthetic management of mucormycosis patients associated with problems of airway management, predisposing factors, and adverse effect of antifungal therapy who underwent surgical resection of necrotized tissues.ResultsFifty-six patients presented with uncontrolled diabetes mellitus. All patients had history of COVID-19 infection and received steroid during treatment. Nasal endoscopic debridement was done in 43 patients, total maxillectomy in 14 patients. Temporalis flap was needed in five patients, and orbital exenteration was required in three patients. Central venous catheter was inserted in 17 patients, and invasive arterial monitoring was done in ten patients. All patients administered lyophilized amphotericin B (deoxycholate) in combination with surgical debridement.Thirteen patients were shifted to ICU for further management and continuous hemodynamic monitoring. Fifteen patients were expired, and the mortality rate was 26.31%.ConclusionsChallenges include difficult intubation and renal function impairment due to prolonged antifungal therapy. Postoperative ICU management is important in mucormycosis patients due to comorbidities and rapid progressive infection after surgery.

Acute invasive fungal rhinosinusitis presenting with subperiosteal cheek abscess: A case report

Mucormycosis is a severe, rapidly progressive fungal infection, seen in immunocompromised patients. We report an unusual case of mucormycosis of maxilla, presenting only with cheek abscess. The patient was a young male with uncontrolled diabetes. This presentation of mucormycosis is rare, complete examination and high degrees of suspicion are necessary. The rapid progression in lack of active treatment is often fatal.

TAKE DIVERSION ǃ - A PERIODONTIST POINT OF VIEW ON MUCORRMYCOSIS.

A new recently emerged complication of COVID-19 is a rare fungal infection also called the black fungus caused by a group of fungi called mucormycetes. These group of fungi commonly appear throughout the environment, particularly in association with decaying organic matter and in the soil. Oral health is essential to general health and greatly inuences the quality of life. Mucormycosis is a rapidly progressive fungal infection characterized by endothelium invasion and the development of thrombi in blood vessels resulting in necrosis. Mucormycosis localized to the periodontal tissues (i.e., gingiva and alveolar bone) is exceedingly rare. The clinical manifestation of mucormycosis also overlaps with the dental ndings of periodontal abscess, due to which it is misdiagnosed as lesion of periodontal origin. Early diagnosis is crucial in order to promptly initiate therapeutic interventions necessary for preventing progressive tissue invasion and its devastating sequelae and improving outcome and survival. Diagnosis of mucormycosis remains challenging. Clinical approach to diagnosis has a low sensitivity and specicity, it helps however in raising suspicion and prompting the initiation of laboratory testing. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Another emerging imaging technique, which may eventually aid in the diagnosis and management of mucormycosis is the Cone Beam computed tomography(CBCT). Periodontal disease is not a fatal disease, but it can lead to any systemic or life threatening complications, which can be avoided by accurate diagnosis.

Murine Models of Hematopoietic Cell Transplantation to Investigate Fungal Infections.

Animal models are fundamental to unravel the complex nature of fungal infections in the host context. Here, a versatile murine model of hematopoietic cell transplantation (HCT) is described. This model can be used to investigate the establishment and progression of fungal infections after HCT and to elucidate how different transplant variables affect the recovery of host immunity.

A Case of Chronic Invasive Rhinocerebral Mucormycosis with Pott’s Puffy Tumor

Mucormycosis is one of the most fatal and rapidly progressive fungal infections in humans; among its many forms. rhinocerebral mucormycosis is the most common. It is known to occur as opportunistic infection in patients with uncontrolled diabetes, metabolic disorders, organ transplantation, or autoimmune disease with prolonged steroid use. Pott’s puffy tumor is the subperiosteal abscess of the frontal bone caused by trauma complication or frontal sinusitis. It is considered as a very rare complication since the dawn of antibiotic treatments. We report a case of chronic rhinocerebral mucormycosis involving Pott’s puffy tumor in a patient receiving immunosuppressive therapy after lung transplantation.

Rapidly progressive fatal orbito-cerebral mucormycosis in an immunocompetent patient following entry of an insect into his eye; a case report and literature review

Mucormycosis, an uncommon and rapidly progressive fungal infection, is mainly seen in immunocompromised patients. However, immunocompetent individuals can also be infected. Here, we present a rapidly progressive orbito-cerebral mucormycosis in an immunocompetent patient, who had a history of entry of an insect into his eye. We report an immunocompetent patient, who had a history of entry of an insect into his eye, presented with left eye panophthalmitis, cellulitis and loss of vision. He underwent orbital exenteration. Then, mucormycosis was diagnosed and amphotericin B was initiated. Left cavernous sinus and internal carotid artery involvement were found in brain magnetic resonance imaging (MRI) and cerebrovascular accident (CVA) was diagnosed. Surgical debridement of necrotic tissue was performed, and postoperatively, our patient died following CVA. Mucormycosis, as a fatal fungal infection, requires early diagnosis, appropriate early surgical and rapid antifungal management so that successful outcome can be achieved.

Invasive Mucormycosis with Lung Involvement in a Female Patient with Aplastic Anemia

Mucormycosis is an infection caused by one of several types of mold. Invasive mucormycosis is the most aggressive, rapidly progressive fungal infection. The disease is characterized by high attributable mortality. The early and accurate diagnosis of invasive mucormycosis determines the choice of an adequate therapeutic policy, by improving the prognosis of the disease. The method of choice for diagnosing pulmonary mucormycosis is computed tomography that allows accurate determination of the location and extent of the lesion, the state of the lung parenchyma, and the presence of concomitant complications. The paper describes a clinical case of damage to the lung and skin in invasive mucormycosis in a 28-year-old woman with aplastic anemia. The case is of interest due to a larger number of immunocompromised patients, especially those susceptible to the disease.

Preparation and in vivo evaluation of a highly skin- and nail-permeable efinaconazole topical formulation for enhanced treatment of onychomycosis

Onychomycosis is a progressive fungal infection of the nails that involves the deeper nail layer and nail bed. It is important to maintain sufficient drug concentration in the diseased tissues after topical application. In this study, a stable topical delivery system for efinaconazole (EFN) was designed to enhance absorption potential through the skin and nail plate by incorporating ethanol, diethylene glycol monoethyl ether (Transcutol P) and isopropyl myristate, and cyclomethicone into the topical solution as a delivery vehicle, permeation enhancers, and a wetting agent, respectively. In addition, the stability of EFN in the formulation was significantly improved by adding butylated hydroxytoluene, diethylenetriamine pentaacetic acid, and citric acid as an antioxidant, chelating agent, and pH-adjusting agent, respectively, without discoloration. The optimum EFN formulation (EFN-K) showed 1.46-fold greater human skin permeation than that of the reference control (commercial 10% EFN topical solution). Furthermore, after a 24-hour incubation, the amount of infiltrated EFN from EFN-K in the human nail plate was 4.11-fold greater than that of the reference control, resulting in an 89.7% increase in nail flux at 7 days after treatment. EFN-K significantly accelerated structural recovery of the keratin layer in a Trichophyton mentagrophytes-infected guinea pig onychomycosis model, decreasing the mean viable fungal cell count by 54.3% compared to the vehicle-treated group after once-daily treatment for 4 weeks. Thus, the accelerated skin and nail penetration effect of EFN-K is expected to achieve good patient compliance, and improve the complete cure rate of onychomycosis.

Skin Targeting of Oxiconazole Nitrate Loaded Nanostructured Lipid- Carrier Gel for Fungal Infections.

The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxiconazole nitrate (OXZN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of the fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size and percentage entrapment efficiency (% EE) as dependent variables. The OXZN-NLCs were characterized for particle size, particle morphology and entrapment efficiency. The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.

Acute invasive fungal rhinosinusitis: Survival analysis and the prognostic indicators.

Acute invasive fungal rhinosinusitis (AIFR) is a highly mortal, progressive fungal infection of the paranasal sinuses and surrounding structures that is almost always seen in patients who are immunocompromised. Despite the use of newer antifungal treatments and early diagnosis, the prognosis of AIFR does not improve significantly. Due to the higher incidence of patients who are immunocompromised and have more complex disease, AIFR is a growing medical issue in tertiary medical centers. The aim of this study was to present the outcomes and analyze the prognostic indicators of patients with AIFR who underwent surgery. Between October 2009 and November 2014, 37 patients who underwent surgery for AIFR at a tertiary care university hospital were included in the study. Overall survival and disease-specific mortality and survival rates were calculated to estimate survival function. The impact of age, sex, underlying disease, extent of AIFR, applied medical treatment, and causative species (mucormycosis, aspergillosis) were also taken into consideration. Also, the effect of a variety of laboratory parameters, such as hemoglobin, leukocyte, neutrophil, lymphocyte, platelet, and C-reactive protein (CRP) levels, to survival were evaluated. The median follow-up time was 58 days (interquartile range = 304). Overall and disease-specific mortality rates were 64.9 and 51.4%, respectively. Fever was the most common symptom (86.5%), along with nasal obstruction and/or fullness (48.6%) and epistaxis (48.6%). Age and sex did not have a significant impact on survival (p > 0.05). Palate involvement was significantly associated with mortality (p < 0.05). According to the results of Cox, regression analysis for disease-specific mortality rate, leukocyte and neutrophil counts as well as CRP levels had a significant effect on survival function (p < 0.05). Palatal involvement was associated with a higher mortality in our study. Also, leukocyte counts, neutrophile counts, and CRP values had a significant impact on survival function. The reversal of the underlying disease and immunosuppression is as important as the medical and surgical treatment.

The outcome of pulmonary resection for invasive fungal infection complicating haematological malignancy

The aim of this study was to clarify clinical outcomes of pulmonary resection of invasive fungal infection (IFI) complicating haematological malignancy. Between 1985 and 2010, 28 patients underwent 31 pulmonary procedures for IFI complicating haematological malignancy. Retrospective chart review was performed. Seventeen patients underwent therapeutic resection and 11 patients underwent diagnostic biopsy. Survival and progression of fungal infection were analysed with the Kaplan-Meier method and prognostic factors were analysed with the Cox proportional hazards model. The median follow-up was 9.5 months (range 0-139 months). The rate of operative complications is significantly higher in the therapeutic resection group (P=0.036) in multivariate analysis. Median survival was 12 and 5 months in the diagnostic and therapeutic group, respectively. In the diagnostic group, 10 patients (91%) survived surgery and were cured of fungal infection; the management was changed based on biopsy in 3 patients (27.3%), and preoperative anaemia (P=0.044) adversely affected survival in multivariate analysis. In the therapeutic group, anaemia (P=0.018) and perioperative transfusion (P=0.038) adversely affected survival following therapeutic resection in univariate analysis. The rate of fungal progression in the therapeutic group was 29.4%. In multivariate analysis, only presence of bilateral lesions (P=0.0005) was a significant factor of fungal progression after therapeutic resection. Diagnostic biopsy contributes to good diagnostic yield with long-term cure from fungal infection. The long-term outcome (overall survival) of diagnostic and therapeutic patients relied on the severity of anaemia, which appears related to underlying haematological diseases. Presence of bilateral lesions was a significant factor of fungal progression after therapeutic resection.

P-168THE OUTCOME OF PULMONARY RESECTION FOR INVASIVE FUNGAL INFECTION COMPLICATING HAEMATOLOGIC MALIGNANCY

Pulmonary resection for invasive fungal infection complicating haematologic malignancy is a clinical challenge. The aim of this study is to clarify clinical outcomes and identify prognostic factors associated with survival and progression of fungal infection. Between 1985 and 2010, 28 patients underwent 31 pulmonary procedures for invasive fungal infection complicating haematologic malignancy. Retrospective chart review was performed. Seventeen patients were resected (therapeutic) and 11 were biopsied only (diagnostic). In the therapeutic resection group, survival and progression of fungal infection were analyzed with Kaplan-Meier method and prognostic factors were analyzed with Cox proportional hazards. Median follow-up was 9.5 months (range 0-139 months). Operative mortality was 23.5% and 8.3% in the therapeutic and diagnostic group respectively. Median survival was 5 months and 12 months in the therapeutic and diagnostic group respectively. Anaemia (P = 0.018) and perioperative transfusion (P = 0.038) adversely affected survival following therapeutic resection in univariate analysis. The rate of fungal progression in the therapeutic group was 29.4 %. In multivariate analysis, only bilateral lesion (P = 0.0005) was a significant factor of fungal progression after therapeutic resection. In the diagnostic group, 10 patients (91%) were cured of fungal infection and in 3 patients (27.3%), the management was changed based on biopsy. Diagnostic biopsy contributes to good diagnostic yield with low perioperative complication. Survival following therapeutic resection significantly relied on the severity of preoperative anaemia and perioperative transfusion. All authors have declared no conflicts of interest.

Successful treatment of rhino-orbital mucormycosis by a new combination therapy with liposomal amphotericin B and micafungin

Mucormycosis is a rapidly progressive fungal infection that usually occurs in patients with diabetes mellitus or in immunocompromised patients. Sinus involvement is the most common clinical presentation and the rates of mortality increase with the orbital extension. The treatment of mucormycosis includes aggressive surgical debridement and systemic antifungal therapy. Early diagnosis and prompt initiation of effective antifungal drugs are essential for successful outcome. However, the role of orbital exenteration for the case of orbital involvement remains controversial, and the drugs effective against mucormycosis are limited. We present a successfully treated case with rhino-orbital mucormycosis caused by Rhizopus oryzae in a diabetic and dialysis patient. The early diagnosis, surgical debridement and a new combination therapy with liposomal amphotericin B and micafungin were effective. This new combination antifungal therapy will be useful for the treatment of mucormycosis.

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.

Changes in antioxidant compounds in white cabbage during winter storage

Cabbage is an important source of dietary antioxidants, available throughout the year. Using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry we studied changes in antioxidant compounds in white cabbage during 6 months of commercial storage. Cabbages were harvested at the end of November and stored until the end of May in pallet bins in a refrigerated shed under natural-air conditions. Samples were collected four times during storage in November, February, April and May. Antioxidant compounds identified in cabbage included: ascorbic and dehydroascorbic acid (vitamin C), pyridoxine and pyridoxamine (vitamin B6), nicotinamide and nicotinic acid (vitamin B3), pantothenic acid (vitamin B5); flavonoids (artemetin, betanidin, butein/naringenin chalcone, chalcone, cyanidin, equol, flavone, hydroxyflavone, kaempferol/luteolin, malvidin, naringenin/tetrahydrochalcone, nobiletin, pelargonidin, purpurogallin and quercitol); phenolic acids (benzoic, caffeic, cinnamic, coumaric/hydroxycinnamic, dimethoxybenzoic, gallic/trihydroxybezoic, phenylacetic, rosmarinic, syringic, vanillic and veratric). Fresh-harvested cabbages contained the highest levels of ascorbic acid and pyridoxine. Vitamins B3 and B5 and D2 were below the detection limit. During the first 3 months of storage cabbage lost all pyridoxamine and ∼80% of ascorbic acid. At the end of storage, however, the content of ascorbic acid and vitamins B3 and B5 increased, which may reflect preparation of cabbage for a new growth. A large variety of flavonoids were present in fresh-harvested cabbages. More than half of these compounds were lost during the first 5 months of storage. However, at the end of storage an increase in the levels of some flavonoids was detected. Among 11 phenolic acids found in this study, 7 compounds were present during all the storage period, 2 compounds were lost and 3 other compounds appeared during storage. Starting from April, the appearance of dark lesions on the outer cabbage leaves and detection of ergosterol in cabbage samples indicated the progression of fungal infection. This could trigger synthesis of flavonoids and phenolic acids associated with pathogen resistance in the last months of storage. The study demonstrates that changes in antioxidant compounds in cabbage during long-term storage reflect several ongoing processes, such as postharvest senescence, biennial cycle and response to fungal infection.

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.

Primary Cutaneous Zygomycosis in Two Immunocompromised Children

Zygomycosis, often referred to as ''mucormycosis'' or ''phycomycosis,'' is a rapidly progressive fungal infection which usually occurs in immunocompromised individuals, and is characterized by soft tissue destruction and invasion of blood vessels. The rare and easily misdiagnosed primary cutaneous form may present as a superficial erosion with a painless, gradual onset and slow progression of symptoms or a gangrenous, necrotic ulceration due to rapid tissue and vascular invasion. With the latter form, the mortality rate among affected individuals is high even after aggressive surgical debridement and amphotericin B administration, emphasizing the importance of early recognition and proper diagnosis. We present two instances of gangrenous cutaneous zygomycosis in immunocompromised children and review the literature with regard to etiology, diagnosis and treatment, highlighting the pediatric population.