Lipid Formulations Of Amphotericin Research Articles

Drug induced reversible cardiomyopathy reported for liposomal amphotericine B: a rare documented adverse event

Liposomal amphotericin B (LAmB), lipid formulation of amphotericin B (AmB) is used in the treatment of fungal infections, including invasive disease and cryptococcal meningitis and is associated with fewer nephrotoxic and infusion-related adverse effects than conventional amphotericin B. Cardiac toxicity due to LAmB is a rarely reported adverse event in literature. Here we report a case of 53 years female known case of vitiligo, Diabetes mellitus Type 2 diagnosed as case of sinonasal mucormycosis and started on inj LAmB, developed chest pain on day 4 of inj LAmB. ECG and 2D ECHO showed VPBs and ventricular ectopics that were transient and completely recovered on reducing the dose of LAmB. As LV function has recovered on reducing Liposomal AMB, and patient was not on any other cardiotoxic drugs. It was concluded that the patient developed Transient Cardiomyopathy also known as Takotsubo Cardiomyopathy likely due to Liposomal AMB that improved on reducing dose of the drug LAmB. Although very rare but reversible cardiomyopathy also known as Takotsubo Cardiomyopathy due to LAmB is a documented adverse effect. Therefore, ECG monitoring or cardiac monitoring (2D ECHO) should be done when patient is started on LAmB and if at any point cardiotoxicity is suspected then drug should be stopped or reduced in dose immediately. These adverse effects are reversible which recovere on stopping or reducing the dose of LAmB.

Cryptococcosis in kidney transplant recipients: Current understanding and practices.

Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.

Treatment of Fusarium Infection of the Central Nervous System: A Review of Past Cases to Guide Therapy for the Ongoing 2023 Outbreak in the United States and Mexico.

Fusariosis of the central nervous system (CNS) is extremely uncommon. Treatment and outcome data from previously published cases may provide some guidance in light of the ongoing fungal meningitis outbreak in 2023 involving Fusarium spp. in the United States and Mexico. We reviewed the published literature describing cases of invasive fusariosis of the (CNS) that included data on patient demographic characteristics, treatment, and outcome. Twenty-six cases met inclusion criteria. The mean age was 36years, 55% involved females, 60% had underlying hematologic malignancy, and another 16% were on immunosuppressants. The majority of infections were from Fusarium solani species complex. Overall 72% of patients died. The majority received monotherapy with amphotericin B, although some received voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole with or without adjuvant surgery. Among the survivors, 3 received amphotericin B monotherapy, 2 voriconazole monotherapy, 1 combination therapy of both, and one surgery only. The overall mortality rate in published cases of fusariosis of the CNS was high, although-unlike during the current outbreak-the preponderance of patients were severely immunocompromised. While historically the majority were treated with amphotericin B monotherapy, some recent patients were treated with voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole. Current guidelines recommend monotherapy with voriconazole or lipid formulations of amphotericin B or combination of both for the treatment of invasive fusariosis, which is in line with the findings from our literature review and should be considered during the ongoing 2023 outbreak.

Mucormycosis: Issues, Pathophysiology, Diagnosis and Treatment

Mucormycosis (Black fungus) is an infection caused by opportunistic fungi of order Mucorales affecting the immune-compromised individuals. Cases of Aspergillus and Candida (White fungus) were also reported. The cases of fungal co-infection in COVID-19 patients are increasing globally affecting mainly diabetic patients and individuals that have undergone corticosteroid therapy. Iron metabolism and hypoxia plays an important role in pathophysiology of this disease. Mucormycosis causes thrombosis of blood vessels hindering the blood circulation causing black discoloration of affected site. Histopathological examination of specimen is the most effective way of its diagnosis. Surgical removal of affected site is the best treatment practice in rhino-orbital and cutaneous cases whereas lipid formulation of Amphotericin B is effective in other forms of fungal infection.

Refractory Pneumonia in a 12-year-old Girl with Hemoglobin SS Disease

Refractory Pneumonia in a 12-year-old Girl with Hemoglobin SS Disease

Blastomycosis: A Review of Mycological and Clinical Aspects.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.

The Review on Mucormycosis (Black Fungus)

The presentation aims at overview of Mucormycosis, its basic introduction, sign & symptoms, present perspective of disease through the way of progressive research. Recent therapeutic advances have the potential to improve outcomes of mucormycosis. Lipid formulations of amphotericin B (LFAB) have evolved as the cornerstone of primary therapy for mucormycosis. Posaconazole may be useful as salvage therapy, but it cannot be recommended as primary therapy for mucormycosis on the basis of available data.A definitive trial is needed to confirm these results. Combination therapy with LFAB and the iron chelator, deferasirox, also improved outcomes in animal models of mucormycosis. Early initiation of therapy is critical to maximizing outcomes; recent developments in polymerase chain reaction technology are advancing early diagnostic strategies. Prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis. Also the presentation focuses on the treatment, the target area prevention and the precaution measures with respect to disease.

Current treatments against mucormycosis and future directions.

Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis (pansinusitis, rhino-orbital, or rhino-cerebral) as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented.

S4.1a Fusariosis: MICs, mono versus combination therapy and fosmanogepix

S4.1 Treatment of rare mold infections in 2021: the role of new and old antifungals, September 22, 2022, 10:30 AM - 12:00 PM Fusarium is one of the most clinically prevalent rare molds causing superficial infections such as keratitis in immunocompetent hosts and severe disseminated infections frequently presenting as fungemia in the immunocompromised. These fungi are ubiquitous in nature and are found in soil and air. Only a few of the ˃ 70 Fusarium spp. are opportunistic pathogens in humans. F. solani and F. oxysporum species complexes are specifically important, causing ˃50% and about 20% of severe fusariosis cases, respectively. Although galactomannan and also beta D glucan may result positive in fusariosis, fungal culture from either blood, BAL, or skin biopsy remains the most frequently utilized test for diagnosing fusariosis. Susceptibility testing of isolates recovered in culture should be used for epidemiologic purposes in defining the range of minimal inhibitory concentrations (MIC) distribution of Fusarium spp., however, studies that prove that susceptibility testing results should be utilized to inform antifungal drug choice are lacking. Although there are no interpretive breakpoints for antifungal agents against Fusarium spp., compounds with MICs that are off-scale, such as >16 μg/ml, at the highest range of concentrations are unlikely to be active in vivo or in patients. Initial combination therapy with a lipid formulation of amphotericin B plus voriconazole, deescalated to monotherapy once MICs come back, is, therefore, a frequently chosen management pathway. A number of drugs in the antifungal pipeline will present additional treatment options for Fusarium, including Fosmanogepix and Olorofim.

Diagnosis and Treatment of Invasive Mold Diseases.

Although invasive fungal diseases are relatively less common than superficial diseases, there has been an overall increase in their incidence. Here, I review the epidemiology, diagnosis, and treatment of invasive mold diseases (IMDs) such as aspergillosis, mucormycosis, hyalohyphomycosis, and phaeohyphomycosis. Histopathologic demonstration of tissue invasion by hyphae or recovery of mold by the culture of a specimen obtained by a sterile procedure provides definitive evidence of IMD. If IMD cannot be confirmed through invasive procedures, IMD can be diagnosed through clinical criteria such as the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Instituteof Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. For initial primary therapy of invasive aspergillosis, voriconazole or isavuconazole is recommended and lipid formulations of amphotericin B are useful primary alternatives. Echinocandins are representative antifungal agents for salvage therapy. Treatment of invasive mucormycosis involves a combination of urgent surgical debridement of involved tissues and antifungal therapy. Lipid formulations of amphotericin B are the drug of choice for initial therapy. Isavuconazole or posaconazole can be used as salvage or step-down therapy. IMDs other than aspergillosis and mucormycosis include hyalohyphomycosis and phaeohyphomycosis, for which there is no standard therapy and the treatment depends on the clinical disease and status of the patient.

A review on liposomal amphotericin b in antifungal therapy

To reduce the in-vivo toxicity of the broad-spectrum antifungal drug amphotericin B, various lipid formulations of amphotericin B, ranging from lipid complexes to small unilamellar liposomes, have been developed and subsequently commercialized. These structurally diverse formulations differ in their serum pharmacokinetics as well as their tissue localization, tissue retention, and toxicity. This difference can affect the choice of formulation for a given infection, the time of initiation of treatment, and the dosing regimen. Although preclinical studies have shown similarities in the in-vitro and in-vivo antifungal activity of the formulations with comparable dosing, their acute, and chronic toxicity. Profiles are not the same, and this has a significant impact on their therapeutic indices, especially in high-risk, immunosuppressed patients. With the recent introduction of new antifungal drugs to treat the increasing numbers of infected patients, the amphotericin B lipid formulations are now being studied to evaluate their potential in combinational drug regimens. With proven efficacy demonstrated during the past decade, it is expected that amphotericin B lipid formulations will remain an important part of antifungal drug therapy.

Clinical outcome and toxicity in post-COVID suspected cases of mucormycosis treated with amphotericin B at dedicated COVID hospital: a prospective observational study

Background: Recently, several cases of mucormycosis in people with COVID-19 have been increasingly reported world-wide, in particular from India. Lipid formulations of amphotericin B are often used as first-line treatment. Present study aims to assess and analyze clinical outcome and toxicity in post-COVID suspected cases of mucormycosis treated with amphotericin B at dedicated COVID hospital.Methods: The present study was a prospective observational study conducted at government medical college, Jalgaon which was a dedicated COVID hospital. Clinically suspected cases of mucormycosis treated with Amphotericin B were included in the study. We collected the data of previous treatment records, demographics, comorbidities, laboratory investigations and clinical outcome from the case files of patients admitted with diagnosis of clinically suspected mucormycosis with history of COVID-19 infection.Results: Out of 57 patients, majority of them belonged to age group of 51-60 years comprising of 21 patients (37%) and 86% had involvement of one or more paranasal sinus/es. On analyzing prescription pattern and outcomes in patients of present study, it was found that majority of the patients had recovered completely comprising of 40 patients (70%), of which 21 patients (37%) had received liposomal amphotericin B, followed by lipid emulsion amphotericin B in 12 patients (21%).Conclusions: The present study was first of its kind to analyze the prescribing trend of amphotericin B and outcomes in clinically suspected post-COVID cases of mucormycosis. Liposomal amphotericin B was found to be more effective and safer in terms of better recovery rate and less adverse events.

Tailoring amphotericin B as an ionic liquid: an upfront strategy to potentiate the biological activity of antifungal drugs.

Aspergillus species are the primary cause of invasive aspergillosis, which afflicts hundreds of thousands of patients yearly, with high mortality rates. Amphotericin B is considered the gold standard in antifungal drug therapy, due to its broad-spectrum activity and rarely reported resistance. However, low solubility and permeability, as well as considerable toxicity, challenge its administration. Lipid formulations of amphotericin B have been used to promote its slow release and diminish toxicity, but these are expensive and adverse health effects of their prolonged use have been reported. In the past decades, great interest emerged on converting biologically active molecules into an ionic liquid form to overcome limitations such as low solubility or polymorphisms. In this study, we evaluated the biological activity of novel ionic liquid formulations where the cholinium, cetylpyridinium or trihexyltetradecylphosphonium cations were combined with an anionic form of amphotericin B. We observed that two formulations increased the antifungal activity of the drug, while maintaining its mode of action. Molecular dynamics simulations showed that higher biological activity was due to increased interaction of the ionic liquid with the fungal membrane ergosterol compared with amphotericin B alone. Increased cytotoxicity could also be observed, probably due to greater interaction of the cation with cholesterol, the main sterol in animal cells. Importantly, one formulation also displayed antibacterial activity (dual functionality), likely preserved from the cation. Collectively, the data set ground for the guided development of ionic liquid formulations that could improve the administration, efficacy and safety of antifungal drugs or even the exploitation of their dual functionality.

1172. Mucormycosis Treated with Isavuconazole: A matched-Pair Analysis from the FungiScope® Registry

BackgroundIsavuconazole (ISAV) is a novel, broad-spectrum triazole antifungal, available in both intravenous and oral formulations, for the treatment of adult patients with invasive aspergillosis or mucormycosis. In this retrospective case collection study, we compared outcomes for patients with invasive mucormycosis treated with ISAV versus other systemic antifungal therapies, in order to evaluate the real-world effectiveness of ISAV.MethodsProven and probable invasive mucormycosis cases treated with ISAV for a minimum of four consecutive days between 2016 and 2019 were identified from the FungiScope® registry. Matched controls were defined as patients treated with lipid formulations of amphotericin B (lipid-AMB), posaconazole, or a combination of both, as first-line therapy between 2011 and 2019. Case-matching criteria included disease severity, presence of hematological malignancy or allogeneic stem cell transplantation, and surgery for fungal disease. Baseline patient characteristics and clinical outcomes were compared descriptively.ResultsEach of 30 ISAV cases was matched to 1–3 controls, including 25 ISAV cases each matched to 2 or 3 controls, which resulted in a total of 69 control cases. In 70.0% of ISAV cases (n=21), ISAV was administered as a treatment for invasive mucormycosis in patients who had received prior lipid-AMB. In the remaining cases, ISAV was administered after prior voriconazole treatment (n=3) or as first-line therapy (n=6). All control patients received either lipid-AMB, posaconazole, or a combination of both.Baseline demographic and clinical characteristics and causative pathogens were similar between ISAV cases and controls (Table). Overall response rates (defined as achieving a complete or partial response) at the final assessment were 50.0% (15/30) for ISAV cases and 50.7% (35/69) for controls. All-cause mortality was 43.3% (13/30) in ISAV cases as compared to 46.4% (32/69) in controls (Figure).Table. Demographic and clinical characteristics of 30 isavuconazole cases and 69 control cases Figure. Clinical response at final assessment and all cause mortality for 30 isavuconazole cases and 69 control cases ConclusionIn this retrospective analysis of cases from the FungiScope® registry, patients with invasive mucormycosis showed similar overall treatment response and all-cause mortality rates with ISAV compared to treatment with lipid-AMB and/or posaconazole. These data support the effectiveness of isavuconazole in clinical practice.Disclosures Danila Seidel, PhD, Basilea (Other Financial or Material Support, travel grant) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Philipp Koehler, MD, Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker’s Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker’s Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees) Nikolay Klimko, n/a, Astellas (Speaker’s Bureau)Gilead (Speaker’s Bureau)Merck/MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Farima Barmaki-Rad, n/a, Basilea Pharmaceutica International Ltd. (Employee) Mikael Saulay, n/a, Basilea Pharmaceutica International Ltd. (Employee) Marc Engelhardt, n/a, Basilea Pharmaceutica International Ltd. (Board Member, Consultant, Employee, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Shareholder, Speaker’s Bureau, Independent Contractor, Other Financial or Material Support)Basilea Pharmaceutica International Ltd. (Employee) Kamal Hamed, n/a, Basilea Pharmaceutica International Ltd. (Employee)

Mucormycosis in Hematopoietic Cell Transplant Recipients and in Patients With Hematological Malignancies in the Era of New Antifungal Agents.

BackgroundThe survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined.MethodsThis multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America.ResultsSixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136).ConclusionsLong-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

Comparing the results of invasive candidiasis prevention with anidulafungin vs. the lipid formulation of amphotericin B in high-risk patients in the early postoperative period after liver transplantation

Introduction. The development of invasive candidiasis leads to high mortality after liver transplantation. Choosing an effective prophylaxis is an important task.The study purpose was to compare the results of invasive candidiasis prevention with anidulafungin vs. the lipid formulation of amphotericin B in high-risk patients in the early postoperative period after liver transplantation. Material and methods. The study included 80 patients with risk factors for the development of invasive mycosis who underwent liver transplantation. Patients were divided into 2 groups. In the first group (n = 40), anidulafungin was prescribed for prophylaxis; in the 2nd group (n = 40), the lipid complex of amphotericin B was used.Results. The most common of Candida spp. isolated in the patients of our study, as expected, was Candida albicans accounting for 31.2%, significantly less than a half. Neither fungal infection breakthrough nor invasive mycosis development were reported in any patient. In group 2, renal replacement therapy was significantly more frequently used. In two cases, the amphotericin B lipid complex was canceled and the conversion to echinocandin was undertaken due to the occurrence of adverse events (chills and fever) associated, in our opinion, with the drug used. Conclusions. 1. Patients after liver transplantation with 2 or more risk factors have absolute indications to invasive mycosis prevention. 2. Anidulafungin and the lipid formulation of amphotericin B are effective for prophylaxis and prevention of fungal infection breakthrough. 3. Anidulafungin has an advantage in safety over the lipid formulation of amphotericin B.

Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) remains difficult to diagnose and to treat. Most common risk factors are prolonged neutropenia, hematopoietic stem cell or solid organ transplantation, inherited or acquired immunodeficiency, administration of steroids or other immunosuppressive agents including monoclonal antibodies and new small molecules used for cancer therapy. Critically ill patients are also at high risk of IPA. Clinical signs are unspecific. Early computed tomography (CT)-scan identifies the two main aspects, angioinvasive and airway invasive aspergillosis. Although CT-scan findings are not fully specific they usually allow early initiation of therapy before mycological confirmation of the diagnosis. Role of 18F-fludeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is discussed. Confirmation is based on microscopy and culture of respiratory samples, histopathology in case of biopsy, and importantly by detection of Aspergillus galactomannan using an immunoassay in serum and bronchoalveolar lavage fluid. Deoxyribonucleic acid detection by polymerase chain reaction is now standardized and increases the diagnosis yield. Two point of care tests detecting an Aspergillus glycoprotein using a lateral flow assay are also available. Mycological results allow classification into proven (irrespective of underlying condition), probable or possible (for cancer and severely immunosuppressed patients) or putative (for critically ill patients) IPA. New antifungal agents have been developed over the last 2 decades: new azoles (voriconazole, posaconazole, isavuconazole), lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex), echinocandins (caspofungin, micafungin, anidulafungin). Results of main trials assessing these agents in monotherapy or in combination are presented as well as the recommendations for their use according to international guidelines. New agents are under development.

Mucormycosis.

Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result from ingestion of contaminated food, inhalation of spores into the nares or lungs, or inoculation into disrupted skin or wounds. In developed countries, mucormycosis occurs primarily in severely immunocompromised hosts (e.g., those with hematological malignancies, organ transplantation, neutropenia, autoimmune disorders, or other impairments in immunity). Only 6 to 10% of cases occur in subjects with no underlying disease. In contrast, in developing countries, most cases of mucormycosis occur in persons with poorly controlled diabetes mellitus or in immunocompetent subjects following trauma. Mucormycosis exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis, and infarction of tissue. Mortality associated with invasive mucormycosis is high (> 30-50%), with 90% mortality associated with disseminated disease. Mortality rates are much lower, though still significant (10-30%), among patients with localized cutaneous disease.The diagnosis of mucormycosis relies upon histopathology and culture. Blood tests are of limited diagnostic value. Even with disseminated disease, blood cultures are usually negative. Mucorales have a distinct histological appearance, with irregular, nonseptate hyphae that branch at right angles. Cultures and/or polymerase chain reaction (PCR) are important to identify the genera.Based on anatomic localization, mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal (GI), (5) disseminated, and (6) mucormycosis of uncommon sites. Among diabetics, ROCM is the most common clinical presentation, whereas lung involvement is uncommon. In contrast, among organ transplant recipients or patients with hematological malignancies (HemeM), pulmonary and disseminated diseases are most common. Mucormycosis can progress rapidly, and delay in initiation of treatment by even a few days markedly worsens outcomes.Due to the rarity of mucormycosis, randomized controlled therapeutic trials have not been performed. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but the newer triazoles, posaconazole (POSA) and isavuconazole (ISAV) (the active component of the prodrug isavuconazonium sulfate), may be effective in patients refractory to or intolerant of LFAB. Early surgical debridement or excision plays an important adjunctive role. Additional studies are required to assess the optimal duration of therapy as well as the specific roles of LFAB and the triazoles in the treatment of mucormycosis.

Pediatric visceral leishmaniasis in Tartous, Syria.

ABSTRACTBackground:Visceral leishmaniasis (VL) type in Syria is Lashmania infantum, a fatal incapacitating disease, which is mostly seen in infants.Subjects and Methods:Hospital records of 19 children with VL were retrospectively reviewed. The period of the study was from June 2016 to July 2019.Results:The median age of the patients was 45.5 months. None was coinfected with human immunodeficiency virus or known to be immunocompromised. Pallor and anemia were observed in all cases, fever in 13 (68.42%), splenomegaly in 18 (94.7%), hepatomegaly in 11 (57.9%), thrombocytopenia in 15 (78.95%), and leukopenia in nine (47.4%). A bone marrow aspirate was obtained and Leishmania amastigotes were detected in all patients. All patients were initially treated with meglumine antimonate; one child did not respond and was treated with lipid formulations of amphotericin B.Conclusions:Presentation of VL in the pediatric age group is characterized by pallor, fever, splenomegaly, and hepatomegaly. Hematological and biochemical indices are typical with cytopenias. In all cases, microscopic examination provided a positive diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimonate treatment appears to be still highly effective in Syria.

Invasive Aspergillosis in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.