Formulations Of Amphotericin Research Articles

A Comprehensive Review on Mucormycosis as co infection of Immunodeficiency Diseases

Mucormycosis is a fatal, life-threatening fungal infection occurring in humans that is associated with considerable morbidity and mortality. It is caused by a group of ubiquitous saprophytic molds, which typically affect patients with weak immune defences such as diabetes mellitus, diabetic ketoacidosis, malignant hematological diseases, post-hematopoietic stem cell or solid organ transplants, as well as those with neutropenia. Mucormycosis is mostly related to the current COVID-19 epidemic and the overuse of steroids but can also be caused by haemato-oncological conditions and other health conditions, such as unbalanced diabetes or caustic injuries. It mostly impacts the nose and sinuses, affecting the eyes and other parts of the body. Immediate treatment of mucormycosis is required, consisting of reversal of underlying risk factors, prompt antifungal therapy (preferably as lipid formulations of amphotericin B or isavuconazole), and early surgical debridement. However, the stringent neutropenic and metabolic status of these patients prevents early diagnosis and withholds aggressive antifungal and surgical treatments. The ability of mucormycosis to invade blood vessels and cause angioinvasion, thrombosis, tissue infarction, and the formation of fungal emboli, increases mortality among patients. New surveillance strategies, novel preventive strategies, new applicative detection techniques, novel antifungal agents, or screening for effective agent repurposing are immediately needed to pave the way to enhance the survival of these high-risk patient populations from this deadly infection and reduce the global burden. The present review aimed to provide an exhaustive overview of mucormycosis, including basic information, etiology, epidemiology and incidence, pathogenesis, risk factors, clinical manifestations, diagnosis modalities, and treatment.

Comparison of antifungal drugs in the treatment of invasive pulmonary aspergillosis: a systematic review and network meta-analysis.

Voriconazole, isavuconazole, and amphotericin (AmB) formulations are currently recommended to treat invasive pulmonary aspergillosis (IPA). We aimed to estimate the efficacy of different antifungal drugs in the initial treatment of IPA. We included all available randomized controlled trials (RCTs) evaluating first-line treatments for IPA by searching PubMed, Medline, EMBASE, the Cochrane Library, and the ClinicalTrials.gov database. We performed a network meta-analysis to compare the relative efficacy of different drugs in treating IPA. The primary outcomes were the overall response and all-cause mortality (ACM). Eight studies were identified that compared different drugs including voriconazole, isavuconazole, posaconazole, anidulafungin, liposomal AmB (L-AmB) at standard, high and low doses (3-5 mg/kg/d; 10 mg/kg/d; 1 mg/kg/d), AmB deoxycholate (dAmB) and amphotericin B colloidal dispersion (ABCD). We found that second-generation triazole antifungal drugs containing voriconazole, isavuconazole, and posaconazole exhibited significantly superior overall response to dAmB and ABCD. Voriconazole was ranked as the best drug on network rank analysis. We found no difference in efficacy between triazole antifungals and L-AmB. A combination of voriconazole with anidulafungin, isavuconazole and voriconazole showed significantly better safety than dAmB. The efficacy of second-generation triazole antifungal drugs for the first-line treatment of IPA is comparable with L-AmB and is better than both dAmB and ABCD. Isavuconazole may show better safety than voriconazole and posaconazole. Combination therapy with voriconazole and anidulafungin may serve as an alternative option for IPA patients with limited drug tolerance. https://inplasy.com/.

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.

Novel nanoformulation for enhanced amphotericin B efficacy and sustained release using vetiver root cellulose nanofibers against Candida albicans

The formidable antifungal agent, Amphotericin B, is well-known for its potency; however, its clinical application has been significantly limited due to toxicity and poor solubility. This study aims to address these challenges by developing and evaluating a novel nano-cellulose-based formulation of Amphotericin B to enhance its efficacy. Amphotericin B was encapsulated within cellulose nanofibers at varying ratios to optimize formulation parameters, including drug concentration, particle size, zeta potential, and entrapment efficiency. Notably, a composition ratio of 10:1 of cellulose nanofibers to Amphotericin B achieved an impressive encapsulation efficiency of 96.64%. Subsequent physicochemical characterizations employing techniques such as FTIR, DLS, XRD, and SEM provided insights into structural attributes and interactions within formulation. Controlled and extended-release profiles were observed at various physiological pH levels, with the Korsmeyer-Peppas model showing the highest correlation, indicating predominant drug diffusion. Importantly, nanoformulation demonstrated non-toxicity to A431 cells and human erythrocytes up to a maximum concentration of 20 μg/ml, as corroborated by MTT and hemolysis assays. Furthermore, antimicrobial susceptibility and efficacy assessments, conducted using agar disc diffusion and broth micro-dilution methods, revealed enhanced inhibition of Candida albicans growth. The nanoformulation produced a larger diameter of the inhibition zone (DIZ) of 19.66 mm compared to a DIZ of 16.33 mm for Amphotericin B alone. Impressively, the nanoformulation exhibited a minimum inhibitory concentration (MIC) of 25 μg/ml against Candida albicans, underscoring its heightened efficacy. Additionally, the formulation's ability to improve the targetability and bioavailability of Amphotericin B holds promise for enhancing its antifungal effectiveness while reducing associated toxicity.

A Review of Published Cases Regarding the Amphotericin B Deoxycholate Overdose in the Pediatric Population and a Case Report.

Considering the fact that two available and commonly used formulations of amphotericin B could be used instead of each other by mistake. Also, an updated and comprehensive data regarding management of this medication error was not available; the current review was conducted to gather available data among the pediatric population and discuss management and outcome of patients in case such an error occurs. We review all the cases of amphotericin B overdose which reported in PubMed and google scholar so far then discuss an 8-years-old girl diagnosed with Ewing sarcoma who inadvertently received five times more than therapeutic dose of amphotericin B deoxycholate (5mg/kg/day).In total, ten of the cases were exactly matched to our purpose of the study. In our case, fluid and electrolyte management was aggressively undertaken and she was put under cardiac monitoring for 7 days following detection of the medication error. Finally, she was discharged from hospital with stable condition. Reviewed data in this manuscript showed that amphotericin B deoxycholate overdose could cause severe complications and lead to cardio toxicity, electrolyte imbalance and death. Aggressive cardiac, fluid and electrolyte monitoring and management of any problem as soon as they were detected was the pathway followed by the authors of this review and others who faced this medication error. The role of NAC and hydrocortisone in the managing amphotericin B deoxycholate overdose requires further investigation.

Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex.

The Mucor species complex comprises a variety of opportunistic pathogens known to cause mucormycosis, a potentially lethal fungal infection with limited therapeutic options. The only effective first-line treatments against mucormycosis consist of liposomal formulations of amphotericin B and the triazoles posaconazole and isavuconazole, all of which target components within the ergosterol biosynthetic pathway. This study uncovered M. circinelloides Erg3 and Erg6a as key enzymes to produce ergosterol, a vital constituent of fungal membranes. Absence of any of those enzymes leads to decreased ergosterol and consequently, resistance to ergosterol-binding polyenes such as amphotericin B. Particularly, losing Erg6a function poses a higher threat as the ergosterol pathway is channeled into alternative sterols similar to cholesterol, which maintain membrane permeability. As a result, erg6a mutants survive within the host and disseminate the infection, indicating that Erg6a deficiency may arise during human infections and confer resistance to the most effective treatment against mucormycoses.

Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis.

Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an orally administered lipid nanocrystal formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to Rhizopus arrhizus var. delemar or Mucor circinelloides f. jenssenii DI15-131. In R. arrhizus var. delemar-infected mice, 15 mg/kg of MAT2203 qd was as effective as 10 mg/kg of LAMB in prolonging median survival time vs placebo (13.5 and 16.5 days for MAT2203 and LAMB, respectively, vs 9 days for placebo) and enhancing overall survival vs placebo-treated mice (40% and 45% for MAT2203 and LAMB, respectively, vs 0% for placebo). A higher dose of 45 mg/kg of MAT2203 was not well tolerated by mice and showed no benefit over placebo. Similar results were obtained with mice infected with M. circinelloides. Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in Rhizopus delemar or M. circinelloides lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with R. delemar vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis.

AmBisome® Formulations for Pediatrics: Stability, Cytotoxicity, and Cost-Effectiveness Studies.

Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be challenging due to the spontaneous tendency of amphotericin B to form aggregates with different biological activity. In this study, the colloidal stability of the liposomes and the chemical stability of amphotericin B were investigated over time at storage conditions. Three liposomal formulations of amphotericin B at 4.0 mg/mL, 2.0 mg/mL, and 0.2 mg/mL were prepared and assayed for changes regarding the dimensional distribution, zeta potential, drug aggregation state, and onset of by-products. Our analyses highlighted that the most diluted formulation, kept at room temperature, showed the greatest changes in the aggregation state of the drug and accordingly the highest cytotoxicity. These findings are clinically relevant since the lower dosages are addressed to the more vulnerable patients. Therefore, the centralization of the dilution of AmBisome® at the pharmacy is of fundamental importance for assuring patient safety, and at the same time for reducing medication waste, as we demonstrated using the cost-saving analysis of drug expense per therapy carried out at the G. Gaslini children hospital.

Multidisciplinary expert consensus on the clinical rational application of different formulations of amphotericin B (2024 edition)

Amphotericin B (AmB) is a broad-spectrum and potent polyene antifungal drug for the treatment of invasive fungal diseases (IFDs). Currently, amphotericin B deoxycholate (AmB-D) and three AmB lipid formulations, namely liposomal amphotericin B (L-AmB), amphotericin B colloidal dispersion (ABCD), and amphotericin B lipid complex (ABLC) are available for clinical use. In view of clinical concerns and misperceptions in the selection of different formulations of AmB, the present consensus summarized their pharmaceutical characteristics, antifungal mechanism, pharmacokinetics/phamacodynamics, drug interactions, indications, dosage, local administration, and adverse reactions based on the latest clinical research evidence, guidelines, and clinical experience. This consensus also recommends formulation selection and dosage adjustment for the treatment of target IFDs and in special populations, thereby providing expert consensus for clinical decision-making and standardized application of AmB.

“Black Fungus Unveiled”: Exploring the Menace and Medication

In recent years, there has been significant progress in treating mucormycosis. Beginning therapy as early as possible is crucial to achieve better outcomes. Therefore, maintaining a high level of suspicion and performing biopsies on possible lesions aggressively is essential. Whenever feasible, surgical removal of infected or necrotic tissue should be performed as the data supports its need. Lipid formulations of amphotericin B are now the standard treatment for mucormycosis as they are superior in safety and efficacy. Posaconazole may be useful as salvage therapy, but there is insufficient data to recommend it as the primary therapy. Preclinical and limited retrospective clinical data suggest that the combination of lipid formulations of amphotericin and echinocandin improves survival during mucormycosis. Therefore, additional studies are required to explore the potential of iron acquisition abrogation as an adjunctive treatment of mucormycosis. Combination polyene-posaconazole therapy was not beneficial in preclinical studies. For selected patients, adjunctive therapy with recombinant cytokines, hyperbaric oxygen, and/or granulocyte transfusions can be considered. Large-scale, prospective, randomized clinical trials are necessary to define optimal management strategies for mucormycosis.[1]

High-dose amphotericin: yay or nay? A case series and literature review.

Invasive fungal infections pose significant morbidity and mortality risks, particularly those caused by moulds. Available antifungal classes are limited by toxicities and are increasingly susceptible to resistance, particularly amongst challenging fungal pathogens. The purpose of this case series and literature review was to characterize the use of a high-dose lipid formulation of amphotericin B. A case series is presented including patients who received high-dose lipid formulation amphotericin B (≥7.5 mg/kg/day) between June 2012 and August 2021. Additionally, a systematic literature review was conducted by searching the PubMed database for English-language studies involving individuals who received high-dose amphotericin B therapy (≥7.5 mg/kg) using lipid formulations. Nine patients were included in the case series, receiving an average of 8.9 ± 1.3 mg/kg liposomal amphotericin B over a mean of 11.0 ± 10.8 days predominantly for mould infections including Mucorales, aspergillosis and Fusarium. The patients were primarily cared for in intensive care units, with varying treatment histories and outcomes. A total of 11 studies (n=260 patients) met inclusion criteria for the literature review. Responses to high-dose liposomal amphotericin B ranged from 8% to 100%, often showing favourable outcomes. High doses of liposomal amphotericin B were well tolerated both in the case series and in published literature, with serum creatinine changes being the most commonly reported adverse event. However, multi-patient studies continue to report less than favourable (range 8-62%) response rates. High-dose liposomal amphotericin B, either alone or in combination with other antifungal agents, might be a viable strategy for managing invasive fungal infections when few treatment choices exist. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.

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.

Evaluation of the pharmacokinetics of liposomal amphotericin B and analysis of the relationship between pharmacokinetics, efficacy and safety in patients with hematological diseases

IntroductionThis study aimed to identify factors responsible for changes in blood concentrations of a liposomal formulation of amphotericin B (AMPH-B, L-AMB) and analyze the relationships between blood concentrations and efficacy or toxicity. MethodsL-AMB was administered to 30 patients being treated for hematological diseases. AMPH-B plasma concentrations were determined right before the initiation (Cmin) and at the end (Cmax) of infusion on at least 1 day, beginning on Day 3 of L-AMB treatment. The relationships of Cmin divided by dose (C/D ratio) to body weight, age, hepatic function, renal function, serum albumin, C-reactive protein (CRP), response, hypokalemia, and renal impairment were evaluated. ResultsC/D ratio was not correlated with age, hepatic function, renal function, or serum albumin. Body weight adjusted C/D ratio was negatively correlated with CRP. Cmax and Cmin were compared between responders and non-responders, those with or without hypokalemia, and those with or without renal impairment. A higher Cmax in patients with hypokalemia was the only significant difference seen. ConclusionsThe negative correlation between CRP and plasma concentrations was likely caused by higher distribution of L-AMB from the blood to infected tissue in patients with a greater degree of infection, with a resulting decrease in plasma concentrations. AMPH-B plasma concentrations were not related to response. Higher Cmax of AMPH-B were observed in patients with hypokalemia, but no relationship between plasma concentration and renal toxicity was observed, suggesting that AMPH-B plasma concentrations appear to be minimally related to PD when used as L-AMB.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

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.

Antifungal drugs

Fungal infections continue to emerge as an important cause of infectious disease and mortality in humans. Amphotericin B deoxycholate (ABD), was the first antifungal that was discovered, and it was released in 1958, and flucytosine, which was developed later and is effective against Candida and Cryptococcus, was introduced in 1978. The discovery of first-generation azoles (fluconazole and itraconazole) in the 1990s has created a new step in the treatment of fungi. In the years that followed, with the development of lipid formulations of amphotericin B, the introduction of second-generation azoles, and the release of the most recently developed class, echinocandins, the foundations of today’s existing antifungal classes were laid. This article is aimed to review the mechanism of action, side effects and clinical use indications of the main antifungal drugs used in the treatment of systemic fungal infections.

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.

Efficacy of combination therapy of amphotericin and posaconazole in treatment of mucormycosis

Background: Mucormycosis is an opportunistic systemic fungal infection which is debilitating caused by order Mucorales. The standard management of mucormycosis consists of aggressive debridement of the infected tissue and parenteral anti-fungal therapy with Amphotericin B. Liposomal amphotericin B is a “true” liposomal formulation of amphotericin B with greatly reduced nephrotoxicity and minimal infusion-related toxicity. Very minimal data is available on the usefulness of combining different antifungal agents for an effective outcome. Our study was undertaken at a time when there was a huge turnover of mucormycosis cases during Covid 19 pandemic with resultant shortage of important resources including liposomal amphotericin B. In effect, combination of liposomal amphotericin B with posaconzole gave a promising outcome. Objectives: To study the efficacy of combination therapy of liposomal amphotericin B and posaconazole in the treatment of mucormycosis. Methodology: It is a prospective study of 43 patients with mucormycosis who received combination therapy based on their disease severity. Results: In our study, 16 (37%) were considered as patients with mild disease, 18 (41.8%) were considered as patients with moderate disease and 9 patients (20.9%) were considered as severe. 20 (58%) patients out of 34 patients with mild to moderate disease showed improvement after combination therapy. Conclusion: A significant percentage of patients in our study showed improvement with combination therapy of liposomal amphotericin B and posaconazole in terms of survival and disease recurrence.

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

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

Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.