Cardiac Toxicity of Azole Antifungals

Cardiac toxicity is an uncommon side effect of anti-fungal therapy. Until the recent reports of itraconazole (ITZ) associated cardiac failure, amphotericin was the antifungal most frequently reported with arrhythmias. We evaluated the cardiac effect of azole antifungals, specifically ITZ, and possible mechanisms of toxicity. Ex vivo live-heart studies were performed utilizing Sprague Dawley rats. Short exposure (<5 minutes), random crossover, dose ranging studies were performed with each pharmacologic agent. ITZ focused trials also included dose ranging utilizing a non-crossover design. The only azole found to have significant toxicity was ITZ. At ITZ ~ ED25 (2 - 2.5 ug/mL) exposures, contractility decreased by 22.2% ± 15.7% and amplitude of left ventricular pressure decreased by 11% ± 0.17%. Electron micrograph and alterations in mitochondrial respiration suggest mitochondrial toxicity as an underlying mechanism. In conclusion, ITZ was associated with reductions in contractility, possibly secondary to mitochondrial dysfunction and dilated cardiomyopathy.

Antifungal pipeline:Is there light at the end of the tunnel?

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms,diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets.Despite this pressing need for new treatments,the antifungal drug pipeline has been largely stagnant for the past three decades,primarily due to the high risks and costs associated with antifungal drug development,compounded by uncertain market returns.Extensive research durations,special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to market.In response,the“push-pull”incentive model has emerged as a vital strategy to invigorate the pipeline and encourage innovation.This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents,such as Fosmanogepix,Ibrexafungerp,and Olorofim,while also unraveling the multifaceted challenges faced in new antifungal drug development.The generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance,but it is premature to declare them as definitive solutions.Their future role hinges on thorough clinical validation,costeffectiveness assessments,and continuous post-marketing surveillance.Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development,addressing both the resistance crisis and the treatment challenges.

Bioactive chemical constituents from the marine-derived fungus Cladosporium sp.DLT-5

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

Curcuminoids Inhibit Botrytis cinerea and Colletotrichum gloeosporioides

The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioides.The results showed that the four curcuminoids inhibited the mycelial growth of the two pathogens in a concentration-dependent manner.Bisdemethoxycurcumin at 600 mg/L exerted the strongest inhibitory effect on the mycelial growth of B.cinerea and C.gloeosporioides,with the relative inhibition rates of 98.19%and 100%,respectively;followed by demethoxycurcumin;curcumin exerted the worst inhibitory effect.Toxicity test results also showed that four curcuminoids all had a certain toxicity to B.cinerea and C.gloeosporioides,among which,bisdemethoxycurcumin exhibited the strongest toxicity,with the EC_(50)of 131.125 and 122.235 mg/L,respectively;while curcumin had the lowest toxicity,with the EC_(50)of 273.143 and 194.943 mg/L,respectively.

Assessing the Efficacy of Lemongrass (Cymbopogon citratus) and Sambong (Blumea balsamifera) Extracts in Combating Black Pod Disease: Sustainable Solutions for Controlling Phytophthora megakarya in Cameroon’s Cocoa Plantations

The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effective. This study evaluated the effectiveness of Cymbopogon citratus and Blumea balsamifora leaf extracts, both individually and in combination, against Phytophthora megakarya. We assessed the efficacy of the most promising combination (75% B. balsamifera, 25% C. citratus) after storage at room temperature for up to 9 days. Agar microdilution and in vivo bioassays were conducted to determine antifungal susceptibility and effectiveness. Blumea extract exhibited the highest overall inhibitory activity, with the lowest minimum inhibitory concentration (117 µl mL−1) while C. citratus had a narrower range of MIC (146 to 233 µl mL−1). The combination of C. citratus and B. balsamifera demonstrated a synergistic effect against P. megakarya, achieving growth inhibition on V8 media (92.72 ± 4.20% to 100%) and on artificially infected detached pod cortex (92.24 ± 4.53% to 98.75 ± 1.25%), which was not significantly different from the positive control (Ridomil). Furthermore, this combination maintained its effectiveness for up to 9 days at room temperature. These findings suggest that combining plant extracts can enhance their antifungal properties.

Global Burden of Fungal Infections and Antifungal Resistance from 1961 to 2024: Findings and Future Implications

Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.

Antimicrobial and synergistic effects of lemongrass and geranium essential oils against Streptococcus mutans,Staphylococcus aureus,and Candida spp.

BACKGROUND The oral cavity harbors more than 700 species of bacteria,which play crucial roles in the development of various oral diseases including caries,endodontic infection,periodontal infection,and diverse oral diseases.AIM To investigate the antimicrobial action of Cymbopogon Schoenanthus and Pelargonium graveolens essential oils against Streptococcus mutans,Staphylococcus aureus,Candida albicans,Ca.dubliniensis,and Ca.krusei.METHODS Minimum microbicidal concentration was determined following Clinical and Laboratory Standards Institute documents.The synergistic antimicrobial activity was evaluated using the Broth microdilution checkerboard method,and the antibiofilm activity was evaluated with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay.Data were analyzed by one-way analysis of variance followed by the Tukey post-hoc test(P≤0.05).RESULTS C.schoenanthus and P.graveolens essential oils were as effective as 0.12%chlorhexidine against S.mutans and St.aureus monotypic biofilms after 24 h.After 24 h P.graveolens essential oil at 0.25%was more effective than the nystatin group,and C.schoenanthus essential oil at 0.25%was as effective as the nystatin group.CONCLUSION C.schoenanthus and P.graveolens essential oils are effective against S.mutans,St.aureus,Ca.albicans,Ca.dubliniensis,and Ca.krusei at different concentrations after 5 min and 24 h.

Epidemiology, Clinical Features and Antifungal Resistance Profile of Candida auris in Africa: Systematic Review

Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.

A Bronchopulmonary Onset of Candidemia Revealing a Granulomatosis with Polyangiitis

Candidemia is defined as being a yeast infection confirmed by the presence of at least one positive Candida blood culture. It is a life threatening infection causing high mortality. The clinical signs are generally compatible with the causative agent (whether there is a deep venous catheter or not). On the other hand and according to the 2012 Revised Chapel Hill Classification, granulomatosis with polyangiitis GPA is classified as a vasculitis associated with antineutrophil cytoplasmic antibodies ANCA. It is a systemic disease characterized by the anatomopathological aspect of granuloma. We report the case of a patient who presented an atypical and a very rare revealing mode of GPA which was a bronchopulmonary candidiasis complicated by candidemia. Despite its controversy, the combination in the acute phase of antifungal treatment based on intravenous voriconazole and glucocorticoid therapy has made it possible to control candidemia and calm vasculitis.

Antifungal activity against Fusarium oxysporum of quinolizidines isolated from three controlled-growth Genisteae plants:structure-activity relationship implications

The Genisteae tribe belongs to the Fabaceae family.The wide occurrence of secondary metabolites,explicitly high-lighting the quinolizidine alkaloids(QAs),characterizes this tribe.In the present study,twenty QAs(1-20),including lupanine(1-7),sparteine(8-10),lupanine(11),cytisine and tetrahydrocytisine(12-17),and matrine(18-20)-type QAs were extracted and isolated from leaves of three species(i.e.,Lupinus polyphyllus(’rusell’hybrid),Lupinus muta-bilis,and Genista monspessulana)belonging to the Genisteae tribe.These plant sources were propagated under greenhouse conditions.The isolated compounds were elucidated by analyzing their spectroscopical data(MS,NMR).The antifungal effect on the mycelial growth of Fusarium oxysporum(Fox)of each isolated QA was then evaluated through the amended medium assay.The best antifungal activity was found to be for compounds 8(IC_(50)=16.5μM),9(IC_(50)=7.2μM),12(IC_(50)=11.3μM),and 18(IC_(50)=12.3μM).The inhibitory data suggest that some QAs could effi-ciently inhibit Fox mycelium growth depending on particular structural requirements deduced from structure-activity relationship scrutinies.The identified quinolizidine-related moieties can be involved in lead structures to develop further antifungal bioactives against Fox.

Fusarium wilt of banana:Current update and sustainable disease control using classical and essential oils approaches

Fusarium species were reported to produce biofilms.Biofilms are superficial societies of microbes bounded and endangered by being situated or taking place outside a cell or cells.The most destructive fungal diseases caused by phytopathogens are as a result of biofilms formation.Fusarium wilt of banana(Panama disease)is caused by a soil-borne pathogen called Fusarium oxysporum f.sp.cubense.Fusarium oxysporum occurs in a form of a species complex(FOSC)which encompasses a crowd of strains.Horizontal genetic factor transfer may donate to the observed assortment in pathogenic strains,while sexual reproduction is unknown in the FOSC.Fusarium wilt is a notorious disease on several crops worldwide.Yield loss caused by this pathogen is huge,and significant to destroy crop yields annually,thereby affecting the producer countries in various continents of the world.The disease is also resistant to various synthetic chemical fungicides.However,excessive use of synthetic fungicides during disease control could be lethal to humans,animals,and plants.This calls for alternative eco-friendly management of this disease by targeting the biofilms formation and finally suppressing this devastating phytopathogen.In this review,we,therefore,described the damage caused by Fusarium wilt disease,the concept of filamentous fungal biofilms,classical control strategies,sustainable disease control strategies using essential oils,and prevention and control of vegetables Fusarium wilt diseases.

In Vitro Antifungal Activity of Dihydrochelerythrine and Proteomic Analysis in Ustilaginoidea virens

Dihydrochelerythrine(DHCHE)is an isoquinoline compound,which has distinct antifungal activity and can induce apoptosis.The antifungal activity of DHCHE against five rice pathogenic fungi was studied in vitro.At the concentration of 7.5 mg/L,DHCHE exhibited the highest efficacy among tested compounds in inhibiting mycelium growth,with an inhibition rate of 68.8%in Ustilaginoidea virens,which was approximately 2.4 times of that of validamycin(28.7%).After exposure to DHCHE,transmission electron micrographs revealed spores showed incomplete organelles,malformed cell walls and nuclear membranes,as well as irregular lipid spheres.Reactive oxygen species accumulation in treated spores was markedly higher than that in control spores.DHCHE induced cell damage increased in a dose-dependent manner,as indicated by the decrease in mitochondrial membrane potential and initiation of apoptosis.The differences of expression levels of Fip1,ACP1,PMS2 and COX13 that are important for oxidative phosphorylation and mismatch repair pathway were significant,which may be some of the reasons for the induction of apoptosis in DHCHE-treated U.virens.The protein levels of Fip1,ACP1,PMS2 and COX13 agreed with protein fold change ratio from parallel reaction monitoring Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed proteins were further analyzed.These findings will help to elucidate the mechanisms associated with antifungal and pro-apoptotic effects of DHCHE on U.virens,thereby aiding the potential development of novel pesticides.

The antifungal properties of terpenoids from the endophytic fungus Bipolaris eleusines

A series of terpenoids(1-17),comprising six new compounds designated bipolariterpenes A-F(1-6)and eleven rec-ognized compounds(7-17),were isolated from the wheat culture of the potato endophytic fungus Bipolaris eleusines.Their structures and stereochemistry were clarified by HRESIMS,NMR,DP4+probability analyses,and computations for electronic circular dichroism(ECD).All compounds are made up of six meroterpenoids,four sesterterpenes and seven sesquiterpenes.Among them,four sesterterpenes(4,5,10,11)were investigated for their antifungal,antibacterial and cytotoxic properties,and six meroterpenoids(1-3,7-9)were evaluated for their antifungal properties.The compounds 7,9,and 10 had substantial antifungal activity against Epidermophyton floccosum at a concentration of 100μM.No antibacterial and cytotoxic activities were observed.

Antimicrobial activities of Acacia genus:A review

More than 1 300 species of the vast genus Acacia are found in tropical habitats. They are crucial economic plants since they produce traditional medicines, timber, and gum. The pharmacological uses of the Acacia genus include anti-diarrheal, anti-malarial, chronic pain relief, wound healing, anti-cancer, anti-rheumatism, and antidiabetes activities. It is also used for treating various illnesses such as gastroenteritis, allergies, Alzheimer’s disease, cough, and cardiovascular disease. The present review aims to summarize the antimicrobial activities including the antibacterial and antifungal activity of the Acacia genus. The literature was searched in books and online databases including SciFinder, Google Scholar, Scopus, Pub Med, and scientific journals using the most relevant keywords: Acacia+antimicrobial, Acacia+antibacterial, and Acacia+antifungal.

Quality assurance of postharvest grapes against Botrytis cinerea by terbinafine

Worldwide,fruit is an indispensable treasure house of nutrition for human beings,occupying a vital position of human diet.Postharvest fruit storage requires efficient antifungal agents to control Botrytis cinerea,which is a vital postharvest disease affecting fruit and leading to enormous losses.However,with the enormous abuse of existing antifungal drugs,the problem of drug-resistant fungi is imminent,making the controlling diseases caused by pathogenic fungi even more challenging.Drug repurposing is an efficient alternative method,we evaluated a well-known antifungal chemical,terbinafine,against the agricultural pathogen,B.cinerea in vitro,as a result,terbinafine showed strong anti-fungal activity.Furthermore,the in vivo antifungal activity of terbinafine was evaluated,the results showed that terbinafine could reduce the decay area on grapes.Terbinafine could disrupt the cell membrane integrity,increase cell membrane permeability,and eventual cell death of B.cinerea.In addition,terbinafine reduced decay incidence,and weight loss and maintained the soluble solids,titratable acidity,ascorbic acid,total phenolic,and malondialdehyde content during the storage period of grapes.Overall,terbinafine could be an antifungal preservative for postharvest table grapes fresh-keeping.

Bioactivity profile of dissolved organic matter and its relation to molecular composition

Dissolved organic matter(DOM)occupies a huge and uncharted molecular space.Given its properties,DOM can be presented as a promising biotechnological resource.However,research into bioactivities of DOM is still in early stages.In this study,the biotechnological potential of terrestrial and marine DOM,its molecular composition and their relationships are investigated.Samples were screened for their in vitro antibacterial,antifungal,anticancer and antioxidant activities.Antibacterial activity was detected against Staphylococcus aureus in almost all DOM samples,with freshwater DOM showing the lowest IC50 values.Most samples also inhibited Staphylococcus epidermidis,and four DOM extracts showed up to fourfold higher potency than the reference drug.Antifungal activity was limited to only porewater DOM towards human dermatophyte Trichophyton rubrum.No significant in vitro anticancer activity was observed.Low antioxidant potential was exerted.The molecular characterization by FT-ICR MS allowed a broad compositional overview.Three main distinguished groups have been identified by PCoA analyses.Antibacterial activities are related to high aromaticity content and highly-unsaturated molecular formulae(O-poor).Antifungal effect is correlated with highly-unsaturated molecular formulae(O-rich).Antioxidant activity is positively related to the presence of double bonds and polyphenols.This study evidenced for the first time antibacterial and antifungal activity in DOM with potential applications in cosmeceutical,pharmaceutical and aquaculture industry.The lack of cytotoxicity and the almost unlimited presence of this organic material may open new avenues in future marine bioprospect-ing efforts.

Development of Molecular Marker Linked with Cercospora Leaf Spot (CLS) Disease Resistance in Vigna radiata, Cloning, and Expression for Evaluating Antifungal Activity against Cercospora canescens

We developed a molecular marker for MAS of mungbean resistant varieties against CLS from the consensus sequence(MB-CLsRG)of identified RGAs(MB-ClsRCaG1 and MB-ClsRCaG2).The MB-CLsRG sequence-specific primer pair was used to screen Cercospora leaf spot(CLS)resistant varieties of mungbean in genomic analysis that showed congruency with phenotypic screening.Validation of molecular marker linkage with CLS resistance was performed using rtPCR in transcriptomic analysis.The sequenced PCR products showed 100%homology with MB-CLsRG sequence and putative disease resistance proteins that confirmed the linkage of molecular marker with CLS resistance in mungbean.The antifungal potential of MB-CLsRG gene encoding protein was assessed.The MB-CLsRG gene sequence was cloned in the E.coli expression vector for recombinant protein production.The recombinant protein was then investigated for its in vitro antifungal potential against Cercospora canescens.The in vitro investigation showed strong antifungal activity of recombinant protein as it restricted the growth of fungal mycelial mass.The results validated the linkage of developed marker with CLS-resistant mungbean varieties;therefore,it can be used to screen resistant varieties from a large population in MAS.Moreover,the recombinant protein of the MB-CLsRG gene sequence revealed antifungal potential,which proved the gene sequence could be suitable to use in transgenic plants technology to develop fungal-resistant transgenic crops.

Profiling of Antifungal Activities from the Leaf Extract of Selected Apiaceae Family Plants against Aspergillus fumigates

Many ethnic plants are used as a source of traditional medicine to cure a variety of illnesses in both humans and animals. Developing secondary metabolites in plants with antifungal characteristics, offer alternative medications for reasonably priced and safe treatments. In the present study, methanolic, ethanolic, hexane and ethyl acetate leaves extracts of fifteen Apiaceae family plants were taken on the premise of their ethno botanical uses. The antifungal activity was assessed against significant fungal strain;Aspergillus fumigates by measuring minimum inhibitory concentration (MIC) and Zone of inhibition compared with standard drug fluconazole. Ethanol and methanol extracts of the plants were more effective than the hexane and ethyl acetate extracts against A. fumigates. Extracts of Cuminum cyminum, Pastinca sativa, Carum carvi, Dacus carota, Centella asiatica, Anthriscus cerefolium, Trachyspermum ammi, Pimpenella anisum and Apium graveolens showed relatively low inhibition effects between 3.5 to 8.5 mm. The MIC value of extracts was determined ranging between 0.8 to 0.43 μg/ml. The extract of Petroselinum crispum, Foeniculum vulgare, Ferula assaefoetida, Bunium persicum, Anethum graveolens and Coriander sativum could be considered as potential source of antifungal compounds for treating diseases in humans. Conclude remarks that these six extracts show astonishing fungicidal properties that can be used to discover drugs of very high potential.

Anticandidal Activity of Moroccan Medicinal Plants

The prevalence of oral candidiasis has increased over recent years in patients with the compromised general condition. There are a large number of plant species that have been traditionally used for oral diseases by the Moroccan population. These species could provide a source for discovering new active principles of natural origin against Candida albicans involved in the appearance of candidiasis infections. Information was acquired using the electronic databases Web of Science, Scopus and PubMed. In the first part, this review presents the medicinal plants used by the Moroccan population for the treatment of oral disorders (Toothaches, gingivitis, ulcers, stomatitis, abscesses, ...). The second part describes different studies regarding the antifungal activity of essential oils and organic extracts of some Moroccan species against Candida albicans. Inhibition zone diameter (IZD), Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of essential oils and plant’s extracts were noted. The third part concerns Moroccan plants with the antifungal activity that can be used in medical and agricultural fields. Several species of Moroccan plant proved their effectiveness against Candida albicans and can be used for the treatment of oral candidiasis. Further research should be undertaken in the future to investigate the toxicity of essential oils and plant extracts with antifungal properties for clinical use. This review provided an update on Moroccan plants presenting antifungal activity and especially those active against Candida albicans.

Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.