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.

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.

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.

Research Progress of Volatile Substances Analysis and Sensory Evaluation of Soymilk

Soybean is one of the important crops in China. Soymilk, a traditional neutral plant-based protein drink, is rich in high quality proteins. Although soybean milk is rich in nutrients, its marketing among consumers, especially those in Western countries who are used to peaceful flavor, has been limited due to the adverse flavor impact brought by its special composition. In recent years, with the increasing attention to the nutritional value of soymilk, the flavor of soymilk has become a popular research object for scholars at home and abroad. The flavor components of soymilk are mainly volatile small molecular compounds produced by enzymatic reactions catalyzed by lipoxygenase(LOX). After formation, they interact with protein macromolecules to form the overall flavor of soymilk. At present, there are many methods to control the off-odor of soymilk at home and abroad, including physical heating methods, chemical methods, biological enzymatic digestion methods, mask methods, and a variety of breeding methods. These methods effectively reduce the off-odor of soymilk, but all of them have shortcomings. Currently, the sensory characteristics of the beany odor in soymilk are evaluated mainly by traditional human sensory scoring along with the assistance of modern instrument analysis of volatile flavor substances using headspace solid phase microextraction(SPME) gas chromatography coupled with-mass spectrometry(GC-MS). This paper summarized the research results of volatile flavor substances in soymilk in recent years and the sensory evaluation methods of soymilk at home and abroad, and looked forward to the future development direction, hoping to provide some theoretical bases and reference detection methods for solving the problem of soymilk flavor in the future.

Evaluation of Rhizobium tropici-Derived Extracellular Polymeric Substances on Selected Soil Properties, Seed Germination, and Growth of Black-Eyed Peas (Vigna unguiculata)

Rhizobium tropici-derived extracellular polymeric substances (EPS) have been used in soils to enhance soil structures and mitigate soil erosions. However, information on their use to improve soil health and fertility indicators, and plant growth is limited. In a greenhouse study, we investigated their effects on some soil health, soil fertility indices, and the growth of black-eyed peas (Vigna unguiculate). Results showed that soils incubated with EPS significantly increased basal soil respiration, soil microbial biomass, permanganate oxidizable carbon (POC), and potentially mineralizable nitrogen (PMN). The EPS shifted microbial populations from bacteria to fungi and Gram (−ve) to Gram ( ve) bacteria. However, it had little or no effects on soil pH, soil organic matter (SOM), and cation exchange capacity (CEC). The EPS decreased soil moisture loss, increased soil aggregate stability, but delayed blacked-eyed peas germinations in the soils. At 0.1% (w/w) concentrations in soils, there was increase in plant root nodulations and vegetative growth. This study was carried out within 40 days of incubating soils with EPS or growing the black-eyed peas in a greenhouse study. The plant growth parameters were taken before flowering and fruiting. Further studies of the effects of incubating soils with the extracellular polymeric substances on plant growth. Soil microbial biomass, microbial diversities, and other soil fertility indices are deemed necessary.

Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune cells.Developing precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial drugs.This,in turn,holds the potential to mitigate the alarming issue of bacterial drug resistance.Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds.Considering the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric materials.This ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches.In this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions.Additionally,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric methods.Furthermore,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges.This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm formation.This insight opens up a new avenue for exploration within this research domain.

Preserving the Ozone Layers: Battling Illegal Trade in Ozone-Depleting Substances

The depletion of the ozone layer, a vital shield protecting the Earth from harmful ultraviolet (UV) radiation, is now a worldwide environmental concern. Human activities, particularly the release of ozone depleting substances (ODS), have led to the thinning of this protective layer over recent decades. Simultaneously, illegal trade has emerged as a global challenge, giving rise to economic issues, losses of tax revenue, heightened criminal activities, health risks, and environmental hazards. The depletion of the ozone layer, a critical shield protecting the Earth from harmful ultraviolet (UV) radiation, has become a global environmental concern. This paper delves into the legal dimensions surrounding ozone-depleting substances (ODS), their impact on the ozone layer, and the subsequent risk of skin cancer. As countries navigate international agreements, domestic regulations, and enforcement mechanisms, the intricate interplay between legal frameworks and the health implications of ozone layer depletion comes to the forefront. The paper highlights particular instances of illegal trade in ozone depleting substances, drawing from data reported by the parties to the Montreal Protocol. Notably, China stands out as a significant source of contraband ODS, with other countries such as Bulgaria, Lithuania, Poland, and France reporting numerous cases. Analyzing these case instances offers insights into the efficacy of legal frameworks and enforcement measures. The paper offers a comprehensive set of recommendations to strengthen global control and enforcement against the illegal trade of ozone depleting substances. These recommendations span diverse aspects such as production monitoring, customs collaboration, mutual verification, cross-border agreements, public-private partnerships, international cooperation, detection equipment, global regulatory standards, resource allocation, public awareness campaigns, alternative substance development, and controlling the trade at its source. By applying these recommendations and enhancing enforcement measures, we aim to protect the ozone layer and create a healthier and safer world for future generations and achieve sustainable development goals.

The Role of Jasmonates as Antibulbing Substances in the Bulb Formation of Onion

Onion plants form spherical bulbs under long-day conditions.Substances regulating bulb formation remain unknown.In the course of chemical studies on the bulb formation,α-linolenic acid was isolated from onion extracts as an antibulbing substance,the amount of which was synchronized with the bulb formation.Since allene oxide synthase inhibitor canceled the antibulbing activity ofα-linolenic acid,it was disclosed that jasmonic acid concerns this regulation.Structure-activity-relationship study revealed that its(3R,7S)stereochemistry is necessary for showing its antibulbing activity.It is concluded that(3R,7S)-jasmonate derived fromα-linolenic acid actually participates in the regulation of bulb formation.

Analyzing the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells

Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.

Advances in Research Methods of Pharmacodynamic Substances in Traditional Chinese Medicines and Their Application in the Teaching of Traditional Chinese Medicine Analysi

With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.

Study on Mutagenic Breeding of Bacillus Subtilis and Properties of Its Antifungal Substances

Bacillus subtitles JA isolated by our laboratory produced a large amount of anti-fungal substances, which had strong inhibitory activity against various plant pathogenic fungi, such as Rhizoctonia solani, Fusarium graminearum and so on. Ion beam implantation as a new mutagenic methods was applied in our studay. After B. subtitles JA was implanted by N+ ions, a strain designated as B. subtitles JA-026 was screened and obtained, which had a higher ability to produce those antifungal substances. A series of experiments indicated that the antifungal substances were thermostable and partially sensitive to proteinases K and tryproteinase. When the fermentating broth was fractionated with ammonium sulphate of a final saturation of 70%, the precipitate-enhanced inhibitory activity while the supernatant lost this activity. It appeared that the antifungal substances were likely to be protein.

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.

Medium Optimization for Antifungal Active Substance Production from Streptomyces Lydicus Using Response Surface Methodology

Response surface methodology was used to optimize the medium for antifungal active substance production from Streptomyces lydicus E12 in flask cultivation.Initially,the component factors,which influence antifungal substance production,were studied by varying one factor at a time.Starch,soybean cake powder,K_2HPO_4·3H_2O and MgSO_4·7H_2O were found to have a significant effect on the production of antifungal substances by the traditional design.Then,a Box-Behnken design was applied for further optimization.A quadratic model was found to fit antifungal active substance production.The analysis revealed that the optimum values of the tested variable were starch 84.96 g/L,soybean cake powder 4.13 g/L,glucose 5 g/L,MgSO_4·7H_2O 1.23 g/L,K_2HPO_4·3H_2O2.14 g/L and NaCl 0.5 g/L.The test result of 67.44%antifungal inhibition agreed with the prediction and increased by 14.28%in comparison with the basal medium.

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.

Effect of extracellular polymeric substances on Dolichospermum aggregation during temperature rise

Dolichospermum,a typical model filamentous of cyanobacteria,has the potential to cause severely bloom.Extracellular polymeric substances(EPSs)are considered to influence the aggregation of the algae,and temperature is a significant factor affecting EPSs secretion.However,the mechanism of how EPSs affects the aggregation of Dolichospermum is still unclear because the structure and composition of EPSs are complex.In this study,the effects of EPSs on the aggregation of Dolichospermum during the rise of temperature(7-37℃)were determined.The results showed that the concentration of extracellular polysaccharides and proteins changed significantly with increasing temperature(P<0.01).Firstly,during the increasing temperature,the polysaccharide content of EPSs increased from 20.34 to 54.64 mg/L,and the polysaccharides in the soluble EPS(S-EPS)layer changed significantly.The protein content reached maximum value at 21℃(14.52 mg/L)and varied significantly in S-EPS and loosely bound EPS(LB-EPS).In the EPSs matrix,humus substances and protein were main components of S-EPS and LB-EPS,and protein was the main component of tightly bound EPS(TB-EPS).Secondly,the cell density of Dolichospermum increased during the temperature rise while the aggregation ratio decreased.Moreover,zeta potential and surface thermodynamic analysis of Dolichospermum revealed that the interfacial free energy and electrostatic repulsion increased gradually with increasing temperature,which further reduced the aggregation of Dolichospermum.Finally,principal component analysis(PCA)analysis showed the aggregation of Dolichospermum was directly related to the changes of protein in EPSs(especially S-EPS and LB-EPS)and zeta potential,and polysaccharides in EPSs inhibited the aggregation of Dolichospermum.Based on these results,it was illustrated that the composition and concentration of EPSs affected the cell surface properties of Dolichospermum with the change of temperature and thus affected the aggregation of Dolichospermum.

Comparative Evaluation of Humic Substances: Effect at Cell Level and Chlorophyll Retention during Accelerated Senescence

The influence of humic substances (HS) formulations derived from sedimentary and compost sources was studied on plant growth at cell level and chlorophyll retention during accelerated senescence of leaf tissue. The direct effect of HS formulations was studied on cell expansion using cucumber and radish cotyledon expansion test. The cucumber hypocotyl elongation test was used to study the effect on cell elongation. Chlorophyll pigment retention in excised leaf tissue incubated in dark with high temperature was assessed to study the effect on leaf senescence. Explant tissues were incubated directly in the solutions of the formulations at the concentration recommended for foliar application to the crop plants. HS formulations showed significant variations in their direct bio-stimulatory effects. Formulations derived from compost sources were found superior in terms of inducing a direct stimulatory effect on cell expansion and cell elongation and in maintaining chlorophyll pigment retention during accelerated senescence. HS from sedimentary sources stimulated cell expansion and delayed chlorophyll degradation to a lesser extent compared to HS from compost. However, HS formulations derived from sedimentary sources used in this study were not effective in inducing cell elongation in the cucumber hypocotyl elongation test. The direct bio-stimulatory effect of HS formulations differed significantly between the formulations that were evaluated.

Role of extracellular polymeric substances in resistance to allelochemical stress on Microcystis aeruginsosa and its mechanism

Using allelochemicals to suppress cyanobacteria growth is a prospective method for its high efficiency and ecological safety.However,the suppression efficiency is affected inevitably by the extracellular polymeric substances(EPS)produced by cyanobacteria,and the knowledge about the roles of EPS in resistance to allelochemical stress is scarce.For the study,two typical anti-cyanobacterial allelochemicals were adopted to investigate the role of EPS in resistance to allelochemical stress on Microcystis aeruginosa.Results show that EPS was crucial in alleviating the toxicity of allelochemicals to algae,especially in stabilizing the metabolism and photosynthetic activity of algal cells.The aggregation rate of algal cells increased with the increase of EPS secretion,which alleviated the stress of allelopathy.Tryptophan proteins and humic acids in EPS provided a binding site for allelochemicals,and the EPS-allelochemicals complex were formed by chemical bonding.This study improved our comprehension of the role of EPS in algal inhibition by allelochemicals.

Chemical substances present in discharge water generated by laundry industry:Analytical monitoring

To our knowledge,precise data concerning the pollution in terms of qualitative and quantitative fluctuations in discharge water from the laundry sector have seldom been reported.This study investigated the chemical composition of the discharge water from a laundry industry.Over 160 chemical substances and 15 standard water parameters were monitored.The results showed that the discharge water presented both inorganic and organic polycontamination with a high degree of qualitative and quantitative variability.However,of all monitored substances,only five metals(Al,Cu,Fe,Sr,and Zn),five minerals(P,Ca,K,Na,and S),and alkylphenols were systematically present and quantifiable.For a daily average water flow of 129 m^(3),the released metal flux was 356 g/d.Substances,such as trichloromethane,brominated diphenyl ether(BDE)47,and fluorides,were occasionally found and quantified.Other substances,such as chlorophenols,organo-tins,and pesticides were never identified.All the samples had quantifiable levels in the chemical oxygen demand(COD),biological oxygen demand(BOD),and hydrocarbons.Only the concentrations of Zn(8.3 g/d),Cu(21.4 g/d),and BOD(57.4 g/d)were close to or above the regulatory values:74.0 g/d for Zn,9.0 g/d for Cu,and 57.0 kg/d for BOD.The data obtained from this study are useful to the choice of additional treatments for the reduction of pollutant fluxes.

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.

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.