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.

Fungal infections following liver transplantation

With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions.Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities,a major portion of these patients continue to be affected by post-transplant infections.Of these,fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose.This mini-review aims to discuss the incidence of fungal infections following liver transplantation,the different fungi involved,the risk factors,which predispose these patients to such infections,associated diagnostic challenges,and the role of prophylaxis.The population at risk is increasingly old and frail,suffering from various other co-morbid conditions,and needs special attention.To improve care and to decrease the burden of such infections,we need to identify the at-risk population with more robust clinical and diagnostic parameters.A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.

Invasive Fungal Infections in People Living with HIV/AIDS

The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analyze the frequency of invasive fungal infections in people living with HIV. In most studies evaluated, Pneumocystis pneumonia was the most frequent invasive fungal infection among people living with HIV, and cryptococcosis was the second most frequent. Invasive fungal infections are associated with greater morbidity and mortality in people living with HIV. The most important highlighted information is that the lack of epidemiological data on fungal infections in the studied populations was reported by most studies. Therefore, there is a need for further studies to assess the frequency of invasive fungal infection in people living with HIV, which may serve as subsidies for the implementation of strategies for the prevention and management, with a consequent increase in the quality of life and reduction of morbidity/mortality in this population.

Delivery strategies of amphotericin B for invasive fungal infections

Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.

Caspofungin versus liposomal amphotericin B for treatment of invasive fungal infections or febrile neutropenia

Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections （IFIs）,compared with L-AmB.Methods Electronic databases （up to July 31,2013） PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks （RRs） and 95% confidence intervals （C/s）.Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat （MITT） patients.The results showed that caspofungin produced equal efficacy in favorable overall response （RR=1.02,95% Cl 0.88-1.18; P=0.81） and mortality rate （RR=1.53,95% Cl 0.38-6.27,P=0.55）,safer in clinical adverse events （RR=0.20,95% Cl 0.08-0.54; P=0.001）,laboratory adverse events （RR=0.69,95% Cl 0.57-0.84; P=0.0002）,and discontinuation rate （RR=0.26,95% Cl 0.08-0.83,P=0.02）,compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.

Fungal arthritis:A challenging clinical entity

There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are also involved.Candida infections are mostly reported,but patients may also develop infections secondary to non-Candida fungi,especially Aspergillus.Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifungal therapy.Despite this,these infections are associated with high morbidity and mortality.This review described the clinical features,risk factors,and therapeutic interventions required to manage fungal arthritis.

Epidemiology of opportunistic invasive fungal infections in China： review of literature

Objective To summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections （IFIs） in China and discuss the relevant social, economical reasons and medical factors. Data sources We performed a comprehensive search of both English and Chinese literatures of opportunistic IFIs from China up to April 2012. Study selection Relevant literatures involving researches and cases/case sedes were identified, retrieved and reviewed. Results The incidence of opportunistic IFIs in China was steadily increasing. The incidence and mortality of IFIs were different in patients with various underlying conditions/diseases, from 4.12% to 41.18% and 9.8% to 60.0%, respectively. Candida species, Aspergillus species and Cryptococcus neoformans species complex were the most frequent isolated pathogens. Other uncommon opportunistic IFIs were also been reported, including trichosporonosis, mucormycosis, hyalohyphomycosis （hyaline hyphomycetes） and phaeohyphomycosis （dematiaceous hyphomycetes）. Reports of Chinese patients differed from those of many other countries as there were a higher number of patients without identifiable underlying diseases/conditions. Conclusions Because of the rapid economic development, changing population structure and a growing number of immunocompromised hosts with risk factors, today opportunistic IFIs in China have a significant impact on public health, associated with high morbidity/mortality and higher care costs. Now information related to the epidemiology of opportunistic IFIs in China is still sparse, so we need more organized groups of clinical scientists performing related researches to help the clinicians to obtain more accurate epidemiological characteristics.

Pulmonary fungal infections after bone marrow transplantation： the value of high-resolution computed tomography in predicting their etiology

Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography （HRCT） findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT. Methods Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis （n=52）, candidiasis （n=19） and cryptococcosis （n=14） groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality. Results Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent （k 〉0.75）. There was a significant difference in occurrence ratio of mass among the three groups （P=-0.02）. Occurrence ratio of mass （43.3%, 13/30） in the group with invasive aspergillosis was higher than in each of other two groups （20.0%, 2/10; 14.3%, 1/7）. There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation. Conclusions The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.

Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections

As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.

Surgical management of invasive fungal infections in adult leukemia patients:experience from a large tertiary center in Southeast-Asia

Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be necessary to improve the survival outcomes of these patients.The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients,median age 46 years(range 19–65),underwent 20 surgical procedures as management for IFI.Three patients had proven IFI diagnoses prior to surgery.Sixteen patients underwent surgery for both diagnostic and therapeutic purposes.Post-surgery,the diagnostic yield for proven IFI increased by a factor of 5,and 15 patients had definitive IFI diagnoses.Surgical complications included 2 pleural effusions,4 pneumothoraxes,and 1 hydropneumothorax.The median duration of hospitalization for patients with complications was 9 days(range 3–64).Thirteen patients benefited overall from the procedure,3 had temporary clinical benefits,and 2 had progression of IFI.After surgery,the 3-month and 2-year overall survival rates were 89.5%and 57.9%,respectively.The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients,as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk,thereby allowing patients to proceed with curative chemotherapy and HSCT.

Pulmonary fungal infection in a neonate with methylmalonic acidemia:A case report

BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmonary fungal infection has been reported yet.CASE SUMMARY We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA.Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father,and a c.658-c.660delAAG variant in exon 4 from the mother,which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia.CONCLUSION Invasive fungal infection might occur in some infants with MMA.Therefore,early diagnosis is recommended for unexplained pulmonary infection.

Chromoblastomycosis:a tropical-subtropical fungal disease with pathognomonic features not to be neglected in a global health scenario

Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.

鼻颅底真菌感染误诊1例

1临床资料患者,男,72岁,因反复头痛、咽喉痛3年,于2022-09-04收入重庆市人民医院。入院时患者头痛呈持续性隐痛,以后枕部为甚;咽喉痛放射至全颈,颈部活动受限,只能进流食。3年前患者无明显诱因出现头痛、咽喉痛,伴双耳痛及双耳持续流脓,多在当地医院对症处理。

Invasive fungal infection before and after liver transplantation

Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.

Dectin-1 rs3901533 and rs7309123 Polymorphisms Increase Susceptibility to Pulmonary Invasive Fungal Disease in Patients with Acute Myeloid Leukemia from a Chinese Han Population

This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.

Modified ulcer debridement in the treatment of the superficial fungal infection of the cornea

AIM： To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS： A total of 209 patients（209 eyes） with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS： The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes（93.3%）, with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty（PK）（1 eye）, anterior lamellar keratoplasty（LK）（7 eyes）, conjunctival flap covering（4 eyes） or amniotic membrane transplantation（2 eyes）. The best corrected visual acuity（BCVA） was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon（P=0.036） and ever using steroid（P=0.025）.CONCLUSION： Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality

BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS In this case-control study,22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran,Iran,between 2014 and 2019.The control group comprised 38 patients without IA infection matched for age and sex.The information obtained included the baseline characteristics of liver transplant patients,operative reports,post-transplantation characteristics of both groups and information about the fungal infection of the patient group.RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%.The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant,renal replacement therapy,antithymocyte globulin induction therapy,post-transplant bile leakage,posttransplant hepatic artery thrombosis,repeated surgery within 30 d after the transplant,bacterial pneumonia before the aspergillosis diagnosis,receiving systemic antibiotics before the aspergillus infection,cytomegalovirus infection,and duration of post-transplant hospitalization in the intensive care unit.The most prevalent form of infection was invasive pulmonary aspergillosis,and the most common chest computed tomography scan findings were nodules,pleural effusion,and the halo sign.In the case group,prophylactic antifungal therapy was administered more frequently than in the control group.The antifungal therapy response rate at 12 wk was 63.7%.The 3-and 12-mo mortality rates of the patients with IA were 36.4%and 45.4%,respectively(compared with the mortality rate of the control group in 12 mo,which was zero).CONCLUSION In this study,the prevalence of IA among liver transplant recipients was relatively low.However,it was one of the leading causes of mortality following liver transplantation.Targeted antifungal therapy may be a factor in the low incidence of infections at our facility.Identifying the risk factors of IFIs,maintaining an elevated level of clinical suspicion,and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

An Incidental Finding and Unusual Presentation of Atypical Coccidioidomycosis in a 72-Year-Old Man: A Case Report

This case report presents an unusual and challenging diagnostic scenario involving a 72-year-old man who recently returned from a trip to Maui, Hawaii. While in Maui, the patient presented with a fever and fatigue that resolved spontaneously. However, he had an observable rash on his head and was given a steroid injection to resolve the rash. Later on his trip, the patient experienced a dry, nonproductive cough which resolved with a five-day course of prednisone. While visiting Michigan, the patient began to experience neck pain and visited Troy Beaumont Hospital for further treatment. Meningitis tests were negative. Vancomycin was given due to the detection of gram positive coccidioidomycosis in the culture, but this was later proven to be a contaminant. Coccidiomycosis does not initially have specific symptoms. Despite negative coccidioidomycosis antigen tests, the patient exhibited features more consistent with blastomycosis and cryptococcus, highlighting the complexities of diagnosing fungal infections with atypical presentations. The case emphasizes the importance of considering alternative fungal pathogens native to endemic regions and pursuing comprehensive diagnostic measures to establish an accurate diagnosis. Lastly, the discussion about recommendations for antifungal therapy and preventative measures for individuals at risk of respiratory fungal infections is critically important for the advancement of early detection of fungal infections.

Donor-Derived Transmission of Scedosporiosis in Kidney Transplant Recipients from a Systemic lupus erythematosus donor

Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.

Candida endocarditis: Update on management considerations

The rise in incidence rates of invasive candidiasis warrants an increase in atten-tion and efforts toward preventing and treating this virulent infection.Cardiac involvement is one of the most feared sequelae and has a poor prognosis.Despite the introduction of several novel antifungal agents over the past quarter century,complications and mortality rates due to Candida endocarditis have remained high.Although fungal endocarditis has a mechanism similar to bacterial endocar-ditis,no specific diagnostic criteria or algorithm exists to help guide its manage-ment.Furthermore,recent data has questioned the current guidelines recommen-ding a combined approach of antifungal agents with surgical valve or indwelling prostheses removal.With the emergence of multidrug-resistant Candida auris,a focus on improved prophylactic measures and management strategies is nece-ssary.