This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections（IFI） in emergency intensive care unit（EICU）. A retrospective analysis was p...This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections（IFI） in emergency intensive care unit（EICU）. A retrospective analysis was performed in patients with IFI who were treated in the authors＇ institution, a grade III first class hospital in Beijing, China, between Feb. 2013 and Feb. 2015. The age of patients ranged from 35 to 90 years old with the mean age of（75.1±11.1） years old. The study population comprised 36 male and 32 female patients. Total response rate was 60.3%. The response rates in definitive diagnosis, clinical diagnosis and presumed diagnosis were 33.3%, 59.5% and 65.2%, respectively（P〈0.05）. The empirical treatment should be provided for patients with presumed diagnosis as earlier as possible. Eleven（16.2%） cases had adverse drug event（ADE） during treatment. The main signs were hepatic functional impairment and hypokalemia of ADE. The clinical efficacy and safety of intravenous itraconazole were precisely assessed. To reduce the adverse drug reaction（ADR）, hepatic and renal function and other biochemical criterion should be closely monitored.展开更多
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 pa...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.展开更多
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)i...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.展开更多
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 analy...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, <em>Pneumocystis</em> 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.展开更多
BACKGROUND Invasive fungal sinusitis(IFS)can present as a mild disease to life-threatening infection.A recent surge in cases was seen due to the coronavirus disease 2019(COVID-19)pandemic.Many patients require surgica...BACKGROUND Invasive fungal sinusitis(IFS)can present as a mild disease to life-threatening infection.A recent surge in cases was seen due to the coronavirus disease 2019(COVID-19)pandemic.Many patients require surgical debridement and hence imaging[contrast-enhanced computed tomography(CECT)of the paranasal sinuses(PNS)]to document the extent of the disease.However,there was no scoring system using CECT to describe the severity of IFS.This study proposes a computed tomography(CT)severity index(CTSI)to describe the severity of rhino-orbital-cerebral involvement in symptomatic COVID-19 patients and hypothesizes that higher CTSI correlates with disease severity and thus slow response/non-response to treatment.AIM To propose a scoring system using CECT to describe the severity of IFS and correlate it with clinical outcomes.METHODS A prospective study on 66 COVID-19 positive patients with CECT PNS done for IFS was performed.Split-bolus single-phase CT technique was used.Based on the extent of involvement,a CTSI was designed.Disease in four major subsite areas was assessed.Each subsite involvement was given points according to this model and then summated.Based on the final summated CTSI,the disease was classified as mild,moderate,or severe.Two subsets were subsequently analyzed including survival and death;and responders and non-responders.RESULTS The study cohort was 66 COVID-19-positive patients with suspected IFS with a median age of 48.5 years.Mild disease was noted in 34(51.52%),moderate in 28(42.42%),and severe disease in 4(6.06%)patients.There was a significant association of mortality and poor clinical response(P=0.02)with disease bilaterality.Laterality and CTSI were significant predictors of response to treatment.The mean CTSI of responders was 6.3,of non-responders was 12.9 and the response to treatment was significantly associated with CTSI(t-test,P<0.001).Receiver operating characteristic curve analysis(Liu method)to distinguish between responders and non-responders showed that the cut-off value for CTSI of 11 had a sensitivity of 78.26%and a specificity of 95.35%to predict response assessment.CONCLUSION CTSI can help in quantification of the disease burden,mapping out disease extent,triaging patients,and response assessment;especially patients with underlying comorbidities.A higher score would alert the clinician to initiate aggressive treatment,as severe disease correlates with slow response/non-response to the treatment.展开更多
Fungal infections have emerged as a critical global health threat,exerting substantial negative impacts on both human health and the economy.According to a worldwide study published in 2024,the invasive fungal infecti...Fungal infections have emerged as a critical global health threat,exerting substantial negative impacts on both human health and the economy.According to a worldwide study published in 2024,the invasive fungal infection(IFI)causes 6.55million cases and 3.75 million deaths annually.About 2.55 million of these deaths were directly attributable[1].Fungal infection has a geographic signature;for example,renal mucormycosis in India accounts for 90%of global cases,mostly due to agricultural practices and uncontrolled diabetes[1].展开更多
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 t...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.展开更多
Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infectio...Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infection for burn victims is increasing dramatically during recent years. This guideline, organized by Chinese Society of Burn Surgeons, aims to standardize the diagnosis, prevention and treatment of burn invasive fungal infection. It can be used as one of the tools for treatment of major burn patients.展开更多
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 ai...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.展开更多
Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×...Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.展开更多
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...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.展开更多
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 im...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.展开更多
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 als...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.展开更多
Mucormycosis is an invasive fungal infection with an acute onset,rapid progression,and high mortality rate.Since its incidence is lower than that of common fungal infections such as Aspergillus,Candida,and Cryptococcu...Mucormycosis is an invasive fungal infection with an acute onset,rapid progression,and high mortality rate.Since its incidence is lower than that of common fungal infections such as Aspergillus,Candida,and Cryptococcus,it is often overlooked in clinical practice.[1]However,in recent years,the incidence of mucormycosis has increased worldwide,potentially correlating with the growing population of diabetic patients.展开更多
Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS).This fungal sinusitis v...Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS).This fungal sinusitis variant demonstrates unhealthy mucosa by endoscopy with fungal invasion,but lacks angioinvasion microscopically,representing what clinically behaves as a ‘pre-invasive’ subtype of fungal sinusitis.Unlike non-IFS disease,patients with preinvasive fungal sinusitis were still felt to require anti-fungal medications due to histologic presence of invasive fungus.While sharing some clinical features of IFS,these ‘intermediate’ patients were successfully spared extended and repeated surgical debridements given the microscopic findings,and have been successfully treated with shorter courses of antifungal therapy.These select patients have had favorable outcomes when managed in a judicious and semi-aggressive manner,in an undefined zone between the treatments for routine fungal ball and aggressive IFS.展开更多
AIM:To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis.METHODS:We performed a prospective study of 127patients who underwent endoscopic retrograde cholangiopancreatogra...AIM:To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis.METHODS:We performed a prospective study of 127patients who underwent endoscopic retrograde cholangiopancreatography,for various biliary disorders,at 3 tertiary referral centers in Germany from July 2011through July 2012(ClinicalTrials.gov:NCT01109550).Bile,buccal,and stool samples were collected.When indicated,endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections.RESULTS:Candida species were detected in 38 of the 127 bile samples(29.9%).By multivariate analysis patients’age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis(P<0.05).Patients with immunosuppression(P=0.058)and recent long-term antibiotic therapy(>7 d)(P=0.089)tend to be at risk for biliary candidiasis.One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically.Of Candida subspecies detected,36.7%were azole-resistant,such as C glabrata.Eight patients received anti-mycotic therapy,based on our algorithm.Of these,3 had cancer with biliary tract involvement,2had secondary sclerosing cholangitis,1 had retroperitoneal fibrosis,and 5 had septicemia.In all patients contamination was ruled out by smears of the endoscope channel.CONCLUSION:Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders.Our suggested algorithm facilitates the further clinical management.展开更多
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 ...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.展开更多
BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received ch...BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.展开更多
Invasive fungal infections(IFIs)have become prominent global health threats,escalating the burden on public health systems.The increasing occurrence of invasive fungal infections is due primarily to the extensive appl...Invasive fungal infections(IFIs)have become prominent global health threats,escalating the burden on public health systems.The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy,immunosuppressive therapies,and broad-spectrum antifungal agents.At present,therapeutic practices utilize multiple categories of antifungal agents,such as azoles,polyenes,echinocandins,and pyrimidine analogs.Nevertheless,the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance,thereby substantially restricting their therapeutic utility.Consequently,there is an imperative need to expedite the discovery of novel antifungal agents.This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation.These emerging compounds exhibit unique benefits concerning their modes of action,antimicrobial spectra,and pharmacokinetic characteristics,potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens.It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.展开更多
文摘This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections（IFI） in emergency intensive care unit（EICU）. A retrospective analysis was performed in patients with IFI who were treated in the authors＇ institution, a grade III first class hospital in Beijing, China, between Feb. 2013 and Feb. 2015. The age of patients ranged from 35 to 90 years old with the mean age of（75.1±11.1） years old. The study population comprised 36 male and 32 female patients. Total response rate was 60.3%. The response rates in definitive diagnosis, clinical diagnosis and presumed diagnosis were 33.3%, 59.5% and 65.2%, respectively（P〈0.05）. The empirical treatment should be provided for patients with presumed diagnosis as earlier as possible. Eleven（16.2%） cases had adverse drug event（ADE） during treatment. The main signs were hepatic functional impairment and hypokalemia of ADE. The clinical efficacy and safety of intravenous itraconazole were precisely assessed. To reduce the adverse drug reaction（ADR）, hepatic and renal function and other biochemical criterion should be closely monitored.
文摘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.
基金the National Natural Science Foundation of China(No.81500105).
文摘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.
文摘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, <em>Pneumocystis</em> 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.
基金Supported by All India Institute of Medical Sciences,New Delhi,No.A-COVID-80.
文摘BACKGROUND Invasive fungal sinusitis(IFS)can present as a mild disease to life-threatening infection.A recent surge in cases was seen due to the coronavirus disease 2019(COVID-19)pandemic.Many patients require surgical debridement and hence imaging[contrast-enhanced computed tomography(CECT)of the paranasal sinuses(PNS)]to document the extent of the disease.However,there was no scoring system using CECT to describe the severity of IFS.This study proposes a computed tomography(CT)severity index(CTSI)to describe the severity of rhino-orbital-cerebral involvement in symptomatic COVID-19 patients and hypothesizes that higher CTSI correlates with disease severity and thus slow response/non-response to treatment.AIM To propose a scoring system using CECT to describe the severity of IFS and correlate it with clinical outcomes.METHODS A prospective study on 66 COVID-19 positive patients with CECT PNS done for IFS was performed.Split-bolus single-phase CT technique was used.Based on the extent of involvement,a CTSI was designed.Disease in four major subsite areas was assessed.Each subsite involvement was given points according to this model and then summated.Based on the final summated CTSI,the disease was classified as mild,moderate,or severe.Two subsets were subsequently analyzed including survival and death;and responders and non-responders.RESULTS The study cohort was 66 COVID-19-positive patients with suspected IFS with a median age of 48.5 years.Mild disease was noted in 34(51.52%),moderate in 28(42.42%),and severe disease in 4(6.06%)patients.There was a significant association of mortality and poor clinical response(P=0.02)with disease bilaterality.Laterality and CTSI were significant predictors of response to treatment.The mean CTSI of responders was 6.3,of non-responders was 12.9 and the response to treatment was significantly associated with CTSI(t-test,P<0.001).Receiver operating characteristic curve analysis(Liu method)to distinguish between responders and non-responders showed that the cut-off value for CTSI of 11 had a sensitivity of 78.26%and a specificity of 95.35%to predict response assessment.CONCLUSION CTSI can help in quantification of the disease burden,mapping out disease extent,triaging patients,and response assessment;especially patients with underlying comorbidities.A higher score would alert the clinician to initiate aggressive treatment,as severe disease correlates with slow response/non-response to the treatment.
基金funding from the MOST Key R&D Program of China(Grant number 2022YFC2304703)the Natural Science Foundation of China(Grant number 32422004)+5 种基金The Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University(Grant number 24X010301328)the Natural Science Foundation of China(Grant number 32270202)the Computational Biology Program(Grant number 25JS2810200)of Science and Technology Commission of ShanghaiMunicipality(STCSM)the MOST Key R&D Program of China(Grant number 2020YFA0907200)the Program of Shanghai Academic Research Leader(Grant number 23XD1422300)the Innovative research team of high-level local universities in Shanghai.
文摘Fungal infections have emerged as a critical global health threat,exerting substantial negative impacts on both human health and the economy.According to a worldwide study published in 2024,the invasive fungal infection(IFI)causes 6.55million cases and 3.75 million deaths annually.About 2.55 million of these deaths were directly attributable[1].Fungal infection has a geographic signature;for example,renal mucormycosis in India accounts for 90%of global cases,mostly due to agricultural practices and uncontrolled diabetes[1].
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘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.
文摘Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infection for burn victims is increasing dramatically during recent years. This guideline, organized by Chinese Society of Burn Surgeons, aims to standardize the diagnosis, prevention and treatment of burn invasive fungal infection. It can be used as one of the tools for treatment of major burn patients.
文摘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.
基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)[2021-I2M-1-017]and[2021-I2M-C&T-B-080]Haihe Laboratory of Cell Ecosystem Innovation Fund[HH22KYZX0036].
文摘Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation(82372206)the Project of Jiangsu Provincial Health Commission(H2023107)the Project of Basic and Clinical Research on Cardiac Arrest in the Emergency and Critical Care Department of the Second Affiliated Hospital of Soochow University(XKTJ-XK202408-2).
文摘Mucormycosis is an invasive fungal infection with an acute onset,rapid progression,and high mortality rate.Since its incidence is lower than that of common fungal infections such as Aspergillus,Candida,and Cryptococcus,it is often overlooked in clinical practice.[1]However,in recent years,the incidence of mucormycosis has increased worldwide,potentially correlating with the growing population of diabetic patients.
文摘Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS).This fungal sinusitis variant demonstrates unhealthy mucosa by endoscopy with fungal invasion,but lacks angioinvasion microscopically,representing what clinically behaves as a ‘pre-invasive’ subtype of fungal sinusitis.Unlike non-IFS disease,patients with preinvasive fungal sinusitis were still felt to require anti-fungal medications due to histologic presence of invasive fungus.While sharing some clinical features of IFS,these ‘intermediate’ patients were successfully spared extended and repeated surgical debridements given the microscopic findings,and have been successfully treated with shorter courses of antifungal therapy.These select patients have had favorable outcomes when managed in a judicious and semi-aggressive manner,in an undefined zone between the treatments for routine fungal ball and aggressive IFS.
基金Supported by An Investigator-Initiated Studies Program of MSD Sharp and Dohme GmbHa research fellowship(to Lenz P)from the Faculty of Medicine,Westfaelische Wilhelms Universitat Muenster
文摘AIM:To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis.METHODS:We performed a prospective study of 127patients who underwent endoscopic retrograde cholangiopancreatography,for various biliary disorders,at 3 tertiary referral centers in Germany from July 2011through July 2012(ClinicalTrials.gov:NCT01109550).Bile,buccal,and stool samples were collected.When indicated,endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections.RESULTS:Candida species were detected in 38 of the 127 bile samples(29.9%).By multivariate analysis patients’age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis(P<0.05).Patients with immunosuppression(P=0.058)and recent long-term antibiotic therapy(>7 d)(P=0.089)tend to be at risk for biliary candidiasis.One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically.Of Candida subspecies detected,36.7%were azole-resistant,such as C glabrata.Eight patients received anti-mycotic therapy,based on our algorithm.Of these,3 had cancer with biliary tract involvement,2had secondary sclerosing cholangitis,1 had retroperitoneal fibrosis,and 5 had septicemia.In all patients contamination was ruled out by smears of the endoscope channel.CONCLUSION:Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders.Our suggested algorithm facilitates the further clinical management.
文摘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.
基金Supported by the Scientific Research Project of Peking University Shenzhen Hospital,No.JCYJ2018011the San-Ming Project of Medicine in Shenzhen,No.SZSM201812059.
文摘BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.
基金supported by grants from the National Science Fund for Distinguished Young Scholars,China(82225029 to Chenhui Wang)the Key Program of National Natural Science of China(82430076 to Chenhui Wang)the Youth Fund of the National Natural Science Foundation of China(82301989 to Ruirui He,82302628 to Yanyun Du,82301987 to Bo Zeng and 82402704 to Yangyang Li).
文摘Invasive fungal infections(IFIs)have become prominent global health threats,escalating the burden on public health systems.The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy,immunosuppressive therapies,and broad-spectrum antifungal agents.At present,therapeutic practices utilize multiple categories of antifungal agents,such as azoles,polyenes,echinocandins,and pyrimidine analogs.Nevertheless,the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance,thereby substantially restricting their therapeutic utility.Consequently,there is an imperative need to expedite the discovery of novel antifungal agents.This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation.These emerging compounds exhibit unique benefits concerning their modes of action,antimicrobial spectra,and pharmacokinetic characteristics,potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens.It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.
