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.

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.

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.

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.

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.

急性侵袭性真菌性鼻窦炎并发颈内动脉栓塞1例

1临床资料患者,男,58岁,因右鼻塞头痛10 d,加重伴右眼肿胀4 d,于2022-09-13入院治疗。患者既往有糖尿病酮症酸中毒病史。查体:右侧鼻腔黏膜充血、肿胀,鼻腔内见大量脓性分泌物,清理后见右侧中鼻道附近及中鼻甲游离缘霉菌块。右眼肿胀、上下眼睑及内眦周围皮下淤血,不能自睁,对光反射无,瞳孔无法窥及。右侧面颊部肿胀明显,皮温高。入院后急查血糖29.02 mmol/L,积极控制血糖,完善相关术前检查。

Disseminated infection by Fusarium solani in acute lymphocytic leukemia:A case report

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.

Clinical efficacy and safety of intravenous itraconazole in patients with invasive fungal infections in emergency intensive care unit

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.

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.

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.

Guideline for diagnosis, prophylaxis and treatment of invasive fungal infection post burn injury in China 2013

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.

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.

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.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

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.

Multilocus sequence typing indicates diverse origins of invasive Candida tropicalis isolates in China

Background According to data from the China Hospital Invasive Fungal Surveillance Net （CHIF-NET） 2010, Candida tropica/is （C. tropica/is） is the third most common pathogen causing invasive candidiasis. Moreover, the majority of fluconazole-resistant C. tropicalis isolates were from a single hospital. Therefore, a molecular epidemiological survey is necessary to investigate the genetic relatedness of C. tropica/is isolates in China. Methods In this study, 48 C. tropicalis isolates causing invasive fungal infections from four tertiary hospitals in China were studied. All the isolates were identified by sequencing the internal transcribed spacer region. Antifungal susceptibility to triazoles, amphotericin B, and caspofungin was determined by the Clinical and Laboratory Standards Institute standard broth microdilution method. Multilocus sequence typing （MLST） was performed, and phylogenetic analysis was further performed by the eBURST and maximum parsimony （MP） methods to characterize the genetic relatedness of isolates. Results MLST discriminated 40 diploid sequence types （DSTs） among 48 isolates, including 36 novel DSTs, and the XYR1 gene showed the highest discriminatory power. The DSTs obtained from this study were compared with those of previously reported C. tropicalis isolates, and there was poor type alignment with regional strains. Nine groups and 11 singletons were identified by eBURST, whereas two groups and 10 subgroups were clustered by MP analysis. Generally, there were no obvious correlations between clonal clusters generated and the specimen source or hospital origin. Seven fiuconazole-resistant isolates were confirmed and assigned to three distinguishable branches. Conclusions The results suggested diverse origins of invasive C. tropicalis isolates in China. Although most invasive C. tropicalis strains in the mainland of China were clustered with previously characterized Asian isolates, major C. tropicalis clusters identified in this study were genetically distinct from those of other geographic regions.