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.

Comparison of fungal vs bacterial infections in the medical intensive liver unit:Cause or corollary for high mortality?

BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou

AIM:To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.METHODS:The clinical data of 155 patients were retrospectively collected in this study,and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed.RESULTS:Among the 155 patients(age from 12 to 87 years old,with an average age of 57,99 males and 56 females)with eye infections(160 eyes:74 in the left eye,76 in the right eye and 5 in both eyes,all of which were exogenous),71(45.81%)strains were gram-positive bacteria,23(14.84%)strains were gram-negative bacteria and 61(39.35%)strains were fungi.Gram-positive bacteria were highly resistant to penicillin and erythromycin(78.87%and 46.48%respectively),but least resistant to vancomycin at 0.Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole(100%and 95.65%respectively),but least resistant to meropenem at 0.Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences(P<0.05)in the resistance of both to cefoxitin,cotrimoxazole,levofloxacin,cefuroxime,ceftriaxone and ceftazidime,and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria.The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva,cornea,aqueous humor or vitreous body and other eye parts.Besides,Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections.CONCLUSION:Gram-positive bacteria are the dominant bacteria in eye infections,followed by gram-negative bacteria and fungi.Considering the resistance of gramnegative bacteria to multiple drugs,monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.

Candidemia chronicles:Retrospective analysis of candidemia epidemiology,species distribution,and antifungal susceptibility patterns in Bahrain

BACKGROUND Invasive fungal infections,particularly candidemia,pose significant clinical challenges globally.Understanding local epidemiology,species distribution,and antifungal susceptibility patterns is crucial for effective management despite regional variations.AIM To investigate the epidemiology,species distribution,antifungal susceptibility patterns,and associated risk factors of candidemia among patients in Bahrain from 2021 to 2023.METHODS This retrospective study analyzed demographic data,Candida species distribution,antifungal susceptibility profiles,and risk factors among candidemia patients treated at a tertiary care hospital in Bahrain over three years.Data was collected from medical records and analyzed using descriptive statistics.RESULTS A total of 430 candidemia cases were identified.The mean age of patients was 65.7 years,with a mortality rate of 85.5%.Candida albicans(C.albicans)was the most common species,followed by Candida parapsilosis,Candida tropicalis(C.tropicalis),and emerging multidrug-resistant Candida auris(C.auris).Antifungal susceptibility varied across species,with declining susceptibility to azoles observed,particularly among C.albicans and C.tropicalis.Major risk factors included central venous catheters,broad-spectrum antibiotics,and surgical procedures.CONCLUSION This study highlights the substantial burden of candidemia among older adults in Bahrain,characterized by diverse Candida species.It also concerns levels of antifungal resistance,notably in C.auris.The findings underscore the importance of local epidemiological surveillance and tailored treatment strategies to improve outcomes and mitigate the spread of multidrug-resistant Candida species.Future research should focus on molecular resistance mechanisms and optimizing therapeutic approaches to address this growing public health concern.

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.

Intracranial Fungal Infections: Overview from Two Large Tertiary Hospital in Upper Egypt and Literature Review

Purpose: Fungal infections of the central nervous system (CNS) are potentially lethal conditions with high morbidity and mortality. In this review, we summarise the most common clinical manifestations, diagnostic methods, and treatment strategies for intracranial fungal infection at two tertiary care teaching hospitals. Material and methods: Prospective hospital study is carried out at Department of Neurosurgery;Assiut and Suhaj University Hospitals between January2010 to January 2018 (Minimum 12-months follow-up). Radiographs and hospital data of 74 patients with proven intracranial fungal infections were gathered and analyzed. There were no exclusion criteria: age, gender, clinical presentations, immunity status, radiological findings, laboratory, and microbiological data, types of management and outcome. In surgically treated patients, diagnosis was confirmed by pathologic evaluation. Gathered data were coded and entered into a computer and analyzed using SPSS version 22. Results: The greatest number of the patients had 40 to 60 years old (49;66%) and the mean age was 44 years. There was an overwhelming male patient’s ranged preponderance 66%;49 cases. Sixty-three patients (85%) were immunosuppressed;11 cases (15%) were immunocompetent. The most common causes of immunosuppression were diabetes 27 patients;43%, on chemotherapeutic agents 19 patients;31%, on corticosteroid 16 patients;25% and AIDS in one patient;1%. Five different fungal types were identified but Cryptococcus spp. was the most common cause of CNS fungal infection, occurring in 39 patients (53%). This was followed by Candida spp. in 14 patients (19%), Aspergillus in 11 patients (15%), Blastomyces in 7 patients (9%) and Coccidiosis in 3 patients (4%). Headache was the most common presenting symptom, occurring in 33 patients (45%). Other relatively common symptoms were nausea or vomiting 11 patients (15%), fever 10 patients;(13%), seizures 9 patients (12%), acute mental status changes 8 patients;(11%) and stroke like Symptoms 3patients (4%). Different surgical procedures were done. Stereotactic biopsy is in 19 patients (deep;located in an eloquent region of the brain or multiple small lesion) or excision in 38 patients (cortical, relatively accessible regions of the brain), and CSF shunting in 17 patients. All patients received parenteral and, in some cases, oral antifungal chemotherapy in addition to surgical therapy. Overall mortality was 52.7% (39 deaths). An additional 8 surviving patients exhibited permanent morbidity due to neurological deficits and seizure disorders. Conclusion: This prospective population study demonstrates an insight into the intracranial fungal infection and management. CNS fungal infections have increased in frequency, particularly in immunocompromised patients;most infections are caused by Cryptococcus spp. Diabetes was the most common cause of immunosuppression and headache was the most common symptom at presentation. CNS fungal infection is still associated with a high mortality and morbidity. Prompt diagnosis;early and appropriate medical and surgical management are fundamental to optimize the outcome.

Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions

Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early posttransplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa(P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.

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.

Revision on the Recent Diagnostic Strategies of Fungal Infections

Many invasive fungal diseases have no characteristic signs or symptoms, and may give negative blood cultures;therefore, clinician may decide to start empirical antifungal therapy particularly in high risk patient (e.g., hematopoietic stem cell transplant, solid organ transplant, and AIDS patients). This increases the incidence of appearance of resistant fungal strains to antifungal drugs. Traditional methods for diagnosis such as wet mount examination and microbiological cultures remain the gold standard methods for fungal disease diagnosis. However, they are time-consuming, insensitive, and have a limited impact on clinical decision-making. Significant progress has recently achieved in diagnostic tools of fungal disease. Antigen and antibody based assays, molecular techniques, and MALDI TOF spectrometry technique and nanotechnology offer more rapid, sensitive and accurate results.

Effects of UV-, Visible-, Near-Infrared Beams in Three Therapy Resistance Case Studies of Fungal Skin infections

Fungal and bacterial diseases, directly infecting various parts of body, have received much attention in recent years. Bacterial infections, such as Tinea Pedis, Pityriasis versicolor and Mycetoma can secondarily occur in superficial fungal damaged skin. They often occur in immune compromised individuals including diabetics and patients with peripheral arterial diseases. Mycetoma infections can travel through the bloodstream affecting different organs. In this paper, we investigate the photo-inactivation of the pathogens causing Tinea Pedis, Pityriasis versicolor, and Mycetoma infections in three therapy resistant patients without photosensitizing drugs. We have used a combination of visible to near-infrared (VIS/NIR) laser beams in association with blue (B), red (R) and ultra-violet (UV) light emitted diodes (LEDs) with incident doses of 0.63 - 21.43 J/cm2. These beams have minimum side effects on the normal part of the skin. According to the physicians’ assessments, all case study patients achieved an observable progress such as decreases in inflammatory lesions, rapid process of wound healing and scars improvements. Side effects such as inflammation, crusting, or hypopigmentation were not observed. The presented irradiation protocol may be a valuable complementary treatment for patients suffering from fungal and bacterial skin infections.

Prevalence of Bacterial and Fungal Infected Chronic Leg Ulcers at a Teaching Hospital in Ghana

Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and serious complications such as tissue necrosis and osteomyelitis, can result without the timely control of infections. Recent studies have also reported an increase in the association of fungal infections with chronic non-healing ulcers. Aim: To determine the prevalence of bacterial and fungal infections among patients reporting with chronic leg ulcers in participants without co-morbidities. Methods: A prospective cross-sectional study was conducted among patients with chronic leg ulcers at the National Reconstructive Plastic Surgery and Burns Centre, Korle-Bu Teaching Hospital (NRPS/BC-KBTH) and those who consented were enrolled. Characteristics of the wound as well as micro-organisms cultured from wound swabs were recorded. Results: A total of 50 participants were enrolled for the study with the mean (SD) age of 40.7 (10.7) years. Eighty percent of the participants presented with post traumatic leg ulcers with 80% being artisans and traders in the age group 31 - 50 years. There was no statistically significant association between sex and the organism cultured for post traumatic and cellulitis (p-value > 0.05). The prevalence of bacterial and fungal infection was 79.3% and 20.7% respectively. Pseudomonas species was the most isolated bacteria (61.5%) while Aspergillus niger was the most isolated fungi (41%). Conclusion: From this study, fungal infections should be included in managing chronic leg ulcers, especially among artisans, famers and gardeners even though there was a significantly higher burden of bacterial infections.

Characteristics of invasive fungal infections in obstetric and gynecologic patients

Objective:To investigate the diagnosis and treatment of invasive fungal infections(IFI) in the patients admitted to the Department of Obstetrics and Gynecology in Peking Union Medical College Hospital(PUMCH). Methods:The IFI data from the clinical laboratory and medical records of PUMCH from January,2003 to December, 2009 were studied retrospectively.The patients were classified by diagnostic criteria as confirmed,clinical-diagnosed or suspected cases,and classified by treatment protocols into surgery,chemotherapy or end-stage of malignant tumors.The distribution,pathogens,risk factors and treatment outcomes of IFIs in these patients were discussed. Results:The data of 220 obstetric-gynecologic cases of IFIs were retrieved(52 cases confirmed,11 clinical-diagnosed and 157 suspected).The incidence of confirmed urinogenital IFIs in obstetric-gynecologic patients was greater than overall incidence of urinogenital IFIs in PUMCH(46.2%vs.18.7%,P<0.001).The possible risk factors of IFIs in the obstetric-gynecologic patients included hypoalbuminemia(87.3%in all the confirmed and clinical -diagnosed patients),neutropenia(52.4%) and chemotherapy or radiotherapy(50.8%).The treatment effectiveness in the surgical,chemotherapeutic and end-stage patients were 100.0%(108/108),91.6%(87/95) and 52. 9%(9/17),respectively(P<0.001). Conclusion:The IFIs in the patients from the Department of Obstetrics and Gynecology had more severe cases, diverse risk factors,and special distribution of infection sites.The curative effect was excellent for those receiving surgery or chemotherapy.

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.

Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective

Spontaneous bacterial peritonitis is a complication of ascitic patients with end-stage liver disease(ESLD); spontaneous fungal peritonitis(SFP) is a complication of ESLD less known and described. ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients,not even the antifungals used for the prophylaxis,neither optimal treatment. We reviewed,in order to focus the epidemiology,characteristics,and,considering the high mortality rate of SFP,the use of optimal empirical antifungal therapy the current literature.

Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review

Spontaneous bacterial(SBP) and spontaneous fungal peritonitis(SFP) can be a life-threatening infection in patients with liver cirrhosis(LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant(MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.

Natamycin in the treatment of fungal keratitis : a systematic review and Meta-analysis

AIM: To review published clinical studies examining the effect of natamycin in the treatment of fungal keratitis.METHODS: We selected the publications in CENTRAL,MEDLINE, EMBASE, CNKI, and CBM. This study systematically reviewed published randomized controlled trials(RCTs) that compared natamycin to other antifungal agents, and conducted feasible Meta-analysis of efficacy results using Revman 5.2 software.RESULTS: We included seven trials which were mainly carried out in developing countries of Asia, with five trials conducted in India, one each in China and Bangladesh. A total of 804 participants were randomized to following comparisons: 2% econazole versus 5%natamycin showed little difference in the effects of treatment of fungal keratitis [RR =0.99, 95% confidence interval(CI), 0.8 to 1.21]; chlorhexidine gluconate versus5% natamycin indicated that the results on healing of the ulcer at 21 d was less conclusive(RR=0.77, 95% CI, 0.55 to 1.08; I2=0%); 1% voriconazole versus 5% natamycin suggested that natamycin treatment appeared to be significantly better outcomes than voriconazole(regression coefficient =-0.18 log MAR; 95% CI,-0.30 to-0.05; P =0.006), especially in Fusarium cases(regression coefficient=-0.41 log MAR; 95% CI,-0.61 to-0.20; P 【0.001);natamycin versus fluconazole showed a significant difference in cure rate(χ2=5.048, P 【0.05) and natamycin group was more effective than fluconazole in average period of therapy(t =7.94, P 【0.01).CONCLUSION: Natamycin was a preferable choice in the treatment of fungal keratitis, especially in the early period of Fusarium cases.

Effect of corneal graft diameter on therapeutic penetrating keratoplasty for fungal keratitis

AIM: To evaluate the effect of corneal graft diameter on therapeutic penetrating keratoplasty(PKP) for fungal keratitis. METHODS: A total of 116 patients (116 eyes) suffered from fungal keratitis underwent PKP at the Affiliated Hospital of Medical College Qingdao University from May 2006 to May 2010. They were divided into two groups according to the corneal graft diameter. 64 eyes' corneal graft diameter was 8.00mm or larger and 52 eyes' graft diameter was smaller than 8.00mm. The follow-up time was 2 years. The postoperative visual acuity and complications were documented and compared. RESULTS: Sixty-two (96.88%) eyes and fifty (96.15%) eyes preserved eyeballs respectively in two groups. There was no statistical difference in postoperative visual acuity (P = 0.961), corneal graft dear rate (P=0.132) or the incidence of recurred fungal infection (P=0.770) between two groups. But there was a higher incidence of graft rejection (P=0.020) and secondary glaucoma (P=0.039) in group with corneal graft diameter 8.00mm or larger. CONCLUSION: PKP is an effective treatment approach for fungal keratitis. There is a higher incidence of complications in large-diameter PKP for fungal keratitis.Effective, preventive and therapeutic measures can improve the prognosis.

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.