念珠菌病的临床研究进展

念珠菌病是由念珠菌属的某些种群引起的条件致病真菌感染,是人类真菌感染性疾病中最多见的疾病。临床上分为浅部皮肤黏膜念珠菌病和深部念珠菌病（亦称系统性念珠菌病）。近年来深部念珠菌病的发病率有上升趋势,该病涉及临床各科室,危害性大,病死率高,是临床研究的热点。现复习近年国内外文献,就其致病念珠菌的动态流行病学、分子流行病学以及该病的实验室诊断进展及防治现状加以简要的介绍。     

Microbiological non-culture methods for the diagnosis of invasive candidiasis: usefulness of surrogate markers

The usefulness of surrogate markers in the diagnosis of invasive candidiasis is based on their ability to detect the infection caused by the different Candida spp. and to differentiate when the fungus is a colonizer or it is causing an invasive disease. This differentiation has been tried by detecting antigens, antibodies and other Candida components in the patient's sera. In this paper we will review the antigens, antibodies and other Candida components which may be useful in the laboratory diagnosis of invasive candidiasis in the non-neutropenic critically ill patient.     

Clinical spectrum of invasive candidiasis in critically ill non-neutropenic patients

Invasive Candida spp. infections in non-neutropenic critically ill patients admitted to intensive care units can be classified as focal and systemic. Both types of infection usually occur after episodes of candidemia, although some focal infections may be of exogenous development, like those occurring after trauma or be device-related.The clinical spectrum of invasive Candida spp. infections includes focal urinary tract, abdominal, ocular, respiratory tract, renal and hepato-biliary infections, as well as systemic infections like candidemia and acute systemic candidiasis with multiorgan involvement after hematogenous seeding. Candida spp. isolates in "significant" samples, like synovial fluid, cerebrospinal fluid and blood cultures, represent true infection. However, the diagnosis of invasive infection based on "non-significant" samples, like surgical drains and digestive tract exudates, requires additional criteria. The total number of isolates from different sites, the presence of risk factors, the clinical host response, as well as severity of illness need to be taken into account for the diagnosis of invasive candidiasis. The clinical signs of systemic infection due to Candida spp. are completely non-specific and cannot be differentiated from bacterial peritonitis, urinary tract infection or bacteremia. These infections may be associated with signs of sepsis,severe sepsis, septic shock or multiorgan dysfunction. In the future clinical multicentre observational and interventional studies are necessary to reach agreement on clinical definitions and classification of invasive Candida spp. infections in critically ill non-immunocompromised patients.     

慢性阻塞性肺疾病并念珠菌性口炎患者病原学及危险因素分析

目的 探讨入院慢性阻塞性肺疾病(COPD)并念珠菌性口炎患者的病原学特征以及相关危险因素.方法 采用病例研究,对2007年4月1日至2011年1月31日入院的82例COPD并念珠菌性口炎患者和82例无念珠菌性口炎COPD患者进行匹配,应用SPSS 17.0统计软件行条件logistic回归模型分析COPD患者念珠菌性口炎发生的危险因素.结果 (1)从念珠菌性口炎患者假膜培养共分离出念珠菌83株,以白念珠菌(90.4％)为最多,其次为光滑念珠菌(3.6％)、克柔念珠菌(2.4％)、热带念珠菌(2.4％)、近平滑念珠菌(1.2％);(2)统计学分析结果显示全身应用、吸入糖皮质激素是入院患者口腔念珠菌感染的独立危险因素.结论 白色念珠菌是COPD患者口腔部念珠菌感染的主要病原菌,规范使用全身糖皮质激素、正确吸入糖皮质激素是预防COPD患者口腔念珠菌感染的关键.     

Proteomics-based identification of novel Candida albicans antigens for diagnosis of systemic candidiasis in patients with underlying hematological malignancies

Systemic candidiasis remains a major cause of disease and death, particularly among patients suffering from hematological malignancies. In an attempt to contribute to the discovery of useful biomarkers for its diagnosis and therapeutic monitoring, we embarked on a mapping of Candida albicans immunogenic proteins specifically recognized by antibodies produced during the natural course of systemic Candida infection in this high-risk population. About 85 immunoreactive protein species were detected with systemic candidiasis patients' serum specimens by using immunoproteomics (i.e., two-dimensional electrophoresis followed by Western blotting), and identified through a combination of peptide mass fingerprinting by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), de novo peptide sequencing using nano-electrospray ionization-ion trap (ESI-IT) MS, and genomic database searches. This proteomic approach has led to the characterization of 42 different housekeeping enzymes as C. albicans antigens. Their biological significance is also discussed. Furthermore, this study is the first to report that 26 of them exhibit antigenic properties in C. albicans, and 35 of them become targets of the human antibody response to systemic candidiasis. Our findings suggest that the production of antibodies to C. albicans phosphoglycerate kinase and alcohol dehydrogenase during systemic candidiasis could be associated with a differentiation of the human immune response. We also highlight the relationship between changes in maintenance of circulating levels of specific anti-Candida antibodies and patients' outcome. Some of these variations, especially the rise of high anti-enolase antibody concentrations, appear to be related to recovery from systemic candidiasis in these patients, which might serve as markers for predicting their outcome. This approach could therefore provide new challenges for diagnosis and clinical follow-up of these fungal infections, and even for antifungal drug or vaccine design.     

Management of hand and upper-extremity infections in heart transplant recipients

Hand and upper-extremity infections are routinely managed by antibiotics, immobilization, and limited incision and drainage. However, in immunocompromised patients, these infections may be more aggressive and they may require more emergent treatment. The authors performed a retrospective review of the Stanford University Medical Center experience with hand and upper-extremity infections in 911 cardiac transplant recipients over the past 30 years. Thirteen heart transplant recipients were treated for infections of the hand and upper extremity on an inpatient basis. Ten patients (77 percent) required operative debridement, and three (23 percent) required more than one operative procedure. Nine patients (69 percent) had bacterial infections, six (46 percent) had fungal infections [four of these patients (31 percent) had both bacterial and fungal infections], one (7.7 percent) had a mycobacterial infection, and one (7.7 percent) was not cultured. Hand and upper-extremity infections in transplant recipients frequently resulted in deep-space infections, tenosynovitis, and osteomyelitis. The authors believe such infections represent a surgical emergency, requiring immediate evaluation by hand surgeons and early, aggressive treatment.     

Point prevalence, microbiology and antifungal susceptibility patterns of oral Candida isolates colonizing or infecting Mexican HIV/AIDS patients and healthy persons

We have conducted a longitudinal study over a 3-year period to address the point prevalence, microbiological characteristics and antifungal susceptibility patterns of yeast isolates colonizing or infecting the oral cavities of 111 HIV-infected (51 adults, 60 children) and 201 non HIV-infected (109 adults, 92 children) Mexican persons. Regarding the epidemiology of oral candidiasis, Candida albicans was the most frequent species isolated. Seventy-one out of 85 isolates from colonized persons were C. albicans (83.5%), 27 isolates of them were from HIV-infected children and 44 from non HIV-infected patients. Sixty-two isolates belonged to serotype A which was the most prevalent serotype of C. albicans. Non-albicans species (Candida glabrata, Candida tropicalis and Candida parapsilosis, and Saccharomyces cerevisiae) were isolated from 16.5% of colonized patients and from 38.5% patients with candidiasis or Candida-related lesions. There were nine episodes of infection or colonization by at least 2 different yeast species. In the case of HIV/AIDS patients, it was determined that yeast carriage was not associated with the number of CD4+ cells or the viral load, but HAART reduced the prevalence of oral candidiasis. Overall, most patients harbored strains in vitro susceptible to fluconazole, however 10.8% of the yeasts were resistant to one or more azole antifungal agents and 29% were intermediate susceptible to them. On the contrary, 5-fluorocytosine was very active against all isolates tested, and amphotericin B was active against 97.9% of them.     

Isolated Cutaneous Granuloma Caused by <Emphasis Type="Italic">Candida glabrata</Emphasis>: A Rare Case Report and Literature Review

The incidence of candidiasis due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata often invades immunocompromised hosts and causes systemic or mucosal infections, whereas cutaneous infections are rarely reported. We present a rare case of cutaneous infection caused by C. glabrata and review all similar cases available in the PubMed database. A patient was admitted to the hospital with a 2-month history of a plaque on the face. Histopathological examination displayed typical infectious granulomas in the deep dermis, and the pathogen was finally confirmed as C. glabrata using a series of microbial examinations (fungal culture, biochemical test, and PCR-directed sequencing). The patient was completely cured after 4 months of treatment with oral itraconazole combined with topical terbinafine. We reviewed similar reports of cutaneous infection caused by C. glabrata. All the data suggested that an accurate diagnosis of cutaneous candidiasis depends mainly on histological and fungal examinations, especially molecular biological assays. Antifungal agents based on microbial susceptibility tests are the first-line treatment choice for C. glabrata infection, but the prognosis might be more dependent on the basic condition of the host.     

Part I – Young Girls with Non-Refluxing Ureters

This paper is the study of 144 girls with histories of urinary tract infection followed at the Stanford Medical Center who were found to be free of ureterovesical reflux. The mean age at onset of infection for the entire group was about four years and ranged from the first few months of life to age 10. Ninety-two percent of the 505 infection episodes in these children presented with symptoms referable to the lower tract, and bacterial localization studies confirmed that 85 percent of the infections were limited to the bladder. Escherichia coli was the most common organism isolated and most infections were caused by a pure culture of a single bacteria.In only two of the 144 patients studied was there any evidence of upper tract damage related to infection. The possibility that these patients had reflux at an earlier age could not be discounted.In response to short-term antibacterial therapy in 66 of the patients followed closely for an average of 40 months each, 20 percent of the patients had no further infections and 80 percent went on to recurrence. With each succeeding treatment an additional 20 percent of the patients were “cured,” but the remainder experienced recurrent infections during the follow-up. This reinfection pattern supports the use of long-term antibacterial prophylaxis in all girls who have more than three or four recurrences of infections. Urethral dilation appeared to have no value in reducing the reinfection rate. While it appears that in the absence of ureterovesical reflux few, if any, of these children will go on to develop upper tract damage, long-term prophylactic suppressive medication can clearly be justified on the grounds of reducing patient morbidity.     

Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice

Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) play an important role in the recruitment of PMNs at the site of invasive Candida infection. In the absence of either TNFalpha or IL-6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G-CSF (rG-CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicans from the organs of rG-CSF-treated mice is significantly decreased. Treatment with the combination of rG-CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candida infection, rG-CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life-threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candida infection.     

THIS ARTICLE HAS BEEN RETRACTEDHamycin treatment of candidiasis in normal and diabetic rats

Hamycin, a heptaene antifungal antibiotic was compared with amphotericin B in the treatment of established systemic infection with Candida albicans in normal and diabetic rats. In normal rats, orally administered hamycin at 10 mg kg(-1) per day for 7 days reduced Candida colony counts in the kidneys and livers as well as amphotericin B did and was nearly as effective as amphotericin B in a 21-day treatment trial. There was no further reduction in Candida colony counts when normal rats were treated with hamycin at 25 mg kg(-1) twice a day for 7 days. In streptozotocin induced diabetic rats, hamycin at 20 mg kg(-1) per day for either 7 or 21 days compared favourably with amphotericin B in efficacy. Results of the present study suggest that oral hamycin may be useful in the treatment of established disseminated candidiasis in normal as well as diabetic hosts.     

The 'bull's eye' pattern in hepatic tomography

Invasive fungal infections are more commonly found in patients who develop neutropenia after chemotherapy. A 4-year-old girl with diagnosis of acute lymphoid leukemia developed febrile neutropenia after chemotherapy. Broad spectrum antibiotics and antimycotic therapy were initiated. Candida albicans was isolated and Entamoeba histolytica was observed in stool examination. Chronic disseminated candidiasis had developed and was treated with amphotericin B, initially, and fluconazol. Computed tomography images were obtained that demonstrated a classic 'bull's eye' pattern; a concurrent histological study confirmed the diagnosis. Candida spp. is the major cause of opportunistic mycosis in immunosuppresed patients receiving chemotherapy for haematologic malignancies. An initial infection results in disseminated candidiasis, which persists and becomes chronic. In the 4-year-old patient, the identified risk factors consisted of a previous therapy with broad spectrum antibiotics, the gastrointestinal tract colonization with Candida albicans and prolonged neutropenia. Imaging diagnoses are made by ultrasonography, computed tomography and magnetic resonance. With ultrasound and tomography, 4 distinct patterns have been described. Pattern 1 ('wheels within wheels') and 2 ('bull's eye') are important, since they are characteristic of chronic disseminated candidiasis. The third pattern (hypoechoic image) is the most common finding with both techniques. In the current patient, patterns 2 and 3 were seen and the diagnosis was confirmed by histological study.     

Prevalence of Candida albicans and Trichomonas vaginalis in pregnant women in Havana City by an immunologic latex agglutination test

We aimed to estimate the prevalence of Candida albicans and Trichomonas vaginalis in immunocompetent pregnant women living in Havana City, Cuba, with or without symptoms of vaginitis, using a sample of 640 women from 6 Gyneco-obstetrics hospitals, which represents 2.5% of total yearly pregnant women. Diagnosis was made using a new latex agglutination kit (Newvagin C-Kure, La Habana, Cuba). Clinical sensitivity and specificity of this assay were validated against culture method, with 467 and 489 clinical specimens for Candida albicans and Trichomonas vaginalis, respectively. Results showed that the kit clinical sensitivity was 100% for Candida albicans and 86.7% for Trichomonas vaginalis compared with a clinical specificity of 93.3% for Candida albicans and 95.1% for Trichomonas vaginalis by culture. The prevalence of candidiasis was determined to be 42.3% (95% confidence interval [CI] 3.8%); the prevalence of trichomoniasis was 9.84% (95% CI 2.3%). In our sample, 48.7% of the women tested negative with respect to both candidiasis and trichomoniasis. Only 6.41% of the cases yielded inconclusive results. The test has high sensitivity, and our results indicate a relatively high prevalence of both infections. However, a significant difference (P < .001) was also observed in candidiasis and trichomoniasis prevalence among hospitals corresponding to the quantity of women with clinical vaginitis. No difference was observed between diabetics and nondiabetics, probably due to the special care of diabetic pregnant women. We conclude that the method is useful for this kind of vaginitis prevalence study and that candidiasis and trichomoniasis prevalences in pregnant women of Havana are 38.5% to 46.2 % (95% CI) and 7.5% to 12.1% (95% CI), respectively.     

The use of immunoenzyme analysis in the diagnosis of candidiasis in patients with different variants of hemoblastosis]

A total of 84 blood sera taken from patients with tumors of the hematopoietic system, among them 63 blood sera from patients with candidiasis and 21 blood sera from patients without symptoms of Candida infection have been tested in the enzyme immunoassay (EIA). This assay has been found suitable for the diagnosis of the visceral forms of candidiasis in patients with acute leukemia and hematosarcoma. EIA has proved to be an inadequate method for the detection of Candida infection in chronic lympholeukemia patients, as well as in patients with acute leukemia and hematosarcoma, suffering from such local forms of candidiasis as candidiasis of the oral cavity.     

Candidiasis — Do we need to fight or to tolerate the<Emphasis Type="Italic">Candida</Emphasis> fungus?

Candidiases, infections caused by germination forms of the Candida fungus, represent a heterogeneous group of diseases from systemic infection, through mucocutaneous form, to vulvovaginal form. Although caused by one organism, each form is controlled by distinct host immune mechanisms. Phagocytosis by polymorphonuclears and macrophages is generally accepted as the host immune mechanism for Candida elimination. Phagocytes require proinflammatory cytokine stimulation which could be harmful and must be regulated during the course of infection by the activity of CD8+ and CD4+ T cells. In the vaginal tissue the phagocytes are inefficient and inflammation is generally an unwanted reaction because it could damage mucosal tissue and break the tolerance to common vagina antigens including the otherwise saprophyting Candida yeast. Recurrent form of vulvovaginal candidiasis is probably associated with breaking of such tolerance. Beside the phagocytosis, specific antibodies, complement, and mucosal epithelial cell comprise Candida eliminating immune mechanisms. They are regulated by CD4+ and CD8+ T cells which produce cytokines IL-12, IFN-gamma, IL-10, TGF-beta, etc. as the response to signals from dendritic cells specialized to sense actual Candida morphotypes. During the course of Candida infection proinflammatory signals (if initially necessary) are replaced successively by antiinflammatory signals. This balance is absolutely distinct during each candidiasis form and it is crucial to describe and understand the basic principles before designing new therapeutic and/or preventive approaches.     

Chronic recurrent candidiasis of the genitalia in females due to non-albicans Candida spp.]

1346 women with the symptoms of chronic recurrent urogenital infection were examined. The diagnosis of genital candidiasis was confirmed by the clinical manifestations (not less than its 4 episodes a year) and laboratory tests: budding fungal cells, mycelium and/or pseudomyselium in the vaginal smears detected microscopically, growth of Candida spp. on the Sabouraud's medium. The species of the isolates were determined by the standard morphological and biochemical tests. The in vitro susceptibility to fluconazole and voriconazole was evaluated by the disk diffusion method (Protocol CLSI M44-A). The frequency of chronic recurrent genital candidiasis in women with chronic urogenital infection amounted to 19%. The pathogens of the disease belonged to 12 species of Candida. The main pathogen was Candida albicans (83%). Most of the isolates (88%) were susceptible to fluconazole. 99.5% of the isolates was susceptible to voriconazole. The isolates resistant to fluconazole mainly belonged to non-albicans (41% vs. 1% of Candida albicans) and were obviously more frequent under the following conditions: the age of the females above 36 years (including the periods of peri- and postmenopause), frequent relapses (at least 7 a years), atypical clinical and laboratory signs.     

Irradiation as an Alternative to Mastectomy for Early Breast Cancer—An Important Consideration Because of Changes in Laws

Between May 1973 and December 1980 there were 76 patients (78 breasts) with clinical stage I or II breast carcinoma treated by biopsy and definitive radiotherapy at Stanford University Medical Center. Local-regional control has been achieved thus far in 76 of 78 cases (97 percent) with a median follow-up time of 26 months. Transient lymphedema of the breast, arm edema and breast fibrosis were the most commonly noted complications. The cosmetic result was analyzed and scored as excellent in 78 percent, satisfactory in 18 percent and unsatisfactory in 4 percent. The three unsatisfactory results occurred in patients in whom severe fibrosis developed as a result of suboptimal radiation techniques. Interdisciplinary cooperation among surgical, medical and radiation oncologists is important. The 97 percent local-regional control and the 96 percent excellent-to-satisfactory results support the use of primary radiotherapy in early stage breast carcinoma.     

Neutrophil Fc gamma RI as target for immunotherapy of invasive candidiasis

Invasive candidiasis represents a life-threatening disease for immunocompromised patients. This study focused on new immunotherapeutic approaches for systemic Candida albicans infections in a human FcgammaRI-transgenic mouse model. FcgammaRI (CD64) is a potent immunoactivating receptor on phagocytic and dendritic cells. In vivo targeting of C. albicans toward neutrophil-FcgammaRI by bispecific Abs and G-CSF effectively protected FcgammaRI-transgenic mice from lethal candidiasis. Nontransgenic mice were not protected, and treatment with bispecific Ab or G-CSF alone did not reduce mortality. Furthermore, infected FcgammaRI-transgenic mice developed high titers of anti-C. albicans IgG, and survival was extended on secondary infection without further treatment. These findings document the capacity of FcgammaRI to initiate potent anti-C. albicans immunity and support the development of FcgammaRI-directed immunotherapy of invasive fungal disease.     

The continuous changes in the aetiology and epidemiology of invasive candidiasis: from familiar <Emphasis Type="Italic">Candida albicans</Emphasis> to multiresistant <Emphasis Type="Italic">Candida auris</Emphasis>

Recent changes in the aetiology and epidemiology of invasive candidiasis have serious implications for current and future diagnosis, treatment and prognosis. The aim of the current review was to discuss the epidemiology of invasive candidiasis, the distribution of Candida species in different regions of the world, the medical concerns of the changing aetiology and the emergence of antifungal resistance. Overall burden of invasive candidiasis remains high, especially in vulnerable persons, such as the elderly, immunosuppressed or debilitated patients. Moreover, there is a progressive shift in the aetiology of invasive candidiasis from Candida albicans to other species of Candida, probably related to the increased use of azole drugs with a clear trend towards increased antifungal resistance. Finally, the emergence and rise of multiresistant species, such as Candida auris or Candida glabrata, is a major threat making necessary invasive candidiasis worldwide surveillances. These changes have serious implications for the diagnosis, treatment and prognosis of invasive candidiasis. Updated knowledge of the current local epidemiology of invasive candidiasis is critical for the clinical management.     

Candidiasis: Predisposing Factors,Prevention, Diagnosis and Alternative Treatment

Candidiasis is the most common opportunistic yeast infection. Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. Due to rapid increase in the incidence in these infections, this is the subject of numerous studies. Recently, the focus of attention is the treatment and, above all, the prevention of those complications. The diagnosis of candidiasis could become quite complicated. Prevention is the most effective “treatment,” much more than eradication of the yeast with antifungal agents. There are several aspects to consider in the daily routine that can provide a strength protection. However, a therapeutic approach is necessary when the infection is established, and therefore, other alternatives should be explored. This review provides an overview on predisposition factors, prevention and diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.