普外科真菌感染84例临床调查

目的：探讨普外科真菌感染的现状及临床特性．为外科手术后真菌感染的防治提供参考依据。方法：回顾性调查2002年1月-2003年12月本院普外科疑似真菌感染患者的临床概况，对其中经真菌涂片、培养阳性，并伴有临床症状、体征诊断为真菌感染患者的感染类型、危险因素和病原菌分布作进一步分析。结果：①我科2年中共有242株真菌培养阳性的临床标本。其中确诊或疑诊为真菌感染者84例。感染部位以消化道最常见。病原菌以白念念珠菌最常见，占58．2％。其次为光滑念珠菌、热带念珠菌和克柔念珠菌。②外科手术、长时间用抗菌药、恶性肿瘤、胃肠外营养是最常见的危险因素，50％以上的患者存在上述情况。③与感染有关的手术类型最多见的是胰十二指肠切除术．各病种中亦以胰腺肿瘤及炎症最多。④除抗厌氧菌药物外，第三代头孢菌素、亚胺培南、去甲万古霉素是曾有真菌感染的患者最常使用的抗生素。结论：①白念念珠菌仍为外科真菌感染的主要致病菌，而非白念念珠菌感染呈上升趋势。②我院普外科真菌感染以消化道感染为主。③尽量减少手术创伤、合理使用抗生素、尽早使用肠内营养、规范各类导管操作和护理等均是真菌感染的重要预防措施。     

Treating systemic fungal infections in AIDS patients. Prolonging life against the odds

Fungal infections have become one of the major causes of death among immunocompromised patients, particularly patients with AIDS. Accurate and quick diagnosis is difficult; therefore, empirical therapy is often necessary. This scenario is complicated by the fact that most antifungal agents are toxic at the doses used or relatively ineffective against deep-seated mycoses. Because the population of AIDS patients is increasing, physicians will be faced more often with the management of systemic fungal infections. Despite the current bleak prognosis for these patients, several new antigen detection tests are being developed and triazole agents are proving to be effective and less toxic than their predecessors. Many cases of systemic mycoses do result in mortality, but appropriate treatment can both prolong life and improve its quality.     

Trichosporon species infection in bone marrow transplanted patients

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.     

Endogenous Candida endophthalmitis

Intraocular Candida infections, although uncommon, represent an important clinical problem owing to the potential for visual loss, which can be bilateral. Candida chorioretinitis and endophthalmitis are complications of systemic candidiasis with extension of the fungal pathogens to the uvea and retina. Early diagnosis and prompt management significantly affect the visual prognosis for these patients. This review evaluates the current literature on Candida endophthalmitis and includes discussion on presentation, diagnosis and management strategies. New systemic and intravitreal antifungal agents are also reviewed in the context of the management of intraocular fungal infection.     

Prevention and therapy of fungal infections in cancer patients

This review of recent publications in the field of fungal infections in cancer patients clearly confirms that protracted severe granulocytopenia is a major risk factor for their development. Because severe and prolonged granulocytopenia plays such a major predisposing role for fungal infections, it is likely that the use of the colony-stimulating factors, which are able to reduce the duration and the severity of granulocytopenia, might prove effective in decreasing the frequency and the severity of these infections. Another conclusion is that certain categories of patients with granulocytopenia might benefit from antifungal prophylaxis and empiric therapy. Conversely, there are other populations who will benefit only marginally from such strategies. Imidazoles, namely fluconazole, for the prevention of local and systemic Candida infections have been shown to be effective in granulocytopenic patients. So far, the development of resistance has not been a major problem. In patients at the greatest risk of developing severe fungal infections, such as those receiving high-dose corticosteroid therapy for GVHD after allogeneic bone marrow transplantation, early administration of low doses of amphotericin B seems to be effective in reducing the development of systemic fungal infection. In terms of therapy, amphotericin B is still the standard approach, especially for empiric treatment, prior to the recognition of a specific pathogen.     

Prevention and management of oral infections in cancer patients

 The successful prevention and management of oral infections and infections from the oral cavity in cancer patients are based on identification of risk patients, selection of patients for prophylactic measures, diagnosis of infection and implementation of directed or empiric antimicrobial therapy. Identification of patients at risk for infection is based on each patient's type of oral microbial colonization and the presence of latent viral infections. Systemic and local resistance to infection will be decisive, and in many patients the risk can be estimated from the expected myelosuppressive effect of anticancer treatment. Diagnosis of infection is often based on clinical findings together with the results of microbiological investigations. Biopsies could be useful, but can seldom be obtained. Blood samples are mandatory for isolation of microorganisms involved in systemic infections in myelosuppressed patients. Prevention of infection requires both local and systemic measures. Elimination of the risk of a breach in the first line of defence is urgent, and the maintenance of mucosal integrity is important. Monitoring microbial colonization is common, as is the institution of antiviral prophylaxis in patients with increased anti-HSV IgG (ELISA >10 000). Antifungal prophylaxis, to avoid colonization and superinfection, should be instituted in patients with low neutrophil counts. Gastrointestinal prophylaxis with quinolones is also commonly used in these patient groups. Treatment of oral infections in cancer patients should include systemic antimicrobial agents in most cases. Special attention should be directed to oral infections in neutropenic (<0.5×l0⁹/l) patients in whom oral microorganisms are the leading cause of bacteraemia. Invasive fungal infections of the oral cavity can be associated with systemic fungal infection and are indications for the use of liposomal amphotericin B. Published online: 21 May 1999     

Diagnosis and treatment of invasive fungal infections in cancer patients

Fungal infections continue to cause major complications in cancer patients. With the increasing use of aggressive chemotherapy causing prolonged granulocytopenia, and the progress made in the prophylaxis and treatment of bacterial infections, the risk of invasive mycoses has increased, particulaly in patients with hematological malignancies. The prognosis of these infections is poor unless they are diagnosed and treated promptly. Early diagnosis, particularly in neutropenic cancer patients, is often difficult and antifungal therapy is frequently unsuccessful because it is not instituted until the infection is in an advanced, fatal phase. In order to reduce the mortality associated with invasive fungal infections, antifungal therapy, usually amphotericin B, has been empirically carried out in neutropenic patients with fever unresponsive to broadspectrum antibacterial therapy. However, the absence of a marker of the fungal infection, the frequent occurrence in these patients of non-infective fever, which does not require any antimicrobial therapy, and the possible toxicity of amphotericin B represent the major limits of empiric antifungal therapy. In view of the above, the study of improved and less toxic antifungal agents, and the evaluation of new clinical and laboratory methods for an early diagnosis, have been the major goals in research on the opportunistic invasive fungal infections in the last years.Presented as an invited lecture at the 4th International Symposium: Supportive Care in Cancer, St. Gallen, Switzerland, 24–27 February 1993     

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.     

The place for itraconazole in treatment

The incidence of systemic fungal infections has risen sharply in the last two decades, reflecting a rise in the number of patients who are predisposed to these diseases because they are immunosuppressed or immunocompromised. The growing use of intensive chemotherapy to treat cancer, highly immunosuppressive drug regimens (not only in transplant recipients), widespread prophylactic or empirical broad-spectrum antibiotics, prolonged parenteral nutrition, long-term indwelling lines, improved survival in neonatal and other intensive care units, together with the AIDS epidemic have led to an upsurge in the number of patients at risk. In addition, there have been changes in the epidemiology of systemic fungal infections, with Aspergillus spp. and Candida spp. other than Candida albicans becoming increasingly common causes. These changes have affected the selection of drugs for first-line or prophylactic use, as not all agents have the critical spectrum of activity required. The management of systemic fungal infections can be divided into four main strategies: prophylaxis, early empirical use, pre-emptive and definite therapy. Antifungal prophylaxis is given based on the patient risk factors, but in the absence of infection. Empirical antifungal therapy is given in patients at risk with signs of infection of unclear aetiology (usually persistent fever) but of possible fungal origin. Therapy is given pre-emptively in patients at risk with additional evidence for the presence of an infective agent in a way predisposing for infection (e.g. Aspergillus colonization; high Candida colonization index). Finally, definite treatment is used in patients with confirmed fungal infection. The distinction between risk-adapted prophylaxis, early empirical therapy, and pre-emptive use of antifungals often becomes unclear and clinical decision making depends largely on local epidemiology and resistance patterns, adequate definition of patient risk categories, early diagnosis and the calculation of cost-benefit ratios. This article addresses the use of itraconazole in the treatment of invasive fungal infections in the haematology patient.     

1,3β-D葡聚糖检测在新生儿侵袭性真菌感染中的诊断意义

在新生儿病房中真菌成为引起院内感染常见的病原菌,对侵袭性真菌感染(IFI)的早期诊断是降低病死率的关键。血清1,3β-D葡聚糖定量检测(BG试验)对IFI的诊断具有灵敏度和特异度高的优点,可用于早期快速诊断真菌感染。动态监测有助于判断治疗效果,虽不能鉴别出所感染的真菌的属种,但并不影响对IFI的及时治疗。     

Endogenous Candida endophthalmitis

Intraocular Candida infections, although uncommon, represent an important clinical problem owing to the potential for visual loss, which can be bilateral. Candida chorioretinitis and endophthalmitis are complications of systemic candidiasis with extension of the fungal pathogens to the uvea and retina. Early diagnosis and prompt management significantly affect the visual prognosis for these patients. This review evaluates the current literature on Candida endophthalmitis and includes discussion on presentation, diagnosis and management strategies. New systemic and intravitreal antifungal agents are also reviewed in the context of the management of intraocular fungal infection.     

血流感染分子诊断的研究进展

血流感染是一种严重的全身感染性疾病,血培养仍是目前诊断细菌性血流感染的金标准,但仅有30%~40%的血流感染可通过培养发现致病菌。分子生物学方法可通过分析患者血液标本中病原微生物的核酸成分,快速提供准确的细菌、真菌或病毒感染信息,甚至提供常见病原菌的耐药基因检测结果。目前,应用于临床实验室血流感染检测的分子生物学技术主要包括核酸杂交技术、核酸扩增及DNA序列分析、基因芯片和质谱检测技术等。对常见致病菌、分枝杆菌、苛养菌、少见病原菌等使用多种检测技术联合应用进行快速鉴定及耐药分析,可以在较短时间内为临床提供可靠的诊断结果,提示临床合理用药,提高血流感染患者的存活率。     

Candida infections in the intensive care unit: epidemiology, risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice

Worldwide rates of systemic fungal infections, including three of the major pathogens responsible for such infections in North America (Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis), have soared recently, spurring interest in developing vaccines. The development of Th1 cells is believed to be crucial for protective immunity against pathogenic fungi, whereas the role of Th17 cells is vigorously debated. In models of primary fungal infection, some studies have shown that Th17 cells mediate resistance, while others have shown that they promote disease pathology. Here, we have shown that Th1 immunity is dispensable and that fungus-specific Th17 cells are sufficient for vaccine-induced protection against lethal pulmonary infection with B. dermatitidis in mice. Further, vaccine-induced Th17 cells were necessary and sufficient to protect against the three major systemic mycoses in North America. Mechanistically, Th17 cells engendered protection by recruiting and activating neutrophils and macrophages to the alveolar space, while the induction of Th17 cells and acquisition of vaccine immunity unexpectedly required the adapter molecule Myd88 but not the fungal pathogen recognition receptor Dectin-1. These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective.     

分子诊断学在细菌和真菌的血流感染检测中的应用

血流感染（bloodstream infection,BSI）是严重的感染性疾病.血液培养被认为是诊断血液感染的金标准,但是要花费数日鉴定出病原体.能够快速、准确地鉴定血流感染的病原体,可以明显改善病人预后.随着技术进步,分子诊断与临床实验室诊断关系愈加密切,能够为血流感染提供快速、准确的诊断.文章对分子诊断学在细菌和真菌性血流感染检测中的作用进行综述.     

降钙素原和超敏C反应蛋白检测在再生障碍性贫血合并肺部感染患者病原菌诊断中的意义

目的探讨降钙素原（PCT）和超敏C反应蛋白（hs-CRP）在再生障碍性贫血合并肺部感染患者病原菌诊断中的意义。方法将98例再生障碍性贫血合并肺部感染患者分为细菌感染组（n=28）、真菌感染组（n=28）、细菌合并真菌感染组（n=28）、支原体或病毒感染（n=14）,并以健康体检者作为对照组（n=28）。检测各组患者降钙素原（PCT）和超敏C反应蛋白（hsCRP）及WBC。结果与对照组比较,细菌感染组、真菌感染组、细菌合并真菌感染组患者PCT和hs-CRP均有不同程度升高,而支原体或病毒感染组的变化不明显。各感染组患者WBC明显低于对照组（P〈0.01）。与单纯真菌感染相比,革兰阳性菌和革兰阴性菌感染患者的PCT和hs-CRP均有不同程度升高,差异有统计学意义（P〈0.05）。与总体真菌感染患者比较,念珠菌感染患者PCT值高于曲霉菌感染（P〈0.05）。结论 PCT和hs-CRP检测对再生障碍性贫血合并肺部感染患者的病原菌诊断具有重要意义。     

Candida infections in the intensive care unit: epidemiology,risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

Candida infections in non-neutropenic children after the neonatal period

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.     

造血干细胞移植后早期侵袭性真菌感染的临床分析

目的:探讨更好地诊断和治疗移植后早期真菌感染。方法:分析6例异基因造血干细胞移植(HSCT)后真菌感染患者的临床特征及治疗情况,并评价疗效。结果:6例HSCT患者在移植后38～86d内发生真菌感染。6例中确诊真菌感染者2例,临床诊断2例,临床拟诊2例。病原学检测结果显示,1例确诊为中枢神经系统新型隐球菌感染,3例为念珠菌感染。6例中4例治疗有效。结论:积极预防、早期诊断及经验性或早期干预性治疗是控制HSCT后侵袭性真菌感染的关键,对提高真菌感染治疗有效率和移植后生存率具重要临床意义。     

Laboratory diagnosis of fetal infections.

In utero infections of the fetus can lead to significant morbidity and mortality in the newborn child. The signs and symptoms of clinical disease, however, do not always suggest a given pathogen. The laboratory must be able to provide an early and accurate diagnosis of the causative agent so that prompt and appropriate antimicrobial therapy and medical care can be initiated. The scope of this article includes the methods employed by the laboratory to assist in the diagnosis of bacterial, fungal, parasitic, and viral infections of the fetus. Where appropriate, detection methods were addressed for the diagnosis of the major pathogens responsible for infection during the birth process.