涉及临床各科的侵袭性真菌感染

真菌数量大、种类多、分布广。真菌感染因菌种的毒力、感染途径和宿主免疫状态等差异而出现不同的临床表现,临床各科医生都会遇到真菌病患者。真菌病的诊断取决于在病变组织内发现病原真菌成分如菌丝和(或)孢子。从病变组织中分离出真菌是菌种鉴定前提,也是抗真菌治疗的依据。“重视临床、强调菌学”是医学真菌研究的基本思路。真菌学家应该在联系临床与实验室中起关键作用。     

Invasive fungal infection in patients with systemic lupus erythematosus: Experience from a single institute of Northern China

Invasive fungal infection (IFI) is a life-threatening infection occurring most often in patients with systemic lupus erythematosus (SLE) and few data has been reported in SLE patients particularly in China. This present study was aimed to determine IFI prevalence, associated risk factors and patterns of infection in Chinese SLE patients. A retrospective study was conducted in a single institute of Northern China from July 2004 and October 2010. Demographic characteristics, clinical and laboratory data, and mycological examinations were collected. Among 1534 patients included, 20 (1.6%) were diagnosed with IFI, of whom there were 18 females and 2 males with the average age of 35.4±15.1years old. Involved sites included nine lungs, six central nervous system and five disseminated cases. 6 of 20 IFIs cases (30%) were non-survivors including 2 lungs, 2 central nervous system and 2 disseminated cases. Compared with survivors, non-survivors had significantly higher equivalent prednisone doses, elevated level of serum C reactive protein (CRP), higher erythrocyte sedimentation rate (ESR), higher thrombocytopenia rate and higher systemic lupus erythematosus disease activity index (SLEDAI) score. These results strongly demonstrated that prednisone doses, CRP, ESR, thrombocytopenia and SLEDAI could be associated risk factors in the prognosis of SLE patients with IFI.     

Interdigital and foot fungal infection in patients with onychomycosis

In patients with onychomycosis (OM) 71.5% of them have been reported with plantar fungal infection. The aim of this study was to study the frequency and distribution of plantar and interdigital affection in diabetic patients and in a control group without diabetes, all of them with OM. Diabetic patients with OM were more frequently diagnosed with plantar (61.2%) than interdigital (46.7%) infection. In the control group similar results were obtained; patients with OM in 76.5% had plantar mycotic infection and 67.1% interdigital involvement.     

Invasive fungal infections in solid organ transplant recipients

Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Development of invasive disease hinges on the interplay between host factors (e.g., integrity of anatomical barriers, innate and acquired immunity) and fungal factors (e.g., exposure, virulence and resistance to prophylaxis). In this article, we describe the epidemiology and clinical features of the most common fungal infections in organ transplantation. Within this context, we review recent advances in diagnostic modalities and antifungal chemotherapy, and their impact on evolving prophylaxis and treatment paradigms.     

Cytomegalovirus infection of the thyroid in immunocompromised adults

Cytomegalovirus (CMV) inclusions were discovered at autopsy in the thyroid follicles in five immunocompromised adults, four of whom had acquired immune deficiency syndrome (AIDS). Although reports of viral infections of the thyroid are uncommon in adults, our experience suggests that the thyroid gland may be commonly involved in patients with disseminated CMV, and the possibility exists that CMV infection of the thyroid has the potential to cause clinical dysfunction.     

Invasive fungal infections in critically ill patients: different therapeutic options and a uniform strategy

The high morbidity, mortality, and healthcare costs associated with the invasive fungal infections, especially in the critical care setting, is of importance since the prophylactic, empiric, and pre-emptive therapy interventions, based on early identification of risk factors, is of common occurrence. In the last years alone there have been important developments in antifungal pharmacotherapy. Evidence-based studies using new antifungal agents are now emerging as important players in the pharmacotherapy of invasive fungal infections in seriously ill and difficult patients. However, data on critically ill patients are more limited and usually recovered from general studies. This study shows the benefits obtained by the new antifungal agents on different clinical situations in critical care units. The increasing number of non-C. albicans species and the high mortality rates in these settings suggest that the application of early de-escalation therapy in critically ill patients with fungal infection should be mandatory. The possibility of using antifungal combination therapy in these types of patients should be considered.     

肝移植患者真菌感染的流行病学特点及耐药性分析

目的了解肝移植术后真菌感染的种类及耐药特性,为临床治疗提供依据。方法分析2003年6月至2006年6月,我院67例肝移植患者术后感染的标本,鉴定真菌种类,分析其耐药性。结果67例肝移植患者有21例发生真菌感染,占肝移植患者的31.3%;共检出73株真菌,以酵母菌感染为主,占98.6%,其中近平滑念珠菌、白色念珠菌、热带念珠菌、季也蒙念珠菌、克柔念珠菌的检出率分别是53.4%、21.9%、9.6%、8.2%、2.7%。曲霉菌感染1例。药敏试验显示73株真菌对两性霉素B(AMB)、5-氟胞嘧啶(5-FC)、制霉菌素(MYS)、酮康唑(KTC)、益康唑(ECO)和咪康唑(MIC)的平均敏感率分别为98.6%、95.7%、87.1%、70.0%、65.7%和64.3%。结论加强肝移植术后真菌的鉴定和耐药性监测,对指导临床治疗具有重要意义。     

76例恶性肿瘤患者院内深部真菌感染调查

目的探讨深部真菌感染对于恶性肿瘤患者的影响,以及住院期间应注意的问题。方法调查分析2005年1月到2008年12月期间住院的76例恶性肿瘤患者院内深部真菌感染情况,分析患者一般状态、诊治方法的影响。结果76例患者中真菌感染的部位以呼吸道为主（70．9％）,泌尿系次之（17．7％）;病原学检测标本共培养出真菌79株,以白色念珠菌占第1位（60．8％）,热带念珠菌占第2位（21．5％）;老年（≥60岁）、一般状态评分（Ps评分）〉2分、晚期肿瘤差异均有显著性;多数有侵入性操作者（100％）、经过抗生素治疗者（97．4％）、经过激素治疗者（90．8％）和经过放化疗治疗者（82．9％）。结论肿瘤患者的年龄、病情分期、一般状态是本组病例发生院内深部真菌感染的基本病因,抗生素不合理使用及住院期间侵入性操作、既往放化疗及激素治疗等医疗措施是院内深部真菌感染的危险因素。     

Factors influencing Pneumocystis infection in the immunocompromised rat.

A compromised immune system is the primary predisposing condition for Pneumocystis infection. Factors that contribute to this underlying state of immunosuppression are poorly understood. The presence of common rodent viruses and the role of anti-Pneumocystis antibodies on the progression of natural infection in the corticosteroid-treated rat model of Pneumocystis pneumonia were evaluated. The development and intensity of infection were not affected by the presence or absence of antibodies to these viruses or to major Pneumocystis antigens. A significant increase in survival of Pneumocystis-infected viral antibody-positive rats was observed when these rats were housed under barrier conditions.     

艾滋病合并真菌感染研究概述

真菌感染是艾滋病患者最常见、比重最大的机会性感染,是最重要致死原因之一。常见的机会性真菌感染包括：念珠菌病、卡氏肺孢子菌病、隐球菌病、马尔尼菲蓝状菌感染、组织胞浆菌病、球孢子菌病。本文介绍了机体的CD4⁺T淋巴细胞与机会性真菌感染关系以及常见的真菌感染的流行病学、发病机制、临床表现、诊断、治疗、预防等方面研究进展。提高临床医生对这类真菌感染系统全面的认识,有助于做到早期诊断、早期治疗,合理选择抗真菌药物,从而提高患者生存质量,延长生存时间。     

血液系统肿瘤患者侵袭性肺部真菌感染的外科手术治疗

目的探讨怀疑肺部有侵袭性真菌感染(invasivefungalinfection,IFI)的血液恶性肿瘤患者行手术切除肺部病灶的安全性及有效性。方法分析2005年4月～2009年7月之间因血液系统肿瘤合并疑似侵袭性肺部真菌感染而接受肺切除术的10名患者,总结术后并发症及死亡率来探讨手术的有效性和安全性。结果手术均在全身麻醉下进行,5例为胸廓切开术,5例为胸腔镜下手术。3例为病灶楔形切除术,7例为肺叶切除术。术后组织病理:确诊真菌感染6例(60%),慢性细菌感染1例,3例未见明确病原菌。术后4例出现并发症:3例为轻度并发症(30%),其中2例气胸后自行吸收,1例局限性肺不张;1例严重并发症为血胸(10%)。术后30d死亡率为10%。术后真菌复发率为16%。随访至2009年8月31日,中位随访时间为3.8个月(0.7～31.1个月),4例(40%)死亡,但手术相关死亡率为0%。结论手术切除不仅有助于明确诊断而且还可以清除病灶、防止IFI复发和允许进一步的免疫抑制治疗,手术本身是安全的。     

Multicentric and localized tineas in immunocompromised patients

From the dermatological point of view, multifocal or multicentric tineas are widespread dermatophytic infections affecting two or more anatomical areas. In the immunosuppressed patient, these lesions are frequently atypical and the risk factors are not well established. The aims of this study were: to determine the risk factors associated to multicentric tinea in immunocompromised patients; to evaluate the immune response by trichophytin and candidin skin test, to determine the etiological agent and to quantify some serum interleukines. Thirty-six multicentric tinea and 37 localized tinea patients, both with immunocompromised factors, were included. By means of a questionnaire several risk factors were identified; the trichophytin and candidin skin test was evaluated after 48 hours. Mycological direct examination and culture were performed. The interleukins IL-2, IL-4, IL-10 and interferon gamma were quantified by ELISA. Statistical analysis was made by Chi-square, U Mann Whitney and logistic regression. In disseminated tinea patients a predominance of females (69%) versus localized tinea patients (30%) was observed. Prednisone, azathioprine and cyclophosphamide treatment was associated to multicentric tinea. Trichophytin was negative in all disseminated tinea patients and positive in only three localized tinea cases, candidin was positive in six and eight cases of multicentric and localized tinea respectively. Trichophyton rubrum was the most frequent etiological agent. No differences in interleukin concentrations were found. Female gender and some immunosuppressor treatments were associated with a high probability to develop multicentric tinea. In this study a defect in the cellular immune response was the possible explanation for the extensive reactions.     

The role of IgG avidity determination in diagnosis of Epstein-Barr virus infection in immunocompetent and immunocompromised patients

There is a high degree of variability in the serologic response to Epstein-Barr virus (EBV) infection, especially in viral capsid antigen (VCA)-IgM antibodies. Therefore, additional tests are needed to confirm primary infection. We evaluated the value of IgG avidity determination in diagnosis of EBV infection in immunocompetent and immunocompromised patients. A total of 236 serum samples from immunocompetent patients with symptoms suggestive of EBV infection were tested for the presence of VCA-IgM/IgG antibodies and IgG avidity. Using IgG avidity, acute primary infection was confirmed in 56.7% of the immunocompetent patients with positive and in 1.8% of patients with negative VCA-IgM. Recent primary infection was documented in 8.9% of the IgM positive and 3.5% of the IgM negative patients. In patients with indeterminate serology (equivocal IgM), 6.7% were classified by avidity index (AI) as acute primary infection, 10.0% as post-acute and 83.3% as past infection cases. Concerning the 32 immunocompromised patients, recent primary infection was documented in 3 of the 14 IgM positive patients. High AI was detected in 11 of these patients, indicating an IgM response due to reactivation. Determination of IgG avidity in combination with classical serologic markers seems to be a reliable method to confirm primary infection both in immunocompetent and immunocompromised patients. It may be especially useful to differentiate cases of primary infection in patients with undetectable VCA-IgM antibodies or indeterminate routine EBV serology.     

Combination of sepsis biomarkers may indicate an invasive fungal infection in haematological patients

Background: Invasive fungal infections are a major threat to a large cohort of immunocompromised patients, including patients with chemotherapy-associated neutropenia. Early differential diagnosis with bacterial infections is often complicated, which leads to a delay in empirical antifungal therapy and increases risk for adverse outcome. Accessibility and performance of specific fungal antigen and PCR-tests are still limited, while sepsis biomarkers are more broadly used in most settings currently.

Methods: Haematological patients hospitalized to receive chemotherapy with proven or probable invasive fungal infection or microbiologically proven bacterial bloodstream infection were included in the study. C-reactive protein was assessed daily during the profound neutropenia period, while procalcitonin or presepsin were measured during the first 48?hours after the onset of febrile episode.

Results: There were totally 64 patients included in the study, 53 with bacterial bloodstream infections and 11 with invasive fungal infections. Combination of CRP >120 with PCT <1.25 or presepsin <170 was shown to be a possible combined biomarker for invasive fungal infections in immunocompromised patients, with areas under the ROC-curves: 0.962 (95% CI 0.868 to 0.995) for PCT-based combination and 0.907 (95% CI 0.692 to 0.990) for presepsin-based combination.     

Strategies to enhance T-cell reconstitution in immunocompromised patients

Immune deficiency, together with its associated risks such as infections, is becoming an increasingly important clinical problem owing to the ageing of the general population and the increasing number of patients with HIV/AIDS, malignancies (especially those treated with intensive chemotherapy or radiotherapy) or transplants (of either solid organs or haematopoietic stem cells). Of all immune cells, T cells are the most often affected, leading to a prolonged deficiency of T cells, which has important clinical consequences. Accordingly, strategies to improve the recovery and function of T cells, as we discuss here, should have a direct impact on reducing the morbidity and mortality of many patients and should increase the efficacy of therapeutic and prophylactic vaccinations against microbial pathogens or tumours.