对1例肺隐球菌感染患者的药学监护

1例42岁女性患者,因咳嗽、咳痰伴胸闷1月余,咯血3d入院。结合肺隐球菌的病理结果,先后给予抗真菌药物氟康唑和伊曲康唑治疗。住院期间药师及时评估治疗方案,并对患者的肝肾功能监测、抗真菌药物潜在药物相互作用以及药物配制注意事项等提供药学监护。患者首次静脉滴注伊曲康唑结束后,出现一过性视物模糊,11d后再次静脉滴注自觉症状加重,第13天停药后未再出现视物模糊,考虑为伊曲康唑的不良反应。接受抗真菌药物治疗32d后,因症状较前改善,患者出院继续接受抗真菌治疗。鉴于肺隐球菌病长期正规治疗的重要性,提示患者关注氟康唑的药物相互作用,谨慎合用其他药物。     

原发性肺隐球菌病临床与病理对照观察

目的探讨原发性隐球菌病（PC）的临床表现与病理变化特点。方法对23例肺原发性肺隐球菌病临床及病理资料进行对比分析,组织化学染色及光镜观察。结果23例中8例术前经肺穿刺活检明确诊断,15例开胸探查,病理证实为此真菌病,病理诊断5例为粘液胶样病变,炎性肉芽肿病变12例,结节状纤维肉芽肿病变6例,所有病例均检出新型隐球菌并行手术病灶切除,粘液卡红（Mc）,过碘酸雪夫染色（PAS）及六胺银（GMS）组织化学染色隐球菌呈阳性。术后3例并发隐球菌性脑膜炎,占本组病例13％（3／23）,本组病例术后经6周～3个月不同疗程的抗真菌治疗,术后随诊3个月～1年,均无隐脑及肺部复发。结论PC的临床与影像学表现均无特异性,肺穿刺活检病理检查有助于此病的诊断,术后应常规抗真菌治疗,以防发生隐脑与肺部复发。     

无基础疾病的肺隐球菌性病临床分析

目的探讨无基础疾病的原发性肺隐球菌病（PC）临床特点。影像学表现及临床常用的确诊方法。方法回顾2006年至今我科确诊的无基础疾病的肺隐球菌性病10例对其临床资料及、影像学特点及确诊方法进行分析及研究。结果10例病人均青壮年,无基础疾病,男性7例,女性3例,其中1例为体检发现,其余9例仅有轻微的咳嗽、咳痰症状,体格检查均无异常发现,影像学表现为：肺结节肿、块型、肺炎型其中1例有空洞形成,2例可见“晕轮征”。8例通过经皮肺穿刺活检确诊的,2例行隐球菌乳胶凝集试验阳性诊断。8例病人给以氟康唑治疗,2例给以伊曲康唑治疗病灶均明显吸收。结论原发性肺隐球菌病临床表现缺乏特异性,随着近年来发病率的增高,特别是无基础疾病的人群中应提高诊断意识,避免误诊,并应积极开展经皮肺穿刺活检及TBLB检查,避免开胸活检。     

32例肺隐球菌病的临床分析

 目的 通过分析32例肺隐球菌病患者的临床表现、辅助检查结果、治疗及预后特点,从而提高临床上对本病的早期诊断与治疗的水平。方法 全面统计及分析我院2006年5月至2006年5月住院的32例肺隐球菌病患者的性别、年龄分布、职业情况、伴随的基础疾病、临床症状、实验室检查、影像学特征、治疗方案及预后等各方面特点。结果 肺隐球菌病发病年龄有年轻化趋势,临床特点及影像学表现缺乏特异性,极易误诊及漏诊。治疗方法及药物少,病程长。结论 肺隐球菌病虽然临床表现缺乏特异性,但从病例分析结果来看诊治该病仍有一定规律可循,亟需提高对本病的认识,遇到疑似病例应行血清乳胶凝集试验及肺活检或手术病理予以明确,药物治疗需要足够疗程。     

Cryptococcus gattii as an important fungal pathogen of western North America

Cryptococcus gattii, a pathogenic fungus historically appreciated to be endemic to tropical regions, was recognized to emerge in a more temperate zone of North America in the 1990s. Early reports focused on an outbreak that was first apparent on Vancouver Island (BC, Canada), involving both the veterinary and human population. More recently, it has been recognized that this organism is endemic to a wider geography in western North America, with recognized disease caused by unique molecular subtypes in both healthy and immunosuppressed human hosts and a variety of domestic and wild animals. A number of cases of disease caused by C. gattii isolates that are unrelated to the Vancouver Island–Pacific Northwest outbreak strains have also been recognized in different parts of the USA. As microbiology laboratories have historically not identified these organisms to the species level, our current understanding of the scope of this infection is probably an underestimate. Ongoing public health epidemiologic efforts will be facilitated by increased attention towards culture-confirmed diagnosis and species identification in clinical microbiology laboratories. Early experience presents a strong rationale for increasing diagnostic attention, with multiple clinical features that are unique to this infection, including variability in antifungal susceptibilities and a heightened need for aggressive management of inflammatory responses. Larger prospective studies to evaluate and optimize clinical management are needed.     

Parotid gland involvement in advanced AIDS

OBJECTIVE: This study describes the involvement and the histological alterations found in the parotid glands of 100 patients who died with AIDS. MATERIALS AND METHODS: Sex, age, CD4 cell count and clinical history were obtained from the files of 100 patients who died with AIDS. Histological analysis of the parotid glands was performed using H&E, Gomori-Grocott, Ziehl-Neelsen and Mucicarmine. Histological findings were grouped in reactive, infectious, cystic, neoplastic and concomitant lesions. RESULTS: None of the patients presented complaints or symptoms related to salivary gland alterations prior to death. The mean age of the patients and CD4 cell count were 36.4 years and 76.07 cells microliter-1, respectively. Histological alterations of the parotid glands were found in 51% of the patients. The most common alteration was non-specific chronic sialadenitis (29 cases), followed by infectious conditions (22 cases). Mycobacteriosis was the most common infectious disease (10 cases), followed by cytomegalovirus (nine cases), cryptococcosis (three cases) and histoplasmosis (two cases). Lymphoepithelial cysts occurred in six cases, Warthin's tumor and non-Hodgkin Lymphoma in one case each. CONCLUSIONS: These results indicate that infection and other lesions in the parotid glands are more frequent than hitherto described in the specialized literature in AIDS patients. Clinicians should consider parotid gland involvement, when evaluating disease extension in advanced AIDS patients.     

Incidence of endomycoses in the autopsy material of the Berlin Charité Hospital

From 1970 to 1993, a total of 93 endomf1p4es confirmed by post-mortem examination was diagnosed in the autopsy material of the Berlin Charité, a large hospital with an average of 1,500 hospital beds and maximum medical care. These comprised 51 candidoses (54.8%), 24 aspergilloses (36.6%), five cryptococcoses (5.4%), one zygomycosis, 1 trichosporosis and one coccidioidomycoses. This corresponded to 0.7% of the 13,375 decreased persons autopsied during this period. The frequency of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain dissection was performed. An adequate clinical putative diagnosis was made in only six out of 28 patients (18 adults, 10 children) with histologically confirmed cerebral mycosis [11 candidoses (39.3%), 10 aspergilloses (35.7%), five cryptococcoses (17.9%), one trichosporosis and one coccidioidomycosis]. About 80% of the mycoses of the CNS thus remained undetected while the patients were alive. Against the background of the continuing reduction in the frequency of autopsy in the Federal Republic of Germany, the observations made in the present paper underscore the demand for improved efficiency of mycological in-vivo diagnoses in the hospital and laboratory.     

Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.     

Systemic lupus erythematosus‐associated cutaneous cryptococcosis treated successfully with an intermittent 3‐day on/off cycle of itraconazole

We describe a case of systemic lupus erythematosus (SLE)‐associated cutaneous cryptococcosis. A 32‐year‐old woman with SLE and lupus nephritis presented with the erythematous maculae on the chest and the extremities, in which encapsulated yeasts were revealed, and was diagnosed with secondary cutaneous cryptococcosis. We administered fluconazole (FLCZ) and then itraconazole (ITCZ) instead of amphotericin B (AMPH‐B) to avoid the risk of renal toxicity of AMPH‐B in the patient. While treatment with FLCZ was not particularly effective, repeated intermittent administration of ITCZ on a “3‐day on/off cycle” (i.e. medication on 3 consecutive days and suspension for the next 3 days in turn) achieved complete remission of the cryptococcosis.     

IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans

We examined the role of IL-12 in host resistance to Cryptococcus neoformans using a murine model of pulmonary and disseminated infection. In this model, mice were infected intratracheally with viable yeast cells. Mice untreated with IL-12 allowed an uncontrolled multiplication of yeast cells in the lung with infiltrations of few inflammatory cells, and a cryptococcal dissemination to the brain and meningitis by 3 weeks, resulting in death of all animals within 4–6 weeks. IL-12, when administered from the day of tracheal infection for 7 days, induced a marked infiltration of inflammatory cells, consisting mostly of mononuclear cells, and significantly reduced the number of viable yeast cells in the lung. The treatment suppressed brain dissemination, as shown by a marked reduction of yeast cells in the brain and prevention of meningitis. These effects resulted in a significant increase in the survival rate of infected mice. In contrast, late administration of IL-12 commencing on day 7 after instillation of yeast cells failed to protect the mice against infection with C. neoformans. In further experiments, early administration of IL-12 markedly induced interferon-gamma (IFN-γ) mRNA in the lungs of infected mice, while no IFN-γ mRNA was detected without this treatment. Our results indicate that IL-12 is effective when administered in the early period of pulmonary cryptococcal infection.