艾滋病合并新型隐球菌肺炎和新型隐球菌脑膜炎2例

新型隐球菌(Cryptococcus neoformans)广泛存在于自然界土壤中,鸽粪为隐球菌的重要传染媒介[1],当机体免疫功能低下时,经呼吸道进入体内,导致肺、骨、皮肤及中枢神经系统感染,主要引起新型隐球菌脑膜炎(Cryptococcus meningitis).新型隐球菌也是艾滋病合并机会感染的常见机会感染真菌.本文报告我院2005年10月至2007年8月收治的540例艾滋病患者中,2例合并新型隐球菌肺炎、新型隐球菌脑膜炎.……     

肾移植术后受者新型隐球菌感染的临床分析

目的分析肾移植术后患者新型隐球菌感染的临床特点。方法回顾性分析9例肾移植术后新型隐球菌感染受者的临床资料,包括受者的感染部位、临床表现、真菌学、组织病理学、影像学检查结果及治疗经过和转归。结果 9例肾移植受者术后常规应用他克莫司(FK506)+吗替麦考酚酯(MMF)+泼尼松三联免疫抑制治疗。发病中位时间为术后6(1～13)年。其中单纯隐球菌性脑膜炎1例、隐球菌性脑膜炎合并隐球菌肺炎5例、单纯隐球菌肺炎2例、皮肤隐球菌病1例。隐球菌肺炎临床多表现为发热、咳嗽、咳痰、气促及胸痛等症状,胸部CT示结节、胸腔积液等。主要经肺穿刺活组织检查(活检)及肺泡灌洗液墨汁负染色确诊。隐球菌性脑膜炎患者临床表现以发热、阵发性头痛伴呕吐症状居多,主要经血培养及脑脊液墨汁负染色确诊。皮肤隐球菌病表现为右肩部包块,经皮肤活检确诊。所有患者分别给予两性霉素B、氟康唑等规范抗真菌治疗,免疫抑制剂减量治疗。9例受者中1例死亡,其余受者预后情况良好。结论肾移植术后受者新型隐球菌感染多发生于术后中晚期,临床症状缺乏特异性,对怀疑隐球菌病者应及时做血培养、肺穿刺活检、脑脊液等检查以确诊。规范抗真菌治疗可降低病死率。     

HIV感染与非HIV感染患者新型隐球菌脑膜炎临床特点比较

新型隐球菌广泛分布在自然界中,可引起人类感染,大多经呼吸道吸入,在肺部引起轻度炎症,或隐性传染,亦可由破损皮肤及肠道传人.当机体免疫功能下降时可向全身播散,主要侵犯中枢神经系统.新型隐球菌感染的风险因素包括HIV感染、肝硬化、糖尿病、实体器官移植、恶性肿瘤、类风湿性疾病、皮质激素的使用和慢性肾脏疾病等¨].在未知或没有免疫抑制的人群中,也会发生隐球菌感染[2].在HIV感染高流行区,新型隐球菌性脑膜炎发病率高,且预后差.艾滋病患者并发隐球菌脑膜炎的病死率为9％ ～ 55％,非HIV感染者病死率为15％ ～44％[3].新型隐球菌脑膜炎的诊断和治疗对临床医师来说仍是一个挑战.本研究比较分析我院非HIV感染与HIV感染患者新型隐球菌脑膜炎的临床特点,为提高疾病的诊治水平积累经验.     

类似结核的HIV相关隐球菌肺病三例临床分析

国内关于非HIV感染隐球菌肺炎的临床及影像学特征已有较多描述,该类人群隐球菌感染常累及肺下叶,影像学特征多表现为结节或团块状阴影,然而全身播散导致隐球菌性脑膜炎并不常见[1-3].相比之下,HIV相关隐球菌肺病容易播散,导致隐球菌性脑膜炎,肺部影像学主要表现为弥漫性间质浸润影,严重时可致急性呼吸衰竭[4-6].肺部影像学表现类似结核的HIV相关播散性隐球菌病在国内鲜见报道.本文报道3例类似播散性结核的HIV隐球菌肺病,重点关注肺部影像学特征,加强临床医师对该病的认识.     

隐球菌性脑膜炎病原治疗的护理

对84例隐球菌性脑膜炎患者采用两性霉素B行病原治疗，强调其护理重点是给药护理、特殊护理、情感支持、人文关怀、健康教育、出院指导等，结果65例患者治愈无复发，12例好转，7例死亡。提示预防隐球菌性脑膜炎感染的关键是落实一级预防措施。     

获得性免疫缺陷综合征合并隐球菌性脑膜炎患者的眼部护理

目的总结获得性免疫缺陷综合征（AIDS）合并隐球菌性脑膜炎患者的眼部并发症及眼部护理方法。 方法回顾性分析42例AIDS合并隐球菌性脑膜炎患者的眼部并发症,总结其护理方案。 结果19例患者（37只眼）出现视乳头水肿,6例患者（12只眼）出现视神经萎缩,2例患者（4只眼）出现脉络膜病灶,3例患者（6只眼）出现复视,1例患者单眼合并巨细胞病毒性视网膜炎（CMVR）。11例患者眼底正常。42例患者（84只眼）中17只眼视力为光感～0.1,12只眼视力为0.12～0.3,视力≤ 0.3的患眼占总数的34.5%,55只眼视力为0.4～1.0。 结论临床护理工作中应密切观察患者的颅内压、视力及眼底变化,对低视力患者加强生活技能及视力的训练,有利于控制病情,提高患者的生活质量。     

脑脊液半胱氨酸蛋白酶抑制剂C在隐球菌性脑膜炎中临床价值的探讨

目的 探讨脑脊液半胱氨酸蛋白酶抑制剂C(cystatin C)在隐球菌性脑膜炎(CM)中的临床应用价值.方法 前瞻性观察和对比分析本院2007年1月~2011年5月所收治的隐球菌性脑膜炎(n = 14)、单纯结核性脑膜炎(n = 61)和结核性脑膜脑炎患者(n = 37)脑脊液cystatin C水平及相关生物化学指标的差异.结果 隐球菌性脑膜炎患者脑脊液cystatin C水平(3.18 ± 1.14 mg/L)显著低于单纯结核性脑膜炎的患者(4.62 ± 1.42 mg/L)(P< 0.01),而与结核性脑膜脑炎患者脑脊液cystatin C水平(3.68 ± 1.42 mg/L)相比,差异无统计学意义(P> 0.05);CM组的其他脑脊液生化标志物,如糖(Glu)、氯化物(Cl-)、总蛋白(TP)、腺苷脱氨酶(ADA)、乳酸(LAC)、C-反应蛋白(CRP)和微量蛋白(mALB)等,与其他两组比较均无统计学意义(P> 0.05).HIV(+)的隐球菌性脑膜炎患者(6例)cystatin C水平为(3.48 ± 1.16 mg/L),与HIV(-)隐球菌性脑膜炎组(8例)(2.96 ± 1.15 mg/L)相比,差异无统计学意义(P> 0.05).结论 脑脊液cystatin C可作为脑膜疾病鉴别诊断的一种新的标记物,有利于隐球菌性脑膜炎与结核性脑膜炎的鉴别,但其与结核性脑膜脑炎的鉴别诊断应慎重考虑.     

脑脊髓液中腺苷脱氨酶活性对结核性脑膜炎诊断价值的临床研究

目的 探讨脑脊髓液中腺苷脱氨酶（CSF-ADA）活性对结核性脑膜炎的诊断价值及在病程中的动态变化.方法 选择160例患者纳入本研究,76例结核性脑膜炎为病例组;84例非结核性脑膜炎为对照组,其中细菌性脑膜炎36例,病毒性脑膜炎30例,隐球菌性脑膜炎18例.每例患者均于治疗前抽取CSF,采用酶耦联Trinder法测定CSF-ADA活性,结果以（-x）±s表示,组间差异使用Mann-Whitney U检验.47例结核性脑膜炎患者于抗结核治疗后2周和6周时再次检测CSF-ADA,治疗前后差异使用配对t检验.结果 结核性脑膜炎组CSF-ADA活性为（12.9±6.4）U/L,非结核性脑膜炎组为（6.0±4.1）U/L,两组比较差异有统计学意义（U=7.860,P＜0.05）.取CSF-ADA≥9 U/L作为临界值时鉴别结核性脑膜炎与非结核性脑膜炎价值最高,灵敏度为84.21%,特异度为83.33%.随着患者病情好转,CSF-ADA活性逐渐降低.结论 CSF-ADA活性≥9 U/L可作为诊断结核性脑膜炎的一项辅助诊断指标,抗结核治疗后CSF-ADA活性可作为疗效判断的参考指标.     

新型隐球菌性脑膜炎的护理体会

隐球菌性脑膜炎是较少见的神经系统真菌性脑膜炎。本病随着抗生素、激素类药物的大量、广泛应用,发病率有逐渐增高的趋势。本病发病隐袭、进展缓慢、病程长,其临床症状并无特异性,常有头痛、恶心、发热等,重症患者治疗及护理较为复杂。我院自1969～1986年共收治7例,其中2例为新型隐球菌性脑膜炎,现从护理角度总结如下:     

隐球菌性脑膜炎病原治疗的护理

对84例隐球菌性脑膜炎患者采用两性霉素B行病原治疗,强调其护理重点是给药护理、特殊护理、情感支持、人文关怀、健康教育、出院指导等,结果65例患者治愈无复发,12例好转,7例死亡.提示预防隐球菌性脑膜炎感染的关键是落实一级预防措施.     

二代测序技术应用于脑脊液检测在结核性脑膜炎中的早期诊断价值

目的评价二代测序技术应用于脑脊液检测在结核性脑膜炎（TBM）患者中的早期诊断价值。 方法前瞻性纳入2018年2月2日至2018年8月2日于山东省胸科医院就诊的临床怀疑TBM的患者共50例,并跟踪随访其诊疗结局。送检脑脊液标本均进行二代测序,测序所得原始序列与病原微生物数据库进行对比得到最终结果。二代测序结果以检测到结核分枝杆菌复合群唯一比对序列为阳性,未检测到唯一比对序列为阴性。以符合脑脊液结核分枝杆菌培养阳性、涂片阳性、Xpert MTB/RIF检测阳性及结核分枝杆菌核酸检测阳性等4项中至少1项即为确诊TBM患者;临床可疑TBM且抗结核治疗有效为临床诊断患者;有其他病原学依据或临床排除TBM者为非TBM患者。分析二代测序在TBM早期诊断中的敏感性和特异度。 结果确诊为TBM患者22例中Xpert MTB/RIF检测阳性13例,培养阳性6例,结核分枝杆菌核酸PCR检测阳性5例,临床诊断为TBM患者12例,非TBM患者16例。在确诊及临床诊断患者中,二代测序技术检测到结核分枝杆菌复合群系列20例,敏感性为58.8%（20/34）,特异度为100%（16/16）。在确诊患者中,二代测序的敏感性为63.6%（14/22）;在同步进行结核分枝杆菌培养、Xpert MTB/RIF检测与二代测序的50例标本中,以临床诊断为标准,3种方法的特异度均为100%（16/16）;传统方法、Xpert MTB/RIF检测及二代测序的敏感性分别为29.4%（10/34）、38.2（13/24）和58.8（20/34）,前两种检测方法与二代测序敏感性差异均有统计学意义（McNemar检验：χ² = 8.333、P = 0.013,χ² = 8.333、P = 0.065）。传统方法与二代测序联合检测的敏感性高达82.4%（28/34）。 结论二代测序技术能够较快速地检测脑脊液中的结核分枝杆菌复合群,且其敏感性和特异度均较高,可作为TBM的早期诊断指标。二代测序联合传统检测方法可提高检出率。     

Cryptococcal meningitis in an immunocompetent patient with obstructive hydrocephalus: A case report

Background

Cryptococcal infections of the central nervous system are very rare in immunocompetent patients. They usually present as meningitis or as fungal cysts with or without hydrocephalus. Rapid diagnosis and treatment is crucial to the prognosis.

A case of cryptococcal meningitis with nephrotic syndrome and renal insufficiency under immunosuppressive therapy

A 76 year-old woman was admitted to our hospital because of pyrexia and fatigue. One year earlier, she was diagnosed as nephrotic syndrome(NS) caused by focal segmental glomerulosclerosis and immunosuppressive therapy was started with marked amelioration of proteinuria. Thereafter, her renal function worsened, but only supportive treatment was continued. After admission, a cerebrospinal fluid (CSF) examination revealed Cryptococcus neoformans (C. neoformans) by india ink staining and a subsequent CSF culture confirmed C. neoformans infection. Accordingly, we made the diagnosis of cryptococcal meningitis and immediately started multiple anti fungal drugs with dosage modification according to her impaired renal function. Immunosuppressive therapy for NS was temporarily terminated. The inflammatory signs and symptoms soon were markedly improved, but the anti cryptococcal antibody titer in the serum and CSF remained high. Immunosuppressive therapy was started again at a low dosage because urinary protein had increased again. One hundred and eight days from admission, she was discharged with a regimen of multiple anti fungal drugs. Proteinuria and renal insufficiency was almost stable during hospitalization. Most fungal infection develops in patients in an immunosuppressive state induced by immunosuppressive drugs, HIV infection and so on. Patients with NS are frequently in an immunosuppressive state because of urinary loss of immunoglobulins and the use of immunosuppressive drugs. Therefore, it should be remembered that patients with NS are at a high risk of suffering from fungal infection.     

Bacterial meningitis in HIV patient: think about co-infections!

The authors report the case of an African 34-year-old patient who was admitted to the intensive care unit for bacterial meningitis due to Streptococcus pneumoniae. A meningeal co-infection due to Cryptococcal neoformans was found the 3rd day in an HIV infection context. Cryptococcus neoformans detection in cerebrospinal fluid, using the India-ink stain, has a low sensibility which imposes the search of cryptococcal antigen and the culture of cerebrospinal fluid. These last two exams have a sensibility of at least 90%.     

Cryptococcal peritonitis in patients on peritoneal dialysis

Peritonitis is an unusual complication of infections caused by Cryptococcus neoformans and has rarely been reported in patients with end-stage renal disease who are maintained on peritoneal dialysis. We report two patients on chronic peritoneal dialysis in whom the first known manifestation of cryptococcal infection was dialysate cultures positive for Cryptococcus neoformans. One patient was on prednisone for systemic lupus erythematosis. The other patient was severely malnourished with type I diabetes mellitus. Both patients were found to have cryptococcal meningitis. Both patients were treated with intravenous (IV) amphotericin B and removal of the dialysis catheter. Evaluation and care of peritoneal dialysis patients with cryptococcal peritonitis include serial cryptococcal cultures and antigen titers, investigation for cryptococcal meningitis, removal of the peritoneal dialysis catheter, and IV amphotericin B.     

Sensitivity and specificity of a latex agglutination test for detection of cryptococcal antigen in meningitis

A cryptococcal latex agglutination test (Crypto-La; International Biological Laboratories, Canbury, New Jersey, USA) was evaluated for its ability to detect cryptococcal antigen in cerebrospinal fluid (CSF) specimens obtained from black patients with a clinical diagnosis of meningitis. Of the 445 Gram-stained and bacterial culture-negative CSF specimens routinely tested for cryptococcal antigen, 34 (7,6%) were positive. With the exception of 1 false-positive result, the remaining 33 specimens were obtained from 12 patients in whom the diagnosis of cryptococcal meningitis was confirmed by the isolation of Cryptococcus neoformans. The Crypto-La test gave false-positive results on 1% (4/384) of control CSF specimens tested. Nonspecific agglutination reactions were observed with 1,6% (13/829) of all CSF specimens and 22% (10) of sera tested. The ethylenediaminetetra-acetic heat-extraction method proved reliable in eliminating false-positives and nonspecific agglutination reactions in CSF and serum specimens.     

The use of ventriculoperitoneal shunts for uncontrollable intracranial hypertension without ventriculomegally secondary to HIV-associated cryptococcal meningitis

BACKGROUND: The risks associated with implanting a cerebrospinal fluid (CSF) shunt in immunocompromised patients with ongoing CSF infection have historically discouraged surgeons from implanting CSF shunts in patients with HIV and cryptococcal meningitis. However, this patient population often requires frequent lumbar punctures to manage elevated intracranial pressure (ICP) secondary to cryptococcal infection. To date, only 7 cases of ventriculoperitoneal (VP) shunting for the treatment of intracranial hypertension in patients with HIV-associated cryptococcal meningitis have been reported. Few of these reports have included outcomes more than 3 months postsurgery. It remains unclear if VP shunts are an effective long-term treatment of intracranial hypertension in this patient population. CASE DESCRIPTIONS: Two patients with HIV/AIDS (CD4 counts of 8 and 81 cells/mm(3)) presented with altered mental status, visual changes, florid cryptococcal meningitis, and elevated ICP (>500 mm CSF) without evidence of hydrocephalus on computed tomography scan. Both patients experienced rapid reversal of symptoms with external lumbar CSF drainage, and remained lumbar drain-dependent after 2 weeks of amphotericin B and flucytosine therapy. Despite evidence of unresolved cryptococcal meningitis, each patient underwent implantation of a VP shunt without complication and was discharged on lifetime fluconazole therapy. They remained asymptomatic at 12 and 16 months after surgery without evidence of shunt infection or malfunction. CONCLUSION: Patients with intracranial hypertension and HIV-associated cryptococcal meningitis who cannot tolerate cessation of external lumbar CSF drainage or frequent lumbar punctures may be considered for VP shunt placement despite severe immunosuppression and persistent CSF cryptococcal infection.     

27例隐球菌性脑膜炎患者的临床分析

目的探讨隐球菌性脑膜炎的临床特征,以提高该病的诊治水平及预后。 方法回顾性分析复旦大学附属华山医院收治的27例诊断为隐球菌性脑膜炎患者的临床资料。 结果88.89%（24例）隐球菌性脑膜炎患者以头痛为首发症状;脑脊液糖（1.81 ± 0.69 mmol/L）降低尤为显著;若并发颅神经损害,多累及视神经和听神经;头颅CT或MR可见脑缺血病灶（37.04%）及软脑膜不同程度强化灶（59.26%）;所有患者均有不同程度的颅内压增高,病原学脑脊液墨汁染色阳性患者22例（占81.48%）,隐球菌培养阳性患者20例（占74.07%）,荚膜多糖抗原检测（乳胶凝集试验）阳性占100%;两性霉素B（AmpB）联合5-氟胞嘧啶（5-FC）治愈好转率100%（17/17）,AmpB + 5-FC +氟康唑治疗的4例患者中好转3例。 结论隐球菌性脑膜炎早期误诊率较高,脑脊液墨汁染色、隐球菌乳胶凝集试验及培养有助于确诊;两性霉素B联合5-氟胞嘧啶仍是目前经典的抗真菌治疗方案,两性霉素B与伊曲康唑联合治疗方案有待大样本的临床验证;早期控制真菌及颅高压是改善预后关键,必要时可尽早外科干预。     

89例新型隐球菌性脑膜炎的临床分析

目的：分析两性霉素B和（或）氟康唑联合氟胞嘧啶治疗新型隐球菌性脑膜炎（CNM）的疗效。方法回顾性分析89例住院CNM患者的临床资料及治疗情况。结果患者首发症状多表现为头痛（89/89,100.0%）和呕吐（62/89,69.7%）。发热、头痛、呕吐和脑膜刺激征为该病主要临床表现。CNM确诊前怀疑为结核性脑膜炎19例,占21.3%;怀疑为巨细胞病毒脑炎8例,占8.9%。经两性霉素B和（或）氟康唑联合氟胞嘧啶抗真菌治疗后,66例好转、治愈,20例自动出院,3例死亡。结论 CNM易出现误诊,两性霉素B和（或）氟康唑联合氟胞嘧啶抗真菌治疗疗效显著。     

Ventriculoperitoneal shunt for hydrocephalus secondary to tuberculous meningitis: a case report

A case of hydrocephalus secondary to tuberculous meningitis is reported. A 6-month-old baby was admitted to our hospital with a 10-day history of high fever. Neurological examination revealed no abnormal findings other than neck stiffness. Cerebrospinal fluid findings suggested tuberculous meningitis, because of pleocytosis (608/mm3, 100% lymphocytes) and reduced sugar content (19 mg/dl). Mycobacterium tuberculosis was found in cerebrospinal fluid culture. Although anti-tuberculous therapy was administered for 2 weeks, deterioration of consciousness and papilledema appeared. CT scan demonstrated enlargement of the entire ventricular system, indicating communicating hydrocephalus. After a ventricular drainage was performed, consciousness disturbance improved, but the high fever persisted. Judging by cerebrospinal fluid findings, the meningitis seemed to be in the active stage. Therefore an Ommaya reservoir was installed instead of a cerebrospinal fluid shunt for fear of disseminating the tuberculous infection through the shunt tube. However, the hydrocephalus was not well controlled. Consequently, a ventriculoperitoneal shunt was placed, despite the fact that the disease was still active. The fever then gradually subsided, and cerebrospinal fluid findings normalized. The patient was discharged without any neurological deficits one month after emplacement of the ventriculoperitoneal shunt. The antituberculous therapy has been continued, and there is no sign of infection propagated through the shunt 13 months following discharge from the hospital. The result suggests that a cerebrospinal fluid shunt can be placed for hydrocephalus even in the active stage of tuberculous meningitis under antituberculous therapy.