肾移植术后马尔尼菲篮状菌肺部感染1例

通过回顾1例肾移植术后肺部感染马尔尼菲篮状菌受者的临床病例资料及诊疗过程, 探讨肾移植术后马尔尼菲篮状菌病(peniciliosis marneffei, PSM)的临床诊断及治疗。本例既往存在肺结核病史, 因尿毒症行肾移植手术, 术后恢复良好出院, 7个月时出现反复咳嗽。纤维支气管镜及肺部CT检查均提示肺结核可能, 最终经肺泡灌洗液二代测序检测及病原菌培养确诊PSM。经调整免疫抑制药物并使用伏立康唑规律抗真菌治疗, 呼吸道症状改善, 肺部CT检查示病灶吸收。提示马尔尼菲篮状菌肺部感染可能出现与肺结核类似的纤支镜表现及影像学征象, 早期的病原学培养及二代基因测序有助于诊断, 伏立康唑等抗真菌药物对于该病治疗有效。     

慢性肾脏病者伴肺孢子虫肺炎漏诊分析

目的探讨慢性肾脏病者伴肺孢子虫肺炎（PCP）漏诊原因。方法回顾性分析3例漏诊的慢性肾脏病伴PCP患者的临床症状、影像学及实验室检查资料,并分析漏诊原因。结果本组3例,IgA肾病2例,肾淀粉样变性病1例。临床表现为发热、咳嗽、胸闷,2例出现Ⅰ型呼吸衰竭,1例出现低氧血症。3例均应用激素治疗,2例同时应用环磷酰胺（CTX）。2例诊断为肺部急性细菌性感染,1例诊断为肺部支原体感染。入院时3例X线征象均不典型,2例有典型CT征像。确诊时2例有典型X线征象,3例有典型CT征象。3例常规痰培养均未发现伊氏肺孢子菌,支气管肺泡灌洗液吉姆萨染色涂片发现伊氏肺孢子菌或痰聚合酶链反应（PCR）法检测伊氏肺孢子菌虫体DNA（＋）。给予卡泊芬净及复方磺胺甲噫唑治疗均治愈。结论PCP是接受激素和（或）CTX治疗的慢性肾脏病患者肺部机会感染之一,早期胸部X线和CT征像常不典型,典型的X线或CT征像对PCP的诊断具有重要意义。接受激素和（或）免疫抑制剂治疗的慢性肾脏病患者若出现发热、抗细菌感染治疗效果不佳,应尽早行痰或支气管肺泡灌洗液吉姆萨染色找伊氏肺孢子菌或PCR法检测伊氏肺孢子菌虫体DNA。     

宏基因组二代测序在鲍曼不动杆菌肺炎混合感染者诊疗中的应用

目的探讨宏基因组二代测序(mNGS)技术对重症监护病房鲍曼不动杆菌肺炎混合感染者诊疗的应用价值。方法回顾性收集扬州大学附属医院2019年1月至2021年5月同时行肺泡灌洗液mNGS技术和传统病原检测的84例肺炎患者的基本资料、细菌培养以及mNGS检测结果、抗菌药物应用等。根据鲍曼不动杆菌感染的诊断标准和mNGS检测结果,将入组患者分为定植菌组(25例)、单一感染组(29例)和混合感染组(30例)。炎性指标、辛普森菌群多样性指数(SDI)、抗菌药物使用时间、使用强度、费用和总药费为正态分布的计量资料,采用t检验或ANOVA检验分析;患者年龄分布、基础疾病、发热时间分布、不同临床疗效和治疗转归占比均采用[例(%)]表示,组间比较采用卡方检验。结果入组的84例患者传统病原和mNGS检测鲍曼不动杆菌均为阳性,其中25例鲍曼不动杆菌定植和59例鲍曼不动杆菌肺炎患者;男性44例、女性40例,年龄[65.4(62,68)]岁。mNGS检测中,30例[50.85%(30/59)]检出混合感染;传统病原检测中,3例[5.08%(3/59)]检出混合感染,显著低于mNGS检测,差异有统计学意义(χ^(2)=30.667、P<0.001)。mNGS检出混合感染居前3位的病原体分别为人疱疹病毒(7例)、肺炎链球菌(5例)和耶氏肺孢子虫(5例)。定植菌组、单一感染组和混合感染组患者SDI分别为(0.77±0.11)、(0.38±0.16)和(0.34±0.17),差异具有统计学意义(F=65.411、P<0.001)。单一感染组与混合感染组患者白细胞计数(t=2.211、P=0.031)、中性粒细胞比率(t=2.068、P=0.043)、C-反应蛋白(t=2.024、P=0.048)、抗菌药物费用(t=2.279、P=0.026)、抗菌药物使用强度(t=2.161、P=0.035)、住院天数(t=2.664、P=0.010)、总药费(t=2.397、P=0.020)和体温降至正常时间(t=-2.178、P=0.034)差异均有统计学意义。单一感染组患者治疗显效率高于混合感染组(82.76%vs.56.67%,χ^(2)=4.735、P=0.047)。结论肺泡灌洗液mNGS技术在检测鲍曼不动杆菌肺炎混合感染方面优势明显,能够辅助临床优选抗菌药物,促进患者康复。     

慢性肾脏病合并肺孢子虫肺炎诊治分析

目的：提高对慢性肾脏病（CKD）患者合并肺孢子虫肺炎（PCP）的认识。方法：回顾性分析4例CKD合并PCP患者的临床症状、影像学及实验室资料,分析诊断及治疗转归情况。结果：4例临床均表现为发热、咳嗽、胸闷等,3例出现Ⅰ型呼吸衰竭,1例顽固性低氧血症。其中3例支气管肺泡灌洗液痰姬姆萨染色找到伊氏肺孢子菌,1例支气管肺泡灌洗液痰PCR检测伊氏肺孢子菌虫体DNA（＋）。4例中IgA肾病2例,肾淀粉样变性1例,膜性肾病1例。4例均应用激素治疗,有2例同时应用环磷酰胺（CTX）,激素及CTX均为常规用法、用量。4例均予卡泊芬净及复方磺胺甲唑治疗,均好转出院,无副反应。结论：PCP是接受激素和（或）CTX治疗的CKD患者肺部机会感染之一。典型的胸部X线尤其是CT征像对PCP的诊断具有重要意义,但早期胸部X线和CT征像多不典型。对接受激素和（或）CTX治疗的CKD患者,如出现发热、进行性呼吸困难,应尽早行痰或支气管肺泡灌洗液姬姆萨染色涂片找伊氏肺孢子菌或PCR检测伊氏肺孢子菌虫体DNA。卡泊芬净及复方磺胺甲唑治疗PCP效果均明确,无明显副作用,卡泊芬净可以作为治疗PCP的首选药物。     

抗干扰素γ自身抗体综合征导致哥伦比亚分枝杆菌播散性感染一例

目的探讨抗干扰素(IFN)γ抗体综合征导致非结核分枝杆菌(哥伦比亚分枝杆菌)播散性感染的临床特点和治疗方法。方法1例66岁的老年女性因“反复发热伴淋巴结肿痛6个月”于2020年11月21日至深圳市第三人民医院住院治疗。分析该例IFN-γ抗体综合征导致的哥伦比亚分枝杆菌播散性感染者的临床诊疗经过,并行相关文献复习。结果该患者于外院行淋巴结活检组织、肺泡灌洗液宏基因组二代测序(mNGS)检测均提示哥伦比亚分枝杆菌感染。正电子发射计算机断层显像(PET-CT)示多处淋巴结肿大伴代谢升高,全身多处骨质破坏,右肺上叶前段病变伴高代谢。查体:全身皮疹,多处浅表淋巴结肿大,部分溃破伴少量脓液。入院查患者外周血:免疫球蛋白G定量、免疫球蛋白A定量、T淋巴细胞绝对计数、CD4^(+)T和CD8^(+)T细胞计数均正常。患者血液标本行IFN-γ抗体检测滴度为32700 ng/ml(正常值<5000 ng/ml),确诊为抗IFN-γ自身抗体免疫缺陷综合征导致的哥伦比亚分枝杆菌播散性感染。给予抗哥伦比亚分枝杆菌治疗,并给予丙种球蛋白和激素治疗,患者皮疹消退,破溃淋巴结愈合,肿大淋巴结明显缩小,病情好转,门诊继续给予抗非结核分枝杆菌治疗并随访。结论临床上对于非结核分枝杆菌播散性感染者,需要考虑到IFN-γ抗体综合征的可能,应行IFN-γ抗体检测,在针对病原体治疗的同时需进行免疫治疗。     

细小脲原体导致腹膜透析相关性腹膜炎1例

病原体检出对改善腹膜透析相关性腹膜炎患者的预后非常重要。该文报道1例采用宏基因组二代测序(metagenomics next-generation sequencing, mNGS)技术诊断由细小脲原体导致的腹膜透析相关性腹膜炎病例。患者为中年女性, 因腹痛伴透出液浑浊入院, 头孢他啶联合万古霉素等抗感染治疗效果不佳, 传统离心法培养未见细菌生长, 采用mNGS技术检出细小脲原体, 改用多西环素抗感染治疗后患者炎症得到控制, 提示mNGS技术对常规培养阴性的腹膜透析相关性腹膜炎患者病原体的检出有重要价值。该文通过病例报道结合文献复习, 为此类患者的诊治提供了临床经验。     

Carinii肺孢子虫肺炎的诊断与治疗

目的 提高对肾脏疾病并发Carinii肺孢子虫肺炎（CPP）的认识。方法 回顾性分析6例肾脏疾病并发CPP患者的资料。结果 6例PCP基础疾病为肾移植，狼疮性肾炎，急进性肾炎，临床表现为发热，咳嗽，呼吸困难，血气分析为I型呼吸功能衰竭。其特点为自觉症状严重，低氧血症发展迅速，但肺部体征很少。胸片表现为双肺广泛斑状浸润。痰和支气管肺泡灌洗液中发现Carinii肺孢子虫。治疗首选复方新诺明（SMZCO)，早期使用皮质类固醇药物，可加用胸腺肽。6例中4例死亡，2例治愈。结论 根据临床表现，结合胸片的动态变化，对PCP的诊断有重要价值；对可疑性病例应及早进行支气管肺泡灌洗液检测病原体；早期诊断并以SMZCO为主的综合治疗，可提高治愈率。     

肺空洞表现的裂褶菌感染2例

肺部普通裂褶菌感染病例在临床上少见, 而以肺空洞为首发影像学表现的病例几乎无报道。本文报道2例以肺空洞为首发表现的裂褶菌感染病例, 均为支气管镜肺泡灌洗液宏基因二代测序明确裂褶菌感染, 经治疗后好转, 供临床参考。     

实时荧光PCR在艾滋病合并肺孢子菌肺炎诊断中的应用

目的 应用实时荧光PCR 技术与六甲基四胺银(GMS)染色法对艾滋病合并肺孢子菌肺炎(PCP)患者支气管肺泡灌洗液(BALF)中的肺孢子菌进行检测,比较两种检测方法的性能.方法 应用实时荧光PCR 技术与GMS染色对57例艾滋病合并肺部感染患者的BALF标本进行肺孢子菌检测,比较两种方法的检测效果.结果 收集本院18例艾滋病合并肺部感染患者的支气管灌洗液标本,采用实时荧光PCR技术检测肺孢子菌DNA,结果显示13例为阳性,阳性率为72.3%(13/18).阳性标本肺孢子菌 DNA定量为1.35 × 103～8.24 × 105 拷贝/ml,平均(1.2 ± 2.13)× 105 拷贝/ml;而GMS染色镜下检测,阳性率为72.3%(13/18),二者具有极高的一致性.收集广州市第八人民医院39例艾滋病合并肺部感染患者的支气管灌洗液标本,实时荧光PCR检测肺孢子菌DNA结果显示21例为阳性,阳性率为53.8%(21/39);而用GMS染色镜下检测,阳性率仅为2.5%(1/18).在标本量少的情况下,实时荧光肺孢子菌方法检测肺孢子菌的敏感性远高于GMS染色法.结论 对艾滋病合并肺孢子菌感染患者支气管灌洗液的肺孢子菌检测中,荧光肺孢子菌与GMS染色有极高的一致性,且敏感性明显高于后者.实时荧光肺孢子菌方法可快速、灵敏、特异性、定量地检测肺孢子菌 DNA,在PCP的诊断、治疗方案选择和疗效观察方面有重要的临床意义.     

肾移植术后并发卡氏肺孢子虫肺炎

目的:探讨肾移植术后并发卡氏肺孢子虫肺炎(PCP)的临床特征。方法:报告5例肾移植术后并发PCP患者的临床资料。PCP发病于术后第95~172天。3例患者经支气管镜肺泡穿刺活检和支气管肺泡灌洗确诊,2例通过诊断性治疗确诊。根据肾功能及耐受情况予以复方新诺明(SMZ50~70mg·kg~(-1)·d~(-1),TMP10~14mg·kg~(-1)·d-1)治疗3周,同时根据患者外周血CD4 /CD8 计数及比值调整免疫抑制方案。结果:5例患者均治愈。结论:PCP确诊有赖于肺组织活检找到病原体,必要时诊断性治疗不失为有效方法。治疗首选复方SMZ,但剂量应结合患者肾功能和耐受情况,并根据患者免疫状态适当减少免疫抑制剂用量。     

Diagnostic studies in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a clinical-radiological diagnosis. Clinical diagnosis comprises severe hypoxemia assessed by arterial oxygen tension/fraction of inspired oxygen ratio of less than 200 and bilateral infiltrate on a chest radiograph in the absence of left atrial hypertension. The sensitivity and specificity of the clinical diagnosis vary based on the underlying etiology for ARDS. Except for presence of bilateral infiltrate on chest radiograph and severe hypoxemia on arterial blood gas, most diagnostic studies are used to exclude mimics of ARDS and potentially modify treatment. Computerized tomography of the chest is helpful in understanding the extent of the disease and is more sensitive in identifying pneumomediastinum and pneumothoraces seen frequently in patients with ARDS, which can be missed on a chest radiograph, especially if they are small in size. Measurements of alveolar dead space ventilation fraction can be helpful in determining the prognosis in individuals with ARDS. Bronchoalveolar lavage, transbronchial lung biopsy, and open lung biopsies can be safely performed in patients with ARDS. Bronchoalveolar lavage fluid in patients with ARDS shows neutrophil predominance with increased edema fluid to serum protein ratio. Diffuse alveolar damage, a pathognomic of ARDS, is seen on histopathology on transbronchial lung biopsy or open lung biopsy. Most common complications of these procedures include transient hypoxemia, respiratory acidosis, and pneumothorax with occasional persistent air leak. The potential risk of diagnostic studies should be balanced against the possible foreseeable benefits of the diagnostic studies.     

Lipoprotein macroaggregates in bronchoalveolar lavage fluid from patients with diffuse interstitial lung disease: comparison with idiopathic alveolar lipoproteinosis.

Lipoprotein macroaggregates were present in cytocentrifuge preparations of bronchoalveolar lavage fluid from four patients with diffuse lung diseases other than idiopathic alveolar lipoproteinosis. In three patients the primary diagnosis was cryptogenic fibrosing alveolitis and in one sarcoidosis. We confirmed the presence of large multilamellar aggregates of lipoprotein by ultrastructural examination in patients with both interstitial lung disease and idiopathic alveolar lipoproteinosis. The small lamellar bodies and amorphous debris found in idiopathic alveolar lipoproteinosis were rare in the patients with interstitial lung disease. The lavage fluid from patient with interstitial lung disease did not show the substantial alterations in phospholipid composition that were seen in lavage fluid in idiopathic alveolar lipoproteinosis. These ultrastructural and biochemical features may help to distinguish idiopathic from other causes of alveolar lipoproteinosis, particularly at an early stage, when differential diagnosis may be difficult.     

副百日咳鲍特菌合并肺炎支原体感染一例并文献复习

目的探讨副百日咳鲍特菌感染的临床及病原学特点。方法收集2020年9月14日就诊于湖北省天门市第一人民医院1例副百日咳鲍特菌合并肺炎支原体感染患儿的病例资料,分析该病例的病程记录和实验室对病原菌的分离鉴定过程并复习相关文献。结果患儿、女、1岁3个月,临床表现为咳嗽、气喘等,轻度吸气三凹征,双肺呼吸音粗糙,可闻及中量哮鸣音、少许湿啰音,实验室检查白细胞计数:12.49×10^(9)/L、红细胞计数:4.36×10^(12)/L、中性粒细胞占比58.4%、血小板计数:260×10^(9)/L、血清铁:7.5μmol/L、肌酐:26.5μmol/L、总二氧化碳:19.6 mmol/L、总钙:2.76 mmol/L、羟丁酸脱氢酶:291 U/L、乳酸脱氢酶:310 U/L、肌酸激酶同工酶:25.20 U/L、肌酸激酶:308 U/L;肺炎支原体IgM抗体:弱阳性。患者胸部影像学CT显示右上肺见片状高密度影。痰培养分离菌经蛋白飞行时间质谱(MALDI-TOF MS)鉴定为副百日咳鲍特菌。该患儿经抗感染治疗后好转出院。结论副百日咳鲍特菌感染相对少见,尽早行病原学诊断对其有效治疗具有重要意义。     

A case of diffuse alveolar hemorrhage developing after open heart surgery

A 47-year-old man was receiving anticoagulant therapy after coronary artery bypass grafting and mitral valve plasty. A chest roentgenogram disclosed alveolar infiltrates throughout both lung fields 6 months postoperatively. Lung biopsy specimens showed the presence of hemosiderin-laden macrophages in the alveolar spaces, establishing a diagnosis of diffuse alveolar hemorrhage. Anticoagulant therapy may have caused the hemorrhage, because the patient had no immunologic disorder or renal disease. The shadows completely disappeared after steroid therapy and discontinuation of anticoagulant therapy. Diffuse alveolar hemorrhage should be considered, when extensive infiltrates develop on chest roentgenogram in patients receiving anticoagulant therapy after open heart surgery. Lung biopsy is essential, when a bronchoalveolar lavage fails to diagnose the disease.     

Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.

Pulmonary function, chest radiographic appearances, and the cellular composition of bronchoalveolar lavage fluid were assessed in 13 patients who were receiving amiodarone treatment. Eight of the patients had developed clinical and radiological evidence of lung disease and five were symptom free. The proportions of lymphocytes (mean 8.6 (SD 6.9)) and neutrophils (mean 3.4 (3.3)) obtained by bronchoalveolar lavage were similar in patients with and without lung complications. Electron microscopic examination of alveolar macrophages showed intralysosomal inclusion bodies in all subjects, regardless of clinical state. There was no significant difference in the mean number of inclusion bodies per macrophage transection between those with and those without lung disease. The differential cell count in bronchoalveolar lavage fluid and the presence of macrophage inclusion bodies were therefore not useful as markers of disease activity. Among those who developed clinical and radiological evidence of lung disease, the cumulative drug dose per kilogram of body weight and the duration of treatment (mean 16.5 (SD 9.0) months) were significantly correlated with the degree of lung restriction as measured by total lung capacity and forced vital capacity. It is concluded that, while the severity of the restrictive pulmonary defect that is induced by amiodarone is largely dose related, the development of lung toxicity is to some extent idiosyncratic.     

Cytopathology of pulmonary alveolar proteinosis complicating lung transplantation.

Pulmonary alveolar proteinosis is a disorder of unknown origin that occurs rarely after lung transplantation. We identified a patient with pulmonary alveolar proteinosis 66 days after undergoing single lung transplantation for idiopathic pulmonary fibrosis. We based the diagnosis on the presence of amorphous clumps or globules of acellular and finely granular material in bronchoalveolar lavage fluid (BALF). This material persisted for an 18.5-month period and was present in 9 of 14 lavage specimens. However, despite its presence in the native lung at autopsy, the material was seen in only 1 of 14 transbronchial lung biopsy specimens. Although uncommon, pulmonary alveolar proteinosis can be diagnosed readily in BALF by its distinctive cytopathologic features and should be considered in the differential diagnosis of pulmonary disease in lung transplant recipients.     

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression. Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.     

宏基因组二代测序技术在假体周围感染病原诊断中的应用

目的探讨基于假体周围组织的宏基因组二代测序技术(metagenomic next-generation sequencing,mNGS)在关节置换术后假体周围感染(periprosthetic joint infection,PJI)的诊断效率和价值。方法回顾性分析2019年6月至2020年6月接受髋或膝关节翻修术33例患者的病历资料。诊断为PJI的病例设为感染组共21例,男9例,女12例;年龄(59.14±14.55)岁(范围:28~84岁);膝关节17例,髋关节4例;体质指数(body mass index,BMI)为(23.7±2.8)kg/m²(范围:17.7~29.4 kg/m²)。诊断为假体无菌性松动的病例设为对照组共12例,男4例,女8例;年龄为(53.08±10.05)岁(范围:39~70岁);膝关节4例,髋关节8例;BMI为(25.2±2.9)kg/m²(范围:18.3~31.2 kg/m²)。收集所有病例关节液和组织微生物培养的结果,收集所有病例mNGS检测假体周围组织的结果。比较微生物培养和mNGS检测对膝或髋关节PJI诊断的敏感性和特异性,总结和比较两种技术检出致病菌的种类,比较取样前2周内抗生素的使用对两种技术检出率的影响。结果感染组21例中mNGS共检出13例阳性,微生物培养共检出6例阳性。对照组12例中mNGS仅检出1例阳性,微生物培养结果均为阴性。在PJI的诊断中,mNGS敏感性(61.9%)与微生物培养(28.6%)的差异有统计学意义(χ2=4.71,P=0.03);mNGS特异性(91.7%)与微生物培养(100%)的差异无统计学意义(χ2=1.04,P=0.31)。在2周内有抗生素暴露的PJI病例中,mNGS阳性率(53.8%)明显高于微生物培养(15.4%),差异有统计学意义(χ2=4.25,P=0.04);而在2周内无抗生素暴露的PJI病例中,mNGS阳性率(66.7%)与微生物培养(44.4%)的差异无统计学意义(χ2=0.90,P=0.34)。在致病菌检出上,mNGS共检出9种细菌(金黄色葡萄球菌、科氏葡萄球菌、奥斯陆莫拉菌、痤疮丙酸杆菌、毗邻颗粒链菌、表皮葡萄球菌、结核分枝杆菌、里昂葡萄球菌、脆弱拟杆菌)和2种真菌(烟曲霉菌、近平滑念珠菌);微生物培养共检出3种细菌(金黄色葡萄球菌、卡他莫拉菌、结核分枝杆菌)和1种真菌(近平滑念珠菌)。mNGS和微生物培养均为阳性的患者共5例,3例检出完全一致的致病菌(金黄色葡萄球菌、结核分枝杆菌、近平滑念珠菌),1例部分一致(mNGS检出更多致病菌),1例完全不同。另外,mNGS在3例结核性PJI的诊断中表现出100%的特异性和敏感性,优于微生物培养。结论基于假体周围组织的mNGS检测技术是诊断PJI和确定致病菌的有效手段。取样前抗生素暴露对mNGS技术检出效力的影响小于微生物培养。