与支原体肺炎感染相关的急性呼吸窘迫综合征

1. Introduction

     M. pneumoniae a respiratory pathogen transmitted from person to person via respiratory droplets evolves as both endemic and epidemic infection. The incubation period prior to symptom emergence may be short or as long as 3 weeks. M. pneumoniae is one of the most common causes of lower respiratory tract infections (LRTI) and accounts for up to 40% of LRTI in the community. M. pneumoniae infection may be asymptomatic and when symptomatic is usually mild, causing upper and/or lower respiratory tract symptoms, often self-limiting. Therefore, the term “walking pneumonia”has been widely used by physicians . M. pneumoniae is much less often involved in severe forms of LRTI as a recent report from the Centers for Disease Control and Prevention, estimated only 2% of detectable pathogens in hospitalized community-acquired pneumonia (CAP) adults patients were due to M. pneumoniae . We report a genuine ARDS due to M. pneumoniae infections whose outcome was favorable.

1. 前言

    肺炎支原体作为一种通过呼吸道飞沫，人与人传播的呼吸道病原体，可发展为地方性和流行性传染。其潜伏期可能很短，也可能长达3周。肺炎支原体是下呼吸道感染最常见的原因之一，占社区下呼吸道感染的40%。肺炎支原体感染可能无症状，当通常症状轻微时，引起上呼吸道和/或下呼吸道症状，常自限。因此,“游走性肺炎”这个词已被内科医生广泛使用。支原体肺炎很少出现严重的下呼吸道感染，美国疾病控制和预防中心的最近一份报告显示，住院社区获得性肺炎(CAP)成人患者中可检测到的病原体估计只有2%是由支原体肺炎造成的。我们报告一例真实的急性呼吸窘迫综合征（ARDS），病因是肺炎支原体感染，其治疗效果良好。

2. Case report

       A 60 years old womanwith post anoxic motor infirmity, living in nursing home, was admitted for acute respiratory failure. Few days prior to admission, she presented abdominal pain and high-grade fever with cough. Her relatives reported an outbreak lower respiratory infection in her nursing home in the past weeks. She has no significant past history of respiratory illness. Physical examination showed superficial polypnea (respiratory rate≥50/min). Chest radiograph showed bilateral extensive infiltrates (Fig. 1). She deteriorated rapidly and necessitated intubation and mechanical ventilation. The PaO 2 /FiO 2 ratio was 65 at 11 cm H 2 O positive end-expiratory pressure. Diagnostic work up of this ARDS did not reveal any extra-pulmonary causal disorder. Intravenous broad-spectrum antibiotics (cefotaxime and spiramycin) were immediately started to cover both pneumococcus and atypical pathogens.

（图 1）

2. 病例汇报

患者，女，60岁，在养老院居住，患有缺氧性运动障碍，因急性呼吸衰竭入院。入院前几天，患者表现为腹痛、高热、咳嗽。其家属陈述：几周前在养老院突发下呼吸道感染，无明显的呼吸道疾病史。体格检查出现浅表呼吸暂停(呼吸频率≥50次/分钟), 饱和度极低(带高浓度氧气面罩情况下血氧饱和度 80%)。胸片X线显示双侧弥漫性浸润(图1)。患者病情恶化迅速，需要插管和机械通气。PaO 2 / fio2比值为65压力。诊断ARDS时未发现肺外因果障碍。立即使用静脉注射广谱抗生素(头孢噻肟和螺旋霉素)，以覆盖肺炎球菌和非典型病原体。

Blood investigations showed 4.83/ m L white blood cell count, mainly formed of neutrophils (3.09/µL) elevated C-reactive protein (263 mg/L) and procalcitonin (2.7µg/L), with normocytic anemia (hemoglobin 11.1 g/dL, MGV 92 fl); platelet 70 cells/mm 3 , BUN 13.9 mmol/L; serum creatinine 93 µmol/L; ASAT 121 IU/L; LDH 456 IU/L. Tracheo-bronchial aspirates obtained on admission, detected Mycoplasma pneumonia by universal polymerase chain reaction (PCR). Blood and urine cultures were negative. Legionella and pneumococcal urinary antigens were negative. According to international guidelines, sedation, prone position, inhaled NO and corticosteroids were administered. Outcome was favorable and the patient was weaned from the ventilator on day 9 and discharged from the ICU on day 13 without residual permanent damage. Serologic tests carried out on admission and 3 weeks after discharge showed 4-fold increase antibodies and the presence of anti M. pneumoniae IgM antibodies.

血液分析显示白细胞计数为4.83/ml，主要是中性粒细胞（3.09/µL），C反应蛋白升高(263 mg/L)和降钙素原(2.7 µg/L)，伴正常细胞性贫血(血红蛋白11.1 g/dL, MGV 92 fl)，血小板70个/mm ³，尿素氮13.9mmol/ L，血清肌酐93 µ mol/L，ASAT 121 IU / L;LDH 456 IU/ L。入院时行气管-支气管吸入，通用聚合酶链反应(PCR)检测肺炎支原体。血和尿培养阴性。军团菌和肺炎球菌尿抗原呈阴性。根据国际指南，行镇静、俯卧位、吸入NO和糖皮质激素。效果良好，患者于第9天停用呼吸机，并第13天离开重症监护室，无永久性损伤。入院时行血清检查，出院3周后检测结果：抗体四倍增加，且存在抗肺炎支原体IgM抗体。

3. Discussion

ARDS caused by M. pneumoniae has rarely been described. In the present case we could establish a rapid and definite diagnosis of M. pneumoniae infection in a patient with ARDS, on the basis of positive PCR together with a negative diagnostic assessment for alternative etiologies.

In 1995 Chan and Welsh reviewed the English-language literature on severe M. pneumoniae CAP from 1966 to 1991 and found a total of 46 cases,13 of which presenting fatal respiratory failure . The average age in this series was 35 years. Miyashita et al. Reported a series 227 cases of M. pneumoniae CAP, of which 13 presented acute respiratory failure . No mortality was reported. Chaudhry et al. reported a genuine ARDS caused by M. pneumoniae and found 10 similar cases in the English literature from 1995 to 2010 . More recently Izumikawa, summarized the Japanese literature from 1979 to 2010 and found a total of 52 cases, 2 of which presenting fatal respiratory failure [9]. As in the previous series, the dominant population was young adults (mean age 42.3 years) without severe underlying diseases. The average duration from onset of infection to the development of respiratory failure was 11.2 days (range, 5e21 days).

2. 讨论

我们很少报道由肺炎支原体引起的急性呼吸窘迫综合征。在本病例中，我们可以建立一个快速明确诊断--急性呼吸窘迫综合征的肺炎支原体感染，此诊断的前提是PCR阳性，其他病因诊断评估阴性。

1995年陈和威尔斯回顾了有关1966 - 1991年的肺炎支原体严重感染的社区获得性肺炎的英语文献，共46例，其中13例表现为致命性呼吸衰竭。文章中涉及到的患者平均年龄是35岁。Miyashita等人报道227例肺炎支原体感染的社区获得性肺炎病例，其中13例出现急性呼吸衰竭。无死亡报告。乔杜里等人报道了一例由肺炎支原体引起的真正的急性呼吸窘迫综合征，1995年至2010年英语文学中发现有10个类似案例。最近，泉川1979年至2010年日本文学进行总结，共发现52例病案报告，其中2例临床表现为致命呼吸衰竭。在以往文献中，占主导地位的人群为青壮年(平均年龄42.3岁)，无严重的潜在疾病。从感染开始到发生呼吸衰竭的平均持续时间为11.2天(范围: 5e21天)。

One of the reasons for the scarcity of reports on M. pneumoniae related ARDS is that ARDS carries a high mortality rate. This indeed does not allow firmly establishing the diagnosis of M. pneumoniae infection when the diagnosis relies on paired antibody titers that require several weeks to show seroconversion. Our case as other recent reports suggest that rapid, accurate, and readily available diagnostic test such as multiplex PCR assay for detection of five pneumonia-causing bacteria may improve detection of M. pneumoniae in ARDS patients .

急性呼吸窘迫综合征相关的支原体肺炎报道较少的原因之一是其死亡率高。当诊断依赖需要数周才能显示血清转换的成对抗体滴度时，确实不能确定肺炎支原体感染的诊断。我们的报告和其他最近报告一样，建议快速、准确和容易获得诊断试验，如用于检测五种引起肺炎的细菌多重PCR法，可提高急性呼吸窘迫综合征患者的肺炎支原体的检出率。

Several factors may account for the severity of pneumonia caused by M. pneumoniae. Delayed administration of adequate antibiotics has been suggested to contribute to the severity of M. pneumoniae pneumonia. Antibiotic resistance although uncommon at least in Europe and northern America may be suspected in case of unresponsiveness to macrolides, although delayed response in the absence of resistance has been reported . Possible co-infection with other respiratory pathogens, such as S. pneumoniaewarrants systematic search for alternative pathogens in severe cases . Hyper-activated cell-mediated immunity may have a strong impact on the course of disease development following M. pneumoniae infection and several authors highlighted the need for steroid administration, early in the course of the disease, at least in severe cases in order to reduce the immune-mediated pulmonary injury .

有几个因素和由肺炎支原体引起重型肺炎有关。延迟给足够的药抗生素是导致严重支原体肺炎的原因之一。尽管至少在欧洲和北美不常见，但在大环内酯无反应的情况下，抗生素耐药性可能被怀疑，尽管在没有耐药性的情况下有延迟反应的报道。可能与其它呼吸道病原体合并感染，像肺炎链球菌，它需要系统寻找其它病原体严重者。过度激活的细胞介导免疫可能对继肺炎支原体感染之后的疾病发展进程有很大影响，许多学者强调疾病早期，以降低免疫力-介导的肺损伤需要注射类固醇。

All these factors argue for the need of antibiotic regimens including M. pneumoniae in their spectrum in severe CAP and also for rapid definite etiologic work-up of severe CAP, including rapid diagnostic tools such as multiplex PCR assay for detection of pneumonia-causing Last, the severity of pulmonary disease caused by M. pneumoniae can dependent on the capacity of various strains to produce the recently discovered, community-acquired respiratory distress syndrome (CARDS) toxin . Although we could not investigate CARDS toxin production in our case, future epidemiologic investigations regarding CARDS toxin production may be helpful in understanding clinical characteristics of M. pneumoniae infections.

所有这些因素都表明需要进行抗生素治疗，包括严重社区获得性肺炎谱系中的肺炎支原体，还需要快速明确病原检查严重社区获得性肺炎，包括像多重PCR检测的快速诊断工具，由肺炎支原体引起的肺炎严重程度取决于不同菌株的能力，以产出最近发现的社区获得性呼吸系统窘迫综合征（CARDS）毒素。虽然在我们的病例报告中，调查不出CARDS毒素产生情况，但是有关产素的未来流行病研究，可能有助于了解支原体肺炎感染的临床特征。