與支原體肺炎感染相關的急性呼吸窘迫綜合征
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
肺炎支原體作為一種通過呼吸道飛沫，人與人傳播的呼吸道病原體，可發(fā)展為地方性和流行性傳染,。其潛伏期可能很短，也可能長達3周,。肺炎支原體是下呼吸道感染最常見的原因之一，占社區(qū)下呼吸道感染的40%,。肺炎支原體感染可能無癥狀,，當通常癥狀輕微時，引起上呼吸道和/或下呼吸道癥狀,，常自限,。因此,“游走性肺炎”這個詞已被內(nèi)科醫(yī)生廣泛使用。支原體肺炎很少出現(xiàn)嚴重的下呼吸道感染,，美國疾病控制和預防中心的最近一份報告顯示，住院社區(qū)獲得性肺炎(CAP)成人患者中可檢測到的病原體估計只有2%是由支原體肺炎造成的,。我們報告一例真實的急性呼吸窘迫綜合征（ARDS）,，病因是肺炎支原體感染，其治療效果良好,。
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.
（圖 1）
2. 病例匯報
患者,，女，60歲,，在養(yǎng)老院居住,，患有缺氧性運動障礙，因急性呼吸衰竭入院,。入院前幾天,，患者表現(xiàn)為腹痛、高熱,、咳嗽,。其家屬陳述：幾周前在養(yǎng)老院突發(fā)下呼吸道感染，無明顯的呼吸道疾病史,。體格檢查出現(xiàn)淺表呼吸暫停(呼吸頻率≥50次/分鐘), 飽和度極低(帶高濃度氧氣面罩情況下血氧飽和度 80%),。胸片X線顯示雙側彌漫性浸潤(圖1)?；颊卟∏閻夯?/span>迅速,，需要插管和機械通氣。PaO 2 / fio2比值為65壓力,。診斷ARDS時未發(fā)現(xiàn)肺外因果障礙,。立即使用靜脈注射廣譜抗生素(頭孢噻肟和螺旋霉素)，以覆蓋肺炎球菌和非典型病原體。
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.
血液分析顯示白細胞計數(shù)為4.83/ml,，主要是中性粒細胞（3.09/μL）,，C反應蛋白升高(263 mg/L)和降鈣素原(2.7 μg/L)，伴正常細胞性貧血(血紅蛋白11.1 g/dL, MGV 92 fl),，血小板70個/mm 3,，尿素氮13.9mmol/ L，血清肌酐93 μ mol/L,，ASAT 121 IU / L;LDH 456 IU/ L,。入院時行氣管-支氣管吸入，通用聚合酶鏈反應(PCR)檢測肺炎支原體,。血和尿培養(yǎng)陰性,。軍團菌和肺炎球菌尿抗原呈陰性。根據(jù)國際指南,，行鎮(zhèn)靜,、俯臥位、吸入NO和糖皮質激素,。效果良好,，患者于第9天停用呼吸機，并第13天離開重癥監(jiān)護室,，無永久性損傷,。入院時行血清檢查，出院3周后檢測結果：抗體四倍增加,，且存在抗肺炎支原體IgM抗體,。
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. 討論
我們很少報道由肺炎支原體引起的急性呼吸窘迫綜合征。在本病例中,，我們可以建立一個快速明確診斷--急性呼吸窘迫綜合征的肺炎支原體感染,，此診斷的前提是PCR陽性，其他病因診斷評估陰性,。
1995年陳和威爾斯回顧了有關1966 - 1991年的肺炎支原體嚴重感染的社區(qū)獲得性肺炎的英語文獻,，共46例，其中13例表現(xiàn)為致命性呼吸衰竭,。文章中涉及到的患者平均年齡是35歲,。Miyashita等人報道227例肺炎支原體感染的社區(qū)獲得性肺炎病例，其中13例出現(xiàn)急性呼吸衰竭,。無死亡報告,。喬杜里等人報道了一例由肺炎支原體引起的真正的急性呼吸窘迫綜合征，1995年至2010年英語文學中發(fā)現(xiàn)有10個類似案例,。最近,，泉川1979年至2010年日本文學進行總結，共發(fā)現(xiàn)52例病案報告，其中2例臨床表現(xiàn)為致命呼吸衰竭,。在以往文獻中,，占主導地位的人群為青壯年(平均年齡42.3歲)，無嚴重的潛在疾病,。從感染開始到發(fā)生呼吸衰竭的平均持續(xù)時間為11.2天(范圍: 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 .
急性呼吸窘迫綜合征相關的支原體肺炎報道較少的原因之一是其死亡率高。當診斷依賴需要數(shù)周才能顯示血清轉換的成對抗體滴度時,，確實不能確定肺炎支原體感染的診斷,。我們的報告和其他最近報告一樣，建議快速,、準確和容易獲得診斷試驗,，如用于檢測五種引起肺炎的細菌多重PCR法，可提高急性呼吸窘迫綜合征患者的肺炎支原體的檢出率,。
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 .
有幾個因素和由肺炎支原體引起重型肺炎有關,。延遲給足夠的藥抗生素是導致嚴重支原體肺炎的原因之一。盡管至少在歐洲和北美不常見,，但在大環(huán)內(nèi)酯無反應的情況下,，抗生素耐藥性可能被懷疑，盡管在沒有耐藥性的情況下有延遲反應的報道,。可能與其它呼吸道病原體合并感染，像肺炎鏈球菌,，它需要系統(tǒng)尋找其它病原體嚴重者,。過度激活的細胞介導免疫可能對繼肺炎支原體感染之后的疾病發(fā)展進程有很大影響，許多學者強調(diào)疾病早期,，以降低免疫力-介導的肺損傷需要注射類固醇,。
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.
所有這些因素都表明需要進行抗生素治療，包括嚴重社區(qū)獲得性肺炎譜系中的肺炎支原體,，還需要快速明確病原檢查嚴重社區(qū)獲得性肺炎,，包括像多重PCR檢測的快速診斷工具，由肺炎支原體引起的肺炎嚴重程度取決于不同菌株的能力,，以產(chǎn)出最近發(fā)現(xiàn)的社區(qū)獲得性呼吸系統(tǒng)窘迫綜合征（CARDS）毒素,。雖然在我們的病例報告中，調(diào)查不出CARDS毒素產(chǎn)生情況,，但是有關產(chǎn)素的未來流行病研究,，可能有助于了解支原體肺炎感染的臨床特征。
