新生兒壞死性肺炎2例報(bào)告并文獻(xiàn)復(fù)習(xí)

張 可 周建國(guó) 胡 蘭 鄧英平 陳 超

復(fù)旦大學(xué)附屬兒科醫(yī)院（上海 201102）

新生兒壞死性肺炎2例報(bào)告并文獻(xiàn)復(fù)習(xí)

張 可 周建國(guó) 胡 蘭 鄧英平 陳 超

復(fù)旦大學(xué)附屬兒科醫(yī)院（上海 201102）

目的分析新生兒壞死性肺炎的臨床特點(diǎn)及診治。方法回顧分析2例新生兒壞死性肺炎患兒的臨床資料，并總結(jié)文獻(xiàn)報(bào)道。結(jié)果2例新生兒均確診為社區(qū)獲得性金黃色葡萄球菌致壞死性肺炎，以發(fā)熱起病，胸片示滲出性改變伴囊性影，CT示為多發(fā)空洞改變，痰/血培養(yǎng)均為金黃色葡萄球菌陽性，萬古霉素治療有效，影像學(xué)檢查隨訪示好轉(zhuǎn)。通過數(shù)據(jù)庫(kù)檢索，共有4篇病例報(bào)道，加上本組2例共7例新生兒壞死性肺炎病例。致病菌均有金黃色葡萄球菌，其中1例合并有銅綠假單胞菌，6例為社區(qū)獲得性感染，均發(fā)生于無免疫缺陷新生兒，6例為原發(fā)性壞死性肺炎，6例為單側(cè)肺受累；5例有發(fā)熱表現(xiàn)，5例合并敗血癥，分別有3例、2例、1例并發(fā)胸腔積液、氣胸或支氣管胸膜瘺，2例有肺外感染；C反應(yīng)蛋白均明顯升高；3例需要機(jī)械通氣，6例預(yù)后良好。結(jié)論新生兒壞死性肺炎以金黃色葡萄球菌為主要致病菌，診斷主要依靠典型影像學(xué)和病原學(xué)檢查，治療主要選擇針對(duì)革蘭陽性球菌的抗生素。

壞死性肺炎； 臨床特點(diǎn)； 新生兒

壞死性肺炎（necrotizing pneumonia）為繼發(fā)于感染的一種肺實(shí)質(zhì)炎性壞死損傷，同時(shí)伴有多個(gè)含氣或液體的薄壁空洞形成[1]，其病理特點(diǎn)為病變肺組織壞死、壞疽[1,2]。近十年報(bào)道兒童壞死性肺炎發(fā)病率有所增加[3]，但是新生兒報(bào)道較為少見。本研究報(bào)道復(fù)旦大學(xué)附屬兒科醫(yī)院收治的2例新生兒壞死性肺炎的臨床資料，并復(fù)習(xí)相關(guān)文獻(xiàn)，以加強(qiáng)兒科醫(yī)師對(duì)本病的認(rèn)識(shí)，早期診斷、及時(shí)治療，降低死亡發(fā)生率。

1 臨床資料

例1，男，19天，因納差4天、發(fā)熱1天入院?；純鹤阍马槷a(chǎn)，出生體質(zhì)量3 400 g，出生時(shí)無異常。Apgar評(píng)分正常，生后早期無特殊表現(xiàn)，配方奶喂養(yǎng)。出生15天時(shí)無明顯誘因下出現(xiàn)納差，伴嘔吐。出生18天時(shí)出現(xiàn)發(fā)熱，熱峰為38.5℃，精神反應(yīng)變差，以新生兒肺炎收住入院。入院體格檢查：反應(yīng)萎，上顎根部可見0.5 cm×0.5 cm潰瘍，呼吸平穩(wěn)，兩肺呼吸音粗，未及啰音。實(shí)驗(yàn)室檢查：血?dú)夥治稣?，肝腎功能正常，血鈉121 mmol/L，余電解質(zhì)正常；血常規(guī)白細(xì)胞計(jì)數(shù)8.7×109/L，中性粒細(xì)胞 57%，血紅蛋白158.1 g/L，血小板計(jì)數(shù)161×109/L；C反應(yīng)蛋白133 mg/L，降鈣素原15.7 ng/mL。血培養(yǎng)、膿液培養(yǎng)均為金黃色葡萄球菌（甲氧西林敏感），痰培養(yǎng)、支原體、衣原體檢查均陰性。免疫球蛋白、CD系列及中性粒細(xì)胞功能檢查無異常。胸片提示兩肺滲出，右下肺、左上肺囊狀影。CT提示雙肺多發(fā)大小不等薄壁空洞（圖1）。入院后予氨芐西林舒巴坦鈉、頭孢他定抗感染。病原學(xué)檢查明確為金黃色葡萄球菌感染后改用萬古霉素抗感染治療。期間因左面頰及牙齦膿腫予切開引流治療。入院后2周C反應(yīng)蛋白恢復(fù)正常，胸片、CT較前好轉(zhuǎn)，治療4周后出院。

圖1 病例1肺部影像學(xué)檢查

例2，女，28天，因發(fā)熱2天入院?；純?4+4周，因雙胎剖宮產(chǎn)娩出，出生體質(zhì)量1 970 g，Apgar評(píng)分10分，混合喂養(yǎng)。于出生26天無明顯誘因出現(xiàn)發(fā)熱，體溫波動(dòng)在36.8℃～38.5℃，伴有哭鬧不安。以新生兒肺炎收住入院。入院體格檢查：精神萎靡，反應(yīng)差，貧血貌，呼吸平穩(wěn)，兩肺呼吸音粗，未及啰音。實(shí)驗(yàn)室檢查：血常規(guī)白細(xì)胞計(jì)數(shù)34.5×109/L，中性粒細(xì)胞78.4%，血小板計(jì)數(shù)579×109/L；血紅蛋白101.0 g/L；C反應(yīng)蛋白＞160 mg/L，紅細(xì)胞沉降率102 mm/h，降鈣素原1.23 ng/mL。血培養(yǎng)、痰培養(yǎng)均為金黃色葡萄球菌（甲氧西林敏感），痰支原體、衣原體檢查均陰性。免疫球蛋白、CD系列及中性粒細(xì)胞功能檢查無異常。肝功能、腎功能、電解質(zhì)檢查正常。胸片示左上肺滲出伴囊狀影。CT示左上肺部分實(shí)變伴多發(fā)空洞形成（圖2）。左肩關(guān)節(jié)增強(qiáng)磁共振成像（MRI）示左側(cè)肱骨近端骨骺斑片狀異常強(qiáng)化灶，左肩關(guān)節(jié)軟組織腫脹；雙下肢長(zhǎng)骨平片示骨質(zhì)改變伴干骺端骨質(zhì)破壞，考慮骨髓炎。入院后予氨芐西林舒巴坦鈉聯(lián)合美羅培南抗感染治療。病原學(xué)檢查明確為金黃色葡萄球菌感染后改萬古霉素抗感染治療，治療47天好轉(zhuǎn)出院。

圖2 病例2肺部影像學(xué)檢查

2 討論

以“壞死性肺炎、新生兒”為關(guān)鍵詞或主題詞，在萬方、維普網(wǎng)、中國(guó)知網(wǎng)全文數(shù)據(jù)庫(kù)中檢索國(guó)內(nèi)文獻(xiàn)，未檢索到相關(guān)病例報(bào)道。以“necrotizing pneumonia”作為主題，限定研究對(duì)象年齡為新生兒（檢索式：necrotizing pneumonia [Title] AND "infant, newborn" [MeSH Terms]），在PubMed檢索至2016年8月的文獻(xiàn)，共檢索到4篇文獻(xiàn)，含5例新生兒壞死性肺炎報(bào)道[4-7]。加上本組2例，共7例新生兒壞死性肺炎。

7例新生兒壞死性肺炎的主要特點(diǎn)：致病菌均為金黃色葡萄球菌，其中1例合并有銅綠假單胞菌；6例為社區(qū)獲得性感染；7列均無免疫缺陷；6例為原發(fā)性壞死性肺炎；6例為單側(cè)肺受累；5例有發(fā)熱表現(xiàn)，僅1例有咳嗽癥狀，5例合并敗血癥，分別有3例、2例、1例并發(fā)胸腔積液、氣胸或支氣管胸膜瘺；2例有肺外感染。C反應(yīng)蛋白均明顯增高。3例需要機(jī)械通氣，1例予激素治療，1例予引流和肺葉切除手術(shù)治療，6例預(yù)后良好。

壞死性肺炎是肺炎的一種嚴(yán)重疾病形式，診斷主要依賴CT等影像學(xué)檢查[8]。CT早期主要表現(xiàn)為肺實(shí)變，可伴有胸腔積液，48小時(shí)內(nèi)即可從液化壞死發(fā)展致空洞形成，故典型影像學(xué)表現(xiàn)為在肺實(shí)變的基礎(chǔ)上出現(xiàn)肺實(shí)質(zhì)缺損及多發(fā)薄壁空洞。壞死性肺炎是介于肺膿腫與肺梗死之間的一種疾病，早期臨床表現(xiàn)相似，但是疾病進(jìn)程及影像學(xué)表現(xiàn)相差較大[1]。肺膿腫病情相對(duì)略輕，一般為單一較大的膿腔，伴有氣液平面，膿腔壁較厚，多與最近的支氣管相通排出膿液[9,10]。肺梗死病情較重，大血管血栓是其發(fā)病的主要因素，表現(xiàn)為梗死肺段鄰近血管充盈缺損和阻塞[11,12]。

新生兒壞死性肺炎多發(fā)生于免疫功能正常新生兒，一般為侵襲性細(xì)菌感染所致。 Sawicki等[8]認(rèn)為感染觸發(fā)了強(qiáng)烈的炎癥反應(yīng)導(dǎo)致壞死性肺炎發(fā)生。Hsieh等[11]則認(rèn)為感染菌分泌毒素遞質(zhì)引起血管炎和血管內(nèi)血栓形成，影響支氣管和肺的血供，進(jìn)一步發(fā)展為壞死性肺炎。

壞死性肺炎的致病病原主要為金黃色葡萄球菌和肺炎鏈球菌[3,8]。本組2例致病菌均為金黃色葡萄球菌。社區(qū)獲得性金黃色葡萄球菌致新生兒感染也呈增多趨勢(shì)[13]，故新生兒壞死性肺炎仍需重視。臨床上多有發(fā)熱表現(xiàn)[8]，持續(xù)發(fā)熱并非反映細(xì)菌清除不佳，而是與炎癥反應(yīng)、組織壞死后持續(xù)釋放致熱源相關(guān)。部分患兒有呼吸困難表現(xiàn)，多累及單側(cè)多個(gè)肺葉[14]。

總結(jié)本組2例及文獻(xiàn)報(bào)道5例患兒，6例為社區(qū)獲得性壞死性肺炎，且均為金黃色葡萄球菌感染。金黃色葡萄球菌需結(jié)合受損的上皮細(xì)胞致病，有報(bào)道其感染與呼吸道的病毒感染相關(guān)[6]，致病機(jī)制則與殺白細(xì)胞素相關(guān)性更強(qiáng)[15,16]，可直接導(dǎo)致肺部發(fā)生炎癥和損傷[17]，同時(shí)也可通過影響免疫相關(guān)基因表達(dá)增加金黃色葡萄球菌的致病危害[18,19]。

新生兒壞死性肺炎多合并敗血癥[1]，且易合并有胸腔積液、氣胸、支氣管胸膜瘺等并發(fā)癥[2]。或許炎癥損傷之后的肺泡、胸膜易脆性改變與氣胸、支氣管胸膜瘺發(fā)生相關(guān)。本組2例新生兒均有肺外感染病灶，例1為皮膚、牙齦膿腫，例2為多發(fā)骨髓炎。金黃色葡萄球菌可導(dǎo)致多部位感染，尤其是骨關(guān)節(jié)部位感染[16]。有報(bào)道認(rèn)為這與其毒力強(qiáng)度有關(guān)[16]，且與USA300（ST8）基因表達(dá)相關(guān)[20,21]。

新生兒壞死性肺炎多伴有白細(xì)胞增高，以中性粒細(xì)胞比例增高為主，可引發(fā)炎癥因子風(fēng)暴損傷致病[15]， C反應(yīng)蛋白明顯增高[16]。

新生兒壞死性肺炎感染癥狀較重，早期發(fā)現(xiàn)、診斷和治療對(duì)疾病的轉(zhuǎn)歸非常重要。新生兒壞死性肺炎需采用綜合支持措施，藥物推薦首先經(jīng)驗(yàn)性使用萬古霉素治療，獲得藥敏結(jié)果后可據(jù)藥敏結(jié)果選藥[16]。若效果不佳，也可選擇試用利奈唑胺治療[6]。其他治療如激素、肺泡灌洗等在新生兒應(yīng)用不多，基于保守治療后病情普遍好轉(zhuǎn)，不推薦手術(shù)治療[8]。

壞死性肺炎的成人病例預(yù)后較差，兒童和新生兒治愈率較成人高[8]。本組2例患兒預(yù)后良好；檢索到的5例中，1例死亡，為出生胎齡25周、出生體質(zhì)量?jī)H700 g的早產(chǎn)兒，生后19天發(fā)病，最終因感染性休克和彌漫性血管內(nèi)凝血而死亡，其余均痊愈。

總之，新生兒壞死性肺炎常以發(fā)熱為主要表現(xiàn)，以金黃色葡萄球菌為主要致病菌，診斷主要依靠典型影像學(xué)和病原學(xué)檢查，經(jīng)敏感抗生素治療后效果好。對(duì)于有發(fā)熱表現(xiàn)，X線有囊性影伴滲出改變者，需警惕金黃色葡萄球菌感染致新生兒壞死性肺炎可能。

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Neonatal necrotizing pneumonia: two case report and literature review

ZHANG Ke, ZHOU Jianguo, HU Lan, DENG Yingping, CHEN Chao
(Department of Neonatology, Children’s Hospital of Fudan University, Shanghai 201102, China)

ObjectiveTo explore the clinical features, diagnosis, and treatment of neonatal necrotizing pneumonia.MethodsThe clinical data of two cases of neonatal necrotizing pneumonia were retrospectively analyzed. The clinical features, diagnosis, and treatment of neonatal necrotizing pneumonia in literatures were summarized.ResultsTwo cases were diagnosed of community-acquired Staphylococcus aureus necrotizing pneumonia and had the onset with fever. The chest X-ray showed exudative change with cystic shadow. The chest CT showed multiple cavity changes. The sputum and blood cultures were positive for Staphylococcus aureus. Both of them were effectively treated by vancomycin. The imaging was improved during the follow-up. Searching the database, 4 related literatures were being found, and there were totally 7 cases of neonatal necrotizing pneumonia including current 2 cases. The main features were as follows: The pathogenic bacteria in all cases include Staphylococcus aureus. One case was combined with pseudomonas aeruginosa. Six cases were community-acquired infections. All of them were non-immune deficiency newborn. Six cases were primary necrotizing pneumonia. Six cases were unilateral lung involvement. Five cases got fever, 5 cases had septicemia, 3 cases had pleural effusion, 2 cases had aerothorax, one case had bronchial chest and 2 cases had extrapulmonary infection. The C-reactive protein was increased in all cases. Three cases need mechanical ventilation. Six cases had a good prognosis.ConclusionsThe main pathogenic bacterium in neonatal necrotizing pneumonia was Staphylococcus aureus. The diagnosis was mainly depends on the typical imaging and pathogenic examination. The treatment is mainly the use of antibiotic for gram positive cocci.

necrotizing pneumonia; clinical feature; neonate

10.3969/j.issn.1000-3606.2017.03.002

2016-12-06）

（本文編輯：鄒 強(qiáng)）

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