劉金榮 姚開虎 高 路 徐保平

·論著·

肺炎鏈球菌致急性化膿性心包炎1例并文獻(xiàn)復(fù)習(xí)

劉金榮1姚開虎2高 路3徐保平1

目的 了解肺炎鏈球菌致急性化膿性心包炎的主要表現(xiàn)，加強(qiáng)對該病的認(rèn)識。方法 報(bào)道1例肺炎鏈球菌所致的急性化膿性心包炎患兒的臨床表現(xiàn)及預(yù)后，并結(jié)合文獻(xiàn)復(fù)習(xí)。結(jié)果 14月齡患兒，既往體健，因“呼吸急促7 d，咳嗽3 d”入院。血常規(guī)WBC、CRP顯著升高。肺CT和超聲心動(dòng)圖均提示心包積液。心包積液培養(yǎng)為肺炎鏈球菌100%，確診為肺炎鏈球菌化膿性心包炎，血清型鑒定為6A型。予利奈唑胺抗感染治療，好轉(zhuǎn)后出院，隨訪6個(gè)月超聲心動(dòng)圖僅提示心包膜稍增厚。檢索PubMed數(shù)據(jù)庫發(fā)現(xiàn)16例該病患兒報(bào)道，結(jié)合本文報(bào)道的1例，男9例，女7例，另1例性別不詳；年齡4月至17歲，其中2歲以下10例；3例有基礎(chǔ)疾病。血常規(guī)提示W(wǎng)BC明顯升高，以多核細(xì)胞為主，CRP明顯升高。心包積液外觀為黃棕色膿性，常規(guī)及生化表現(xiàn)為典型化膿性積液改變；超聲心動(dòng)圖及肺CT/X線檢查均提示中至大量心包積液；合并肺炎2例，胸腔積液4例，心包填塞3例。9例報(bào)道藥物敏感試驗(yàn)結(jié)果，其中8例為青霉素敏感菌株，1例為青霉素耐藥菌株。7例報(bào)道血清型，其中6A、14、23F型各2例，34型1例。2/6例換用萬古霉素，16例行心包穿刺引流。15例預(yù)后較好，2例死亡。結(jié)論 肺炎鏈球菌化膿性心包炎病例有增多趨勢，兒童既往常健康，通過積極治療，預(yù)后較良好。

肺炎鏈球菌； 化膿性心包炎; 兒童

1 病例資料

患兒，男，14月齡，因“呼吸急促7 d，咳嗽3 d”入院。病程中無發(fā)熱，有少許痰，院外給予頭孢類抗生素(具體不詳)治療3 d，患兒精神反應(yīng)較前減弱，呼吸急促較前加重，遂轉(zhuǎn)入首都醫(yī)科大學(xué)附屬北京兒童醫(yī)院(我院)。

既往史及家族史：既往體健，有羊、狗和鴿子接觸史。家族史無特殊。

入院查體：T 36.7℃, BP 90/60 mmHg，P 135·min-1，R 30·min-1。神志清楚，精神反應(yīng)弱，呻吟，卡疤陽性，未見頸靜脈怒張，無明顯鼻翼煽動(dòng)及三凹征，口周發(fā)青，咽稍充血。雙肺呼吸音粗，未聞及干濕啰音。心前區(qū)稍隆起，心音稍低鈍，律齊，各瓣膜聽診區(qū)未聞及雜音。腹軟，肝肋下捫及4 cm，質(zhì)硬，邊銳，肝頸靜脈回流征陰性，脾肋下未捫及。雙下肢未見水腫，神經(jīng)系統(tǒng)查體未見異常。

實(shí)驗(yàn)室檢查：血常規(guī)：WBC 47.0×109·L-1，N 0.85，L 0.13，Hb 74 g·L-1，PLT 679×109·L-1。CRP >160 mg·L-1，ESR 63 mm·h-1。肝功能、腎功能和心肌酶正常。ASO、肺炎支原體抗體(-)。IgG、IgA、IgM和IgE正常。流行性出血熱IgG、IgM均(-)。ANA、dsDNA(-)。CD系列：T輔助淋巴細(xì)胞0.305，NK細(xì)胞0.03，略低于正常。

影像學(xué)檢查：肺CT示雙肺少許實(shí)質(zhì)病變，左側(cè)顯著，左側(cè)胸壁內(nèi)側(cè)梭形低密度影(包裹性胸腔積液)，心包積液，氣管下段管徑略扁，形態(tài)欠規(guī)則(圖1)。胸腔B超示左側(cè)包裹性胸腔積液，單腔小，右側(cè)少量胸腔積液。超聲心動(dòng)圖示各房室內(nèi)徑正常，心包積液(中至大量)，可見絮狀回聲。

入院當(dāng)日予心包穿刺定位行心包穿刺術(shù)，抽出約35 mL暗黃色黏稠液體。心包積液常規(guī)：膿樣混濁，李凡他試驗(yàn)(+)，WBC 84.9×109·L-1，多核細(xì)胞0.77，單核細(xì)胞0.23；心包積液生化：蛋白56.5 g·L-1，LDH 3 689 U·L-1，腺苷脫氨酶99.3 U·L-1，糖0.02 mmol·L-1。心包積液抗酸染色(-)，未找到菌絲及孢子。PPD試驗(yàn)(48～72 h)陰性?？紤]患兒有羊、狗接觸史，血樣送北京市友誼醫(yī)院熱帶病研究所涂片檢查，未見異常。

治療及轉(zhuǎn)歸：入院后予吸氧、絕對臥床，限液量800～1 200 mL·m-2，限液速3～5 mL·kg-1·h-1。患兒入院后即出現(xiàn)中高熱，因精神反應(yīng)弱，呻吟，提示感染中毒癥狀明顯，外周血WBC及CRP明顯增高，考慮細(xì)菌感染可能性大，給予頭孢孟多，同時(shí)予磷酸肌酸鈉保護(hù)心肌，卡托普利口服減輕心臟后負(fù)荷，安體舒通及雙氯噻嗪利尿減輕心臟前負(fù)荷。

入院第6天心包積液細(xì)菌培養(yǎng)示：肺炎鏈球菌100%，經(jīng)鑒定為血清型6A，對青霉素、萬古霉素、頭孢吡肟和美羅培南等敏感。心包積液真菌及結(jié)核分支桿菌培養(yǎng)陰性。確診為肺炎鏈球菌化膿性心包炎。入院第8天呼吸困難較前略減輕，但仍發(fā)熱，且超聲心動(dòng)圖仍提示中等量心包積液，欲行心包開窗引流術(shù)，因患兒痰較多有麻醉風(fēng)險(xiǎn)，故未能行手術(shù)。家長因萬古霉素有聽力損害等不良反應(yīng)，換利奈唑胺抗感染治療，第16天患兒體溫降至正常，精神反應(yīng)較前好轉(zhuǎn)，咳嗽、咳痰較前明顯減輕，復(fù)查超聲心動(dòng)圖提示心包積液極少量(2.0～3.0 mm)，心包腔內(nèi)可見絮狀回聲附著。住院第19天，患兒一般情況可，予以出院，出院后口服頭孢克洛治療2周，出院后6個(gè)月當(dāng)?shù)蒯t(yī)院行超聲心動(dòng)圖檢查僅提示心包膜稍增厚。

圖1 本文患兒肺CT所見

Fig 1 The finding of chest CT of the patient

Notes Chest CT showing massive pericardial effusion and left pleural fluid

2 文獻(xiàn)復(fù)習(xí)

檢索PubMed數(shù)據(jù)庫1980年之后的肺炎鏈球菌(肺炎球菌)化膿性心包炎，僅報(bào)道30余例，其中資料相對齊全的兒童病例16例，結(jié)合本文報(bào)道的1例(表1)。男9例，女7例，1例性別不詳。年齡4月齡至17歲，其中<1歲7例。中國(臺灣2 例，北京1例)、法國各報(bào)道3例；美國、土耳其、德國、西班牙、比利時(shí)、巴西、澳大利亞、以色列、羅馬尼亞、印度、瑞典各報(bào)道1例。

17例患兒中14例既往健康，3例有基礎(chǔ)疾病，其中例15為慢性髓細(xì)胞樣白血病、骨髓移植；例16為系統(tǒng)性紅斑狼瘡；例17為IgG4缺乏。

17例均有發(fā)熱；10例咳嗽，但不劇烈，4例伴有呼吸困難。

6例報(bào)道血常規(guī)WBC結(jié)果，WBC在(18.2～47.0)×109·L-1，以多核細(xì)胞為主。5例報(bào)道了CRP結(jié)果，均明顯升高。6例報(bào)道了心包積液結(jié)果，外觀均為膿性或血性液，常規(guī)及生化均表現(xiàn)為典型化膿性積液改變。

8/9例超聲心動(dòng)圖或肺CT/X線檢查提示中至大量心包積液，例2因合并右心衰竭，導(dǎo)致腹水，胸部X線提示正常大小的心臟。例1和12有肺炎表現(xiàn)，例1、8、12和15可見胸腔積液。

16/17例行心包穿刺引流。9例行心包積液培養(yǎng)均為肺炎鏈球菌陽性，其中8例為青霉素敏感菌株，例2為青霉素耐藥菌株。血清型34型1例，6A、14、23F型各2例。

涉及的合并癥有心包填塞3例(例9、15、17)、心力衰竭(例2)、心律失常(例13)、肺炎球菌腦膜炎(例17)、溶血尿毒癥(例5)、骨髓炎(例9)等。

8例報(bào)道了具體的抗生素使用情況，例3使用阿莫西林，6例應(yīng)用頭孢噻肟或頭孢曲松等三代頭孢菌素，其中例10和12之后換用萬古霉素，例15應(yīng)用亞胺培南和替考拉寧，例10和17在抗感染基礎(chǔ)上均加用3 d糖皮質(zhì)激素。

3 討論

肺炎鏈球菌是社區(qū)獲得性肺炎的最常見病原,可引起非侵襲性疾病，如肺炎、中耳炎和鼻竇炎等，也可導(dǎo)致侵襲性疾病，如腦膜炎、膿毒癥或心包積液等。1943年前，肺炎鏈球菌是兒童和青年人(平均年齡20歲)中化膿性心包炎的最常見病原。但之后由于青霉素應(yīng)用于臨床，侵襲性肺炎鏈球菌感染，如化膿性心包炎較少見，主要發(fā)生于有基礎(chǔ)疾病的人群(平均年齡49歲)，健康兒童極其罕見。近20年，英文文獻(xiàn)中僅30余例肺炎球菌心包炎被報(bào)道，但近5年報(bào)道呈上升趨勢，故需引起重視。

肺炎鏈球菌和侵襲性肺炎球菌疾病的高危因素：年齡(常為2歲以下，65歲以上)、糖尿病、接受免疫抑制劑治療、既往有心外科手術(shù)史、慢性酒精中毒、HIV感染、肥胖和外傷手術(shù)。本文報(bào)道和檢索到共17例患兒<2歲10例，其中<1歲7例，提示2歲尤其是1歲以下患兒易患本病。而3例年長(年齡>13歲)患兒均伴有SLE、慢性髓細(xì)胞樣白血病和IgG4缺乏癥等基礎(chǔ)疾病，與成人的情況有類似之處。對于健康兒童罹患本病的原因，仍不十分明確，可能與肺炎鏈球菌的免疫反應(yīng)導(dǎo)致的組織損傷有關(guān)，仍需進(jìn)一步研究。

患肺炎鏈球菌肺炎時(shí)，肺炎鏈球菌可從鄰近縱隔結(jié)構(gòu)擴(kuò)散到心包，或通過血源性播散導(dǎo)致化膿性心包炎。其臨床表現(xiàn)常不明顯，導(dǎo)致延誤診斷。本病患兒多以發(fā)熱和呼吸道感染表現(xiàn)為主訴而就診，呼吸道癥狀常不顯著，年長兒有時(shí)也常以頭痛、胸痛及背痛等為主訴?？梢鹦陌钊?、敗血癥、腦膜炎、膿毒性休克和多器官衰竭等危象。在臨床上應(yīng)引起重視。

心包積液的有效引流和高劑量的靜脈輸注敏感抗生素是本病的有效治療手段，文獻(xiàn)中6例報(bào)道了抗生素具體使用情況，選擇阿莫西林或三代頭孢菌素，3例換用萬古霉素或亞胺培南和替考拉寧。本文患兒因家長擔(dān)心萬古霉素的不良反應(yīng)，換用利奈唑胺，治療效果較好。本病可導(dǎo)致縮窄性心包炎、慢性右心衰竭等，有時(shí)需行心包切除術(shù)。本病經(jīng)過積極治療，預(yù)后常較好，文獻(xiàn)復(fù)習(xí)2/17例患兒死亡。

從藥敏試驗(yàn)可見8/9例為青霉素敏感菌株，提示青霉素敏感菌株仍可引起較重的化膿性心包炎。但隨著目前抗生素的應(yīng)用，增加的耐多藥肺炎鏈球菌可能會(huì)導(dǎo)致化膿性心包炎的風(fēng)險(xiǎn)更高，故需引起警惕。此外，僅7/17例行血清學(xué)鑒定，主要為6A、14、23F，但因樣本例數(shù)少，尚不足以證實(shí)是否為明顯致病血清型。

肺炎鏈球菌的預(yù)防比治療更加重要，減少侵襲性肺炎球菌疾病的風(fēng)險(xiǎn)，肺炎鏈球菌疫苗的應(yīng)用為最有效的措施，對于高危人群可大幅降低發(fā)病率和病死率。

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Acute purulent pericarditis caused by Streptococcus pneumoniae: a case report and literature review

LIUJin-rong1,YAOKai-hu2,GAOLu3,XUBao-ping1

(BeijingChildren′sHospitalaffiliatedtoCapitalMedicalUniversity, 1RespiratoryandInfectiousDiseasesCenter, 2DepartmentofMicrobiology&Immunology, 3CardiologyCenter,Beijing100045,China)

XU Bao-ping, E-mail: xubaoping@yahoo.com

ObjectiveTo improve the understanding to acute purulent pericarditis caused byStreptococcusPneumoniae(PPSP) ,to report a case of acute PPSP serotype 6A in a Chinese child and 16 reported cases by English literature on this topic up to now.MethodsClinical manifestation and prognosis of 17 patients(including our reported case in this article) with acute purulent pericarditis caused byStreptococcusPneumoniaewere retrospectively analyzed.ResultsA 14-month-old previously healthy boy had a history with 7-day-tachypnea and 3-day-cough. The levels of white blood cell (WBC) and C-reactive protein (CRP) were significantly high.A computed tomographic imaging of the chest and echocardiographic study showed massive pericardial fluid.StreptococcusPneumoniaeserotype 6A was recovered from pericardial fluid and was found to be sensitive to penicillin. The patient was diagnosed as PPSP and treated with intravenous infusion of cefamandole and linezolid successively. On the 19th day of hospitalization the patient was discharged in good general condition and with hemodynamically stable. Over 6 months follow-up, ultrasound cardiography only revealed a little thickening cardiac pericardium.Since 1990,only 16 cases of PPSP have been reported in children in the PubMed databases.17 cases (9 males，7 females，1 unknown) aged from 4 months to 17 years,10 cases were younger than 2 years old. Children were healthy without previous medical conditions and only 3cases had underlying diseases. Its clinical recognition was difficult due to insidiously subtle and varied presentations,but most of cases had fever, dyspnea and cough. The levels of WBC, neutrophil and C-reactive protein were very high. Pericardial fluid was often yellowish-brown and revealed typical manifestation of purulent pericarditis. Echocardiogram and chest CT/X ray showed a large amount of pericardial effusion,many cases showed pneumonia pleural effussion.8 cases were with penicillin susceptible strains, 1 case with penicillin drug resistant strains of S. pneumoniae.1 case of serotype 34, 2 cases of serotype 6A , 14 and 23F were reported respectively.3 cases were with cardiac tamponade.Effective drainage of the pericardium in combined with high dose intravenous antibiotics offered the best results.Most of cases were treated with vancomycin finally. In general，there was often a good outcome without sequelae, but 2 cases died.ConclusionsIn near 20 years，PPSP has been reported in the English literature，and tended to increase in the past 2 years. Its clinical recognition is difficult due to atypical and varied presentations, especially in pediatirc department. Children were often healthy in the past. Despite the serious morbidity, PPSP patients who

prompt treatment could achieve good prognosis without sequelae.

Streptococcus pneumoniae; Purulent pericarditis; Children

首都醫(yī)科大學(xué)附屬北京兒童醫(yī)院 1 呼吸感染中心; 2 微生物免疫室; 3 心臟中心 北京，100045

徐保平，E-mail:xubaoping@yahoo.com

10.3969/j.issn.1673-5501.2013.02.013

2013-02-13

2013-03-20)

丁俊杰)