罕见病例分享!1例毗邻颗粒链菌引起的法洛四联症患者感染性心内膜炎病例

2022-09-12 刘佶 何宏 郝传吉 青岛大学附属医院 “检验医学”公众号

前言

前言

感染性心内膜炎(InfectiveEndocarditis,IE)是由微生物经血流途径从原发感染部位迁徙至心脏,引起的心内膜、心瓣膜或邻近大动脉膜的感染,伴有赘生物的形成。最常见的临床表现为发热,多伴寒战,食欲减退和消瘦等1。其中法洛四联症患者发生感染性心内膜炎的风险很高,但在未矫正的法洛四联症患者中的发生率较小,约占4%,且未经手术干预的法洛四联症患者中只有2%可以生存到第四个10年2,因此未经治疗的法洛患者罹患感染性心内膜炎属罕见病例,由毗邻颗粒链菌引起的法洛四联症患者的感染性心内膜炎还未见报道。本文即介绍了一例未经纠正的成年法洛四联症患者发生毗邻颗粒链菌感染性心内膜炎的治疗成功病例。

案例经过

患者,男,45岁,因“心慌8个月,加重13天”入院,患者8个月前干体力活后出现心慌不适,心动过速并心脏搏动感增强,同时感头晕、眼前黑蒙,未晕倒,休息后自行缓解,自觉无其它明显不适,13天前因情绪波动大,再次出现前述症状,并感全身乏力。曾就诊于我院西海岸院区,行心脏超声发现“先天性心脏病”,建议转至市南院区,遂来我院我区就诊,门诊复查心脏超声,2020年6月3日以“法洛四联症”入院。起病以来,患者神志清楚,精神欠佳,饮食减少,睡眠如常,大小便正常,体重1月下降6斤。

入院体检:T:35.8℃,P:110次/分,R:20次/分,BP:120/70mmHg。口唇无青紫,胸廓对称无畸形,呼吸运动正常,肋间隙无增宽、变窄,呼吸规整;语颤无增强及减弱,无胸膜摩擦感、皮下捻发感;叩诊清音,双肺呼吸音清,肺底可闻及细小湿罗音,语音传导正常,无胸膜摩擦音。心前区未见异常隆起,心尖搏动位于左侧第五肋间隙锁骨中线处,心尖部未触及震颤及心包摩擦感,叩诊心脏相对浊音界无明显扩大;听诊心率110次/分,律不齐,心音正常,心前区广泛可闻及收缩期杂音,以胸骨左缘3-4肋间隙明显,呈Ⅳ/6级收缩期吹风样杂音,P2正常,无分裂,股动脉枪击音(-)。

实验室检查:CRP 102mg/L↑,白细胞13.76×109/L↑,中性粒细胞 10.11×109/L↑,淋巴细胞 2.65×109/L,血红蛋白 158g/L,血小板 136×109/L,血沉 10mm/h,氧分压 22.1mmHg↓,氧饱和度 38.5%↓,D-二聚体 750ng/mL↑。

影像学检查:心脏超声检查(2020-06-02)1.先天性心脏病法洛氏四联征右室漏斗部狭窄(重度),肺动脉瓣及肺动脉发育正常狭窄处强回声占位,弹力纤维瘤,陈旧性赘生物,室间隔缺损(膜周流出道)卵圆孔未闭。2.主动脉瓣反流(轻度),主动脉根部扩张,主动脉窦扩张。3.三尖瓣下腱索及瓣叶冗长,三尖瓣反流(轻度)。4.左室舒张功能减低,收缩功能正常低限(图1)。

图1 心脏超声检查结果

据患者病史、查体及辅助检查结果,法洛四联症室间隔缺损中央型房间隔缺损(卵圆孔型)右室流出道狭窄,感染性心内膜炎赘生物诊断明确,手术指证具备,各项化验检查未见手术禁忌,准备行外科手术治疗。患者入院后即给予哌拉西林/他唑巴坦抗感染治疗(6.3-6.11,q8h)。6月4日患者出现发热,最高体温达39.1℃,患者右室流出道有赘生物,且体温波动,考虑感染性心内膜炎,予以留血培养,通过临床药学会诊,予以加用万古霉素(6.5-6.29,q12h)抗感染治疗,继续哌拉西林/他唑巴坦抗感染等治疗。6月6日血培养双侧需氧瓶及一侧厌氧瓶共三瓶报阳(图2),显微镜检查显示链状排列的革兰阳性球菌,2日后在血平板上生长出针尖样灰白色凸起小菌落,经MALDI-TOFMS(Bruker Daltonik, Bremen,Germany)与形态学及生长特点相结合进行鉴定,为毗邻颗粒链菌(图3),立即通知临床。

临床继续哌拉西林/他唑巴坦、万古霉素联合抗感染治疗。患者入院后经积极强心、利尿、营养心肌等药物治疗,病情好转稳定,然而患者仍间断发热,体温最高达39.8℃,通过临床药学会诊,考虑感染性心内膜炎所致,哌拉西林/他唑巴坦已用10天,予以停用,停用哌拉西林/他唑巴坦后患者体温仍有较大波动,单用万古霉素效果不佳,加用亚胺培南(06.14-6.16q12h,6.17-6.23q6h)抗感染治疗。并于6月17日行法乐氏四联症根治术+卵圆孔未闭修补术+心脏病损(赘生物)切除术+三尖瓣机械瓣膜置换术+心外膜电极置入术,术中送检赘生物细菌培养,三日后未培养出细菌。患者术后病情持续好转稳定,但于6月28日出现双上肢皮疹,考虑为抗生素迟发副反应,至6月30日,双上肢、腰腹部及双侧股部皮疹增多,更换抗生素为利奈唑胺(6-30至7-12,q12h),皮肤表面红疹较前好转,直至7月6日全身皮肤红疹消退。7月16日,患者病情平稳,术后恢复顺利,予以出院。至2022-01-18,患者经6次超声复查,人工机械瓣均正常,恢复良好,未有复发及再感染。

A

B

图2 A: 需氧阳性瓶;B: BD EpiCenter中显示的三个阳性报警瓶及相应报阳时间

图3 MALDI-TOFMS 鉴定峰图及毗邻颗粒链菌得分情况

案例分析

临床案例分析

如何治疗法洛患者毗邻颗粒链菌心内膜炎?

感染性心内膜炎在获得血培养结果之前,可采用经验治疗方案,本病例属自体瓣膜心内膜炎,推荐采用青霉素类抗生素进行治疗1,本病例入院后首先启用哌拉西林/他唑巴坦进行治疗,然而病情并不稳定,即加用万古霉素覆盖IE常见病原菌肠球菌与葡萄球菌(包括甲氧西林耐药菌株),在血培养明确毗邻颗粒链菌感染后,考虑其引起的感染性心内膜炎治疗的失败率与死亡率远高于其他链球菌3,且具有很高的青霉素耐药率,而对万古霉素100%敏感4-5,则继续维持使用万古霉素与哌拉西林/他唑巴坦联合抗感染。而抗菌药物治疗后患者体温仍有较大波动,单纯抗生素治疗很难完全控制感染,且法洛四联症的畸形亟需纠正,因此在通过积极强心、利尿、营养心肌等药物治疗,病情好转稳定后,通过手术去除赘生物感染灶,更换人工瓣膜,同时进行抗生素抗感染治疗,最终患者得到治愈。

检验案例分析

如何帮助临床诊断和治疗毗邻颗粒链菌感染性心内膜炎?

感染性心内膜炎根据瓣膜类型可分为天然瓣膜心内膜炎和人工瓣膜心内膜炎,其中引起天然瓣膜心内膜炎的最常见病原体为草绿色链球菌,而人工瓣膜心内膜炎则为葡萄球菌。由毗邻颗粒链菌引起的感染性心内膜炎相对少见。患者罹患法洛四联症,是感染性心内膜炎的易感人群。本实验室综合质谱结果、菌落生长特点及涂片结果最终鉴定为毗邻颗粒链菌,并积极与临床主动沟通,告知该菌特点和推荐治疗方案,助力临床诊疗,患者最终痊愈出院,并未复发。

知识拓展

毗邻颗粒链菌,与缺陷乏氧菌、苛养颗粒链菌和副毗邻颗粒链菌分别隶属于两个属四个种,统称为营养变异链球菌,以往这类细菌被认为是草绿色链球菌,尤其是缓症链球菌的营养变异体。这类细菌在普通的绵羊血平板上不易生长,可在非支持培养基中添加半胱氨酸或吡哆醛进行培养。本病例中患者尽管在抽取血培养标本时已使用抗生素,但仍在含树脂可吸附抗生素的BDBactec PlusAerobic/F需氧血培养瓶及Anaerobic/F厌氧血培养瓶中生长良好,并经过固体培养基的标准孵育可以得以恢复,此种菌株以该方式多次在我实验室分离,并有相关文献报道5,可见BDBactec PlusAerobic/F及Anaerobic/F血培养瓶具有较强的培养此菌的能力。

卫星试验是鉴定该菌的重要依据,将待测菌密集划线接种于其不生长或生长不良的培养基上,采用金黄色葡萄球菌(ATCC25923)在接种区划线,35℃富含CO2的环境下孵育,颗粒链菌只在葡萄球菌附近生长。而目前已广泛应用于临床的MALDI-TOFMS为该菌的鉴定提供了更为准确迅速的方式,可与传统的细菌形态学、生长特性和卫星试验相结合进行鉴定,为感染性心内膜炎的诊断提供重要证据。

案例总结

先天性心脏病患者由于心内结构异常,喷射或涡流血流直接冲击心内膜或心瓣膜,容易引起内膜受损,受损的内膜易于引起细菌的聚集繁殖,这可能是其引起心内膜炎的病理生理机制。

本病例为罹患法洛四联症的中年男性,具有感染性心内膜炎的高危因素,心脏超声发现赘生物,发热,血培养阳性为毗邻颗粒链菌,符合改良的Duke诊断标准中符合一条主要标准和三条次要标准的要求1,感染性心内膜炎诊断明确。通过明确的诊断,针对毗邻颗粒链菌进行抗菌药物治疗,联合对法洛四联症的纠正手术及更换人工瓣膜,患者得以痊愈。

专家点评

营养变异链球菌是存在于口腔、肠道和泌尿生殖道的正常菌群,很少引起菌血症和心内膜炎,仅占总心内膜炎病例的3%,偶可分离自其他类型感染,如眼部感染、中枢神经系统感染,腹膜炎、关节炎等。该菌由于其特殊的营养要求难于培养,可能易被诊断为“培养阴性”的心内膜炎。目前越来越多的营养变异链球菌可以被培养与快速鉴定,也得益于优秀的商品化血培养瓶及MALDI-TOFMS的广泛使用,而微生物实验室正是应当将传统的形态、生化方法与新兴的质谱乃至分子技术相结合,共同助力临床诊疗。(彭丽静,主任技师,青岛大学附属医院)

【参考文献】

1.中华医学会心血管病学分会,中华心血管病杂志编辑委员会.成人感染性心内膜炎预防、诊断和治疗专家共识[J], 中华心血管病杂志,2014,42(10), 806-816

2.PedroSousa, Walter Santos, Nuno Marques, Pedro Cordeiro, Rui Ferrinha, Salomé Pereira, Ana Almeida, Ilídio Jesus.a72-year-old woman with an uncorrected tetralogy of Fallot presenting with possible pulmonary endocarditis: a case report[J], 2013, 7, 150

3.Bruce M Jones, Roby M Hersey, Irwin J Trestman, Christopher M Bland. Successful treatment of a penicillin-intermediate and ceftriaxoneresistantGranulicatellaadiacens presumed prosthetic valve endocarditis with vancomycin [J],Int J Antimicrob Agents, 2018, 51(3), 508-510

4.Michael O Alberti, Janet A Hindler, Romney M Humphries. Antimicrobial Susceptibilities of Abiotrophiadefectiva, Granulicatellaadiacens, and Granulicatella elegans[J],2015, 60(3):1411-1420

5.Rebekah EDumm, Anna Wing, Aaron Richterman, Jerry Jacob, Laurel J Glaser, Kyle G Rodino, The Brief Case: A Variant on a Classic—Abiotrophiadefectiva Endocarditis with Discitis[J], Clin Microbiol, 2021, 59(10): e0309320.

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#插入话题
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  2. [GetPortalCommentsPageByObjectIdResponse(id=1708726, encodeId=36fe1e08726b6, content=<a href='/topic/show?id=4c2d3051535' target=_blank style='color:#2F92EE;'>#内膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30515, encryptionId=4c2d3051535, topicName=内膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=730431558473, createdName=12498974m61暂无昵称, createdTime=Sat Sep 24 23:50:35 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034203, encodeId=961a2034203e2, content=<a href='/topic/show?id=97b5e95599f' target=_blank style='color:#2F92EE;'>#罕见病例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79559, encryptionId=97b5e95599f, topicName=罕见病例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=845e216, createdName=cqlidoudou, createdTime=Sat May 20 22:50:35 CST 2023, time=2023-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1655539, encodeId=083816555394c, content=<a href='/topic/show?id=7c2853311ac' target=_blank style='color:#2F92EE;'>#感染性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53311, encryptionId=7c2853311ac, topicName=感染性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=583d24724321, createdName=charl1234575, createdTime=Sun Jul 30 13:50:35 CST 2023, time=2023-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1350778, encodeId=2d6a1350e783f, content=<a href='/topic/show?id=a32d508e8c3' target=_blank style='color:#2F92EE;'>#心内膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50878, encryptionId=a32d508e8c3, topicName=心内膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421519, encodeId=e43b1421519d9, content=<a href='/topic/show?id=068c6486e77' target=_blank style='color:#2F92EE;'>#法洛四联症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64867, encryptionId=068c6486e77, topicName=法洛四联症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f87f3671641, createdName=tongyongming, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1467674, encodeId=2ee8146e67453, content=<a href='/topic/show?id=ef32e9539e8' target=_blank style='color:#2F92EE;'>#罕见#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79539, encryptionId=ef32e9539e8, topicName=罕见)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=29f36868190, createdName=syscxl, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1248564, encodeId=f34e124856420, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Mon Sep 12 22:57:08 CST 2022, time=2022-09-12, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1708726, encodeId=36fe1e08726b6, content=<a href='/topic/show?id=4c2d3051535' target=_blank style='color:#2F92EE;'>#内膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30515, encryptionId=4c2d3051535, topicName=内膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=730431558473, createdName=12498974m61暂无昵称, createdTime=Sat Sep 24 23:50:35 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034203, encodeId=961a2034203e2, content=<a href='/topic/show?id=97b5e95599f' target=_blank style='color:#2F92EE;'>#罕见病例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79559, encryptionId=97b5e95599f, topicName=罕见病例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=845e216, createdName=cqlidoudou, createdTime=Sat May 20 22:50:35 CST 2023, time=2023-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1655539, encodeId=083816555394c, content=<a href='/topic/show?id=7c2853311ac' target=_blank style='color:#2F92EE;'>#感染性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53311, encryptionId=7c2853311ac, topicName=感染性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=583d24724321, createdName=charl1234575, createdTime=Sun Jul 30 13:50:35 CST 2023, time=2023-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1350778, encodeId=2d6a1350e783f, content=<a href='/topic/show?id=a32d508e8c3' target=_blank style='color:#2F92EE;'>#心内膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50878, encryptionId=a32d508e8c3, topicName=心内膜炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421519, encodeId=e43b1421519d9, content=<a href='/topic/show?id=068c6486e77' target=_blank style='color:#2F92EE;'>#法洛四联症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64867, encryptionId=068c6486e77, topicName=法洛四联症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f87f3671641, createdName=tongyongming, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1467674, encodeId=2ee8146e67453, content=<a href='/topic/show?id=ef32e9539e8' target=_blank style='color:#2F92EE;'>#罕见#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79539, encryptionId=ef32e9539e8, topicName=罕见)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=29f36868190, createdName=syscxl, createdTime=Tue Sep 13 09:50:35 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1248564, encodeId=f34e124856420, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Mon Sep 12 22:57:08 CST 2022, time=2022-09-12, status=1, ipAttribution=)]
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    2022-09-13 syscxl
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    2022-09-12 医鸣惊人

    认真学习了

    0

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