细菌性感染性疾病的诊断分级
细菌性感染性疾病的诊断分级
二级诊断包括拟诊断(possible,suspected)、确定诊断(proven,definite,confirmed)。拟诊断指基于临床表现的诊断;确定诊断指在拟诊的基础上,有确定的微生物学证据的诊断。因为启动微生物学检查的前提就是临床表现,所以感染性疾病领域中,很多时候确定诊断等同于微生物学确定诊断,如感染性心内膜炎等[5,6,7]。
细菌学领域是否有三级诊断?细菌学领域极似诊断的证据是什么?现从病原学、疾病角度予以阐述。
本文作者宁永忠的著作
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共识:降钙素原在成人下呼吸道感染性疾病分级管理中的应用(2021)
一、病原学角度
另外,对于宋内志贺菌、肺炎链球菌和军团菌病的研究均有三级诊断[8,14,15]。
二、疾病角度
(一)细菌性脑膜炎
Riehm等[9]将细菌性脑膜炎三层诊断定义为:确定诊断、极似诊断和拟诊断。
1.确定诊断(confirmed bacterial meningitis):
②脑膜炎临床表现+血培养有细菌性病原生长,并排除其他感染源所致菌血症。
2.极似诊断(probable bacterial meningitis):
原文指出这是WHO的标准。但笔者认为原文稍有纰漏––无细菌学证据应该具体指无流感嗜血杆菌证据(该文主旨是讨论流感嗜血杆菌)。其他细菌的革兰染色、免疫学检查和PCR检查阳性,也应该作为极似诊断层面证据。
3.拟诊断(suspected bacterial meningitis):
此外,因为有部分患者不能采集脑脊液,所以单纯典型临床表现本身,似也可归入本层诊断。
而2007年Nguyen等[16]在细菌性脑膜炎研究中,满足纳入标准和排除标准的前提下,确诊(definite bacterial meningitis)指脑脊液中检测到细菌(革兰染色或吖啶黄染色阳性,脑脊液乳胶凝集试验阳性),或脑脊液、血液培养有细菌分离;极似诊断(probable bacterial meningitis)指未检测到细菌,无细菌分离,也无替代诊断。细菌性脑膜炎分为三层诊断已经成为业界共识[17]。
(二)肺炎
结合这两个文献可见,监测指南中probable VAP对应的病原,其实就是确证病原;如果患者表现(包括影像学)符合临床标准,则probable VAP对应的诊断就是确定诊断。这里使用probable一词可能会引起混淆,但probable VAP一词定义的内涵、范畴是明确的,分层理念也是明确的。
(三)尿路感染
参考文献[22]中,尿路感染一章明确提到极似诊断,与肺炎一样用presumptive diagnosis一词。其证据包括尿沉渣镜检(主要是白细胞)、中性粒细胞酯酶、亚硝酸盐和菌体镜检(主要是革兰染色)。淋病奈瑟菌感染所致尿道炎时,衣原体、支原体阳性时也要一并治疗[23,24]。此时二者的治疗属于假设性治疗(presumptive therapy),对应的诊断也是极似诊断。此时菌种明确,为什么是极似诊断而非确诊,笔者认为,有淋病奈瑟菌感染症状时,很难区分衣原体等所致表现;而二者本身感染时,也有很多患者症状不明显。因此没有使用确诊一词。
(四)新生儿早期脓毒症(early-onset neonatal sepsis, EONS)
Kuhn等[25]的研究将该疾病诊断分为三级。
1.确定诊断(confirmed)EONS:
指血培养和(或)脑脊液培养阳性。
2.极似诊断(probable)EONS:
指有脓毒症的临床和生物学体征,伴胃抽吸物和(或)皮肤表面培养阳性。皮肤表面标本包括咽拭子、耳拭子、眼拭子、脐带拭子、皮肤拭子等。
3.拟诊断(possible)EONS:
指有脓毒症的临床和生物学体征,但培养阴性。
(五)血流感染
血流感染领域也将诊断分为三级[26]。德国近期发表的血液病和恶性肿瘤患者中心静脉插管(CVC)相关感染诊断、处置、预防指南,将插管相关性血流感染(CRBSI)分为三级[27]。
1.确诊(definite)CRBSI:
②外周静脉血培养和经CVC静脉血培养分离微生物相同,差异报警时间≥2 h,或匹配定量血培养CVC浓度≥3倍外周血浓度。
2.极似诊断(probable)CRBSI:
外周静脉血培养和经CVC静脉血培养分离微生物相同,不符合确诊标准,且分离株是血浆凝固酶阴性葡萄球菌、金黄色葡萄球菌或假丝酵母菌属,且排除其他位点感染。
3.拟诊CRBSI:
③CVC拔除后48 h内发热缓解,且无其他位点感染。
(六)输血传播性细菌感染
加拿大指南将该感染分为三级[28]
1.拟诊(possible diagnosis):
受体血液培养阳性(不是取血污染或实验室污染所致);受体有脓毒症表现,除输血所致外无其他形成因素可以解释;未对输注的血液、血液制品或组分进行培养,原因或是无标本,或无医嘱。
2.极似诊断(probable diagnosis):
或受体血液培养阴性,受体同时服用抗菌药物。
3.确诊(definite diagnosis):
受体血液培养和输注的血液、血液制品或组分培养有相同的细菌生长,不是留取标本污染或实验室污染所致。
而微生物学证据中,有些如革兰染色,只能看见菌体,不知道菌种。这种情况没有确诊(分离到菌株,鉴定到菌种)那么明确,却比拟诊进了一步,自然对应分出中间一层。
有时感染性疾病病理学证据会被盲目地等同于确诊证据(在真菌性感染诊断中表现尤其突出)。其实病理学证据也应分层,结果能明确菌种(如引入种特异性单克隆抗体或种特异性核酸),则基于临床表现可以认为是确诊证据,否则不是确诊证据。
对细菌学/真菌学而言,非人体定植菌群的分离株,正常无微生物部位的分离株(二者尤其是高浓度分离时)存在时,既使无临床症状也要考虑感染的可能,不能笼统以污染视之。相信随着基础研究、转化医学的进步,必然会有更多生物学标志物,早于临床表现而为临床所知。
由此,极似诊断/抢先治疗理念应运而生。且真菌培养、病毒培养耗时,所以极似诊断/抢先治疗的理念最先获得共识。而细菌培养稍快,极似诊断/抢先治疗理念取得共识反而较慢。
就治疗而言,三层诊断也有明确的价值。抗菌药物的使用分为四层:预防用药、经验治疗、抢先治疗、靶向治疗。其中后三层用药和三层诊断一一对应[30]。
1.经验治疗(empiric therapy):
因为尚无证据针对病原谱治疗,所以经验治疗选药错误的概率高,选药正确时也容易失之于过[过广和(或)过强]。这是临床为什么要确诊(亦即微生物学确定诊断)的原因之一。
2.抢先治疗(presumptive therapy):
需要注意的是,欧洲目前不再用抢先治疗一词,改用诊断驱动的治疗(diagnosis-driven therapy)[31]。这个英文词组字面含义过于宽泛,理解应用时要小心。
3.靶向治疗(target therapy,pathogen specific therapy):
对应确定诊断。病原明确,针对病原进行治疗,这是感染性疾病治疗的最佳状态。
综上所述,分层诊断体现了对诊断认识的深入、升华,体现了对客观证据的分级评价和分门别类,也体现了对治疗选择的精细区分。三层诊断是医学发展的必然,细菌性感染性疾病的诊断也必然体现这一规律。可以预见,随着客观检查手段的深入细致,希望将来细菌性感染性疾病会出现更多分层。
参考文献
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