肺炎支原体:不好确诊该咋办?
在 肺炎支原体:有可靠的检测方法吗?提到了目前医院里两个靠谱的化验方法--不管是高端大气的咽拭子取鼻咽部分泌物做核酸检测(PCR),还是普通的抽血查肺炎支原体抗体化验(IgM),都没有办法把真正的肺炎支原体感染和正常的携带/定植区分开来--这种正常的携带/定植在儿童中非常多见,我见到最多的报道是56.3%以上的健康孩子,都能检测到肺炎支原体阳性。
那别的检查呢?
先说化验血常规,大多数肺炎支原体肺炎化验血常规都是正常的,没有特殊意义。
资料来源:儿童肺炎支原体肺炎诊治专家共识(2015年版)
再说胸片,肺炎支原体肺炎单靠胸部X线也很难将其与别的肺炎相鉴别。Uptodate上这样说:没有明显的临床或放射学表现可以把支原体肺炎与衣原体或病毒性肺炎区分开来。
There are no distinguishing clinical or radiologic manifestations that allow a secure diagnosis of mycoplasma pneumonia versus chlamydial or viral pneumonia.
《儿童感染性疾病的临床与实践》这本书也说到:婴幼儿的呼吸道感染以病毒最为多见,临床上几乎不可能把病毒和肺炎支原体感染区分开。
结论:目前还没有好的方法能够对肺炎支原体进行可靠、快速的诊断。现有的检测方法在敏感性和特异性上差别很大,并且似乎不能区分肺炎支原体现症发病和无症状定植,肺炎支原体检查结果必须谨慎解读。
There are no diagnostic tests that allow the reliable, rapid diagnosis of M. pneumoniae. The available tests are variable in sensitivity and specificity and do not appear to differentiate between M. pneumoniae disease and asymptomatic colonization, so the user must be cautious in the interpretation of results. Mycoplasma pneumoniae infection in children Via Uptodate
过度检查/诊断肺炎支原体的危害
浪费时间/浪费钱就不说了,如果盲目按化验阳性判定肺炎支原体肺炎,结果就是肺炎支原体感染被严重高估而蒙不白之冤,有时候逮着个假的支原体,真凶却成漏网之鱼。另外虽然大环内酯类抗生素总体是安全的,但消化道副作用等也不容忽视:很多孩子吃完阿奇霉素都会有腹痛,腹泻和消化不良等副反应。还有一个大问题就是:
抗生素耐药:全球耐大环内酯类抗生素的肺炎支原体在荷兰是0,在中国高达97%!
到底化验不化验肺炎支原体?不化验的话该怎么办?其实各国医生也都在想办法,各种招数都有:
1.先看澳洲的儿童肺炎指南:他们压根就不主张化验肺炎支原体,理由和我前篇谈到的基本一样:不管是鼻咽部分泌物,还是抽血查抗体都不能区分无症状的携带者和有症状的感染者,对指导治疗没有帮助。
NOTE: Testing for atypical bacteria (including nasopharyngeal secretions and nasal swabs for M.pneumoniae PCR or acute and convalescent serology) is not helpful in guiding management as testing cannot differentiate between asymptomatic carriage and symptomatic infection.
资料来源: https://www.rch.org.au/clinicalguide/guideline_index/Pneumonia_Guideline/
那该怎么治疗?看下图就明白了:不严重的肺炎,能口服的,给大剂量阿莫西林。重症肺炎先给头孢曲松加氟氯西林,用药无效,病情持续进展,要考虑肺炎支原体,再给加上阿奇霉素。
2.再看看荷兰医生的建议:
他们同样认为目前的化验方法局限性很大,无法分清楚是真感染还只是正常携带,发热两天以下,支原体肺炎的风险极低,三岁以下孩子支原体肺炎也不多见。可以这样说:三岁以下,发热不到两天,根本就不要考虑支原体肺炎。
3.另外也有医生研究出了一个评分系统:
这个评分参考了年龄,发热以及咳嗽持续时间,≥5分为阳性,儿童年龄越大,发热和咳嗽持续时间越长,肺炎支原体感染的可能性越大。这个评分虽然也有很大的局限性,但某种程度上按照这个评分做的话,可以帮助排除很多的“假”支原体感染。
4. 看uptodate怎么说:
Uptodate参考了美国儿童感染病学会的指南,建议:下呼吸道感染(注意:不是感冒,也不是支气管炎,是肺炎),因为确诊有困难, 临床怀疑肺炎支原体感染可以考虑经验性治疗。 建议用大环内酯类或四环素类抗生素经验性治疗的情况包括:1.住院儿童(重症),疑似或化验肺炎支原体阳性的肺炎患儿。 2.门诊中,学龄儿童和青少年诊断社区获得性肺炎(CAP),符合非典型肺炎表现, 也可以考虑用大环内酯类抗生素治疗。
5. 美国儿科学会对肺炎支原体感染治疗又是什么立场?我们看看他们的红宝书吧(Red Book Atlas of Pediatric Infectious Diseases 3rd Edition):
抗微生物治疗对非住院儿童(轻症)的肺炎支原体引起的下呼吸道感染的益处,缺乏足够的证据。有些数据建议住院儿童(重症)用抗微生物治疗有益。不建议对患有社区获得性肺炎的学龄前儿童进行针对肺炎支原体的抗菌治疗,因为这个人群绝大多数病因都是病毒性感染。 没有证据表明用抗菌药物治疗肺炎支原体感染的其他可能表现(如上呼吸道感染,肺外感染)会改变病程。
Evidence of beneft of antimicrobial therapy for nonhospitalized children with lower respiratory tract disease attributable to M pneumoniae is limited. Some data suggest beneft of appropriate antimicrobial therapy in hospitalized children. Antimicrobial therapy is not recommended for preschool-aged children with community-acquired pneumonia because viral pathogens are responsible for the great majority of cases. There is no evidence that treatment of other possible manifestations of M pneumoniae infection (eg, upper respiratory tract infection, extrapulmonary infection) with antimicrobial agents alters the course of illness. Red Book Atlas of Pediatric Infectious Diseases 3rd Edition
6. 那么,如果症状、体征和各种检查都不能可靠地诊断支原体肺炎,我们又高度怀疑是支原体肺炎,应该什么时候用药?英国胸科学会的指南其实已经给出了建议:如果已经给了阿莫西林或其他β-内酰胺类抗生素,但效果不佳,或者病情非常严重,那就给加上大环内酯类抗生素吧(阿奇霉素/红霉素之类)。说白了就是:确实是肺炎,如果病情不严重,就先按普通肺炎常规用药,用药两三天,无效的话,再考虑肺炎支原体的事,把大环内酯类药加上。但如果病情非常重,就别考虑那么多了,直接用吧。
So, when should we give treatment for suspected mycoplasma pneumonia if the symptoms signs and diagnostic tests are not reliably predictive? The recent British Thoracic Society guidance suggests a macrolide antibiotic may be given if there is no response to amoxicillin (or another β-lactam antibiotic) or in very severe pneumonia. This would be simpler and cheaper than ordering a mycoplasma PCR!
7.不急着给阿奇霉素会不会耽误病情?我国的一个研究其实已经给出了答案:
在肺炎支原体广泛耐药的情况下,阿奇霉素的用药时间与肺炎支原体肺炎的预后没有直接关系——早给晚给是差不多的。
The timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.
总之,我的建议是:
不要轻易查肺炎支原体:门诊/轻症肺炎患儿根本没必要查肺炎支原体,过度检查弊大于利。住院患儿/重症,诊断不明/搞科研,必要时可以做咽拭子核酸检测(PCR),或/和普通查肺炎支原体抗体(IgM)。
没有明显呼吸道症状,虽然肺炎支原体化验阳性,但只是正常携带,不要用药。只是上呼吸道感染/支气管炎的咳嗽,没有肺炎,即使检测出肺炎支原体阳性,也不建议用药。
确实是肺炎,如果病情不严重,就先按普通肺炎常规用药,用药两三天,无效的话,再考虑肺炎支原体的事,把大环内酯类药等加上也不迟。
如果病情非常重,就别考虑那么多了,直接用吧。
参考文献
1.Wood PR, Hill VL, Burks ML, et al. Mycoplasma pneumoniae in children with acute and refractory asthma. Ann Allergy Asthma Immunol 2013; 110:328–334.
2.Infection with and Carriage of Mycoplasma pneumoniae in Children https://www.frontiersin.org/articles/10.3389/fmicb.2016.00329/full
3. https://www.rch.org.au/clinicalguide/guideline_index/Pneumonia_Guideline/
4.Infection with and Carriage of Mycoplasma pneumoniae in Children. https://www.ncbi.nlm.nih.gov/pubmed/27047456
5.https://www.cdc.gov/pneumonia/atypical/mycoplasma/hcp/antibiotic-treatment-resistance.html
6.Red Book Atlas of Pediatric Infectious Diseases 3rd Edition
7.In children with respiratory symptoms are Mycoplasma pneumoniae PCR and serology clinically significant?
https://www.ncbi.nlm.nih.gov/pubmed/24385292
8.Clinical score to rule out pneumonia due to Mycoplasma pneumoniae
https://www.ncbi.nlm.nih.gov/pubmed/24534005
9.Mycoplasma pneomoniae infection in children via Uptodate
10.British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011
https://thorax.bmj.com/content/66/Suppl_2/ii1
11.In children with respiratory symptoms are Mycoplasma pneumoniae PCR and serology clinically significant? https://www.ncbi.nlm.nih.gov/pubmed/24385292
12.The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings. https://www.ncbi.nlm.nih.gov/pubmed/29377957