治疗路径
在 COVID-19 大流行期间,所有出现咳嗽和发热或相关提示性症状的患者,未证实为其他疾病前,均应视为可能患 COVID-19。请参阅2019冠状病毒病专题。
任何肺炎患者的初始治疗都要依据疾病的严重程度、合并症、之前的住院史以及社区耐药细菌来进行。[18]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67. https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
需对患者的水合状态、换气是否充分和血流动力稳定性进行评估。 如需要,应即刻行氧疗和机械通气。
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What are the effects of noninvasive positive pressure ventilation with supplemental oxygen, when compared with Venturi mask oxygen delivery, in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.73/full展示答案
抗生素治疗
非典型细菌性肺炎的病原体通常对 β-内酰胺类抗菌药物治疗无反应,而需要使用大环内酯类、四环素或氟喹诺酮治疗。对于非复杂性社区获得性肺炎,目前肺炎治疗指南推荐经验性使用大环内酯类药物或多西环素,以确保覆盖非典型病原微生物。[18]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[40]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009 Oct;64 Suppl 3:iii1-55.
https://thorax.bmj.com/content/64/Suppl_3/iii1.long
http://www.ncbi.nlm.nih.gov/pubmed/19783532?tool=bestpractice.com
[41]Eliakim-Raz N, Robenshtok E, Shefet D, et al. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD004418.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004418.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/22972070?tool=bestpractice.com
[42]Sligl WI, Asadi L, Eurich DT, et al. Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis. Crit Care Med. 2014 Feb;42(2):420-32.
http://www.ncbi.nlm.nih.gov/pubmed/24158175?tool=bestpractice.com
[ ]
In hospitalized adults with community-acquired pneumonia, is there randomized controlled trial evidence to support the use of empiric atypical antibiotic coverage over typical antibiotic coverage?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.306/full展示答案 对于比较严重疾病以及有并存疾病的患者,也推荐覆盖非典型病原菌。[18]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[40]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009 Oct;64 Suppl 3:iii1-55.
https://thorax.bmj.com/content/64/Suppl_3/iii1.long
http://www.ncbi.nlm.nih.gov/pubmed/19783532?tool=bestpractice.com
[43]König R, Cao X, Oswald M, et al. Macrolide combination therapy for hospitalised CAP patients? An individualised approach supported by machine learning. Eur Respir J. 2019 Dec 12;54(6):1900824.
http://www.ncbi.nlm.nih.gov/pubmed/31537702?tool=bestpractice.com
关于在经验性抗生素疗法中覆盖非典型病原体的建议存在争议;[44]Postma DF, van Werkhoven CH, Oosterheert JJ. Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines. Curr Opin Pulm Med. 2017 May;23(3):204-10.
http://www.ncbi.nlm.nih.gov/pubmed/28198726?tool=bestpractice.com
[45]Naucler P, Strålin K. Routine atypical antibiotic coverage is not necessary in hospitalised patients with non-severe community-acquired pneumonia. Int J Antimicrob Agents. 2016 Aug;48(2):224-5.
http://www.ncbi.nlm.nih.gov/pubmed/27374746?tool=bestpractice.com
[46]File TM Jr, Marrie TJ. Does empiric therapy for atypical pathogens improve outcomes for patients with CAP? Infect Dis Clin North Am. 2013 Mar;27(1):99-114.
http://www.ncbi.nlm.nih.gov/pubmed/23398868?tool=bestpractice.com
但是,该建议得到了现有数据的支持。[47]File TM Jr, Eckburg PB, Talbot GH, et al. Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point. Int J Antimicrob Agents. 2017 Aug;50(2):247-51.
http://www.ncbi.nlm.nih.gov/pubmed/28599867?tool=bestpractice.com
[48]Eljaaly K, Alshehri S, Aljabri A, et al. Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: a systematic review and meta-analysis. BMC Infect Dis. 2017 Jun 2;17(1):385.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457549/
http://www.ncbi.nlm.nih.gov/pubmed/28576117?tool=bestpractice.com
通常不推荐将四环素和氟喹诺酮用于儿童或孕妇,但在使用此类药物的益处大于风险且无其他适当治疗选择的情况下(尤其是在对大环内酯类耐药的情况下),可考虑使用。
当使用可靠的方法明确了肺炎的具体致病菌,应针对相应的病原体行抗生素治疗。 [18]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67. https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com 然而,在过去的数年里,亚洲报道的大环内酯类耐药性肺炎支原体病例日益增多(高达 80%),[49]Liu Y, Ye X, Zhang H, et al. Antimicrobial susceptibility of Mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant strains from Shanghai, China. Antimicrob Agents Chemother. 2009 May;53(5):2160-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681541/ http://www.ncbi.nlm.nih.gov/pubmed/19273684?tool=bestpractice.com 而以下地区耐药率较低:中东 (30%),[50]Averbuch D, Hidalgo-Grass C, Moses AE, et al. Macrolide resistance in Mycoplasma pneumoniae, Israel, 2010. Emerg Infect Dis. 2011 Jun; 17(6):1079-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358208/ http://www.ncbi.nlm.nih.gov/pubmed/21749775?tool=bestpractice.com 欧洲(10%)、[51]Peuchant O, Ménard A, Renaudin H, et al. Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis. J Antimicrob Chemother. 2009 Jul;64(1):52-8. https://academic.oup.com/jac/article/64/1/52/758196 http://www.ncbi.nlm.nih.gov/pubmed/19429926?tool=bestpractice.com [52]Spuesens EB, Meijer A, Bierschenk D, et al. Macrolide resistance determination and molecular typing of Mycoplasma pneumoniae in respiratory specimens collected between 1997 and 2008 in the Netherlands. J Clin Microbiol. 2012 Jun;50(6):1999-2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372106/ http://www.ncbi.nlm.nih.gov/pubmed/22495561?tool=bestpractice.com [53]Uldum SA, Bangsborg JM, Gahrn-Hansen B, et al. Epidemic of Mycoplasma pneumoniae infection in Denmark, 2010 and 2011. Euro Surveill. 2012 Feb 2;17(5):20073. https://www.eurosurveillance.org/content/10.2807/ese.17.05.20073-en#html_fulltext http://www.ncbi.nlm.nih.gov/pubmed/22321137?tool=bestpractice.com 和美国(10%)。[54]Wolff BJ, Thacker WL, Schwartz SB, et al. Detection of macrolide resistance in Mycoplasma pneumoniae by real-time PCR and high-resolution melt analysis. Antimicrob Agents Chemother. 2008 Oct;52(10):3542-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565909/ http://www.ncbi.nlm.nih.gov/pubmed/18644962?tool=bestpractice.com 这可能是由于过度使用大环内酯类药物治疗社区获得性肺炎而导致的。四环素和氟喹诺酮对肺炎支原体大环内酯类耐药菌株高度有效。[55]Cao B, Qu JX, Yin YD, et al. Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance. Clin Respir J. 2017 Jul;11(4):419-29. https://www.doi.org/10.1111/crj.12379 http://www.ncbi.nlm.nih.gov/pubmed/26365811?tool=bestpractice.com [56]Waites KB, Xiao L, Liu Y, et al. Mycoplasma pneumoniae from the respiratory tract and beyond. Clin Microbiol Rev. 2017 Jul;30(3):747-809. https://www.doi.org/10.1128/CMR.00114-16 http://www.ncbi.nlm.nih.gov/pubmed/28539503?tool=bestpractice.com 当诊断为嗜肺军团菌感染时,应使用大环内酯类或者氟喹诺酮,而对于这两类药物任一种无偏好。[57]Gershengorn HB, Keene A, Dzierba AL, et al. The association of antibiotic treatment regimen and hospital mortality in patients hospitalized with Legionella pneumonia. Clin Infect Dis. 2015 Jun 1;60(11):e66-79. https://academic.oup.com/cid/article/60/11/e66/356290 http://www.ncbi.nlm.nih.gov/pubmed/25722195?tool=bestpractice.com
研究发现,对于急性呼吸道感染患者,利用降钙素原(一种生物标志物)指导抗生素治疗的启动和持续时间可降低死亡风险,减少抗生素使用,并降低副作用风险。[58]Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12;10(10):CD007498. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007498.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/29025194?tool=bestpractice.com [59]Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan;18(1):95-107. https://www.doi.org/10.1016/S1473-3099(17)30592-3 http://www.ncbi.nlm.nih.gov/pubmed/29037960?tool=bestpractice.com 然而,一项综述发现,短期死亡率没有差异,尤其在危重症患者中,而另一项研究发现,降钙素原指导的治疗并没有减少疑似下呼吸道感染患者的抗生素使用。[60]Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med. 2018 May;46(5):684-90. http://www.ncbi.nlm.nih.gov/pubmed/29293146?tool=bestpractice.com [61]Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018 Jul 19;379(3):236-49. https://www.doi.org/10.1056/NEJMoa1802670 http://www.ncbi.nlm.nih.gov/pubmed/29781385?tool=bestpractice.com
住院患者的门诊医疗照护服务
疾病严重程度的评分有助于决定患者是在门诊接受治疗或住院治疗或入住ICU治疗。最常使用肺炎严重性指数(PSI)进行评估。 [62]Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243-50. http://www.nejm.org/doi/full/10.1056/NEJM199701233360402#t=article http://www.ncbi.nlm.nih.gov/pubmed/8995086?tool=bestpractice.com [ 成人社区获得性肺炎严重程度指数 (pneumonia severity index, PSI) ] PSI也称为肺炎患者治疗效果研究团队模型,已重新定位为一种在线工具。一共评估20个因素,包括年龄、呼吸频率、脉搏、血压和体温,总评分为各项评分之和。CURB-65是另外一种由英国胸科协会发明的严重度评分系统。 [40]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009 Oct;64 Suppl 3:iii1-55. https://thorax.bmj.com/content/64/Suppl_3/iii1.long http://www.ncbi.nlm.nih.gov/pubmed/19783532?tool=bestpractice.com [ CURB-65 肺炎严重程度评分 ]
在明确患者是否需收入ICU治疗和住院治疗方面,与PSI和CURB-65评分系统相比,新评分系统可能有一些优势。[63]Yandiola PP, Capelastegui A, Quintana J, et al. Prospective comparison of severity scores for predicting clinically relevant outcomes for patients hospitalized with community-acquired pneumonia. Chest. 2009 Jun;135(6):1572-9. https://journal.chestnet.org/article/S0012-3692(09)60363-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/19141524?tool=bestpractice.com [64]España PP, Capelastegui A, Gorordo I, et al. Development and validation of a clinical prediction rule for severe community-acquired pneumonia. Am J Respir Crit Care Med. 2006 Dec 1;174(11):1249-56. http://www.ncbi.nlm.nih.gov/pubmed/16973986?tool=bestpractice.com [65]Charles PG, Wolfe R, Whitby M, et al; Australian Community-Acquired Pneumonia Study Collaboration. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008 Aug 1;47(3):375-84. https://academic.oup.com/cid/article/47/3/375/315583 http://www.ncbi.nlm.nih.gov/pubmed/18558884?tool=bestpractice.com [66]Ewig S, Woodhead M, Torres A. Towards a sensible comprehension of severe community-acquired pneumonia. Intensive Care Med. 2011 Feb;37(2):214-23. http://www.ncbi.nlm.nih.gov/pubmed/21080155?tool=bestpractice.com 两项研究表明,血氧饱和度低于 92% 与不良反应和病情较严重有关,因此需入院治疗。[65]Charles PG, Wolfe R, Whitby M, et al; Australian Community-Acquired Pneumonia Study Collaboration. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008 Aug 1;47(3):375-84. https://academic.oup.com/cid/article/47/3/375/315583 http://www.ncbi.nlm.nih.gov/pubmed/18558884?tool=bestpractice.com [67]Majumdar SR, Eurich DT, Gamble JM, et al. Oxygen saturations less than 92% are associated with major adverse events in outpatients with pneumonia: a population-based cohort study. Clin Infect Dis. 2011 Feb 1;52(3):325-31. https://academic.oup.com/cid/article/52/3/325/305087 http://www.ncbi.nlm.nih.gov/pubmed/21217179?tool=bestpractice.com
皮质类固醇的作用
皮质类固醇在重度社区获得性肺炎患者中的应用长期以来都是一个备受争议的问题。当前指南通常推荐不将皮质类固醇用于非重度或重度社区获得性肺炎患者;不过拯救脓毒症运动指南认可以下做法:对于难治性脓毒性休克患者,可考虑使用这类药物,还可视临床情况将这类药物用于治疗并存疾病(例如,COPD、哮喘、自身免疫性疾病)。此推荐基于以下事实:目前没有数据表明非重度社区获得性肺炎患者有死亡率或器官衰竭方面的获益,仅有有限的数据支持在重度社区获得性肺炎患者中的应用。[18]Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67. https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
对有关社区获得性肺炎住院成人患者的研究进行荟萃分析发现,使用皮质类固醇可减少机械通气需求、缩短住院时间、降低临床治疗失败率、减少并发症(包括脓毒性休克)、降低 C 反应蛋白(C-reactive protein,CRP)水平和降低全因死亡率。然而,似乎只有重度社区获得性肺炎患者的死亡率出现下降。在非重度疾病患者中,辅助性皮质类固醇可降低并发症发生率,但不会降低死亡率。[68]Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163(7):519-28. http://www.ncbi.nlm.nih.gov/pubmed/26258555?tool=bestpractice.com [69]Bi J, Yang J, Wang Y, et al. Efficacy and safety of adjunctive corticosteroids therapy for severe community-acquired pneumonia in adults: an updated systematic review and meta-analysis. PLoS One. 2016;11(11):e0165942. https://www.doi.org/10.1371/journal.pone.0165942 http://www.ncbi.nlm.nih.gov/pubmed/27846240?tool=bestpractice.com [70]Briel M, Spoorenberg SMC, Snijders D, et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Jan 18;66(3):346-54. http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com [71]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;(12):CD007720. https://www.doi.org/10.1002/14651858.CD007720.pub3 http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com [72]Wu WF, Fang Q, He GJ. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2018 Feb;36(2):179-84. http://www.ncbi.nlm.nih.gov/pubmed/28756034?tool=bestpractice.com [73]Huang J, Guo J, Li H, et al. Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Mar;98(13):e14636. http://www.ncbi.nlm.nih.gov/pubmed/30921179?tool=bestpractice.com [74]Jiang S, Liu T, Hu Y, et al. Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia: a meta-analysis. Medicine (Baltimore). 2019 Jun;98(26):e16239. https://journals.lww.com/md-journal/Fulltext/2019/06280/Efficacy_and_safety_of_glucocorticoids_in_the.96.aspx http://www.ncbi.nlm.nih.gov/pubmed/31261585?tool=bestpractice.com 日本的一项研究表明,皮质类固醇激素在治疗肺炎支原体肺炎方面可能没有任何优势。[75]Okubo Y, Michihata N, Morisaki N, et al. Recent trends in practice patterns and impact of corticosteroid use on pediatric Mycoplasma pneumoniae-related respiratory infections. Respir Investig. 2018 Mar;56(2):158-65. http://www.ncbi.nlm.nih.gov/pubmed/29548654?tool=bestpractice.com
接受皮质类固醇疗法的患者发生高血糖的风险增加。[70]Briel M, Spoorenberg SMC, Snijders D, et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Jan 18;66(3):346-54. http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com [71]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;(12):CD007720. https://www.doi.org/10.1002/14651858.CD007720.pub3 http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com 其他不良反应包括超级感染和上消化道出血。
尚未对辅助性皮质类固醇治疗用于孕妇或儿童群体进行研究,因此目前不作推荐。
氟喹诺酮类抗生素的安全性
使用氟喹诺酮类药物前,应考虑安全性问题。美国食品药品监督管理局(Food and Drug Administration,FDA)已发布警告指出,服用氟喹诺酮类药物的患者发生主动脉夹层、严重低血糖以及精神不良反应的风险增加。[76]Food and Drug Administration. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. July 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about-serious-low-blood-sugar-levels-and-mental-health-side [77]Food and Drug Administration. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. December 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics
2018 年,欧洲药品管理局(European Medicines Agency,EMA)完成了一项与氟喹诺酮类药物相关的严重、致残性和可能不可逆转不良反应的审评。此类不良反应包括肌腱炎、肌腱断裂、关节痛、神经病变和其他肌肉骨骼或神经系统不良反应。年龄较大、存在肾脏损伤或实体器官移植病史的患者,以及正在接受皮质类固醇治疗的患者,出现肌腱损伤的风险更高。如果可能,应避免联用氟喹诺酮类药物和皮质类固醇。这项审评导致欧洲设置了处方限制,即仅允许将氟喹诺酮类药物用于重度感染。[78]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. March 2019 [internet publication]. https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products


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