有关大流行期间诊断和管理共存疾病的最新信息,请参阅专题“COVID-19 共存疾病管理”。
诊断为 CAP 后,下一步就是确定患者是否需要门诊治疗、住院治疗或收住重症监护病房(intensive care unit,ICU)。微生物检查和抗微生物治疗的可及性将取决于治疗的地点。关于治疗地点的选择存在很大差异,可从医院到诊所,决策时还应考虑除严重程度外的其他因素。
门诊患者的选择和治疗
为确定患者是否应在门诊治疗,除了根据临床判断外,还要使用经过验证的临床预测规则(肺炎严重度指数 [Pneumonia Severity Index,PSI] 优于 CURB-65)评估预后。PSI 优于 CURB-65,因为 PSI 可将更大比例的患者识别为低风险患者,并且在预测死亡率方面有更高的鉴别能力。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
推荐对以下患者进行门诊治疗:[80]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 Jan 23;336(4):243-50.
http://www.nejm.org/doi/full/10.1056/NEJM199701233360402#t=article
http://www.ncbi.nlm.nih.gov/pubmed/8995086?tool=bestpractice.com
[81]Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377-82.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746657
http://www.ncbi.nlm.nih.gov/pubmed/12728155?tool=bestpractice.com
应知晓严重程度评分存在局限性,在评估患者是否适合门诊治疗时应考虑其他因素,例如是否存在门诊治疗的禁忌证(例如无法维持口服)、药物滥用史、严重并存疾病、认知障碍、功能障碍状态或门诊支持性资源可用情况。
建议患者不要吸烟,多休息,并充分补液。此外,还应建议患者报告胸痛、严重或逐渐加剧的呼吸短促或者昏睡等症状。
在 48 小时时重新评估患者。在这段时间内经过适当的治疗,症状应得到改善。对于 48 小时内未得到改善的患者,应考虑入院治疗。约有 10% 的门诊患者对抗生素治疗无反应,需要住院治疗。[90]Niederman M. In the clinic: community-acquired pneumonia. Ann Intern Med. 2009 Oct 6;151(7):ITC42-14.
http://www.ncbi.nlm.nih.gov/pubmed/19805767?tool=bestpractice.com
如果患者对治疗的反应达到满意效果,应在 10-14 天后复查。如果症状在 5-7 天内消退,则不推荐常规进行胸部影像学检查随访。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
相比住院治疗的患者,没有住院治疗就已经恢复健康的门诊患者能够更快地恢复正常活动。住院治疗会增加感染抗生素耐药或毒性更强细菌的风险。[91]Halm EA, Teirstein AS. Clinical practice: management of community-acquired pneumonia. N Engl J Med. 2002 Dec 19;347(25):2039-45.
http://www.ncbi.nlm.nih.gov/pubmed/12490686?tool=bestpractice.com
门诊患者的经验性抗微生物治疗
美国胸科学会(American Thoracic Society,ATS)/美国传染病学会(Infectious Diseases Society of America,IDSA)指南为门诊患者推荐以下口服经验性治疗选择:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
有并存疾病的患者需要使用广谱抗生素治疗方案,因为其中许多患者存在感染耐药病原体的危险因素(例如,有呼吸道分离出耐甲氧西林金黄色葡萄球菌 [methicillin-resistant Staphylococcus aureus,MRSA] 或铜绿假单胞菌的既往史、近期住院史以及过去 90 天内经胃肠外使用过抗生素),如果经验性治疗方案不充分,则他们更容易出现不良结局。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
选用抗生素时,需要针对每例患者进行风险与益处分析,权衡当地的流行病学数据、具体的患者危险因素和并存疾病、禁忌证以及可能的不良反应(例如,大环内酯类药物引起的心律失常;氟喹诺酮类药物引起的血管疾病、骨骼肌肉系统/神经系统不良反应)。虽然氟喹诺酮类药物还存在安全性问题(见下文),但美国胸科学会/美国传染病学会(ATS/IDSA)专家组认为,对于在门诊接受治疗的获得性肺炎伴并存疾病患者,使用氟喹诺酮类药物是合理之举。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
世界各地的指南可能存在差异;请参见当地指南,以获得相关指导。
耐药性的危险因素
感染耐青霉素肺炎链球菌的危险因素包括过去 3 至 6 个月内使用过 β-内酰胺类药物、过去 3 个月内有过住院治疗、误吸、过去一年内肺炎发作、年龄<5 岁或>65 岁以及患有 COPD。[92]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[93]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[94]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[95]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[96]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
耐大环内酯类肺炎链球菌的危险因素包括过去 3 个月内使用过大环内酯类药物、年龄<5 岁或>65 岁以及近期住院治疗。[92]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[93]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[94]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[95]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[96]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
耐氟喹诺酮类肺炎链球菌的危险因素包括既往暴露于氟喹诺酮类药物、居住在养老院、青霉素耐药以及患有 COPD。[92]Furuya EY, Lowy FD. Antimicrobial-resistant bacteria in the community setting. Nat Rev Microbiol. 2006 Jan;4(1):36-45.
http://www.ncbi.nlm.nih.gov/pubmed/16357859?tool=bestpractice.com
[93]Lynch JP 3rd, Zhanel GG. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin Respir Crit Care Med. 2009 Apr;30(2):210-38.
http://www.ncbi.nlm.nih.gov/pubmed/19296420?tool=bestpractice.com
[94]Fenoll A, Granizo JJ, Aguilar L, et al. Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol. 2009 Apr;47(4):1012-20.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668361
http://www.ncbi.nlm.nih.gov/pubmed/19225097?tool=bestpractice.com
[95]Dagan R, Klugman KP. Impact of conjugate pneumococcal vaccines on antibiotic resistance. Lancet Infect Dis. 2008 Dec;8(12):785-95.
http://www.ncbi.nlm.nih.gov/pubmed/19022193?tool=bestpractice.com
[96]Aspa J, Rajas O, de Castro FR. Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia. Expert Opin Pharmacother. 2008 Feb;9(2):229-41.
http://www.ncbi.nlm.nih.gov/pubmed/18201146?tool=bestpractice.com
住院
为了确定患者是否应在门诊治疗,除了根据临床判断外,还要使用经过验证的临床预测规则评估预后(PSI 优于 CURB-65)。PSI 优于 CURB-65,因为 PSI 可将更大比例的患者识别为低风险患者,并且在预测死亡率方面有更高的鉴别能力。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
对于以下情况,推荐入院:[80]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 Jan 23;336(4):243-50.
http://www.nejm.org/doi/full/10.1056/NEJM199701233360402#t=article
http://www.ncbi.nlm.nih.gov/pubmed/8995086?tool=bestpractice.com
[81]Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377-82.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746657
http://www.ncbi.nlm.nih.gov/pubmed/12728155?tool=bestpractice.com
将需要升压药治疗的低血压患者或需要机械通气的呼吸衰竭患者收住 ICU。对于不需要升压药治疗或机械通气的患者,应使用用于确定重度 CAP(参见“诊断标准”部分)的 ATS/IDSA 标准,并结合临床判断来指导是否需要加大治疗强度。将重度 CAP(确定依据为符合 2 项主要标准或至少 3 项次要标准)患者收入 ICU。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
必要时实施氧疗。监测氧饱和度和吸氧浓度,旨在将 SaO₂ 维持在 92% 以上。对于单纯性肺炎患者,可以安全地提供较高的氧气浓度。
[ ]
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 对于并发通气衰竭的 COPD 患者,应根据重复测量的动脉血气水平以指导氧疗。[67]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. British Thoracic Society 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
尽管经过了适当的氧治疗,呼吸衰竭患者仍需要进行紧急气道管理和(有可能)插管。
评估患者是否有容量缺失。如果需要,应根据当地方案给予静脉输液,对于长期疾病患者,应提供营养支持。[67]Lim WS, Baudouin SV, George RC, et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. British Thoracic Society 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
监测患者的体温、呼吸频率、脉搏、血压、精神状态、氧饱和度和吸氧浓度情况,至少每日两次,对于重度肺炎和需要定期氧疗的患者,可提高监测频率。定期监测 C 反应蛋白(C-reactive protein,CRP)的水平,因为它们是肺炎进展的敏感标志物。对于进展情况不理想的患者,应重复进行胸部 X 线检查。如果症状在 5-7 天内消退,则不推荐常规进行胸部影像学检查随访。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
非收住 ICU 的住院患者的经验性抗微生物治疗
对于无 MRSA 或铜绿假单胞菌感染危险因素的非重度 CAP 住院患者,美国 ATS/IDSA 指南推荐以下静脉用经验性治疗选择:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
使用 β-内酰胺类药物(例如,氨苄西林/舒巴坦、头孢噻肟、头孢曲松、ceftaroline)与大环内酯类药物(例如,阿奇霉素、克拉霉素)进行联合治疗。应注意,在美国,克拉霉素仅有口服制剂可用,因此只有当口服途径可行时,才能使用此药
使用呼吸道氟喹诺酮类药物(例如,左氧氟沙星、莫西沙星)进行单药治疗
对大环内酯类和氟喹诺酮类药物均有禁忌的患者,可使用 β-内酰胺类药物联合多西环素。
对于有感染耐 MRSA 或铜绿假单胞菌危险因素的患者,如果当地已证实有这两种病原体中任一病原体的危险因素,则需要加用其他经验性抗生素来进行覆盖:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
感染 MRSA 或铜绿假单胞菌的最强有力危险因素是:存在呼吸道分离出这些病原体的既往史和/或近期住院史以及过去 90 天内经胃肠外使用过抗生素。基于此,ATS/IDSA 给出以下推荐:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
如果患者有呼吸道分离出 MRSA 或铜绿假单胞菌的既往史:应加用适当的抗生素药物进行覆盖,并进行培养(若条件允许,也可进行鼻部聚合酶链反应 [polymerase chain reaction,PCR] 检测),以指导降级治疗或者确认是否需要继续覆盖更多微生物。
如果患者最近住过院并在过去 90 天内接受过胃肠外抗生素治疗,并且当地已证实存在 MRSA 的危险因素:应进行培养和鼻部 PCR 检测。如果 PCR 检测或培养结果为阴性,则停止加用覆盖更多微生物的药物。如果 PCR 检测或培养结果为阳性,则开始加用覆盖更多微生物的药物。
如果患者有近期住院史并在过去 90 天内接受过胃肠外抗生素治疗,并且当地已证实存在铜绿假单胞菌的危险因素:应进行培养,并仅在培养结果为阳性时开始使用覆盖该细菌的抗生素。
如果培养物中没有发现耐药病原菌,并且患者的临床状况有所改善,则考虑在 48 小时后降级为标准抗生素治疗。
对于存在产超广谱 β-内酰胺酶肠杆菌感染危险因素的患者,需要加用其他经验性抗生素药物。咨询感染性疾病专科医生,获取合适的抗生素治疗方案指导。除非怀疑肺脓肿或脓胸,否则不建议对疑似吸入性肺炎患者使用额外的抗生素来覆盖更多病原体。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?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;[97]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
[98]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
[99]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。[100]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
[101]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://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2495-5
http://www.ncbi.nlm.nih.gov/pubmed/28576117?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
世界各地的指南可能存在差异;请参见当地指南,以获得相关指导。
ICU 患者的经验性抗微生物治疗
对于无 MRSA 或铜绿假单胞菌感染危险因素的重度 CAP 住院患者,美国 ATS/IDSA 指南推荐以下经静脉的经验性治疗选择:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
对于有感染耐 MRSA 或铜绿假单胞菌危险因素的患者,如果当地已证实有这两种病原体中任一病原体的危险因素,则需要加用其他经验性抗生素来进行覆盖:[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
加用覆盖更多微生物的其他抗生素药物,并进行培养(若条件允许,可进行针对 MRSA 的鼻部 PCR),以指导降级治疗或者确认是否需要继续治疗。如果培养物中没有发现耐药病原菌,并且患者的临床状况有所改善,则考虑在 48 小时后降级为标准抗生素治疗。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
对于存在产超广谱 β-内酰胺酶肠杆菌感染危险因素的患者,需要加用其他经验性抗生素药物。咨询感染性疾病专科医生,获取合适的抗生素治疗方案指导。除非怀疑肺脓肿或脓胸,否则不建议对疑似吸入性肺炎患者使用额外的抗生素来覆盖更多病原体。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
世界各地的指南可能存在差异;请参见当地指南,以获得相关指导。
氟喹诺酮类抗生素的安全性
在开具氟喹诺酮类药物前,应考虑安全性问题。美国食品药品监督管理局(Food and Drug Administration,FDA)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。[102]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. Jul 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
[103]Food and Drug Administration. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Dec 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)完成了一项关于氟喹诺酮类药物治疗相关严重、致残性和可能不可逆转不良反应的审评。这些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、存在肾脏受损或实体器官移植史的患者,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会更高。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,即仅允许严重感染时使用氟喹诺酮类药物。[104]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. Mar 2019 [internet publication].
https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products
虽然存在这些顾虑,ATS/IDSA 指南仍推荐将氟喹诺酮类药物用作以下患者的一种治疗选择,包括在门诊治疗的有并存疾病的患者、在医院接受治疗的非重度 CAP 患者、重度 CAP 患者。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
抗生素治疗的途径
尽早开始经验性抗生素治疗,应在急诊科开始给予该治疗,以免延误。延误治疗与重度 CAP 患者的死亡风险增加相关。[105]Garnacho-Montero J, Barrero-García I, Gómez-Prieto MG, et al. Severe community-acquired pneumonia: current management and future therapeutic alternatives. Expert Rev Anti Infect Ther. 2018 Sep;16(9):667-77.
http://www.ncbi.nlm.nih.gov/pubmed/30118377?tool=bestpractice.com
初始抗生素治疗的途径取决于严重程度、患者病情以及治疗地点。指南推荐对门诊患者使用口服抗生素,而对于住院治疗的患者,首选途径为静脉使用。然而,对于重度 CAP 患者,应总是采用静脉给药(至少在住院后最初几个小时内),同时每天进行评估,以便尽早更换为口服药物。如果患者血流动力学稳定、临床病情得到改善、可摄入口服药物,并胃肠道功能已恢复正常,则可考虑换为口服疗法。转换为同一药物的口服制剂或同一药物类别中某种药物的口服制剂。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
抗生素治疗的持续时间
最短疗程为 5 天。治疗持续时间应通过经证实的临床稳定性测定指标(例如,生命体征异常是否消退、认知功能是否正常、进食能力如何)来进行指导。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
[106]Uranga A, España PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016 Sep 1;176(9):1257-65.
http://www.ncbi.nlm.nih.gov/pubmed/27455166?tool=bestpractice.com
如果患者已经无发热 48-72 小时且无并发症(心内膜炎、脑膜炎)体征,则可以考虑终止治疗。一项回顾性队列研究发现,2/3 的 CAP 住院患者接受了过度的抗生素治疗,出院后,每增加一天治疗,抗生素相关不良反应的可能性增加 5%。[107]Vaughn VM, Flanders SA, Snyder A, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: a multihospital cohort study. Ann Intern Med. 2019 Aug 6;171(3):153-63.
http://www.ncbi.nlm.nih.gov/pubmed/31284301?tool=bestpractice.com
对于有并发症的患者,如果导致肺炎的病原菌不太常见,建议采用更长的疗程。对于感染 MRSA 或铜绿假单胞菌的患者,建议治疗疗程为 7 天。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
在这些情况下,需要咨询传染病学专家。
微生物学目标导向治疗
如果患者的实验室检查提示致病微生物,应考虑在抗生素药敏性指导下更改为针对特定病原体的抗微生物治疗。
流行性感冒患者的抗病毒治疗
对于流行性感冒检测呈阳性的 CAP 住院患者,应在抗菌药物治疗的基础上加用抗病毒治疗(例如,奥司他韦),这与诊断之前的病程长短无关。对流行性感冒病毒检测呈阳性的门诊患者,考虑进行抗病毒治疗。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
住院治疗患者的皮质类固醇疗法
对于重度 CAP 患者,皮质类固醇的使用问题长期存在争议。目前的 ATS/IDSA 指南通常推荐不对非重度或重度 CAP 患者使用皮质类固醇,不过它们均认同,根据拯救脓毒症运动指南,可考虑将这类药物用于难治性脓毒性休克患者,并且可视临床情况用于治疗并存疾病(例如,COPD、哮喘、自身免疫性疾病)。此推荐基于以下事实:目前并没有任何数据表明非重度 CAP 患者在死亡率或器官衰竭方面受益,仅有有限的数据支持对重度 CAP 患者使用该药。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
针对 CAP 住院成人患者相关研究进行的荟萃分析发现,使用皮质类固醇与减少机械通气需求、缩短住院时长、降低临床失败率、减少并发症(包括脓毒性休克)、降低 CRP 水平和降低全因死亡率存在相关性。然而,该治疗似乎只降低了重度 CAP 患者的死亡率。在非重度疾病患者中,辅助性皮质类固醇治疗可降低并发症发生率,但未降低死亡率。[108]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
[109]Bi J, Yang J, Wang Y, Yao C, 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 Nov 15;11(11):e0165942.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165942
http://www.ncbi.nlm.nih.gov/pubmed/27846240?tool=bestpractice.com
[110]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):346-354.
http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com
[111]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;(12):CD007720.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007720.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com
[112]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
[113]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456091
http://www.ncbi.nlm.nih.gov/pubmed/30921179?tool=bestpractice.com
[114]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://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616855
http://www.ncbi.nlm.nih.gov/pubmed/31261585?tool=bestpractice.com
[ ]
How do corticosteroids compare with placebo in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1978/full展示答案
接受皮质类固醇疗法的患者发生高血糖的风险增加。[110]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):346-354.
http://www.ncbi.nlm.nih.gov/pubmed/29020323?tool=bestpractice.com
[111]Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13;(12):CD007720.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007720.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/29236286?tool=bestpractice.com
[ ]
How do corticosteroids compare with placebo in adults with pneumonia?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1978/full展示答案 其他不良反应包括重叠感染和上消化道出血。
无反应性肺炎
无反应性 CAP 是指进行抗生素治疗 3 至 5 天后疗效并不充分。无反应性肺炎的病因可分为感染性、非感染性以及不明原因。多中心研究表明,6% 至 24% 的 CAP 病例会对抗生素治疗无反应,而在重度肺炎病例中,这一概率可能高达 31%。[19]Torres A, Barberán J, Falguera M, et al. Multidisciplinary guidelines for the management of community-acquired pneumonia [in Spanish]. Med Clin (Barc). 2013 Mar 2;140(5):223.
http://www.ncbi.nlm.nih.gov/pubmed/23276610?tool=bestpractice.com
[115]Aliberti S, Blasi F. Clinical stability versus clinical failure in patients with community-acquired pneumonia. Semin Respir Crit Care Med. 2012 Jun;33(3):284-91.
http://www.ncbi.nlm.nih.gov/pubmed/22718214?tool=bestpractice.com
在一项研究中,作者介绍了无反应肺炎的两种不同临床类型:[116]Menendez R, Torres A. Treatment failure in community-acquired pneumonia. Chest. 2007 Oct;132(4):1348-55.
http://www.ncbi.nlm.nih.gov/pubmed/17934120?tool=bestpractice.com
研究发现,包括 CRP 和降钙素原 (procalcitonin, PCT) 等在内的生物标志物有助于预测宿主反应应答不足。如果初次就诊时 CRP 或 PCT 水平高,则表明存在反应应答不足的危险因素,[74]Menéndez R, Cavalcanti M, Reyes S, et al. Markers of treatment failure in hospitalised community acquired pneumonia. Thorax. 2008 May;63(5):447-52.
http://thorax.bmj.com/content/63/5/447.long
http://www.ncbi.nlm.nih.gov/pubmed/18245147?tool=bestpractice.com
如果水平较低,则具有保护意义。使用降钙素原指导抗生素治疗的开始和持续时间,降低了死亡风险,减少了抗生素消耗,并且降低了副作用风险。[117]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):CD007498.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007498.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/29025194?tool=bestpractice.com
[118]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.
http://www.ncbi.nlm.nih.gov/pubmed/29037960?tool=bestpractice.com
然而,一项综述发现,特别是在危重病患者中,短期死亡率无差异,[119]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
而另一项研究发现,CT 灌注成像指导下的治疗并未导致抗生素的使用减少。[120]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://escholarship.org/uc/item/9bd679z6
http://www.ncbi.nlm.nih.gov/pubmed/29781385?tool=bestpractice.com
共识流程(包含用于确定何时开始或终止抗生素治疗的 PCT 临界值)可能有助于促进安全有效地实施 PCT 指导下治疗。[121]Schuetz P, Bolliger R, Merker M, et al. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials. Expert Rev Anti Infect Ther. 2018 Jul;16(7):555-64.
http://www.ncbi.nlm.nih.gov/pubmed/29969320?tool=bestpractice.com
出现无反应或恶化时,第一反应应该是重新评估初期微生物检测结果。[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-e67.
https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST
http://www.ncbi.nlm.nih.gov/pubmed/31573350?tool=bestpractice.com
如果就诊时未获取培养和敏感性试验结果,则现在获取这些结果可以明确确定临床治疗失败的原因。此外,如果尚未采集任何罕见微生物(包括病毒)感染危险因素的相关病史,则应进一步采集病史。还可能有必要进行进一步的诊断性检测。