抗生素治疗
需要使用具有细胞内活性的抗生素治疗,因为军团菌在细胞内生存和复制。[45]Benin AL, Benson RF, Besser RE. Trends in legionnaires disease, 1980-1998: declining mortality and new patterns of diagnosis. Clin Infect Dis. 2002;35:1039-1046.http://www.ncbi.nlm.nih.gov/pubmed/12384836?tool=bestpractice.com[46]Heath CH, Grove DI, Looke DFM. Delay in appropriate therapy of Legionella pneumonia associated with increased mortality. Eur J Clin Microbiol Infect Dis. 1996;15:286-290.http://www.ncbi.nlm.nih.gov/pubmed/8781878?tool=bestpractice.com美国传染病学学会/美国胸科学会 (Infectious Diseases Society of America/American Thoracic Society, IDSA/ATS) 建议在诊断所有社区获得性肺炎 (CAP) 患者时,在知道致病性病原体之前,使用具有抵抗非典型细菌(包括军团菌)活性的抗生素。[36]Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.http://cid.oxfordjournals.org/content/44/Supplement_2/S27.longhttp://www.ncbi.nlm.nih.gov/pubmed/17278083?tool=bestpractice.com[47]Arnold F, Summersgill JT, Lajoie AS, et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med. 2007;175:1086-1093.http://www.ncbi.nlm.nih.gov/pubmed/17332485?tool=bestpractice.com然而,这种方法目前并没有获得国际共识。[48]Lim WS, Baudouin SV, George RC, et al; British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(suppl 3):iii1-iii55.https://www.brit-thoracic.org.uk/document-library/clinical-information/pneumonia/adult-pneumonia/bts-guidelines-for-the-management-of-community-acquired-pneumonia-in-adults-2009-updatehttp://www.ncbi.nlm.nih.gov/pubmed/19783532?tool=bestpractice.com[49]Mills GD, Oehley MR, Arrol B. Effectiveness of beta lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis. BMJ. 2005;330:456.http://www.bmj.com/cgi/content/full/330/7489/456http://www.ncbi.nlm.nih.gov/pubmed/15684024?tool=bestpractice.com[50]Shefet D, Robenshtok E, Paul M, et al. Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials. Arch Intern Med. 2005;165:1992-2000.http://archinte.ama-assn.org/cgi/content/full/165/17/1992http://www.ncbi.nlm.nih.gov/pubmed/16186469?tool=bestpractice.com
患者应采用氟喹诺酮(如左氧氟沙星)治疗,或采用较新的大环内酯(如阿奇霉素或克拉霉素)治疗。[51]Mykietiuk A, Carratala J, Fernandez-Sabe N, et al. Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy. Clin Infect Dis. 2005;40:794-799.http://www.ncbi.nlm.nih.gov/pubmed/15736010?tool=bestpractice.com红霉素被用于早期爆发,并且据报告其疗效优于 β-内酰胺类抗生素(例如青霉素),但现已被更新的大环内酯类和左氧氟沙星所取代。[52]Edelstein PH, Shinzato T, Doyle E, et al. In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and its pharmacokinetics in guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother. 2001;45:2204-2209.http://aac.asm.org/cgi/content/full/45/8/2204http://www.ncbi.nlm.nih.gov/pubmed/11451675?tool=bestpractice.com有观察性研究表明,相比红霉素或克拉霉素,接受左氧氟沙星治疗的患者治疗效果更好,但其他研究发现三者的疗效难分优劣。[53]Blazquez-Garrido RM, Espinosa-Parra FJ, Alemany-Frances L, et al. Antimicrobial chemotherapy for legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis. 2005;40:800-806.http://www.ncbi.nlm.nih.gov/pubmed/15736011?tool=bestpractice.com[54]Sabria M, Pedro-Botet ML, Gomez J, et al. Fluoroquinolones vs macrolides in the treatment of Legionnaires disease. Chest. 2005;128:1401-1405.http://www.ncbi.nlm.nih.gov/pubmed/16162735?tool=bestpractice.com[55]Griffin AT, Peyrani P, Wiemken T, et al. Macrolides versus quinolones in Legionella pneumonia: results from the Community-Acquired Pneumonia Organization international study. Int J Tuberc Lung Dis. 2010;14:495-499.http://www.ncbi.nlm.nih.gov/pubmed/20202309?tool=bestpractice.com
如果已知患者对这些药物过敏,或者药物不可用,则可以尝试使用四环素类药物。
IDSA/ATS 指南中提供的 CAP 治疗建议可能也适用于军团病患者,因为患者临床状态稳定时,可在患者出院后,将静脉内注射疗法改为口服治疗。[36]Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.http://cid.oxfordjournals.org/content/44/Supplement_2/S27.longhttp://www.ncbi.nlm.nih.gov/pubmed/17278083?tool=bestpractice.com
治疗失败或病情严重
持续发热、排痰性咳嗽、缺氧、高碳酸血症、肺功能恶化以及低血压脓毒症的全身体征可受益于氟喹诺酮和大环内酯联合治疗。[56]Dournon E, Mayaud CH, Wolff M, et al. Comparison of the activity of three antibiotic regimens in severe LD. J. Antimicrob Chemother. 1990;26(Suppl. B):129-139.http://www.ncbi.nlm.nih.gov/pubmed/2258340?tool=bestpractice.com然而,需要注意的是,这种联合治疗具有显著的潜在毒性,如导致 QT 间期延长和可能的尖端扭转性室性心律失常。[57]Roig J, Rello J. Legionnaires' disease: a rational approach to therapy. J Antimicrob Chemother. 2003;5:1119-1129.http://jac.oxfordjournals.org/cgi/content/full/51/5/1119http://www.ncbi.nlm.nih.gov/pubmed/12668578?tool=bestpractice.com虽然大环内酯类/喹诺酮与利福霉素(利福平)的联合治疗是一种经过研究的治疗方法,但由于治疗效果较差(可能与利福霉素诱导大环内酯类或喹诺酮的肝脏代谢有关),即使对于严重病例也不主张采用这种疗法。[58]Grau S, Antonio JM, Ribes E, et al. Impact of rifampicin addition to clarithromycin in Legionella pneumophila pneumonia. Int J Antimicrob Agents. 2006;28:249-252.http://www.ncbi.nlm.nih.gov/pubmed/16870401?tool=bestpractice.com