背景:军团病(LD)是社区获得性肺炎(CAP)的常见但未被诊断的原因,尽管尿液抗原检测(UAT)的快速检测和分子检测的进步改善了诊断。在近三分之一的病例中,LD需要入住重症监护病房(ICU),死亡率从4%到40%不等。这篇综述旨在讨论这种疾病研究的最新进展,并提供最新的诊断,严重LD的发病机制和管理。
结果:近年来,由于具有危险因素的患者数量增加,LD的总体发病率在全球范围内有所增加,尤其是免疫抑制,以及诊断方法的改进。尽管LD只占全因CAP的5%左右,它是导致CAP需要入住ICU的三个最常见原因之一.ICU患者的死亡率,尽管有适当的抗菌治疗,免疫功能低下的患者或医院来源的LD患者仍可达到40%.关于发病机理,没有军团菌特异性毒力因子与严重程度相关;然而,最近的报告发现高的肺军团菌DNA负荷,在最严重的情况下,免疫反应和肺部微生物组受损。临床表现包括需要呼吸和/或血液动力学支持的严重肺损伤,肺外症状和非特异性实验室检查结果。由于UAT的广泛使用和允许检测所有Lp血清群的分子方法的发展,LD诊断方法得到了改善。治疗目前基于大环内酯类,喹诺酮类药物,或者两者的结合,在严重的情况下长期治疗。
结论:影响LD死亡率的因素很多,如ICU入院,潜在的免疫状态,和医院感染源。宿主免疫应答(过度炎症和/或免疫麻痹)也可能与严重程度增加有关。鉴于LD的发病率正在上升,对严重程度的特定生物标志物的研究可能会引起极大的兴趣。现在需要比较不同方案和/或评估宿主导向疗法的进一步评估。
BACKGROUND: Legionnaires\' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.
RESULTS: The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.
CONCLUSIONS: Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.