铜绿假单胞菌(PA)是我国第二常见的医院获得性肺炎(HAP)革兰阴性菌(16.9%-22.0%)。PA在社区获得性肺炎(CAP)中的比例约为1.0%,而在严重CAP中增加到1.8%-8.3%。有PA感染史的患者中PA占CAP的67.0%,支气管扩张,非常严重的慢性阻塞性肺疾病(COPD)或气管切开术。考虑到PA引起的下呼吸道感染(LRTIs)的高疾病负担,加上近年来在这一领域的进展,中国胸科学会肺部感染大会更新了《中国成人下呼吸道铜绿假单胞菌感染管理专家共识(2014版)》,专注于病原体检测,诊断,抗菌治疗,综合管理,感染预防和控制。PA引起急性和慢性LTRI。急性LRTIs主要包括肺炎(CAP,HAP和呼吸机相关性肺炎),气管支气管炎,肺脓肿和脓胸。慢性LTRI的诊断应基于对(1)潜在的慢性结构性肺疾病的综合评估,比如支气管扩张,囊性纤维化,COPD,(2)存在LRTIs的临床表现;(3)在1年内从合格的下呼吸道标本中检测到的PA≥2次(至少间隔3个月)。当从下呼吸道标本中分离出PA时,区分感染与定植很重要。药物敏感性试验是PA耐药性检测的常规方法,是靶向治疗的基础。当药物敏感性试验显示可用药物的活性有限时,联合药敏试验建议选择体外具有累加或协同作用的抗菌药物进行联合治疗。PA分离株抗性机制的快速检测,如碳青霉烯酶表型确认试验,如果有建议。建议不要常规检测抗性基因以选择治疗剂。对于病情危重或有PA感染高危因素的急性LRTIs患者,在采集标本进行微生物学试验后,应启动涵盖PA的经验性抗菌治疗.在非危重的疑似PA肺炎患者中,应选择具有高肺脏浓度的抗PA活性的单一抗菌药物进行经验性治疗。然而,对于患有严重疾病(如败血症)或具有多药耐药(MDR)PA危险因素的患者,应使用两种不同类型的抗微生物药物的组合,这两种药物都可能敏感。抗菌方案应遵循药代动力学/药效学原则,以确保足够的剂量和给药频率。对于已确认的PALRTI,应根据药物敏感性选择抗生素。在没有重大基础疾病的患者中,建议使用具有足够肺部浓度的活性抗菌药物的单一治疗,而不是联合治疗;当所有可用的活性剂的肺内浓度都较差时,联合治疗是必须的。对于耐碳青霉烯PA(CRPA)或难以治疗的耐药性PA(DTR-PA)引起的LRTI,如果是一种新的酶抑制剂,例如头孢特洛赞/他唑巴坦,头孢他啶/阿维巴坦,亚胺培南/西司他丁/来巴坦显示体外敏感性,建议将其作为一线治疗;头孢地洛可以作为二线治疗。也可以考虑基于多粘菌素的联合疗法。耐药PALRTI的其他潜在成功方法包括延长β-内酰胺的输注时间,联合治疗和吸入抗菌治疗。在患有潜在慢性结构性肺病的患者中,抗菌方案(药物,剂量,给药途径,和治疗持续时间)应根据临床特征决定,药物敏感性,和治疗目标(控制加剧的症状,根除新兴的PA,或预防频繁恶化的患者的突然发作)。除了抗菌治疗,包括气道清除治疗(ACT)在内的综合护理,氧疗,应提供营养支持和器官功能保护。从医院感染预防和控制的角度,除了标准预防措施外,建议隔离和预防接触传输以阻止PA传输。有针对性的主动筛查,及时监测和反馈有助于MDR-PA的预防和控制。不建议全身和局部使用预防性抗菌药物。
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Pseudomonas aeruginosa (PA) is the second common Gram-negative bacterium for hospital acquired pneumonia (HAP) in China (16.9%-22.0%). The proportion of PA in community acquired pneumonia (CAP) was about 1.0%, while increased to 1.8%-8.3% in severe CAP. PA accounted for 67.0% of CAP in patients with a history of PA infection,
bronchiectasis, very severe chronic obstructive pulmonary disease (COPD) or tracheotomy. Considering the high disease burden of lower respiratory tract infections (LRTIs) caused by PA, together with the progress in this field in recent years, the Pulmonary Infection Assembly of Chinese Thoracic Society updated the \"Chinese expert
consensus on the management of lower respiratory tract infections of Pseudomonas aeruginosa in adults (2014 version)\", focusing on pathogen detection, diagnosis, antimicrobial therapy, comprehensive management, infection prevention and control.PA causes both acute and chronic LTRIs. Acute LRTIs mainly include pneumonia (CAP, HAP and ventilator-associated pneumonia), tracheobronchitis, lung abscess and empyema. The diagnosis of chronic LTRIs should be based on a comprehensive assessment of (1) underlying chronic structural lung diseases, such as
bronchiectasis, cystic fibrosis, COPD, or immunocompromised conditions; (2) the presence of clinical manifestations of LRTIs; and (3) ≥ two times (at least 3 months apart) of PA detected from eligible lower respiratory tract specimens within 1 year. It is important to distinguish infection from colonization when PA is isolated from lower respiratory tract specimens. Drug susceptibility test is a conventional method for PA resistance detection and serves as a basis for target therapy. When drug susceptibility test shows limited activity of available agents, combined susceptibility test is suggested to select antimicrobial drugs with additive or synergistic effect in vitro for combination therapy. Rapid test of resistance mechanisms of PA isolates, such as carbapenemase phenotype confirmation tests, is recommended if available. It is recommended not to routinely detect resistance genes for choosing therapeutic agents.For patients with acute LRTIs in critical condition or with high risk factors for PA infection, empirical antimicrobial therapy covering PA should be initiated after collecting specimens for microbiological tests. In patients with suspected PA pneumonia who are not critically ill, single antimicrobial drug of anti-PA activity with high lung concentration should be selected for empirical treatment. However, for patients with a serious condition such as sepsis or with risk factors for multidrug-resistant (MDR) PA, a combination of two different classes of antimicrobial drugs that are both potentially susceptible should be used. The antimicrobial regimen should follow pharmacokinetics/pharmacodynamics principles to ensure adequate dosage and administration frequency. For confirmed PA LRTIs, antibiotics should be selected based on drug sensitivity. In patients without significant underlying diseases, single therapy of an active antimicrobial with adequate pulmonary concentration is recommended rather than combination therapy; when all the available active agents have poor intrapulmonary concentrations, combination therapy is obligatory. For LRTIs caused by carbapenem-resistant PA (CRPA) or difficult-to-treat resistance PA (DTR-PA), if an agent of new enzyme inhibitor, such as ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/cilastatin/relebactam shows in vitro sensitivity, it is recommended as the first-line choice; cefiderocol may serve as the second-line treatment. Combination therapy based on polymyxins may also be considered. Other potentially successful approaches for drug-resistant PA LRTIs include extended infusion time of β-lactams, combination therapy and inhaled antimicrobial therapy.In patients with underlying chronic structural lung diseases, the antimicrobial regimen (drug, dosage, route of administration, and duration of therapy) should be decided according to clinical features, drug sensitivity, and treatment goals (control of exacerbated symptoms, eradication of new-emerging PA, or prevention of flare-ups in patients with frequent exacerbation).Along with antimicrobial therapy, comprehensive care including airway clearance therapy (ACT), oxygen therapy, nutritional support and organ function protection should be provided. From the perspective of nosocomial infection prevention and control, isolation and prophylaxis of contact transmission are recommended to block PA transmission in addition to standard prevention measures. Targeted active screening, timely monitoring and feedback can help the prevention and control of MDR-PA. The systemic and topical use of prophylactic antimicrobials is not recommended.
铜绿假单胞菌是难治性下呼吸道感染最常见致病菌之一,由于其耐药严重和易形成生物被膜,特别是近10多年来碳青霉烯类耐药株的出现,使其治疗更为困难;同时新的治疗药物和治疗策略不断问世,有必要加以评估以指导临床合理应用。中华医学会呼吸病学分会感染学组在《铜绿假单胞菌下呼吸道感染诊治专家共识(2014年版)》的基础上进行更新,并以临床诊治和预防的思路和技术为重点,以期为临床医生规范化诊治铜绿假单胞菌下呼吸道感染提供切实可行的参考。.