Chinese expert consensus on the management of lower respiratory tract infections of Pseudomonas aeruginosa in adults(2022)

Abstract

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.