Pseudomonas aeruginosa (PA) is one of the most common pathogens of refractory lower respiratory tract infections, and its related infections are more difficult to treat and have a high mortality rate due to their insensitivity to or severe resistance to many commonly used antimicrobial drugs in clinical practice.
Early recognition of lower respiratory tract infections in PA and timely selection of appropriate and effective antimicrobial therapy are the keys to improving patient outcomes. So, how to identify such infections and how to choose their antimicrobial drugs?
Choice of antimicrobial agent for empiric treatment in acute patients
1. For patients who are critically ill or cannot rule out PA infection (with high-risk factors for PA infection), empiric antimicrobial therapy covering PA can be selected after taking specimens for pathogenic testing. However, patients with CAP should choose drugs with better antimicrobial activity against Streptococcus pneumoniae rather than ceftazidime or aztreonam alone.
2. For non-severe suspected PA pneumonia, an antimicrobial agent with PA activity that can be used alone for lung infection can be selected; If the patient has severe disease such as sepsis or risk factors for drug-resistant infection, a combination of 2 different classes of antimicrobials to which PA may be sensitive is chosen. Patients with mild disease can be given orally, and severe cases should be given intravenously.
3. Drug selection should refer to the local epidemiological data of bacterial resistance, the patient's previous history of lower respiratory tract PA colonization, antimicrobial susceptibility results of infected isolates, and the use of antimicrobial drugs, etc., usually with enzyme inhibitor combinations, cephalosporins, and carbapenems, and given at adequate doses. Penicillin-allergic patients may be replaced with aztreonam.
4. Fluoroquinolones and aminoglycosides can be used in combination therapy when allergic to β-lactams or cannot be used.
Comparison of the efficacy of enzyme inhibitor compounds
The commonly used enzyme inhibitor compound preparations for the treatment of PA infection in China include piperacillin, tazobactam, piperacillin sodium, sulbactam sodium, cefoperazone sodium, cefoperazone sodium, tazobactam sodium, and a new enzyme inhibitor ceftazidime avibactam.
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来自匹兹堡大学医学中心的研究者们评估了接受头孢他啶-阿维巴坦（Ceftazidime-avibactam，CZA）和头孢托唑烷-他唑巴坦（Ceftolozane-tazobactam，C/T）治疗的MDR P. aeruginosa引起的菌血症或肺炎患者的耐药性发生率。
Of the 20 patients treated with CZA, 40% (8/20) developed resistance, while only 10% (9/87) of the 93 patients treated with C/T developed resistance (P=0.003). The median MIC of resistant strains in patients treated with CZA was 16 (8-128) mg/L, while that of patients treated with C/T was 64 (8-512) mg/L. WGS analysis showed that the MDR P. aeruginosa strain had a high degree of diversity, and drug resistance was associated with mutations in ampD, ampC, mexR, and ftsI (PBP3) genes.
Among the 63 patients treated between 2019 and 2021, the incidence of post-treatment resistance with CZA and C/T was 44% (8/18) and 13% (6/45), respectively (P=0.02). Among monotherapy patients, the incidence of resistance was 50% (6/12) in patients treated with CZA, compared with 6% (1/17) in patients treated with C/T (P=0.01).
Propensity score matching analysis showed that patients treated with ceftazidime-avibactam (CZA) had a significantly higher risk of resistance than those treated with ceftorazolidine-tazobactam (C/T) (aOR=7.64, 95% CI: 1.23-610.1, P=0.01). In the strains isolated after treatment in 3 patients (2 CZA, 1 C/T), the resistance threshold for CLSI was not reached, although the MIC increased by ≥4-fold.
The results of the article suggest that ceftazidime-avibactam (CZA) is more likely to lead to the development of drug resistance than ceftorazolidine-tazobactam (C/T) in MDR P. aeruginosa infection. However, due to the single-center retrospective design of the article, the small sample size, and the local epidemiology of Pseudomonas aeruginosa is different, a multicenter study is needed to verify the results of the article before it can be generalized to other regions.
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To guide clinical application and drug development, the Guangzhou Institute of Respiratory Health of the National Medical Center for Respiratory Diseases and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital have targeted the most widely used combination antibiotics in China: ampicillin/sulbactam (AMP/SBT 2:1), cefoperazone/sulbactam (CPZ/SBT 2:1), ceftazidime/sulbactam (CAZ/SBT 1:1 and 2:1), piperacillin/sulbactam (PIP/SBT 1:1 and 2:1), and piperacillin/ Tazobactam (PIP/TAZ 8:1), which was studied for its bacteriostatic activity against clinically isolated strains. In particular, the antibacterial activity of piperacillin, tazobactam, piperacillin, sulbactam and cefoperazone, which are commonly used in clinical practice, was compared and studied. Original link:https://www.hindawi.com/journals/cmmm/2021/1175379/
【Research Results】
Piperacillin/sulbactam (2:1) had high antibacterial activity against several isolates, especially against Pseudomonas aeruginosa and Acinetobacter baumannii, which was better than other test drugs. In the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii, piperacillin/sulbactam is recommended (2:1).
[References]
- Infectious Diseases Group, Chinese Society of Respiratory Diseases. Expert Consensus on the Diagnosis and Treatment of Lower Respiratory Tract Infection of Pseudomonas aeruginosa in China (2022 Edition). Chinese Journal of Tuberculosis and Respiration,2022,45(08):739-752.
- Xiao S, Zhuo C, Zhuo C. In Vitro Activityof Various Sulbactam Compounds and Piperacillin/Tazobactam against ClinicalIsolates of Different Gram-Negative Bacteria. Comput Math Methods Med. 2021 Nov25;2021:1175379. doi:10.1155/2021/1175379. PMID: 34868336; PMCID: PMC8639252.
- Expert Consensus on the Clinical Application of β-lactam Antibiotic/β-lactamase Inhibitor Combination Preparations (2020 Edition)