Sader Helio S, Mendes Rodrigo E, Ryan Arends S J, Doyle Timothy B, Castanheira Mariana
Element Iowa City (JMI Laboratories), 345 Beaver Kreek Centre, Suite A North Liberty, Iowa, IA, 52317, USA.
BMC Pulm Med. 2025 Jan 24;25(1):38. doi: 10.1186/s12890-025-03500-8.
Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals.
Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020-2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing.
Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L.
Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures.
肺炎的初始抗菌治疗通常是经验性的，抗菌药物耐药性对肺炎住院患者的治疗构成了巨大挑战。我们评估了美国医院中引起肺炎的革兰氏阴性菌的频率和抗菌药敏情况。
从肺炎住院患者中连续收集细菌分离株（每位患者1株），并在一个监测实验室通过肉汤稀释法评估革兰氏阴性杆菌（3911株肠杆菌科细菌和2753株非发酵菌）的药敏情况。2020年至2022年期间在69个医疗中心收集分离株。对氨曲南-阿维巴坦进行测试，阿维巴坦固定浓度为4mg/L，并应用≤8mg/L的药代动力学/药效学敏感（S）断点进行比较。对碳青霉烯类耐药肠杆菌科细菌（CRE；对亚胺培南和/或美罗培南的MIC值>2mg/L的分离株）通过全基因组测序筛查碳青霉烯酶。
革兰氏阴性杆菌占分离菌的71.1%。最常见的革兰氏阴性菌是铜绿假单胞菌（占分离菌的22.4%）、肺炎克雷伯菌（8.8%）、大肠埃希菌（6.6%）、粘质沙雷菌（6.2%）、嗜麦芽窄食单胞菌（4.9%）和阴沟肠杆菌复合体（4.8%）。氨曲南-阿维巴坦在≤8mg/L时对100.0%的肠杆菌科细菌有抑制作用，在≤4mg/L时对99.9%的肠杆菌科细菌有抑制作用，并且对CRE显示出强效活性（MIC，0.25/1mg/L）。头孢他啶-阿维巴坦和美罗培南-巴尼巴坦分别对89.4%和88.5%的CRE有活性。氨曲南-阿维巴坦对头孢他啶-阿维巴坦和/或美罗培南-巴尼巴坦不敏感的肠杆菌科细菌仍有活性（n = 19；MIC，0.25/4mg/L）。最常见的碳青霉烯酶是KPC（占CRE的69.2%）、NDM（9.6%）和SME（4.8%）。16.3%的CRE未鉴定出碳青霉烯酶基因。头孢他啶-阿维巴坦和美罗培南-巴尼巴坦对KPC和SME产生菌具有高活性，但对MBL产生菌活性有限。对CRE最有效的对照药物是替加环素（95.2%敏感）、阿米卡星（73.1%敏感）和庆大霉素（60.6%敏感）。在铜绿假单胞菌中，79.1%在氨曲南-阿维巴坦≤8mg/L时被抑制，77.2%对美罗培南敏感，77.2%对哌拉西林-他唑巴坦敏感。氨曲南-阿维巴坦对嗜麦芽窄食单胞菌具有高活性，在≤8mg/L时抑制99.5%的分离株。
氨曲南-阿维巴坦对从肺炎住院患者中分离出的大量当代革兰氏阴性菌显示出强大的体外活性，包括对头孢他啶-阿维巴坦和/或美罗培南-巴尼巴坦耐药的CRE分离株。监测项目的结果对于制定经验性抗菌治疗指南和感染控制措施具有重要价值。
