Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0487322. doi: 10.1128/spectrum.04873-22. Epub 2023 May 15.
Aztreonam-avibactam, eravacycline, and cefoselis are three novel antimicrobial agents for the treatment of serious infections caused by Gram-negative bacteria. We evaluated the activities of the above-mentioned three antimicrobial agents against clinical isolates. A total of 1,202 isolates, including 10 genera or species, were collected from 26 hospitals that cover seven regions of China. The susceptibilities of the 30 antimicrobial agents were interpreted based on the combination of U.S. Food and Drug Administration and Clinical and Laboratory Standards Institute guidelines. The results indicated that all isolates showed high susceptibility to aztreonam-avibactam (98.25%), eravacycline (85.69%), and cefoselis (62.73%). The first two antimicrobial agents also demonstrated potent activities against multidrug-resistant and carbapenem-resistant independent of antimicrobial resistance mechanisms. The rates of susceptibility to aztreonam-avibactam, eravacycline, and cefoselis were lowest in spp. (84.42%), Proteus spp. (33.65%), and Escherichia coli (40.14%), respectively. In general, the lower rates of susceptibility to eravacycline and cefoselis were in the older inpatient group. The strains isolated from urinary tract exhibited the lowest rate of susceptibility (78.97%) to eravacycline, and the lowest rate of susceptibility (45.83%) to cefoselis was observed in nervous system specimens. The strains isolated from intensive care unit (ICU) wards showed significantly reduced susceptibility to cefoselis compared with those isolated from non-ICU wards. The MIC values of aztreonam-avibactam and ceftazidime-avibactam have poor consistency (weighted kappa = 0.243), as did eravacycline and tigecycline (weighted kappa = 0.478). Cefoselis and cefepime showed highly similar activities against (weighted kappa = 0.801). Our results support the clinical development of aztreonam-avibactam, eravacycline, and cefoselis to treat infections caused by . Infections caused by multidrug-resistant (MDR) , especially carbapenem-resistant (CRE), have been a challenging clinical problem due to the limited therapeutic options. Therefore, the need to develop novel antimicrobial agents and evaluate their activities against is urgent. Our results show that the novel antimicrobial agents aztreonam-avibactam and eravacycline retain activities against MDR and CRE isolates, including carbapenemase producers and non-carbapenemase producers. Further analysis combined with clinical information on the strains tested revealed that no significant differences were observed in susceptibility rates of strains with different demographic parameters to aztreonam-avibactam. Age, specimen source, and department were associated with the susceptibility of strains to eravacycline and cefoselis ( ≤ 0.01). Compared with ceftazidime-avibactam, aztreonam-avibactam has its advantages and limitations against . The potent activity of eravacycline against was higher than that of tigecycline. Cefoselis and cefepime showed a highly consistent activity against .
氨曲南-阿维巴坦、依拉环素和头孢噻利是三种新型抗菌药物,用于治疗由革兰氏阴性菌引起的严重感染。我们评估了上述三种抗菌药物对临床分离株的活性。从覆盖中国七个地区的 26 家医院共收集了 1202 株包括 10 个属或种的分离株。根据美国食品和药物管理局(FDA)和临床与实验室标准协会(CLSI)指南的组合,解释了 30 种抗菌药物的药敏性。结果表明,所有分离株对氨曲南-阿维巴坦(98.25%)、依拉环素(85.69%)和头孢噻利(62.73%)均表现出高度敏感性。前两种抗菌药物对多种耐药和碳青霉烯类耐药的独立于抗菌药物耐药机制也表现出强大的活性。对 spp.(84.42%)、普罗维登斯菌属(33.65%)和大肠埃希菌(40.14%)的分离株的敏感性最低。一般来说,较老的住院患者对依拉环素和头孢噻利的敏感性较低。从尿路感染分离的菌株对依拉环素的敏感性最低(78.97%),从神经系统标本中分离的菌株对头孢噻利的敏感性最低(45.83%)。与非 ICU 病房分离的菌株相比,从 ICU 病房分离的菌株对头孢噻利的敏感性显著降低。氨曲南-阿维巴坦和头孢他啶-阿维巴坦的 MIC 值一致性较差(加权 κ=0.243),依拉环素和替加环素也如此(加权 κ=0.478)。头孢噻利和头孢吡肟对 具有高度相似的活性(加权 κ=0.801)。我们的结果支持氨曲南-阿维巴坦、依拉环素和头孢噻利的临床开发,以治疗由 引起的感染。由于治疗选择有限,由多药耐药(MDR),尤其是碳青霉烯类耐药(CRE)引起的感染一直是一个具有挑战性的临床问题。因此,迫切需要开发新的抗菌药物并评估它们对 的活性。我们的结果表明,新型抗菌药物氨曲南-阿维巴坦和依拉环素对 MDR 和 CRE 分离株保留活性,包括碳青霉烯酶产生菌和非碳青霉烯酶产生菌。进一步的分析结合对所测试菌株的临床信息表明,不同人口统计学参数的菌株对氨曲南-阿维巴坦的敏感性率没有观察到显著差异。年龄、标本来源和科室与菌株对依拉环素和头孢噻利的敏感性有关(≤0.01)。与头孢他啶-阿维巴坦相比,氨曲南-阿维巴坦对 的活性具有优势和局限性。依拉环素对 的活性高于替加环素。头孢噻利和头孢吡肟对 具有高度一致的活性。