在与克隆背景、耐药基因、共同耐药和地区相关的情况下，比较分析来自美国和国际地区的产碳青霉烯酶中间或耐药的大肠埃希菌分离株中，普拉佐米星的活性。
Activity of plazomicin against carbapenem-intermediate or -resistant Escherichia coli isolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region.
机构信息
Minneapolis VA Health Care System, Minneapolis, MN, USA.
University of Minnesota, Minneapolis, MN, USA.
出版信息
J Antimicrob Chemother. 2021 Jul 15;76(8):2061-2070. doi: 10.1093/jac/dkab150.
BACKGROUND
Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), threatens therapeutic efficacy. Plazomicin (PLZ), a semisynthetic aminoglycoside approved by the FDA in 2018, overcomes the most common aminoglycoside resistance mechanisms and maintains activity against many carbapenem-intermediate or -resistant (CIR) E. coli strains.
OBJECTIVES
To assess plazomicin susceptibility among CIR E. coli in relation to region and multiple bacterial characteristics.
METHODS
We determined broth microdilution MICs for plazomicin and 11 comparators against 343 CIR clinical E. coli isolates, then compared susceptibility results by bacterial characteristics and region. The collection comprised 203 US isolates (2002-17) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003-17). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant β-lactamase-encoding genes.
RESULTS
Plazomicin exhibited the highest percentage susceptible (89%) after tigecycline (99%). The percentage susceptible to plazomicin varied significantly by phylogroup (63%, group B1; versus >93%, others) and ST131 subclone (92%, H30Rx; versus 87%-89%, H30R1 and non-H30), but not ST. It also varied by resistance genotype [higher with Klebsiella pneumoniae carbapenemase (KPC), lower with metallo-β-lactamases], global region [highest for Latin America (94%), lowest for Asia-West Pacific (69%)], and US region (80%, South, versus 96%-100%, others). Although reduced susceptibility to comparators often predicted reduced susceptibility to plazomicin, even among comparator-intermediate or -resistant isolates the plazomicin-susceptible fraction was ≥77%, except for amikacin (53%).
CONCLUSIONS
The likely utility of plazomicin against CIR E. coli is high overall, but varies with region and multiple bacterial characteristics.
背景
大肠杆菌中新兴的碳青霉烯类耐药性，包括 ST131 型，威胁着治疗效果。PLZ（音译：普拉克索米星）是一种半合成氨基糖苷类药物，于 2018 年被 FDA 批准，可克服最常见的氨基糖苷类耐药机制，并对许多耐碳青霉烯中间或耐碳青霉烯（CIR）的大肠杆菌菌株保持活性。
目的
评估 PLZ 对 CIR 大肠杆菌的药敏性与地区和多种细菌特征的关系。
方法
我们测定了 343 株 CIR 临床大肠杆菌分离株对 PLZ 和 11 种对照药物的肉汤微量稀释 MICs，然后根据细菌特征和地区比较药敏结果。该研究包含了 203 株来自美国（2002-17 年）的分离株和 141 株来自欧洲、拉丁美洲和亚洲-西太平洋地区（2003-17 年）的分离株。对分离株的系统发育群、与耐药相关的序列型（ST）及其亚群以及相关β-内酰胺酶编码基因进行了特征分析。
结果
在替加环素（99%）之后，PLZ 的药敏率最高（89%）。PLZ 的药敏率因进化群（63%，B1 群；与>93%，其他群）和 ST131 亚克隆（92%，H30Rx；与 87%-89%，H30R1 和非 H30）而显著不同，但与 ST 无关。它还因耐药基因型而变化[产 KPC（耐碳青霉烯类肺炎克雷伯菌）时更高，产金属β-内酰胺酶时更低]、全球地区[拉丁美洲最高（94%），亚洲-西太平洋最低（69%）]和美国地区[南部地区 80%（低于其他地区 96%-100%）]。虽然对比较药物的敏感性降低通常预示着对 PLZ 的敏感性降低，但即使在比较药物中介或耐药的分离株中，PLZ 的药敏率仍≥77%，除了阿米卡星（53%）。
结论
PLZ 对 CIR 大肠杆菌的总体疗效较高，但因地区和多种细菌特征而异。
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