Lin Christina K, Page Alex, Lohsen Sarah, Haider Ali A, Waggoner Jesse, Smith Gillian, Babiker Ahmed, Jacob Jesse T, Howard-Anderson Jessica, Satola Sarah W
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
JAC Antimicrob Resist. 2024 Mar 21;6(2):dlae048. doi: 10.1093/jacamr/dlae048. eCollection 2024 Apr.
Heteroresistance (HR), the presence of antibiotic-resistant subpopulations within a primary isogenic population, may be a potentially overlooked contributor to newer β-lactam/β-lactamase inhibitor (BL/BLI) treatment failure in carbapenem-resistant Enterobacterales (CRE) infections.
To determine rates of susceptibility and HR to BL/BLIs ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in clinical CRE isolates.
The first CRE isolate per patient per year from two >500 bed academic hospitals from 1 January 2016 to 31 December 2021, were included. Reference broth microdilution (BMD) was used to determine antibiotic susceptibility, and population analysis profiling (PAP) to determine HR. Carbapenemase production (CP) was determined using the Carba NP assay.
Among 327 CRE isolates, 46% were , 38% and 16% . By BMD, 87% to 98% of CRE were susceptible to the three antibiotics tested. From 2016 to 2021, there were incremental decreases in the rates of susceptibility to each of the three BL/BLIs. HR was detected in each species-antibiotic combination, with the highest rates of HR (26%) found in isolates with imipenem/relebactam. HR or resistance to at least one BL/BLI by PAP was found in 24% of CRE isolates and 65% of these had detectable CP.
Twenty-four percent of CRE isolates tested were either resistant or heteroresistant (HR) to newer BL/BLIs, with an overall decrease of ∼10% susceptibility over 6 years. While newer BL/BLIs remain active against most CRE, these findings support the need for ongoing antibiotic stewardship and a better understanding of the clinical implications of HR in CRE.
异质性耐药（HR），即在原同基因菌群中存在抗生素耐药亚群，可能是耐碳青霉烯类肠杆菌科细菌（CRE）感染中新型β-内酰胺/β-内酰胺酶抑制剂（BL/BLI）治疗失败的一个潜在被忽视的因素。
确定临床CRE分离株对BL/BLIs头孢他啶/阿维巴坦、亚胺培南/瑞来巴坦和美罗培南/伏巴拉坦的敏感性和HR率。
纳入2016年1月1日至2021年12月31日期间来自两家拥有超过500张床位的学术医院的每年每位患者的首例CRE分离株。采用参考肉汤微量稀释法（BMD）确定抗生素敏感性，采用群体分析谱（PAP）确定HR。使用Carba NP试验确定碳青霉烯酶产生情况（CP）。
在327株CRE分离株中，[此处原文缺失部分内容]。通过BMD，87%至98%的CRE对所测试的三种抗生素敏感。从2016年到2021年，对三种BL/BLIs中每种的敏感性率逐渐下降。在每种菌种-抗生素组合中均检测到HR，在亚胺培南/瑞来巴坦的[此处原文缺失部分内容]分离株中发现HR率最高（26%）。通过PAP发现24%的CRE分离株对至少一种BL/BLI耐药或存在HR，其中65%可检测到CP。
所测试的CRE分离株中有24%对新型BL/BLIs耐药或存在异质性耐药（HR），6年期间总体敏感性下降约10%。虽然新型BL/BLIs对大多数CRE仍有活性，但这些发现支持持续进行抗生素管理以及更好地了解CRE中HR的临床意义的必要性。
