智利非产碳青霉烯酶. 临床分离株中，产 PER-3 的 ST309 谱系与头孢他啶/阿维巴坦耐药相关。
Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing .
机构信息
Laboratory of Microbiology, Department of Clinical Laboratories; Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina, Universidad del Desarrollo. Millennium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, Chile.
出版信息
Front Cell Infect Microbiol. 2024 Jun 5;14:1410834. doi: 10.3389/fcimb.2024.1410834. eCollection 2024.
INTRODUCTION
Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant , particularly those that are carbapenem resistant. CZA resistance in producing PER, a class A extended-spectrum β-lactamase, has been well documented . However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing clinical isolates that were ceftazidime and/or carbapenem non-susceptible.
METHODS
Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics.
RESULTS
Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried . One isolate carried but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the evolved isolate.
DISCUSSION
PER-3-producing ST309 is a successful multidrug-resistant clone with gene implicated in resistance to CZA and other β-lactams.
简介
头孢他啶/阿维巴坦（CZA）被用于治疗多种耐药菌，尤其是那些对碳青霉烯类耐药的细菌。产 PER，一种 A 类扩展谱β-内酰胺酶，是导致 CZA 耐药的主要原因，这一点已经得到了充分的证实。然而，关于临床分离株的数据却很少。我们的目的是分析在非碳青霉烯类产生、头孢他啶和/或碳青霉烯类不敏感的临床分离株中，PER 对 CZA 耐药性的贡献。
方法
通过琼脂稀释和肉汤微量稀释法测定抗菌药物敏感性，通过 PCR 筛选 基因。所有 PER 阳性分离株和 5 株 PER 阴性分离株均通过全基因组测序进行分析。通过对编码 PBPs 1b、3 和 4、MexAB-OprM 调节剂 MexZ、MexR、NalC 和 NalD、AmpC 调节剂 AmpD 和 AmpR 以及 OprD 孔蛋白的基因进行序列分析，确定与 CZA 耐药性相关的突变耐药组。通过在 43°C 无抗生素条件下连续传代，诱导 PER 阳性分离株中 基因缺失。
结果
在 287 株研究的分离株中，有 26 株（9.1%）对 CZA 耐药。在 26 株 CZA 耐药分离株中，有 13 株（50%）携带 基因。一株携带 基因但对 CZA 敏感的分离株。产 PER 的分离株对 CZA、阿米卡星、庆大霉素、头孢他啶、美罗培南和环丙沙星的 MIC 值明显高于非产 PER 的分离株。所有产 PER 的分离株均为 ST309，其 基因与 ISCR1 相关，ISCR1 是一种已知能移动邻近 DNA 的插入序列。PER 阴性分离株被分类为 ST41、ST235（两株）、ST395 和 ST253。PER 阴性分离株携带窄谱β-内酰胺酶基因，突变耐药组表明，所有分离株在至少一个分析基因中均有一个主要改变。在进化分离株中， 基因缺失恢复了对 CZA、头孢洛扎他巴坦和其他β-内酰胺类药物的敏感性。
讨论
产 PER-3 的 ST309 是一种成功的多药耐药克隆，其 基因与 CZA 和其他β-内酰胺类药物的耐药性有关。
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