Department of Clinical Microbiology and Microbial Pathogenesis, University Hospital of Heraklion, Heraklion, Crete, Greece.
University of Crete Medical School, Heraklion, Crete, Greece.
Infection. 2022 Apr;50(2):467-474. doi: 10.1007/s15010-021-01735-1. Epub 2021 Dec 2.
The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is of great concern because of limited treatment options. New antimicrobials were recently approved for clinical therapy. This study evaluated the epidemiology of carbapenemase-producing K. pneumoniae isolates collected at a Greek university hospital during 2017-2020, and their susceptibilities to ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam (M/V), imipenem-relebactam (I/R), eravacycline, plazomicin, and comparators.
Minimum inhibitory concentrations (MICs) were evaluated by Etest. Only colistin MICs were determined by the broth microdilution method. Carbapenemase genes were detected by PCR. Selected isolates were typed by multilocus sequence typing (MLST).
A total of 266 carbapenemase-producing K. pneumoniae strains were isolated during the 4-year study period. Among them, KPC was the most prevalent (75.6%), followed by NDM (11.7%), VIM (5.6%), and OXA-48 (4.1%). KPC-producing isolates belonged mainly to ST258 and NDM producers belonged to ST11, whereas OXA-48- and VIM producers were polyclonal. Susceptibility to tigecycline, fosfomycin, and colistin was 80.5%, 83.8%, and 65.8%, respectively. Of the novel agents tested, plazomicin was the most active inhibiting 94% of the isolates at ≤ 1.5 μg/ml. CAZ/AVI and M/V inhibited all KPC producers and I/R 98.5% of them. All OXA-48 producers were susceptible to CAZ/AVI and plazomicin. The novel β-lactam/β-lactamase inhibitors (BLBLIs) tested were inactive against MBL-positive isolates, while eravacycline inhibited 61.3% and 66.7% of the NDM and VIM producers, respectively.
KPC remains the predominant carbapenemase among K. pneumoniae, followed by NDM. Novel BLBLIs, eravacycline, and plazomicin are promising agents for combating infections by carbapenemase-producing K. pneumoniae. However, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship.
碳青霉烯类耐药肺炎克雷伯菌（CRKP）感染的增加令人担忧，因为其治疗选择有限。最近有新的抗菌药物被批准用于临床治疗。本研究评估了 2017-2020 年期间在希腊一家大学医院收集的产碳青霉烯酶肺炎克雷伯菌分离株的流行病学情况及其对头孢他啶-阿维巴坦（CAZ/AVI）、美罗培南-瓦博巴坦（M/V）、亚胺培南-雷巴坦（I/R）、依拉环素、硫酸普拉米星和对照药物的药敏情况。
采用 Etest 法测定最小抑菌浓度（MIC）。仅通过肉汤微量稀释法测定多粘菌素 MIC。采用 PCR 法检测碳青霉烯酶基因。采用多位点序列分型（MLST）对选定的分离株进行分型。
在 4 年的研究期间共分离出 266 株产碳青霉烯酶肺炎克雷伯菌。其中，KPC 最为常见（75.6%），其次是 NDM（11.7%）、VIM（5.6%）和 OXA-48（4.1%）。产 KPC 的分离株主要属于 ST258，产 NDM 的分离株属于 ST11，而 OXA-48 和 VIM 产株则呈多克隆分布。替加环素、磷霉素和多粘菌素的敏感性分别为 80.5%、83.8%和 65.8%。在所测试的新型药物中，硫酸普拉米星对 94%的分离株的抑制作用最强，MIC50 和 MIC90 均为 0.5μg/ml。CAZ/AVI 和 M/V 抑制所有 KPC 产株，I/R 对 98.5%的 KPC 产株有效。所有 OXA-48 产株均对 CAZ/AVI 和硫酸普拉米星敏感。所测试的新型β-内酰胺/β-内酰胺酶抑制剂（BLBLIs）对 MBL 阳性分离株无活性，而依拉环素对 NDM 和 VIM 产株的抑制率分别为 61.3%和 66.7%。
KPC 仍然是肺炎克雷伯菌中最主要的碳青霉烯酶，其次是 NDM。新型 BLBLIs、依拉环素和硫酸普拉米星是治疗产碳青霉烯酶肺炎克雷伯菌感染的有前途的药物。然而，这些药物出现耐药性突显了需要持续监测并应用增强型抗菌药物管理。
