Department of Medical Sciences, Infectious Diseases, University of Turin, 10124 Turin, Italy.
School of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Int J Mol Sci. 2023 Mar 1;24(5):4767. doi: 10.3390/ijms24054767.
The continuous spread of carbapenem-resistant (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to , C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the genotype was detected in all isolates revealing D179Y mutation in the () gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.
碳青霉烯类耐药（CP-Kp）菌株的持续传播对医疗系统构成了严峻挑战，因为治疗选择有限且死亡率高。自可用以来，头孢他啶/阿维巴坦（C/A）已成为治疗 KPC-Kp 的一线选择，但 C/A 耐药菌株的报告越来越多，尤其是在患有肺炎或先前 C/A 治疗效果不佳的情况下。在都灵市健康与科学城专门收治 COVID-19 患者的重症监护病房（ICU）中，对 2021 年 5 月 1 日至 2022 年 1 月 31 日期间所有住院患者进行了一项回顾性观察研究，主要终点是研究对 C/A 耐药的菌株，其次是描述具有或不具有先前 C/A 暴露的该人群的特征。共纳入 17 例因 、C/A 耐药和对美罗培南（MIC = 2 µg/L）敏感而导致定植或侵袭性感染的患者；所有分离株均检测到 基因型，发现 基因中的 D179Y 突变。聚类分析显示，17 株 C/A 耐药的 KPC-Kp 分离株中有 16 株属于单个克隆。13 株（76.5%）在 60 天内分离。只有 5 例（29.4%）患者先前在其他部位感染过非突变型 KPC。8 例（47.1%）患者接受过先前的广谱抗生素治疗，4 例（23.5%）患者接受过 C/A 治疗。在 COVID-19 大流行期间，需要微生物学家、感染控制人员、临床医生和传染病顾问之间进行跨学科互动，不断解决 基因中的 D179Y 突变的二次传播问题，以正确诊断和治疗患者。
