Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013.
Xiangya School of Medicine, Central South University, Changsha 410013.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 May 28;49(5):737-747. doi: 10.11817/j.issn.1672-7347.2024.230567.
The emergence of polymyxin-resistant (KPN) in clinical settings necessitates an analysis of its antibiotic resistance characteristics, epidemiological features, and risk factors for its development. This study aims to provide insights for the prevention and control of polymyxin-resistant KPN infections.
Thirty clinical isolates of polymyxin-resistant KPN were collected from the Third Xiangya Hospital of Central South University. Their antibiotic resistance profiles were analyzed. The presence of carbapenemase KPC, OXA-48, VIM, IMP, and NDM was detected using colloidal gold immunochromatography. Hypervirulent KPN was initially screened using the string test. Biofilm formation capacity was assessed using crystal violet staining. Combination drug susceptibility tests (polymyxin B with meropenem, tigecycline, cefoperazone/sulbactam) were conducted using the checkerboard method. Polymyxin-related resistance genes were detected by PCR. Multi-locus sequence typing (MLST) was performed for genotyping and phylogenetic tree construction. The study also involved collecting data from carbapenem-resistant (CR)-KPN polymyxin-resistant strains (23 strains, experimental group) and CR-KPN polymyxin-sensitive strains (57 strains, control group) to analyze potential risk factors for polymyxin-resistant KPN infection through univariate analysis and multivariate Logistic regression. The induction of resistance by continuous exposure to polymyxin B and colistin E was also tested.
Among the 30 polymyxin-resistant KPN isolates, 28 were CR-KPN, all producing KPC enzyme. Four isolates were positive in the string test. Most isolates showed strong biofilm formation capabilities. Combination therapy showed additive or synergistic effects. All isolates carried the and genes, while no or genes were detected. MLST results indicated that ST11 was the predominant type. The phylogenetic tree suggested that polymyxin-resistant KPN had not caused a hospital outbreak in the institution. The use of two or more different classes of antibiotics and the use of polymyxin were identified as independent risk factors for the development of polymyxin-resistant strains. Continuous use of polymyxin induced drug resistance.
Polymyxin-resistant KPN is resistant to nearly all commonly used antibiotics, making polymyxin-based combination therapy a viable option. No plasmid-mediated polymyxin-resistant KPN has been isolated in the hospital. Polymyxin can induce resistance in KPN, highlighting the need for rational antibiotic use in clinical settings to delay the emergence of resistance.
临床中出现耐多黏菌素 （KPN） 菌株，有必要对其抗生素耐药特征、流行病学特征和耐药产生的危险因素进行分析。本研究旨在为预防和控制耐多黏菌素 KPN 感染提供参考。
收集 30 株来自中南大学湘雅三医院的耐多黏菌素 KPN 临床分离株，分析其药敏谱，采用胶体金免疫层析法检测碳青霉烯酶 KPC、OXA-48、VIM、IMP、NDM，初筛超毒力 KPN 采用 strings 试验，结晶紫染色法检测生物膜形成能力，棋盘法进行多黏菌素 B 与美罗培南、替加环素、头孢哌酮/舒巴坦联合药敏试验，PCR 检测多黏菌素相关耐药基因，多位点序列分型（MLST）进行基因分型和构建进化树。同时收集碳青霉烯类耐药（CR）-KPN 耐多黏菌素菌株（23 株，实验组）和 CR-KPN 耐多黏菌素敏感菌株（57 株，对照组）的临床资料，通过单因素分析和多因素 Logistic 回归分析，筛选耐多黏菌素 KPN 感染的危险因素，同时还进行了连续暴露于多黏菌素 B 和黏菌素 E 诱导耐药性的实验。
30 株耐多黏菌素 KPN 分离株中 28 株为 CR-KPN，均产 KPC 酶，strings 试验阳性 4 株，大部分菌株生物膜形成能力较强，联合药敏试验显示相加或协同作用，所有菌株均携带 mcr-1 和 mcr-3 基因，未检测到 mcr-2 和 mcr-4 基因，MLST 结果显示以 ST11 型为主，进化树提示医院内未发生耐多黏菌素 KPN 医院感染暴发，使用 2 种或以上不同种类的抗生素和使用多黏菌素被认为是产生耐多黏菌素菌株的独立危险因素，连续使用多黏菌素可诱导耐药性产生。
耐多黏菌素 KPN 对几乎所有常用抗生素均耐药，多黏菌素联合治疗可能是一种可行的选择。医院内未分离到质粒介导的耐多黏菌素 KPN。多黏菌素可诱导 KPN 产生耐药性，提示在临床中应合理使用抗生素，以延缓耐药性的产生。
