Rizvi Mehwish, Khan Noman, Fatima Ambreen, Bushra Rabia, Zehra Ale, Saeed Farah, Gul Khitab
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 75280, Pakistan.
Department of Biosciences, Mohammad Ali Jinnah University, Karachi 75400, Pakistan.
Microorganisms. 2025 Jul 4;13(7):1577. doi: 10.3390/microorganisms13071577.
is a major public health concern due to its role in Gram-negative bacteremia, which leads to high mortality and increased healthcare costs. This study characterizes phenotypic and genomic features of isolates from clinical samples in Karachi, Pakistan. Among 507 isolates, 213 (42%) were carbapenem-resistant based on disk diffusion and MIC testing. Urine (29.7%) and blood (28.3%) were the most common sources, with infections predominantly affecting males (64.7%) and individuals aged 50-70 years. Colistin was the only antibiotic showing consistent activity against these isolates. The whole-genome sequencing of 24 carbapenem-resistant (CR-KP) isolates revealed (45.8%) as the dominant carbapenemase gene, followed by (12.5%) and (54.2%). Other detected variants included , , , and . The predominant beta-lactamase gene was (91.6%), followed by , , and . Sequence types ST147, ST231, ST29, and ST11 were associated with resistance. Plasmid profiling revealed IncR (61.5%), IncL (15.4%), and IncC (7.7%) as common plasmid types. Importantly, resistance was driven not only by acquired genes but also by chromosomal mutations. Porin mutations in OmpK36 and OmpK37 (e.g., P170M, I128M, N230G, A217S) reduced drug influx, while and mutations (e.g., P161R, G164A, P157*) led to efflux pump overexpression, enhancing resistance to fluoroquinolones and tigecycline. These findings highlight a complex resistance landscape driven by diverse carbapenemases and ESBLs, underlining the urgent need for robust antimicrobial stewardship and surveillance strategies.
由于其在革兰氏阴性菌血症中所起的作用，这是一个主要的公共卫生问题，革兰氏阴性菌血症会导致高死亡率并增加医疗成本。本研究对来自巴基斯坦卡拉奇临床样本的分离株的表型和基因组特征进行了表征。在507株分离株中，根据纸片扩散法和最低抑菌浓度测试，有213株（42%）对碳青霉烯类耐药。尿液（29.7%）和血液（28.3%）是最常见的来源，感染主要影响男性（64.7%）和50至70岁的个体。黏菌素是唯一对这些分离株表现出一致活性的抗生素。对24株耐碳青霉烯类肺炎克雷伯菌（CR-KP）分离株进行的全基因组测序显示， bla NDM-1（45.8%）是主要的碳青霉烯酶基因，其次是 bla VIM（12.5%）和 bla IMP（54.2%）。其他检测到的变体包括 bla OXA-48、 bla OXA-181、 bla CTX-M、 bla SHV。主要的β-内酰胺酶基因是 bla CTX-M（91.6%），其次是 bla SHV、 bla TEM、 bla OXA-1。序列类型ST147、ST231、ST29和ST11与耐药性相关。质粒图谱分析显示IncR（61.5%）、IncL（15.4%）和IncC（7.7%）是常见的质粒类型。重要的是，耐药性不仅由获得性基因驱动，还由染色体突变驱动。OmpK36和OmpK37中的孔蛋白突变（例如P170M、I128M N230G、A217S）减少了药物流入，而qnr和acrAB突变（例如P161R、G164A、P157*）导致外排泵过度表达，增强了对氟喹诺酮类和替加环素的耐药性。这些发现突出了由多种碳青霉烯酶和超广谱β-内酰胺酶驱动的复杂耐药格局，强调了迫切需要强有力的抗菌药物管理和监测策略。
