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携带bla、armA和aac(6')-Ib-cr基因的耐碳青霉烯类粘质沙雷氏菌:来自巴基斯坦的首次基线研究。

Carbapenem Resistant Serratia marcescens Harboring bla, armA and aac(6')-Ib-cr Genes: The First Baseline Study from Pakistan.

作者信息

Kausar Amna, Sohail Muhammad, Khurshid Mohsin, Saleem Hafiz Ghulam Murtaza

机构信息

Department of Medical Lab Technology, Faculty of Rehabilitation & Allied Health Sciences, Riphah International University Islamabad, Lahore, 54000, Pakistan.

Institute of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan.

出版信息

Curr Microbiol. 2025 Jun 3;82(7):321. doi: 10.1007/s00284-025-04302-1.

DOI:10.1007/s00284-025-04302-1
PMID:40459633
Abstract

The emergence of Serratia marcescens as a significant healthcare-associated pathogen is compounded by its rising carbapenem resistance resulting in a critical global health challenge. This study is the first in Pakistan to comprehensively characterize the antimicrobial resistance patterns and molecular mechanisms of S. marcescens from clinical specimens. The S. marcescens isolates were obtained from clinical specimens collected at tertiary care hospitals in Lahore and Faisalabad, Pakistan, between October 2023 and September 2024. Isolates were identified using the Vitek-2 system and MALDI-TOF mass spectrometry. The disk diffusion assays, and broth microdilution method were used for antimicrobial susceptibility testing. The antimicrobial resistance determinants were amplified by PCR followed by sanger sequencing. The study revealed concerning resistance rates among S. marcescens isolates: 78% were resistant to third-generation cephalosporins, 52% to carbapenems, and 71.6% to fluoroquinolones. However, no isolates were found to be resistant to the tigecycline. The carbapenem resistance genes were distributed among carbapenem-resistant S. marcescens (CRSM) strains as follows: bla was most prevalent at 69.2%, followed by bla at 20.8%, and bla at 10% of isolates. The 16S methylase gene armA was found exclusively in CRSM strains, present in 73.1% (95/130) of isolates. The aac(6')-Ib-cr gene variant, which confers resistance to aminoglycosides and fluoroquinolones, was found in 37.2% of CRSM isolates. The CRSM isolates co-harboring bla, armA, and aac(6')-Ib-cr genes demonstrated a convergence of carbapenem, aminoglycoside, and fluoroquinolone resistance mechanisms which confer a multi-drug resistance phenotype in these isolates, with tigecycline remaining the sole susceptible agent. These findings expose an escalating AMR crisis in Pakistan driven by high-risk resistance gene combinations among S. marcescens isolates. This underscores the dire necessity for urgent nationwide interventions including rapid diagnostics, genomic surveillance of resistance mechanisms, and strict antibiotic stewardship to curb the increasing antimicrobial resistance threats and nosocomial transmission of such pathogens.

摘要

粘质沙雷氏菌作为一种重要的医疗保健相关病原体出现,其对碳青霉烯类药物耐药性的上升使情况更加复杂,这给全球卫生带来了严峻挑战。本研究是巴基斯坦首次全面描述临床标本中粘质沙雷氏菌的抗菌耐药模式和分子机制。粘质沙雷氏菌分离株取自2023年10月至2024年9月期间在巴基斯坦拉合尔和费萨拉巴德的三级护理医院收集的临床标本。使用Vitek - 2系统和基质辅助激光解吸电离飞行时间质谱法对分离株进行鉴定。采用纸片扩散法和肉汤微量稀释法进行抗菌药物敏感性测试。通过聚合酶链反应(PCR)扩增抗菌耐药决定簇,随后进行桑格测序。该研究揭示了粘质沙雷氏菌分离株令人担忧的耐药率:78%对第三代头孢菌素耐药,52%对碳青霉烯类耐药,71.6%对氟喹诺酮类耐药。然而,未发现分离株对替加环素耐药。碳青霉烯类耐药基因在耐碳青霉烯类粘质沙雷氏菌(CRSM)菌株中的分布如下:bla最为普遍,占69.2%,其次是bla,占20.8%,bla占分离株的10%。16S甲基化酶基因armA仅在CRSM菌株中发现,存在于73.1%(95/130)的分离株中。赋予对氨基糖苷类和氟喹诺酮类耐药性的aac(6') - Ib - cr基因变体在37.2%的CRSM分离株中被发现。同时携带bla、armA和aac(6') - Ib - cr基因的CRSM分离株表现出碳青霉烯类、氨基糖苷类和氟喹诺酮类耐药机制的汇聚,这些机制赋予这些分离株多重耐药表型,而替加环素仍然是唯一敏感的药物。这些发现揭示了巴基斯坦由粘质沙雷氏菌分离株中高风险耐药基因组合驱动下不断升级的抗菌药物耐药危机。这突出了在全国范围内进行紧急干预的迫切必要性,包括快速诊断、耐药机制的基因组监测以及严格的抗生素管理,以遏制日益增加的抗菌药物耐药威胁和此类病原体的医院内传播。

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