评价妥布霉素抗生素组合对多药耐药铜绿假单胞菌的作用及全基因组测序泛耐药分离株的耐药组分析。
Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate.
机构信息
Department of Microbiology, Faculty of Pharmacy, Misr International University (MIU), Cairo, 19648, Egypt.
Department of Microbiology & Immunology, Faculty of Pharmacy-girls, Al-Azhar University, Cairo, 11651, Egypt.
出版信息
BMC Microbiol. 2024 May 14;24(1):164. doi: 10.1186/s12866-024-03316-2.
BACKGROUND
Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate.
METHODS
Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate.
RESULTS
Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents.
CONCLUSION
Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.
背景
多药耐药（MDR）铜绿假单胞菌是一个日益严重的公共卫生问题，用单一抗假单胞菌药物治疗这种无处不在的病原体具有挑战性。令人担忧的是，其基因组的可塑性导致了表达不同耐药表型的铜绿假单胞菌的出现，并且现在是医院环境中显著流行的原因。有鉴于此，我们旨在评估妥布霉素与其他传统抗假单胞菌药物联合使用的协同作用，并分析泛耐药（PDR）分离株的耐药组。
方法
采用标准方法进行抗菌药物敏感性试验分析。棋盘技术用于体外评估妥布霉素与 51 株 MDR 铜绿假单胞菌的抗生素组合，全基因组测序用于确定 PDR 分离株的耐药组。
结果
在 51 株 MDR 铜绿假单胞菌中，妥布霉素与β-内酰胺类药物（美罗培南、头孢他啶和氨曲南）联合使用的协同作用最强，协同率分别为 71%、59%和 43%。值得注意的是，56.8%、39.2%和 37.2%的协同作用测试 MDR 分离株对美罗培南、头孢他啶和氨曲南也有耐药性。妥布霉素与阿米卡星（69%）和头孢吡肟（44%）联合使用对 MDR 铜绿假单胞菌的增效作用最高。PDR 分离株的耐药组分析反映了其与抗生素耐药表型的关联。它确保了存在各种各样的抗生素耐药基因（β-内酰胺酶、氨基糖苷修饰酶和外排泵），使分离株对所有临床相关的抗假单胞菌药物都具有耐药性。
结论
妥布霉素与经典抗假单胞菌药物联合使用对 MDR 铜绿假单胞菌表现出有希望的协同活性。PDR 铜绿假单胞菌的耐药组谱分析增强了对抗生素耐药基因的快速鉴定，这些基因可能与这种耐药表型的出现有关，并可能为解决抗菌药物耐药问题铺平道路。
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