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尿路感染的治疗失败:产超广谱β-内酰胺酶的多重耐药性强毒株的警示例证

Treatment Failure in Urinary Tract Infections: A Warning Witness for Virulent Multi-Drug Resistant ESBL- Producing .

作者信息

Naziri Zahra, Derakhshandeh Abdollah, Soltani Borchaloee Arash, Poormaleknia Meisam, Azimzadeh Negar

机构信息

Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

出版信息

Infect Drug Resist. 2020 Jun 17;13:1839-1850. doi: 10.2147/IDR.S256131. eCollection 2020.

Abstract

BACKGROUND

Global increase in the prevalence of virulent extended-spectrum beta-lactamase (ESBL)-producing uropathogenic (UPEC), which is also multi-drug resistant (MDR), leads to increase in severity of urinary tract infections (UTIs), decrease in the efficacy of the first-line antibiotics, and therefore increase in the morbidity and mortality rates.

METHODS

We investigated the distribution of ESBL-producing UPEC in 78 isolates from community-acquired UTI patients in southern Iran. The prevalence of three major ESBL genes, antimicrobial resistance patterns against 15 conventional antibiotic disks, and the presence of 11 important virulence genes that involve in the development and progression of UTIs were evaluated in these isolates.

RESULTS

Of the UPECs, 34.6% were ESBL-positive and 96.3% of the ESBL-producers were MDR. Among the ESBL-producers, 100% harbored , 63% harbored , and 11.1% harbored genes. ESBL-producers showed a higher level of resistance to the tested cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, and tetracycline than non-ESBL producers. All isolates were resistant to the tested penicillins. Prevalence of resistance to about two-third of the tested antibiotics was higher than 50% and 93.6% of the isolates were MDR. High prevalence of virulence factors particularly the adhesins (82.1% , 73.1% genes) and siderophore (73.1% gene) was seen in the UPECs. But fortunately in MDR isolates, the virulence score and prevalence of hemagglutinin (), hemolysin toxin () and invasin () genes were lower than in non-MDR UPECs. Shockingly, among the 15 common antibiotics, only nitrofurantoin (<20% resistance) could be recommended as an appropriate drug for the treatment of UTIs due to our ESBL-producer UPECs.

CONCLUSION

The alarming level of virulent MDR ESBL-producer strains in this study necessitates the performing of an antibiotic stewardship program, regional screening of ESBL-producers and their virulence properties to select appropriate antibiotic, or designing new therapeutic methods for UTIs by inactivation of the essential virulence factors of UPECs.

摘要

背景

产超广谱β-内酰胺酶(ESBL)的致病性尿路大肠杆菌(UPEC)在全球范围内的流行率不断上升,且该菌具有多重耐药性(MDR),这导致尿路感染(UTI)的严重程度增加、一线抗生素疗效降低,进而使发病率和死亡率上升。

方法

我们调查了伊朗南部社区获得性UTI患者的78株分离菌中产ESBL的UPEC的分布情况。评估了这些分离菌中三种主要ESBL基因的流行率、对15种常规抗生素药敏纸片的耐药模式以及11种参与UTI发生和发展的重要毒力基因的存在情况。

结果

在UPEC中,34.6%为ESBL阳性,96.3%的产ESBL菌为MDR。在产ESBL菌中,100%携带 基因,63%携带 基因,11.1%携带 基因。产ESBL菌对所测试的头孢菌素、氟喹诺酮类、甲氧苄啶-磺胺甲恶唑和四环素的耐药水平高于非产ESBL菌。所有分离菌对所测试的青霉素均耐药。对约三分之二的测试抗生素的耐药率高于50%,93.6%的分离菌为MDR。在UPEC中,毒力因子尤其是黏附素(82.1% 基因、73.1% 基因)和铁载体(73.1% 基因)的流行率较高。但幸运的是,在MDR分离菌中,毒力评分以及血凝素()、溶血毒素()和侵袭素()基因的流行率低于非MDR UPEC。令人震惊的是,在这15种常用抗生素中,由于我们的产ESBL的UPEC,仅呋喃妥因(耐药率<20%)可被推荐为治疗UTI的合适药物。

结论

本研究中产毒力MDR ESBL菌的水平令人担忧,因此有必要开展抗生素管理计划,对产ESBL菌及其毒力特性进行区域筛查以选择合适的抗生素,或通过使UPEC的必需毒力因子失活来设计新的UTI治疗方法。

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