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导致单纯性社区获得性膀胱炎的大肠杆菌分离株中致病标志物与口服抗生素耐药性的关联

Association of Virulence Markers With Resistance to Oral Antibiotics in Escherichia coli Isolates Causing Uncomplicated Community-Acquired Cystitis.

作者信息

Radera Shruti, Agarwal Jyotsna, Srivastava Sugandha, Gupta Prashant, Pandey Amita

机构信息

Microbiology, King George's Medical University, Lucknow, IND.

Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND.

出版信息

Cureus. 2023 May 24;15(5):e39458. doi: 10.7759/cureus.39458. eCollection 2023 May.

Abstract

INTRODUCTION

Uropathogenic (UPEC) strains equipped with putative virulence factors (VFs) are known to cause approximatel 90% of lower urinary tract infections (UTIs) or cystitis affecting individuals of all age groups. Only limited laboratory-based data on the correlation of antimicrobial resistant patterns and VFs of UPEC are available.

MATERIALS AND METHODS

A total of 100 non-duplicate isolates associated with community-acquired UTIs in sexually active women were analysed for antimicrobial susceptibility patterns and putative virulence-associated genes Antimicrobial susceptibility testing (AST) was carried out by the Kirby-Bauer disk diffusion method, and results were interpreted as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The isolates non-susceptible to ≥1 agent in ≥3 different antimicrobial categories were considered multidrug-resistant (MDR). Multiplex polymerase chain reaction assay was performed on each isolate to characterize putative virulence genes (VGs) such as , , , , , , , , , , , , , , , and Results: Capsule synthesis gene (59%)was the most predominant VG present, followed by serum resistance-associated transfer protein gene (58%) and adhesin gene (57%); however, adhesin gene (2%) was the least present. The prevalence of antimicrobial resistance was relatively high for commonly used oral antimicrobials of UTI treatment, such as trimethoprim-sulfamethoxazole (68%) and fluoroquinolones (63%). The majority of isolates were MDR (78%) and resistant to extended-spectrum cephalosporins (63.5%). Isolates resistant to norfloxacin and trimethoprim-sulfamethoxazole were also resistant to almost all available oral antimicrobials. Isolates resistant to extended-spectrum cephalosporins showed increased resistance to aztreonam and trimethoprim-sulfamethoxazole (84.6% each) and fluoroquinolones (ciprofloxacin and norfloxacin; 81.5% each). Fosfomycin and nitrofurantoin were the most sensitive antimicrobials for all these resistant isolates. In a multivariate analysis, it was found that MDR isolates were associated with many of the VGs; (65.4%) being the most frequent followed by (64.1%). (66.2%) and (60.3%) were most commonly present in isolates resistant to trimethoprim-sulfamethoxazole, while66.7% norfloxacin-resistant isolates have them. Isolates resistant to extended-spectrum cephalosporins were most commonly associated with and (66.2% each). However, isolates positive for and were more sensitive to norfloxacin and trimethoprim-sulfamethoxazole and were non-MDR strains predominantly (p < 0.05). Only two VGs ( and )were significantly associated with MDR strains.

DISCUSSION

The results of the present study clearly show the association of VFs with some of the commonly used oral antibiotics emphasizing the need for further molecular studies and surveillance programs to monitor drug-resistant UPEC so as to form optimized diagnostic stewardship and appropriate regimen for patient treatment. The reason behind this phenomenon of association has not been studied in much detail here but it can be assumed that genes responsible for drug resistance may share neighbouring loci with VGs on the mobile genetic elements (e.g., plasmid), which transfer together from one bacterium to another.

摘要

引言

已知携带假定毒力因子(VFs)的尿路致病性大肠杆菌(UPEC)菌株可导致约90%的下尿路感染(UTIs)或膀胱炎,影响所有年龄组的个体。关于UPEC的抗菌耐药模式与毒力因子之间相关性的基于实验室的数据有限。

材料与方法

对100株与性活跃女性社区获得性UTIs相关的非重复分离株进行抗菌药敏模式和假定毒力相关基因分析。采用 Kirby-Bauer 纸片扩散法进行抗菌药敏试验(AST),结果按照临床和实验室标准协会(CLSI)指南进行解释。对≥3种不同抗菌类别中≥1种药物不敏感的分离株被视为多重耐药(MDR)。对每个分离株进行多重聚合酶链反应分析,以鉴定假定的毒力基因(VGs),如、、、、、、、、、、、、、和结果:荚膜合成基因(59%)是最主要的VGs,其次是血清抗性相关转移蛋白基因(58%)和黏附素基因(57%);然而,黏附素基因(2%)含量最少。用于UTI治疗的常用口服抗菌药物的耐药率相对较高,如甲氧苄啶-磺胺甲恶唑(68%)和氟喹诺酮类(63%)。大多数分离株为MDR(78%),对广谱头孢菌素耐药(63.5%)。对诺氟沙星和甲氧苄啶-磺胺甲恶唑耐药的分离株对几乎所有可用的口服抗菌药物也耐药。对广谱头孢菌素耐药的分离株对氨曲南和甲氧苄啶-磺胺甲恶唑(各84.6%)以及氟喹诺酮类(环丙沙星和诺氟沙星;各81.5%)的耐药性增加。磷霉素和呋喃妥因是所有这些耐药分离株最敏感的抗菌药物。在多变量分析中,发现MDR分离株与许多VGs相关;(65.4%)最为常见,其次是(64.1%)。(66.2%)和(60.3%)最常见于对甲氧苄啶-磺胺甲恶唑耐药的分离株中,而66.7%对诺氟沙星耐药的分离株含有这些基因。对广谱头孢菌素耐药的分离株最常与和(各66.2%)相关。然而,和呈阳性的分离株对诺氟沙星和甲氧苄啶-磺胺甲恶唑更敏感,且主要是非MDR菌株(p<0.05)。只有两个VGs(和)与MDR菌株显著相关。

讨论

本研究结果清楚地表明了毒力因子与一些常用口服抗生素之间的关联,强调需要进一步开展分子研究和监测项目,以监测耐药UPEC,从而形成优化的诊断管理和适当的患者治疗方案。此处尚未对这种关联现象背后的原因进行详细研究,但可以假设负责耐药性的基因可能与移动遗传元件(如质粒)上的VGs共享相邻位点,这些元件可从一个细菌转移到另一个细菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/335f/10290217/aabf72d7ec30/cureus-0015-00000039458-i01.jpg

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