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埃及革兰氏阴性菌中黏菌素耐药性的流行情况、趋势及分子见解:一项系统综述和荟萃分析

Prevalence, trends, and molecular insights into colistin resistance among gram-negative bacteria in Egypt: a systematic review and meta-analysis.

作者信息

Azzam Ahmed, Salem Haitham, Nazih Mahmoud, Lotfy Enas Mohamed, Hassan Fatma E, Khaled Heba

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

Faculty of Medicine, Ain Shams University, Cairo, Egypt.

出版信息

Ann Clin Microbiol Antimicrob. 2025 May 10;24(1):32. doi: 10.1186/s12941-025-00799-3.

DOI:10.1186/s12941-025-00799-3
PMID:40349047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12065219/
Abstract

BACKGROUND

This study examines colistin resistance in Gram-negative bacteria in Egypt, analyzing prevalence, trends, geographic variations, colistin-carbapenem resistance correlation, and mcr-mediated plasmid resistance.

METHODS

We conducted a systematic search of articles published between 2014 and 2024 that reported on colistin or mcr-mediated resistance in Gram-negative bacteria isolated from human infections in Egypt, with clearly defined susceptibility testing methods. A random-effects meta-analysis was conducted to estimate colistin resistance prevalence based on broth microdilution (BMD) findings, the gold standard method. To explore the influence of study-level factors-including alternative susceptibility testing methods-a multivariate meta-regression analysis was performed. The results of the meta-regression are reported as regression coefficients (β), representing the difference in colistin resistance, expressed in percentage points. All statistical analyses were conducted using R software.

RESULTS

This analysis included 55 studies. Based on BMD susceptibility testing, colistin resistance was observed in 9% of all recovered Gram-negative isolates (95% CI: 6-14%) and was significantly higher among carbapenem-resistant isolates (31%, 95% CI: 25-38%), with p < 0.001. Multivariate meta-regression analysis further confirmed that colistin resistance was significantly higher in carbapenem-resistant isolates compared to the total recovered isolates (β = 9.8% points, p = 0.001). Additionally, colistin resistance has significantly increased over time, with a β = 1.8% points per year (p = 0.001). The use of the VITEK 2 system was associated with lower detected colistin resistance compared to BMD (β = -7.0, p = 0.02). Geographically, resistance rates were higher in Upper Egypt (β = 9.3, p = 0.04). Regarding mcr plasmid-mediated resistance, mcr-1 was the most prevalent resistance gene, particularly in E. coli. In contrast, mcr-2 was rare, detected sporadically in K. pneumoniae and P. aeruginosa.

CONCLUSION

In Egypt, BMD testing identified colistin resistance in 9% of Gram-negative bacteria, increasing to 31% in carbapenem-resistant isolates. This higher resistance in carbapenem-resistant strains suggests stronger selective pressure from frequent colistin use. Additionally, colistin resistance has shown a rising trend over time, likely driven by increased usage and the spread of plasmid-mediated resistance. These findings underscore the urgent need for strict antimicrobial stewardship and alternative therapies to curb resistance evolution.

摘要

背景

本研究调查了埃及革兰氏阴性菌对黏菌素的耐药性,分析了其流行情况、趋势、地理差异、黏菌素-碳青霉烯耐药性相关性以及由mcr介导的质粒耐药性。

方法

我们系统检索了2014年至2024年间发表的文章,这些文章报道了从埃及人类感染中分离出的革兰氏阴性菌对黏菌素或mcr介导的耐药性,且药敏试验方法明确。基于肉汤微量稀释法(BMD)这一金标准方法的结果,进行随机效应荟萃分析以估计黏菌素耐药率。为探究研究水平因素(包括替代药敏试验方法)的影响,进行了多变量荟萃回归分析。荟萃回归结果以回归系数(β)表示,代表黏菌素耐药性的差异,以百分点表示。所有统计分析均使用R软件进行。

结果

该分析纳入了55项研究。基于BMD药敏试验,在所有回收的革兰氏阴性菌分离株中,9%观察到对黏菌素耐药(95%置信区间:6%-14%),在耐碳青霉烯类分离株中显著更高(31%,95%置信区间:25%-38%),p<0.001。多变量荟萃回归分析进一步证实,与总体回收分离株相比,耐碳青霉烯类分离株中的黏菌素耐药性显著更高(β=9.8个百分点,p=0.001)。此外,黏菌素耐药性随时间显著增加,每年β为1.8个百分点(p=0.001)。与BMD相比,使用VITEK 2系统检测到的黏菌素耐药性较低(β=-7.0,p=0.02)。在地理上,上埃及的耐药率更高(β=9.3,p=0.04)。关于mcr质粒介导的耐药性,mcr-1是最普遍的耐药基因,尤其是在大肠杆菌中。相比之下,mcr-2很少见,偶尔在肺炎克雷伯菌和铜绿假单胞菌中检测到。

结论

在埃及,BMD检测发现9%的革兰氏阴性菌对黏菌素耐药,在耐碳青霉烯类分离株中增至31%。耐碳青霉烯类菌株中这种较高的耐药性表明频繁使用黏菌素带来了更强的选择压力。此外,黏菌素耐药性随时间呈上升趋势,可能是由于使用增加和质粒介导耐药性的传播。这些发现强调了迫切需要严格的抗菌药物管理和替代疗法来遏制耐药性的演变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/1345f3571020/12941_2025_799_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/b2495b3e80c4/12941_2025_799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/5733da402636/12941_2025_799_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/1345f3571020/12941_2025_799_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/b2495b3e80c4/12941_2025_799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/5733da402636/12941_2025_799_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3256/12065219/1345f3571020/12941_2025_799_Fig3_HTML.jpg

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