2010~2022年某院碳青霉烯类药物消耗量与四种革兰氏阴性杆菌碳青霉烯耐药率的相关性分析

doi:10.5246/jcps.2025.07.049

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (7): 664-673.DOI: 10.5246/jcps.2025.07.049

2010~2022年某院碳青霉烯类药物消耗量与四种革兰氏阴性杆菌碳青霉烯耐药率的相关性分析

张绮雯¹^,², 刘克锋¹^,²^,³, 孟海阳¹^,², 杨勇杰¹^,²^,³, 康建¹^,³, 徐岷⁴^,^*(), 卢晓静¹^,³^,^*()

^1. 郑州大学第一附属医院药学部, 河南郑州 450052
^2. 河南省精准临床药学应用与转化工程研究中心, 河南郑州 450052
^3. 河南省药品临床综合评价中心, 河南郑州 450052
^4. 郑州大学第一附属医院检验科, 河南郑州 450052

收稿日期:2024-12-29 修回日期:2025-01-12 接受日期:2025-03-25 出版日期:2025-07-31 发布日期:2025-07-31
通讯作者: 徐岷, 卢晓静

Correlation between carbapenem consumption and resistance trends in four major Gram-negative bacilli: A 12-year study in a tertiary hospital (2010–2022)

Qiwen Zhang¹^,², Kefeng Liu¹^,²^,³, Haiyang Meng¹^,², Yongjie Yang¹^,²^,³, Jian Kang¹^,³, Min Xu⁴^,^*(), Xiaojing Lu¹^,³^,^*()

¹ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
² Henan Province Engineering Research Center of Application & Translation of Precision Clinical Pharmacy, Zhengzhou 450052, Henan, China
³ Henan Drug Clinical Comprehensive Evaluation Center, Zhengzhou 450052, Henan, China
⁴ Department of Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China

Received:2024-12-29 Revised:2025-01-12 Accepted:2025-03-25 Online:2025-07-31 Published:2025-07-31
Contact: Min Xu, Xiaojing Lu
Supported by:
The Henan Key Research and Development and Promotion Project (Grant No. 232102310245) and the Joint Construction Project of Medical Science and Technology of Henan Province (Grant No. LHGJ20220426).

摘要/Abstract

摘要：

抗微生物药物耐药性的出现, 特别是由耐碳青霉烯类革兰氏阴性菌引起的医院感染, 是全球性重大公共卫生问题。碳青霉烯类抗菌药物的广泛使用, 使细菌对此类药物的耐药性逐渐增强。本研究旨在分析碳青霉烯类抗菌药物的消耗量与四种革兰氏阴性菌耐药率之间的关系, 包括大肠埃希菌(Escherichia coli, EC)、肺炎克雷伯菌(Klebsiella pneumoniae, KP)、鲍曼不动杆菌(Acinetobacter baumannii, AB)和铜绿假单胞菌(Pseudomonas aeruginosa, PA)。本研究纳入了郑州大学第一附属医院2010年1月至2022年12月的回顾性数据。通过Mann-Kendall趋势检验和Sen’s斜率估计法分析碳青霉烯类药物消耗量和耐药率的变化趋势和幅度, Spearman相关性分析两者相关性。美罗培南、亚胺培南、比阿培南和碳青霉烯类药物的消耗量均显著增加(|Z| > 1.96, SS > 0); EC和KP对美罗培南或亚胺培南的耐药率显著增加(|Z| > 1.96, SS > 0); EC对美罗培南的耐药率与美罗培南的用药频度(DDDs)呈显著性正相关(r = 0.732, P < 0.05); EC对亚胺培南的耐药率与亚胺培南的DDDs间存在显著性正相关(r = 0.49, P < 0.05); KP对美罗培南和亚胺培南的耐药率与两种药物的DDDs间也呈显著性正相关; 耐碳青霉烯类AB或PA与碳青霉烯的消耗量之间没有显著相关性。亚胺培南和美罗培南的DDDs与EC和KP耐药率呈显著性正相关, 临床应严格控制和管理碳青霉烯类药物的使用, 以遏制或延缓细菌耐药性的出现。

关键词: 碳青霉烯消耗量, 大肠埃希菌, 肺炎克雷伯菌, 鲍曼不动杆菌, 铜绿假单胞菌, 耐药率

Abstract:

The rise of antimicrobial resistance, particularly in healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens, poses a critical global challenge. The extensive use of carbapenems has exacerbated this issue by increasing selective pressure within bacterial populations. This study aimed to investigate the association between carbapenem consumption and resistance rates in four priority Gram-negative bacteria: Escherichia coli (EC), Klebsiella pneumoniae (KP), Acinetobacter baumannii (AB), and Pseudomonas aeruginosa (PA). Retrospective data were collected from the First Affiliated Hospital of Zhengzhou University, covering the period from January 2010 to December 2022. Trends in carbapenem consumption and resistance were analyzed using the Mann-Kendall test to assess statistical significance and the Sen’s slope (SS) estimator to determine the magnitude of change. Correlations between carbapenem use and bacterial resistance rates were evaluated via Spearman correlation analysis. Over the study period, the consumption of meropenem, imipenem, biapenem, and total carbapenems exhibited a significant upward trend (|Z| > 1.96, SS > 0). Correspondingly, the resistance rates of EC and KP to meropenem and imipenem also increased significantly (|Z| > 1.96, SS > 0). A strong positive correlation was observed between the resistance rate of EC to meropenem and the defined daily doses (DDDs) of meropenem (r = 0.732, P < 0.05) and between EC resistance to imipenem and its DDDs (r = 0.49, P < 0.05). Similar significant correlations were identified for KP. However, no significant associations were found between carbapenem resistance in AB or PA and carbapenem consumption. These findings underscored the strong correlation between carbapenem use and the resistance rates of EC and KP, highlighting the urgent need for stringent control and stewardship of carbapenem use in clinical settings to mitigate or delay the development of bacterial drug resistance.

Key words: Carbapenem consumption, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Resistance rates

Supporting:

张绮雯, 刘克锋, 孟海阳, 杨勇杰, 康建, 徐岷, 卢晓静. 2010~2022年某院碳青霉烯类药物消耗量与四种革兰氏阴性杆菌碳青霉烯耐药率的相关性分析[J]. 中国药学(英文版), 2025, 34(7): 664-673.

Qiwen Zhang, Kefeng Liu, Haiyang Meng, Yongjie Yang, Jian Kang, Min Xu, Xiaojing Lu. Correlation between carbapenem consumption and resistance trends in four major Gram-negative bacilli: A 12-year study in a tertiary hospital (2010–2022)[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(7): 664-673.

图/表 5

Table 1. Classification of the change trends.

Figure 1. Trends of annual carbapenem consumption during 2010–2022.

Figure 2. The trends in the number of isolates of Gram-positive and Gram-negative bacteria (A) and trends of isolation rate of the four top-ranked Gram-negative bacteria (B).

Figure 3. Carbapenem resistance rates in four Gram-negative species under study: EC (A), KP (B), AB (C), and PA (D).

Table 2. Correlation between carbapenem consumption and carbapenem resistance.

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2010~2022年某院碳青霉烯类药物消耗量与四种革兰氏阴性杆菌碳青霉烯耐药率的相关性分析

Correlation between carbapenem consumption and resistance trends in four major Gram-negative bacilli: A 12-year study in a tertiary hospital (2010–2022)

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