山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (5): 103-111.doi: 10.6040/j.issn.1671-7554.0.2024.0164
• 公共卫生与管理学 • 上一篇
钱凤同1,2,李洪凯1,2,于金龙3,薛付忠1,2
QIAN Fengtong1,2, LI Hongkai1,2, YU Jinlong3, XUE Fuzhong1,2
摘要: 目的 探讨抗菌药物使用密度与肺炎克雷伯菌耐药率之间的因果关联,并确定抗菌药物使用密度的控制阈值。 方法 基于山东大学第二医院2015—2023年抗菌药物使用密度和肺炎克雷伯菌耐药率的数据,采用断点回归分析确定抗菌药物总用药密度对肺炎克雷伯菌耐药率的影响。采用广义加性模型(generalized additive models, GAMs)的非线性时间序列分析方法来评估抗菌药物使用密度与肺炎克雷伯菌耐药率之间的关联,并确定抗菌药物使用密度的控制阈值。P<0.05和调整后R2>0.3为差异有统计学意义。 结果 在研究期间,所有种类药物使用密度在2015—2019年保持稳定,至2021年呈下降趋势,然后至2023年逐步升高。肺炎克雷伯菌耐药率在2015—2019年呈上升趋势,至2022年逐渐下降,然后至2023年逐步升高。断点回归分析结果显示,抗菌药物总用药密度的增加会导致肺炎克雷伯菌总耐药率升高,差异有统计学意义(β=1.071,P=0.041)。非线性时间序列分析结果显示,肺炎克雷伯菌耐药率与碳青霉烯类、氨基糖苷类、青霉素类和糖肽类药物使用密度显著相关(滞后系数为1~5,P均<0.05,调整后R2为0.589~0.808)。碳青霉烯类、氨基糖苷类和第三代头孢菌素类药物使用的控制阈值分别为5.82、0.06和5.62个DDDs/(100人·d)。 结论 抗菌药物使用密度的增加会导致肺炎克雷伯菌总耐药率上升;本研究确定了抗菌药物使用密度的阈值,为临床实践中采取更合适的治疗策略和有效控制抗菌药物耐药率提供参考。
中图分类号:
[1] Tacconelli E, Sifakis F, Harbarth S, et al. Surveillance for control of antimicrobial resistance[J]. Lancet Infect Dis, 2018, 18(3): e99-e106. [2] 胡付品, 郭燕, 朱德妹, 等. 2021年CHINET中国细菌耐药监测[J]. 中国感染与化疗杂志, 2022, 22(5): 521-530. HU Fupin, GUO Yan, ZHU Demei, et al. CHINET surveillance of antimicrobial resistance among the bacterial isolates in 2021[J]. Chinese Journal of Infection and Chemotherapy, 2022, 22(5): 521-530. [3] 李耘, 郑波, 吕媛, 等. 中国细菌耐药监测(CARST)研究2019—2020革兰阴性菌监测报告[J]. 中国临床药理学杂志, 2022, 38(5): 432-452. LI Yun, ZHENG Bo, LYU Yuan, et al. Antimicrobial susceptibility of Gram-negative organisms: results from China antimicrobial resistance surveillance trial(CARST)program, 2019-2020[J]. The Chinese Journal of Clinical Pharmacology, 2022, 38(5): 432-452. [4] Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae[J]. Front Cell Infect Microbiol, 2018, 8: 4. doi:10.3389/fcimb.2018.00004. [5] Wang GY, Zhao G, Chao XY, et al. The characteristic of virulence, biofilm and antibiotic resistance of Klebsiella pneumoniae[J]. Int J Environ Res Public Health, 2020, 17(17): 6278. doi:10.3390/ijerph17176278. [6] 戴和平. 肺炎克雷伯菌生物膜与耐药及外排泵基因的相关性研究[D]. 合肥: 安徽医科大学, 2023. [7] 葛学顺, 葛倩倩, 陶晓军, 等. 肺炎克雷伯菌及大肠埃希菌的耐药性与抗菌药物使用强度的相关性分析[J]. 实验与检验医学, 2019, 37(3): 364-367. GE Xueshun, GE Qianqian, TAO Xiaojun, et al. Analysis of the correlation between drug resistance of Klebsiella pneumoniae and Escherichia coli and use intensity of antimicrobial agents[J]. Experimental and Laboratory Medicine, 2019, 37(3): 364-367. [8] Arato V, Raso MM, Gasperini G, et al. Prophylaxis and treatment against Klebsiella pneumoniae: current insights on this emerging anti-microbial resistant global threat[J]. Int J Mol Sci, 2021, 22(8): 4042. doi:10.3390/ijms22084042. [9] 钟丽球, 刘锋, 蒙光义, 等. 抗菌药物使用强度对肺炎克雷伯菌耐药性的影响[J]. 西北药学杂志, 2021, 36(1): 145-149. ZHONG Liqiu, LIU Feng, MENG Guangyi, et al. Effect of antimicrobial use density on drug resistance of Klebsiella pneumoniae[J]. Northwest Pharmaceutical Journal, 2021, 36(1): 145-149. [10] 国家卫生计生委办公厅.关于进一步加强抗菌药物临床应用管理遏制细菌耐药的通知[EB/OL].(2017-03-03)[2024-02-18]. http://www.nhc.gov.cn/yzygj/s7659/201703/d2f580480cef4ab1b976542b550f36cf.shtml. [11] Guo W, He Q, Wang ZY, et al. Influence of antimicrobial consumption on gram-negative bacteria in inpatients receiving antimicrobial resistance therapy from 2008-2013 at a tertiary hospital in Shanghai, China[J]. Am J Infect Control, 2015, 43(4): 358-364. [12] van Leth F, Schultsz C. Unbiased antimicrobial resistance prevalence estimates through population-based surveillance[J]. Clin Microbiol Infect, 2023, 29(4): 429-433. [13] López-Lozano JM, Lawes T, Nebot C, et al. A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance[J]. Nat Microbiol, 2019, 4(7): 1160-1172. [14] Aldeyab MA, Bond SE, Gould I, et al. Identification of antibiotic consumption targets for the management of Clostridioides difficile infection in hospitals-a threshold logistic modelling approach[J]. Expert Rev Anti Infect Ther, 2023, 21(10): 1125-1134. [15] 中华人民共和国国务院.病原微生物实验室生物安全管理条例[EB/OL].(2004-11-12)[2024-02-18]. https://www.gov.cn/zhengce/content/2008-03/28/content_6264.htm. [16] Humphries R, Bobenchik AM, Hindler JA, et al. Overview of changes to the Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, M100, 31st edition[J]. J Clin Microbiol, 2021, 59(12): e0021321. doi:10.1128/JCM.00213-21. [17] 国家药典委员会. 中华人民共和国药典(2020年版一部)[M]. 北京: 中国医药科技出版社, 2020: 1088. [18] 陈新谦, 金有豫, 汤光. 新编药物学[M]. 17版. 北京: 人民卫生出版社, 2011. [19] 中华人民共和国卫生部. 抗菌药物临床应用管理办法[J]. 中国医学前沿杂志(电子版), 2013, 5(1): 9-14. [20] López-Lozano JM, Lawes T, Nebot C, et al. A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance[J]. Nat Microbiol, 2019, 4(7): 1160-1172. [21] 向蓉, 欧焕娇, 徐宁, 等. 肺炎克雷伯菌耐药性与抗菌药物使用情况相关性研究[J]. 中国医药导报, 2019, 16(20): 159-163. XIANG Rong, OU Huanjiao, XU Ning, et al. Correlation between drug resistance of Klebsiella pneumoniae and antibiotic use[J]. China Medical Herald, 2019, 16(20): 159-163. [22] Ryu S, Klein EY, Chun BC. Temporal association between antibiotic use and resistance in Klebsiella pneumoniae at a tertiary care hospital[J]. Antimicrob Resist Infect Control, 2018, 7: 83. doi:10.1186/s13756-018-0373-6. [23] 熊丽蓉, 程林, 喻明洁, 等. 某院2014年至2021年肺炎克雷伯菌临床特点及耐药性分析[J]. 中国药业, 2023, 32(14): 119-123. XIONG Lirong, CHENG Lin, YU Mingjie, et al. Clinical characteristics and drug resistance of Klebsiella pneumoniae in a hospital from 2014 to 2021[J]. China Pharmaceuticals, 2023, 32(14): 119-123. [24] Chen SX, Li ZP, Shi JP, et al. A nonlinear time-series analysis to identify the thresholds in relationships between antimicrobial consumption and resistance in a Chinese tertiary hospital[J]. Infect Dis Ther, 2022, 11(3): 1019-1032. [25] Wang Y, Zhong H, Han XY, et al. Impact of antibiotic prescription on the resistance of Klebsiella pneumoniae at a tertiary hospital in China, 2012-2019[J]. Am J Infect Contr, 2021, 49(1): 65-69. [26] Hayajneh WA, Al-Azzam S, Yusef D, et al. Identification of thresholds in relationships between specific antibiotic use and carbapenem-resistant Acinetobacter baumannii(CRAb)incidence rates in hospitalized patients in Jordan[J]. J Antimicrob Chemother, 2021, 76(2): 524-530. [27] 宋曼雅, 刘长鑫, 张侃, 等. 耐碳青霉烯类肺炎克雷伯菌对喹诺酮类药物的耐药特性及机制研究[J]. 解放军医学院学报, 2023, 44(8): 873-878. SONG Manya, LIU Changxin, ZHANG Kan, et al. Resistance characteristics and mechanism of carbapenem-resistant Klebsiella pneumoniae to quinolones[J]. Academic Journal of Chinese PLA Medical School, 2023, 44(8): 873-878. [28] Chong Y, Shimoda S, Shimono N. Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae[J]. Infect Genet Evol, 2018, 61: 185-188. doi:10.1016/j.meegid.2018.04.005. [29] 淡彬志. 耐碳青霉烯类肺炎克雷伯菌的耐药特征及其外排泵机制的相关研究[D]. 合肥: 安徽医科大学, 2023. [30] Guerra MES, Destro G, Vieira B, et al. Klebsiella pneumoniae biofilms and their role in disease pathogenesis[J]. Front Cell Infect Microbiol, 2022, 12: 877995. doi:10.3389/fcimb.2022.877995. [31] Ryu S, Klein EY, Chun BC. Temporal association between antibiotic use and resistance in Klebsiella pneumoniae at a tertiary care hospital[J]. Antimicrob Resist Infect Control, 2018, 7: 83. doi:10.1186/s13756-018-0373-6. [32] 曹春远, 邱付兰, 李美华, 等. 龙岩市肺炎克雷伯菌分子分型与耐药性分析[J]. 中国病原生物学杂志, 2024, 19(1): 15-19. CAO Chunyuan, QIU Fulan, LI Meihua, et al. Analysis of molecular typing and drug resistance of Klebsiella pneumoniae in Longyan City[J]. Journal of Pathogen Biology, 2024, 19(1): 15-19. [33] Park SO, Liu JF, Furuya EY, et al. Carbapenem-resistant Klebsiella pneumoniae infection in three New York City hospitals trended downwards from 2006 to 2014[J]. Open Forum Infect Dis, 2016, 3(4): ofw222. doi:10.1093/ofid/ofw222. [34] Huang JE, Chen YZ, Li M, et al. Prognostic models for estimating severity of disease and predicting 30-day mortality of Hypervirulent Klebsiella pneumoniae infections: a bicentric retrospective study[J]. BMC Infect Dis, 2023, 23(1): 554. doi:10.1186/s12879-023-08528-x. |
[1] | 张文红,王翠翠,王小康,张君,郝薇. 硫酸多黏菌素B治疗极早早产儿感染泛耐药肺炎克雷伯菌1例[J]. 山东大学学报 (医学版), 2022, 60(2): 121-124. |
|