Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (5): 103-111.doi: 10.6040/j.issn.1671-7554.0.2024.0164

• Public Health & Management Sciences • Previous Articles    

Causal correlation between antimicrobial use density and durg resistance rates of Klebsiella pneumoniae and drug control thresholds

QIAN Fengtong1,2, LI Hongkai1,2, YU Jinlong3, XUE Fuzhong1,2   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Healthcare Big Data Research Institute, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250003, Shandong, China;
    3. The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong, China
  • Published:2024-05-29

Abstract: Objective To explore the causal association between antimicrobial use density and Klebsiella pneumoniae drug resistance rate, and to determine the control thresholds of antimicrobial use density. Methods Based on the data of antimicrobial use density and Klebsiella pneumoniae resistance rates in the Second Hospital of Shandong University from 2015 to 2023, the effect of total antimicrobial use density on Klebsiella pneumoniae resistance rate was analyzed by breakpoint regression. Nonlinear time-series analyses using generalized additive models(GAMs)were used to assess the association between antimicrobial use density and Klebsiella pneumoniae resistance rate and to determine the control thresholds for antimicrobial use density. P<0.05 and adjusted R2 > 0.3 were considered statistically significant differences. Results During the study period, the density of all types of drug use remained stable from 2015 to 2019, trended downward through 2021, and then gradually increased through 2023. Klebsiella pneumoniae drug resistance rates trended upward from 2015 to 2019, gradually declined through 2022, and then gradually increased through 2023. The results of breakpoint regression analysis showed that an increase in total antimicrobial use density led to an increase in the total resistance rate of Klebsiella pneumoniae, and the difference was statistically significant(β=1.071, P=0.041). Nonlinear time-series analyses showed that the resistance rates of Klebsiella pneumoniae were significantly associated with the density of carbapenems, aminoglycosides, penicillins, and glycopeptides(lag coefficient ranged from 1 to 5, all P<0.05, adjusted R2 ranged from 0.589 to 0.808). The control thresholds of carbapenems, aminoglycosides, and third-generation cephalosporins use were 5.82, 0.06 and 5.62 DDDs/(100 patient-days), respectively. Conclusion Increased intensity of antimicrobial drug use leads to an increase in the overall resistance rate of Klebsiella pneumoniae; thresholds of antimicrobial use density were identified in this study to inform more appropriate therapeutic strategies and effective control of antimicrobial resistance rates in clinical practice.

Key words: Klebsiella pneumoniae, Antimicrobial use density, Breakpoint regression, Nonlinear time-series analysis, Control thresholds

CLC Number: 

  • R574
[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] Dingpei HAN,Yue YAN,Yuqin CAO,Xin SUN,Yanxia HU,Minxian WANG,Yan LUO,Yongmei SHI,Qing XIE,Junbiao HANG,Hecheng LI. Expert consensus of Ruijin Hospital on the concept of enhanced recovery after surgery in the clinical practice of thoracic surgery [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 11-16.
[2] TIAN Yaotian, WANG Bao, LI Yeqin, WANG Teng, TIAN Liwen, HAN Bo, WANG Cuiyan. Machine learning models based on interpretive CMR parameters can predict the prognosis of pediatric myocarditis [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 43-49.
[3] XIA Xiaona, HUANG Zhaodi, REN Qingguo, LIU Feng, DENG He, REN Guorong, DUAN Jiandong, WANG Shaoyu. Value of double-phase enhancement CT scan in the differential diagnosis of 182 benign and malignant thyroid nodules [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 57-62.
[4] WANG Ning, GUO Zhenjiang, ZHANG Yuanyuan, WANG Jing, GUO Wei, WANG Jinrong, CUI Zhaobo. Value of regular ultrasound examination in the diagnosis and treatment of deep venous thrombosis associated with central venous access device [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 63-67.
[5] Haipeng SI,Wencan ZHANG,Le LI,Xin ZHOU. Research advances on risk factors, diagnosis and treatment of Kümmell's disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 25-32.
[6] Yilong YIN,Xiaoming XI. Advances in the intelligent diagnosis of eye diseases [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 33-38.
[7] Carol Y. Cheung,Anran RAN. Artificial intelligence deep learning in glaucoma imaging: current progress and future prospect [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 24-32, 38.
[8] ZHANG Hongbin, ZHAO Hanhui, WANG Suxia, ZHOU Peng, HE Qingqing, WANG Yanqun, DING Weiping, LIU Gang. Perioperative observation and postoperative risk factors of severe hypocalcemia after parathyroidectomy: a report of 303 cases [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 14-20.
[9] Qiang WU,Zekun HE,Ju LIU,Xiaomeng CUI,Shuang SUN,Wei SHI. A research on multi-modal MRI analysis based on machine learning for brain glioma [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 81-87.
[10] Ju LIU,Qiang WU,Luyue YU,Fengming LIN. Brain tumor image segmentation based on deep learning techniques [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 42-49, 73.
[11] Yilong YIN,Xiaoming XI,Xianjing MENG. Intelligent diagnosis methods of Alzheimer's disease [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 14-21.
[12] . [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 120-122.
[13] Wei ZHANG,Wenhao TAN,Yibin LI. Locmotion control of quadruped robot based on deep reinforcement learning: review and prospect [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 61-66.
[14] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1-6.
[15] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7-14.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!