Causal correlation between antimicrobial use density and durg resistance rates of Klebsiella pneumoniae and drug control thresholds
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 differ-ences.Results During the study period,the density of all types of drug use remained stable from 2015 to 2019,tren-ded 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 R2ranged 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 In-creased 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.
Klebsiella pneumoniaeAntimicrobial use densityBreakpoint regressionNonlinear time-series analysisControl thresholds
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