A Study On The Rationality Of Vancomycin Clinical Application And Factors Influencing Blood Concentration Based On Real-world Data

Objective:By collecting medical records of inpatients using vancomycin（VAN）in a tertiary hospital in Kunming,we comprehensively analyzed the frequency of clinical utilization of vancomycin,clinical treatment effect and the rationality of clinical use in our hospital based on real-world data to analyze the loading dose（LD）,therapeutic drug monitoring（TDM）given by vancomycin.Therapeutic drug monitoring（TDM）,and explore the clinical significance of LD and TDM;To examine the effects of different clinical indicators on vancomycin blood concentration,to develop a precise dosing regimen of VAN suitable for clinical application,and to provide a guiding reference for the rational clinical use of VAN in the future.Method:1.The medical records of inpatients treated with VAN in a tertiary care hospital in Kunming（hereinafter referred to as"our hospital"）from January 2019 to November 2022 were collected.Inclusion and exclusion criteria were established and study subjects were selected.A database was established by querying the medical record system to collect basic information（age,gender,medical history,etc.）,pathogenic bacteria detected,purpose of medication,duration of treatment,dosage,combined medications,routine blood,infectious markers,liver and kidney function,and other clinical information.Rational drug use evaluation criteria are established according to the instructions and guidelines,and their rationality is evaluated.2.According to the instructions and guidelines,the patients included in the study were divided into two groups:loading dose group and control group（maintenance dose group and no loading dose group）,and the differences in general conditions between the loading dose group and the control group were balanced with the help of1:1 propensity score matching（PSM）,and patients whose baseline information remained consistent in both groups were screened for inclusion in the study,To investigate the effect of the loading dose group on clinical efficacy and safety.3.Patients in the TDM group were grouped with those in the control group（non-TDM）based on whether they were monitored for trough concentration(C_min)or not.,and the clinical efficacy and safety of the two groups were compared.The clinical data of patients who monitored C_minwere also collected,and the possible influencing factors of blood concentration were analyzed by one-way anova test and multiple linear regression.Results:1.783 patients were enrolled in the study according to the nadir criteria,the youngest being a newborn at 4 d of age and the oldest being a 97-year-old with an average age of（48.28±25.80）years,and the enrolled patients were distributed in 23departments,mainly in hematology（19.15%）,ICU（14.56%）,pediatrics（14.43%）,etc.The highest percentage of unreasonable rate was in ICU with 6.77%（of the total number of included patients）.The delivery rate of this study was 78.16%,and 645pathogenic strains were detected,of which 271 cases（44.28%）had positive pathogenic examination results,and the most common infection was respiratory infection,accounting for 53.64%.203 cases out of 783 patients were used irrationally,accounting for 25.93%,and the main forms of irrationality were distributed in indications,dosage,dissolution,regimen,and combination The main forms of irrationality were distributed in indications,dosage,solvents,regimen,and combination.The highest incidence was the dosage of VAN.In the evaluation of drug utilization,adults:DUI=0.84,children:CDUI=0.69,both less than 1.The therapeutic efficiency was 75.35%,and the incidence of adverse reactions was 16.99%.2.Patients in the loading dose group and control group（maintenance dose group and no loading dose group）were analyzed by 1:1 PSM according to their gender,age,blood routine,and liver and kidney function.153 and 108 patients in the loading dose group and control group were included before PSM matching,and the incidence of adverse reactions during hospitalization was significantly lower in the loading dose group than in the control group（35.19%vs.15.03%,P<0.001）,but showed no difference in in clinical efficacy.after PSM,71 patients in each of the two groups were included,and the loading dose group did not significantly improve the efficiency of infection treatment compared with the control group,but did not increase the incidence of adverse reactions in patients（26.76%vs.21.13%,P>0.05）.3.Patients were divided into TDM group and control group（non-TDM group）according to the nadir criteria for analysis.In terms of pro-safety,there was a statistical difference between the two groups,and the incidence of renal injury and liver injury was significantly higher when VAN C_minexceeded 15 mg·L^-1.According to the guidelines,VAN blood concentrations were divided into three groups:<10mg·L^-1,10-20 mg·L^-1,and>20 mg·L^-1.The results of univariate analysis showed that in adult patients,the three groups were significantly different in L/S,Urea,CREA,e GFR,Ccr were significantly different;while in neonatal and infant patients,the three groups were significantly different in weight,GGT,Urea,and CREA,indicating that possibly these factors are affecting VAN C_min,but the interference of confounding factors on the results was not controlled,and the statistically significant variables of interest should be further subjected to multiple linear regression analysis.The factors that were statistically different in the univariate analysis above were subjected to multiple linear regression analysis,and the results showed that in adult patients,the effect of e GFR on VAN C_minwas statistically significant and was a significant predictor of VAN C_min.For neonates and infants,weight,CREA were significant predictors of VAN C_min.Conclusion:1.The clinical application of vancomycin in our hospital as a whole tends to be reasonable and there is no abuse.However,in the process of use,the monitoring rate for giving loading dose,maintenance dose and TDM is low in accordance with the guideline,which indirectly reflects that the rationality of clinical use of dose needs to be improved,and it is necessary to strengthen clinicians’attention to VAN blood concentration monitoring,to guide the adjustment of individualized dosing regimen based on vancomycin TDM and clinical actual situation,and to improve TDM level.2.Real-world PSM-based studies of vancomycin’s LD on clinical efficacy and safety studies have provided authenticity and reliability of results.Based on propensity score matching studies,the first dose of vancomycin given as a loading dose does not pose an additional risk of nephrotoxicity.3.Vancomycin TDM improves the incidence of adverse effects in patients and the incidence of nephrotoxicity increases significantly with increasing vancomycin trough concentrations.however,well-designed large-scale randomized controlled trials are still needed to validate the clinical efficacy of vancomycin blood monitoring and to further evaluate other adverse effects and mortality.4.Vancomycin had large individual differences and many influencing factors,so it needs to be analyzed comprehensively according to patients’own physiopathological conditions and co-administered drugs when used clinically,and combined with monitoring results to develop individualized dosing regimens to improve the safety rate and efficiency of clinical use and reduce the incidence of adverse reactions.