Therapeutic Drug Monitoring of 1 106 Cases of Vancomycin Therapy and Analysis of Risk Factors / 医药导报

Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring(TDM).Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury(AKI)during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed.Results A total of 1 106 patients were included,with 70.7％being males and a median age of 60.0(IQR=20)years.Surgical departments accounted for 76.4％of the distribution.The median duration of vancomycin therapy was 10.8 d(IQR=9.0).A total of 21.6％of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8％(518/1 106)of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9％.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are＜10,10-＜15,15-20,and＞20 μg·mL-1,the AKI rates are 15.8％,20.5％,25.8％,and 39.4％,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of＞7-14 d(OR=1.688,P=0.001)and＞14 d(OR=1.744,P=0.002)than with a dosing course of ≤7 d.Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose(OR=1.540,P=0.003).Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.

Analysis of influencing factors for the metabolism of voriconazole in adult patients / 中国药房

OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （c0） and plasma concentration of voriconazole-N-oxide concentration （cN） were determined， and voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Vancomycin and Linezolid dosing in Obese and Overweight Patients: Is There a Universally Accepted Dosing Protocol to Improve their Efficacy?

@#Vancomycin is used to manage methicillin-resistant Staphylococcus aureus (MRSA) and other bacterial infections that are Gram-positive in nature. Linezolid belongs to the oxazolidinone class of antibiotics, which is primarily used to treat vancomycin-resistant Enterococcus (VRE), MRSA, diabetic foot, soft tissue, and skin infections. Here, we discuss vancomycin and linezolid dosing in obese patients, their mechanism of actions, pharmacokinetics, problems with dosing and evaluation of several dosing protocols in the obese patient population. There is no generally accepted dosing protocol for linezolid and vancomycin. Evidence suggests that using trough concentrations alone is insufficient for estimating vancomycin and linezolid exposure accurately as many researchers have revised protocol guidelines, developed more rigorous dosing and monitoring guidelines, or developed novel dosage strategies to meet the needs of overweight patients. Peaks and troughs measurement should be considered because it improves precision and reduces the area under the curve (AUC) estimate bias. To provide better dosing guidelines in this vulnerable group, obese patients must be included in all phases of drug design.

Clinical Characteristics of Voriconazole-induced Neurological ADR and the Occurrence of Hypokalemia and Hyponatremia / 中国药房

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

Application of AUC/MIC as the therapeutic drug monitoring target of vancomycin in patients with severe infections of multi drug resistant gram positive bacteria / 中国临床药理学与治疗学

AIM: To discuss the application and clinical significance of the ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC

Correlation of infliximab related genetic polymorphism, serum trough concentration and efficacy in patients with Crohn's disease / 中国临床药理学与治疗学

AIM: To investigate the correlations of genetic polymorphisms, infliximab(IFX) serum trough concentration, immunogenicity and clinical outcome in patients with Crohn's disease(CD) to provide reference for optimizing IFX treatment in CD patients. METHODS: The clinical data of CD patients treated with IFX in our hospital from September 2017 to September 2019 were prospectively collected. The genotypes TNF-α-308, TNF-α-238, TNF-α-857, TNFRSF1B, ABCB1, FCGR3A were detected by targeted sequencing using multiple PCR combined with high throughput sequencing before administration. The IFX steady-state concentration was determined by ELISA. SPSS 20.0 software was used for statistical analysis and ROC curve was drawn for clinical efficacy and antibody threshold. RESULTS: A total of 111 patients were included in the study, the IFX trough concentration of patients with TNF-α-238GA was significantly lower than that of GG (0.55±0.52) vs. (1.75±1.46) μg/mL (P=0.003), while there was no significant difference in IFX trough concentration among TNF-α-308, TNF-α-857, TNFRSF1B, ABCB1, FCGR3 Agenotypes. Clinical response rate of TNFRSF1B (TG+GG) was significantly higher than that of the wild type (TT) (75.0% vs. 42.3%) (P=0.001), and there was no statistically significant difference in clinical efficacy among patients with different genotypes of other genes (P>0.05). The efficacy of IFX in the treatment of CD and the production of antibody to IFX were significantly correlated with maintenance trough concentration (P1.33 μg/mL had certain predictive significance for biological response, while ≤0.51 μg/mL can be used as a predictor of antibody production.

Effects of Augmented Renal Clearance on Blood Trough Concentration of Patients Receiving High-dose Regimen of Teicoplanin / 中国药房

OBJECTIVE：To study the effects of augmented renal clearance （ARC）on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS ：Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10 mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ，clinical efficacy ，Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS ：A total of 56 patients were included and divided into ARC group （18 cases）and normal renal function group （38 cases）. ARC group had younger age （P＜0.001）and lower serum albumin level （P＝0.025）than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group （P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage （P＝0.003；P＜0.001）. The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal function group ，but there was no statistical difference （P＝0.195；P＝0.223）. There was no liver function damage ，hemocytopenia and allergic reaction in both groups ，but in the normal renal function group ，the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS ：ARC patients are younger ，most of them have hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ，it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.

Characteristics of Vancomycin Blood Concentrations after Intraperitoneal Administration and Its Relationship with Efficacy in PDRP Patients with Peritoneal Dialysis-related Peritonitis / 中国药学杂志

OBJECTIVE: To evaluate the relationship between serum vancomycin level and efficacy in peritoneal dialysis-related peritonitis(PDRP) patients by analyzing our hospital′s data. METHODS: Forty-six PDRP patients admitted in our hospital from August 2015 to April 2018 were collected, then divided into three groups by different regimens(1 g q3d, 1 g q4d, 1 g q5d), the probability of target attainment of the first trough concentration and those after several administrations, the characteristics of distribution of vancomycin serum level and the relation with efficacy were analyzed. RESULTS: The first trough concentrations of 1 g q3d, 1 g q4d and 1 g q5d were (10.51±2.79), (6.78±1.58) and (6.68±1.68) mg·L-1 respectively, with statistical difference between 1 g q3d regimen and 1 g q4d, 1 g q5d (P0.01). The trough concentration after the 3rd administration of 1 g q3d regimen was (16.15±4.79) mg·L-1, the trough concentration after the 2nd administration of 1 g q4d regimen was (10.20±2.0) mg·L-1, and the trough concentration after the 2nd administration of 1 g q5d regimen was (9.49±3.24) mg·L-1. The serum vancomycin level was increasing after repeated administration with obvious statistical difference among the three regimens(P0.01). There was no significant difference in the efficacy between concentration10 mg·L-1 and that ≥10 mg·L-1 or concentration <15 mg·L-1 and that ≥15 mg·L-1(P0.05). CONCLUSION: There is significant inter-individual differences of serum vancomycin level in PDRP patients after IP administration, and vancomycin is accumulated in body after repeated administration. It is suggested to monitor the serum vancomycin concentration and the trough concentration kept above 10 mg·L-1.

Therapeutic drug monitoring of teicoplanin:an overview / 国际药学研究杂志

Teicoplanin is a new glycopeptide antibiotic marketed after vancomycin for the treatment of Staphylo- coccus aureus(SAU)infection. Previous studies have shown that teicoplanin is safer than vancomycin,especially in the nephrotoxicity,so the routine serum concentration monitoring was not performed in the clinical application of teico- planin. In recent years,it has been found that the individual differences frequently appeared in the clinical application of teicoplanin,and thus it has been suggested that the serum concentration monitoring should be carried out in its clinical application. However,the domestic studies on the serum teicoplanin concentration monitoring are rarely conducted,and its clinical application experience is insufficient in China. This paper reviews the therapeutic drug monitoring of teico- planin,in terms of the pharmacokinetic characteristics of teicoplanin,the correlation between the blood concentration with the efficacy and adverse reactions,and the factors influencing the blood concentration of teicoplanin,so as to pro- vide a reference for the therapeutic drug monitoring and the rational clinical application of teicoplanin.

Effects of CYP2D610 on plasma trough concentration of metoprolol in patients with coronary artery disease / 南方医科大学学报

OBJECTIVE@#To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.@*METHODS@#The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.@*RESULTS@#In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.@*CONCLUSIONS@#CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.

Discussion of the Correlation between Voriconazole's Trough Concentration and Mental Abnormity Rate / 中国药学杂志

OBJECTIVE: To explore the correlation between voriconazole's trough concentration and mental abnormity. METHODS: Retrospectively analyze voriconazole's trough concentration and the occurrence of mental abnormity in 151 patients from May 2016 to May 2017 in Xiangya Hospital. RESULTS: In 151 patients, Insomnia rate is 21.85%, binary logistic regression analysis showd that the insomnia rate is positively related to voriconazole's trough concentration(P = 0.02). Illusion rate is 15.23%, binary logistic regression analysis showd that the illusion rate is positively related to voriconazole' s trough concentration (P = 0.002). CONCLUSION: There is a significant correlation between voriconazole's mental abnormity and trough concentration.

Distribution characteristics of plasma concentration of vancomycin and clinical efficacy in pediatric patients with severe pneumonia and congenital heart disease / 中国小儿急救医学

Objective To analyze the distribution characteristics of vancomycin blood concentration in children with severe pneumonia complicated with congenital heart disease( CHD) and children with simple severe pneumonia after using the same dose vancomycin,and observe the clinical efficacy at the same time. Methods Plasma concentrations in pediatric patients with severe pneumonia complicated with CHD ( CHD group) who treated by vancomycin from November 2012 to September 2013 in Shengjing Hospital of China Medical University were collected. Plasma concentrations of children with simple severe pneumonia( control group) treated by vancomycin were also collected at the same period. The blood concentration values and therapeutic effects of the two groups were recorded into the database for statistical analysis. Peak,trough con-centrations and efficacy were analyzed by receiver operating characteristic(ROC) curve. Results Twenty-five children with CHD were collected,the average peak concentration was (28. 39 ± 6. 68) mg/L,the aver-age trough concentration was (13. 34 ± 6. 62)mg/L. Control group were also 25 cases,the average peak con-centration was (16. 23 ± 2. 50) mg/L and the average trough concentration was (2. 77 ± 1. 01) mg/L. Both peak and trough concentrations of CHD children were significantly higher than those of the control group (tpeak =8. 52,Ppeak <0. 05;ttrough =7. 89,Ptrough <0. 05). In the ROC of peak,trough concentrations and effica-cy,area under the curve were 0. 74(95％CI 0. 547-0. 935,P=0. 01) and 0. 77(95％CI 0. 605-0. 935,P=0. 004) respectively,and the difference was statistically significant. Conclusion Plasma concentrations of vancomycin in children with CHD are generally higher,it is necessery to monitor plasma concentration even under regular doses,to make the application of vancomycin more safe and effective in children with CHD. There is a correlation between plasma concentration of vancomycin and clinical efficacy in children,the high-er the blood concentration,the more likely the clinical efficacy is to be effective.

Teicoplanin trough concentrations following different loading doses in critically ill patients / 中国感染控制杂志

Objective To understand serum trough concentrations (Cmin) of teicoplanin and target concentration achieved in severely infected patients after three days treatment with different loading doses of teicoplanin,and find out optimal loading dose.Methods Severely infected patients who admitted to the intensive care unit(ICU) of a hospital from February 1,2016 to February 28,2017 were enrolled in the study.According to different drug loading doses (teicoplanin standard dose:6mg/kg;high dose:10mg/kg) and different creatinine clearance rates (Ccr:50mL/min as standard value),patients were divided into four subgroups:group of standard dose and normal Ccr (GsD1),group of standard dose and low Ccr (GSD2),group of high dose and normal Ccr (GHD1),group of high dose and low Ccr(GHD2).Serum Cmin,percentage of achieving target concentration,and adverse reactions of teicoplanin in different groups were compared.Results A total of 49 patients were enrolled in the study,17 patients were in GSD group,Cmin on 4th day before administration was (5.98 ± 2.67)mg/L;32 patients were in GHD group,Cmin on 4th day before administration was (9.05 ± 4.25)mg/L;Cmin in GHD group was higher than that in GsD group,and there was statistical difference between two groups(t=3.10,P=0.003).Values of Cmin in GSD1,GSD2,GHD1,and GHD2 groups were (5.78±2.72),(6.34±2.78),(8.21 ±3.77),and (12.07±4.81) mg/L respectively,differences among four groups were statistically significant(F =4.766,P =0.006).The Cmin in GHD2 group was higher than those in GHD1,GSD2,and GsD1 groups,percentage of achieving the target concentration were 9.09％ (1/11),16.67％ (1/6),28.00％(7/25),and 71.43％ (5/7) respectively,differences were statistically significant(x2=8.766,P=0.033).Complications associated with teicoplanin such as rash,damage to hepatic and renal function were not observed in all patients during the treatment course.Conclusion Whether the Ccr is normal or not,target Cmin can not be achieved early in patients given teicoplanin with standard loading dose;in patients with low Ccr,given high loading dose,target Cmin can be achieved early;while in patients with normal Ccr,higher loading dose may be needed.

Analysis of Clinical Rational Use Evaluation and Blood Concentration Monitoring of Vancomycin in Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational use of vancomycin. METHODS:The medical records of 299 pa-tients receiving vancomycin in our hospital during Jan. 2015-Jun. 2016 were collected and analyzed statistically in respects of drug use,medication rationality,etiological test results,blood concentration of vancomycin,therapeutic efficacy,adverse drug reac-tion,etc. RESULTS:Vancomycin was mostly used as therapy drug in our hospital,mainly empiric treatment(90.30%);detection rate of samples before medication was 61.82%,and specific pathogens were detected in 52 cases(28.42%). There were 69 cases of irrational drug use(23.08%),which were unsuitable drug concentration. Monitoring rate of vancomycin concentration was 43.33%;trough concentration remained at 10-20 mg/L,accounting for 40.00%. Response rate was 79.39%.The incidence of acute kidney injury was 5.41% after treatment. CONCLUSIONS:The examination rate before medication and blood concentration moni-toring rate of vancomycin are in low level in our hospital. The patients with effective trough blood concentration accounts for low proportion.Clinical application management of vancomycin should be strengthened to promote individual medication.

Analysis of Clinical Rational Use Evaluation and Blood Concentration Monitoring of Vancomycin in Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational use of vancomycin. METHODS:The medical records of 299 pa-tients receiving vancomycin in our hospital during Jan. 2015-Jun. 2016 were collected and analyzed statistically in respects of drug use,medication rationality,etiological test results,blood concentration of vancomycin,therapeutic efficacy,adverse drug reac-tion,etc. RESULTS:Vancomycin was mostly used as therapy drug in our hospital,mainly empiric treatment(90.30%);detection rate of samples before medication was 61.82%,and specific pathogens were detected in 52 cases(28.42%). There were 69 cases of irrational drug use(23.08%),which were unsuitable drug concentration. Monitoring rate of vancomycin concentration was 43.33%;trough concentration remained at 10-20 mg/L,accounting for 40.00%. Response rate was 79.39%.The incidence of acute kidney injury was 5.41% after treatment. CONCLUSIONS:The examination rate before medication and blood concentration moni-toring rate of vancomycin are in low level in our hospital. The patients with effective trough blood concentration accounts for low proportion.Clinical application management of vancomycin should be strengthened to promote individual medication.

PK/PD of vancomycin in patients with severe acute pancreatitis combined with augmented renal clearance / 中华危重病急救医学

Objective To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD)of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD.Methods The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled. Steady-state trough concentrations of vancomycin from patients were collected retrospectively. The SAP patients were divided into augmented renal clearance (ARC) and non-ARC groups, as well as systemic inflammatory response syndrome (SIRS) and non-SIRS groups according to the patients with or without symptom above. Adjustments of increased dosage or 24-hour continuous infusion or increase vancomycin dose were made for patients if the steady-state trough concentrations fell below the target level. Steady state trough concentration for vancomycin intermittent infusion or steady state concentration for vancomycin continuous infusion was determined by the fluorescence polarization immunoassay method. PK parameters of vancomycin were calculated using the Bayesian estimator and the area under the serum drug concentration-time curve (AUCc-t), the minimum inhibitory concentration (MIC) and AUCc-t/MIC was recorded and calculated.Results The steady state trough concentration or steady state concentration from 61 patients with SAP were collected with mean steady state trough concentration of vancomycin of (7.7±4.4) mg/L, which was significantly lower than standard concentration (15 mg/L,P < 0.001). Apparent volume of distribution (Vd) and clearance of vancomycin was (1.06±0.26) L/kg and (8.9±2.8) L/h. The serum steady state trough concentration of vancomycin in ARC group (n = 33) was significantly lower than that in non-ARC group (n = 28; mg/L: 6.7±3.5 vs. 8.2±4.1, P < 0.01), clearance was significantly increased (L/h: 9.8±2.9 vs. 7.7±2.2,P < 0.01). Compared with non-SIRS group (n = 31), the serum steady state trough concentration of vancomycin in SIRS group (n= 30) was significantly lowered (mg/L: 6.1±3.2 vs. 13.0±4.2,P < 0.01), and clearance was significantly increased (L/h: 9.4±2.0 vs. 7.1±2.1,P < 0.05). Compared with the only increasing vancomycin dose group (n = 29), vancomycin continuous infusion for 24 hours (n = 21) could significantly reduce daily dosage (mg/kg: 13.6±3.9 vs. 19.1±3.5,P < 0.01), increase the serum trough concentration (mg/L: 18.1±7.0 vs. 12.6±5.3,P < 0.01), and improve the AUCc-t/MIC.Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients with ARC. The more serious of the SIRS is, the lower the vancomycin trough concentration is. Vancomycin 24-hour continuous infusion could optimize the PK/PD parameters, decrease the daily dose, increase the clinical effect, and reduce the bacterial resistance.

Pharmacokinetics of vancomycin in patients with severe acute pancreatitis and its influencing factors: analysis of 7 years data / 中华危重病急救医学

Objective To observe the change of the serum trough concentration and its pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP), and to analyze the factors influencing vancomycin concentration. Methods A retrospective analysis was conducted. Steady-state trough concentrations of vancomycin from patients (18-80 years old) with SAP concomitantly with G+ infection admitted to Intensive Care Unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2016 were enrolled. According to the usage time of vancomycin, the patients with SAP were divided into early group (onset within 21 days), middle group (onset between 21-28 days) and late group (onset over 28 days). The gender, age, body weight, clinical diagnosis, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score, renal function, and the pharmacokinetic parameters were recorded. Influencing factors of vancomycin was analyzed by multiple linear regression and stepwise regression. Results Fifty-eight patients were enrolled who contained 134 times trough concentrations of vancomycin. There were 41 patients enrolled and 61 times of trough concentrations in the early group, 24 patients enrolled and 33 times of trough concentrations in the middle group, and 28 patients enrolled and 40 times of trough concentrations in the late group. There was no significant difference in gender, age, body weight, serum creatinine, creatinine clearance (CCr), albumin, APACHE Ⅱ score among the three groups. There was significantly difference in the duration from the onset time to vancomycin administration between early, middle groups and late group (days:15.9±3.2, 23.3±2.2 vs. 35.0±6.7, both P 0.05). Compared with the standard concentration (15 mg/L) of vancomycin, the serum trough concentration of vancomycin was significantly reduced in SAP patients [(7.5±4.3) mg/L, P < 0.01]. Apparent volume of distribution (Vd) was (72.4±15.4) L, and clearance rate (CL) was (9.0±2.8) L/h. According to the Bayesian, the serum trough concentration of vancomycin was significantly reduced in early group and middle group compared with late group (mg/L: 5.0±2.1, 7.3±2.5 vs. 11.5±5.1, both P < 0.01), CL was significantly increased (L/h: 10.5±3.0, 8.1±1.9 vs. 7.4±1.9, both P < 0.05), and Vd was significantly increased in early group compared with late group (L: 73.7±15.5 vs. 71.0±12.6, P < 0.05). It was shown by multiple linear regression analysis that there was strong relationship between serum trough concentration and the serum creatinine, CCr, average daily dose and the starting time of vancomycin treatment (r value were 0.449, -0.318, 0.373, 0.763, respectively, all P < 0.05). Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients. And the earlier usage of vancomycin, the lower of the trough concentration is. Therefore, higher dosage regimen was needed to ensure the clinical effect, and reduce the bacterial resistance.

The factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia / 临床儿科杂志

Objective To explore the factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia. Methods The general information, the biochemical test results, and plasma concentration of vancomycin were collected from 93 pediatric patients with severe gram-positive cocci pneumonia. The relative factors influencing trough concentration of vancomycin were analyzed retrospectively. Results With the dosage of 40-60 mg/(kg·d), serum trough concentration of vancomycin were between 10-20 mg/L in 26 patients, <10 mg/L in 54 cases, ≥20 mg/L in 13 cases. The ALT, AST, GFR, and γ-GT were significantly different among three groups (P<0.05); the 10-20 mg/L group had the highest levels of AST and γ-GT, the ≥20 mg/L group had the highest level of ALT and the lowest level of GFR. Multiple linear regression analysis showed that GFR was negatively linearly correlated with the serum trough concentration of vancomycin (R2=0.039, P<0.05). The median serum trough concentration of vancomycin in pediatric patients with GFR≥90, 60–90, 30–60 mL/(min·1.73m2) were 8.66, 18.21, 8.45 mg/L respectively, and the difference is statistically significant (P<0.05). Conclusions The serum trough concentration of vancomycin is negatively linearly correlated with GFR in pediatric patients with severe gram-positive cocci pneumonia. The patients with impaired renal function are easier to reach the target serum trough concentration of vancomycin. Clinical use of vancomycin should follow the low doses in the range the guideline recommended, and the serum trough concentration should be closely monitored.