Teicoplanin Trough Concentration Research Articles

Optimal Teicoplanin Trough Concentration With Therapeutic Drug Monitoring in Children: A Systematic Review and Meta-analysis.

Teicoplanin is used to treat serious Gram-positive bacterial infections. However, the optimal trough concentrations for pediatric patients remain unclear owing to the lack of monitoring guidelines. This study aimed to determine the optimal teicoplanin trough concentration for treating Gram-positive bacterial infections in children. A systematic review was conducted using 4 databases. Stepwise cutoffs within the range of 10-30 mcg/mL were used for efficacy and safety. Studies were included if they reported treatment success rates and/or all-cause mortality, nephrotoxicity, hepatotoxicity, and thrombocytopenia according to the trough concentration. The meta-analysis included 12 studies involving 830 pediatric patients. Teicoplanin cutoff values of 10, 15, 20, and 30 mcg/mL were reported in 9, 8, 9, and 2 studies, respectively. Trough concentrations <10 mcg/mL significantly reduced the treatment success rate, with an odds ratio of 0.07 and a 95% confidence interval ranging from 0.01 to 0.40. The overall treatment success rate was 50.0% versus 95.7% observed at concentrations ≥10 mcg/mL. However, no significant difference was observed at the 15-, 20-, and 30-mcg/mL cutoffs, when compared with lower concentrations. Trough concentrations <20 mcg/mL were associated with a decreased risk of nephrotoxicity (odds ratio = 0.21; 95% confidence interval, 0.08-0.55). However, hepatotoxicity and thrombocytopenia showed no significant associations with trough concentration ranges between 10 and 30 mcg/mL. Although further prospective studies are required for validation, the authors' findings suggest that 10- to 20-mcg/mL teicoplanin is the optimal trough concentration for enhanced clinical success and reduced toxicity in pediatric patients.

Construction and Interpretation of Prediction Model of Teicoplanin Trough Concentration via Machine Learning.

ObjectiveTo establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method.MethodsA retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model.ResultsThree algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors.ConclusionWe firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.

Therapeutic Drug Monitoring and Nephrotoxicity of Teicoplanin Therapy in Chinese Children: A Retrospective Study.

PurposeThis study aims to 1) describe the distribution characteristics of teicoplanin trough concentration (Cmin) and explore the related influencing factors and 2) evaluate the nephrotoxicity of teicoplanin in children.Patients and MethodsA cohort of children who were treated with teicoplanin intravenously were included in this retrospective study. Regression analysis was performed to explore the factors associated with the fluctuations of teicoplanin Cmin and the development of nephrotoxicity. Classification and regression tree analysis was used to identify the population at high risk for teicoplanin nephrotoxicity.ResultsA total of 269 plasma samples from 186 children were collected. Underexposure (Cmin < 10 mg/L) was documented in 52.7% of cases. The Cmin/dose after administering the loading dose was strongly associated with age (P = 0.008), weight (P = 0.039), and serum creatinine (P = 0.022). The Cmin/dose after administering the maintenance dose was strongly associated with gender (P = 0.014) and serum creatinine (P = 0.006). Cmin (P = 0.012) and the concomitant treatment with amphotericin B (P = 0.001) were the independent risk factors for teicoplanin-related nephrotoxicity. Children who were concomitantly treated by amphotericin B with teicoplanin Cmin > 9.81 mg/L or patients with teicoplanin Cmin > 21.94 mg/L were at high risk for nephrotoxicity.ConclusionThe fluctuations of teicoplanin Cmin could be affected by age, weight, gender, and serum creatinine. Cmin and concomitant treatment with amphotericin B were the independent risk factors for nephrotoxicity. We suggested that the therapeutic drug monitoring of teicoplanin should be performed in children.

Therapeutic drug monitoring of the teicoplanin trough level after the loading doses in patients receiving venoarterial extracorporeal membrane oxygenation

The optimal loading dose of teicoplanin in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has never been determined by therapeutic drug monitoring. This study investigated the appropriateness of proposed loading dose regimens of teicoplanin when administered to patients receiving VA-ECMO by using a previously proposed loading dosage and measuring the teicoplanin trough concentration (Ctrough). Patients who initiated teicoplanin therapy while receiving VA-ECMO were enrolled. Every included patient received four loading doses of teicoplanin at a dose of 12mg/kg. The first three doses were administered 12h apart, and the fourth dose was administered 24h after the third dose. Blood samples were collected before administering the maintenance dose (i.e., the fifth dose), and the teicoplanin Ctrough was measured. Serum teicoplanin levels were determined using an Agilent 1290 ultra-high performance liquid chromatography system. The teicoplanin Ctrough was successfully tested in 11 patients. Their median age was 68.2 years, and 81.8% of them were men. The median of each loading dose was 11.6 (range, 10.7-12.8) mg/kg. The median teicoplanin Ctrough was 22.01 (range, 14.85-44.84) mg/L. All patients had a Ctrough of more than 10mg/L, whereas 90.9% (10/11) of the patients achieved a Ctrough of more than 15mg/L. The loading dosage consisting of four doses of teicoplanin administered within the first 72h at a dose of 12mg/kg/dose could achieve an adequate therapeutic Ctrough of teicoplanin in patients receiving VA-ECMO.

Evaluating the optimal dose of teicoplanin with therapeutic drug monitoring: not too high for adverse event, not too low for treatment efficacy.

Therapeutic drug monitoring (TDM) of teicoplanin is aimed at minimizing the clinical impact of pharmacokinetic variability; however, its benefits are still being defined. We performed a retrospective study of teicoplanin TDM focusing on the dose-serum concentration relationship and clinical outcomes in a clinical setting. From January 2017 to December 2018, patients receiving teicoplanin ≥ 72h with TDM were enrolled. Patients were divided into three groups: non-loading (NL) group, low-dose loading (LD) group (loading dose < 9mg/kg), and high-dose loading (HD) group (≥ 9mg/kg). Serum teicoplanin trough concentration (Cmin) and adverse events (AEs) were evaluated in each regimen. A subgroup of patients with bacteremia was analyzed to evaluate clinical efficacy. Among 65 patients, 12, 18, and 35 were grouped in NL, LD, and HD, respectively. Achievement rates of Cmin > 20mg/L within 10days were significantly different among the groups (25.0%, 38.9%, and 68.6% in the NL, LD, and HD groups, respectively; P = 0.014). Fourteen patients (21.5%) had AEs, and higher Cmin over 10days (adjusted odds ratio 2.08 per every 20mg/L increases, 95% CI 1.13-3.84, P = 0.019) and age ≥ 65years (P = 0.009) were identified as independent risk factors. In the subgroup analysis, HD regimen (P = 0.050) and high mean Cmin over 10days (P = 0.025) were significantly associated with treatment success. Although HL regimen could achieve Cmin targets and improve clinical outcome during teicoplanin treatment, high Cmin was associated with AEs during treatment. Routine TDM can be helpful to optimize teicoplanin administration.

Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate-severe Gram-positive infections.

ObjectivesTeicoplanin, an antibiotic, has poor clinical efficacy when using the current drug label’s recommended regimen, which is approved by the China Food and Drug Administration. This study explores the appropriate loading and maintenance doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough concentration (minimum concentration [Cmin]).Subjects and methodsAll patients treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central Hospital were screened for enrollment. A total of 113 subjects were included and then divided into four groups: A (received three to six doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B (received three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D (received one to three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were detected with high-performance liquid chromatography on day 4, 30 minutes before maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were compared among the four groups.ResultsMean Cmin differed significantly among the four groups (A, 18.11±6.37 mg/L; B, 15.91±4.94 mg/L; C, 17.06±5.66 mg/L; D, 11.97±3.76 mg/L) (P<0.001), with creatinine clearance of 89.62 (53.72–162.48), 49.66 (40.69–59.64), 27.17 (9.7–39.45), and 96.6 (17.63–394.73) mL/min, respectively. The ratio of loading dose for 3 days to creatinine clearance and serum Cmin were significantly correlated (R=0.59, P<0.001). The correlation between the estimated probability of success and teicoplanin Cmin was assessed using binary logistic regression (OR 2.049, P<0.001). Hepatotoxicity- and nephrotoxicity-incidence rates did not significantly differ among the four groups (P=0.859 and P=0.949, respectively).ConclusionA loading dose of 400 mg at 12-hour intervals three to six times is needed to achieve the early target range (15–20 mg/L) and improve the clinical efficacy rate for normal-renal-function patients. It is urgently necessary to amend the drug label for the recommended regimen.

Evaluation of factors associated with the achievement of an optimal teicoplanin trough concentration .

Because teicoplanin has a long serum half-life, a longer period of time is needed to achieve a steady-state concentration compared with vancomycin. The administration of an initial loading dose has been recommended to reach an effective teicoplanin serum concentration for the treatment of methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA). However, little is known regarding factors that affect teicoplanin concentration. This study aimed to retrospectively determine which factors are associated with achieving an optimal teicoplanin trough level. We analyzed patients with MRSA infections who were treated with teicoplanin intravenously between January 2010 and July 2014. The effect of loading dose administration was evaluated in patients treated with 1,200mg or 1,600mg of teicoplanin, respectively. Approximately 32% (31/97) of patients achieved the trough concentration target (≥15µg/mL) on the 3^rd or 4^th day. Multivariate analysis showed that loading doses and body surface area (BSA) were associated with trough concentration >15µg/mL on the 3^rd or 4^th day. Moreover, patients treated with the 2-day loading dose (1,600mg group: 800mg/day on 2days) promptly achieved a trough concentration >15µg/mL on the 3^rd or 4^th day compared with those receiving a 1-day loading dose (1,200mg group: 800mg/day on only 1day). The receiver operating characteristic curve showed that the optimal cut-off point of estimated glomerular filtration rate (eGFR) was 56mL/min with 1-day loading dose to achieve a trough concentration target >15µg/mL. These results suggested that patients with decreased renal function (eGFR <56mL/min) can safely achieve an optimal trough level with the 1-day loading dose. In patients with normal renal function (eGFR ≥56mL/min), administration of a 2-day loading dose may be needed to rapidly achieve a trough concentration ≥15µg/mL. .

Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter.

According to a recent study and meta-analysis, trough levels of >10 μg/mL teicoplanin (TEIC) may be acceptable for the treatment of uncomplicated infection, but no method of TEIC personalized medicine has been established. Vancomycin (VCM) and TEIC are glycopeptide antibiotic agents effective against methicillin-resistance Staphyloccocus aureus. This study aimed to establish TEIC personalized medicine at a steady state calculated by VCM pharmacokinetic parameters. Bayesian forecasting and population mean methods were employed to estimate individual total VCM clearance (CL) using existing population pharmacokinetics (PPK) parameter, and the differences between the CL calculated by these two methods were defined as ΔCL. Serum drug concentration data for patients treated with TEIC were collected at a steady state concentration (>96 h post infusion). There was a significant relationship between the prediction error of TEIC trough level and ΔCL. The relation between ΔCL and TEIC trough concentration at steady state was used to develop the following equation to determine the maintenance dose: TEIC (μg/mL)=1.1119X-6.124ΔCL+3.9164 (X is defined as TEIC trough concentration calculated from the PPK parameter). The results of this study indicated that it is possible to improve the prediction error of TEIC trough concentration at a steady state for patients who have received VCM therapy.

Teicoplanin use in adult patients with haematological malignancy: Exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity

In 2010, our hospital introduced a higher target teicoplanin trough concentration of ≥20mg/L by Day 3 for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Considerable variability in trough concentrations was observed, with trough concentrations ≥20mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Dose and day of therapy were positively associated with trough concentration, whilst estimated renal function and, interestingly, acute myeloid leukaemia diagnosis were negatively associated (P<0.05). Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal central line-associated bloodstream infections. Elucidation of a specific target concentration requires further investigation. Teicoplanin was well tolerated renally. Findings suggest a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed, the identified factors affecting trough concentrations attained and the suggested link with clinical outcome, individualised initial dosing followed by therapeutic drug monitoring is recommended to ensure early adequate exposure in this vulnerable patient group.

An assessment of teicoplanin use and monitoring serum levels in a Chinese teaching hospital

To validate a high performance liquid chromatography (HPLC) method for serum teicoplanin measurement and use the method for clinical monitoring of teicoplanin levels to analyze the clinical application of teicoplanin. 55 patient profiles were collected and analyzed for the clinical teicoplanin application. 10 critically ill patients of the 55 cases were monitored for teicoplanin trough concentration using the HPLC method. The modified HPLC method exhibited excellent linearity, with correlation coefficient r = 0.9995. The intra-day and inter-day coefficients of variation were less than 10%. The lower limit of detection of teicoplanin was 5.63 mg/l. The recovery of teicoplanin was above 90%. Of the 55 patients in this study, there were 42 patients without load-dosing. There were only 29 patients treated with teicoplanin documented Gram-positive infections by etiological diagnoses. In the 10 patients with teicoplanin serum trough concentration monitoring, all cases received a loading dose of 400 mg every 12 h for 3 doses, and the mean trough concentration of teicoplanin was 10.82 ± 4.51 mg/l. The mean trough levels were 13.04 ± 6.23 mg/l in 4 patients with microbiological eradication and improvement of symptoms of diseases and 9.34 ± 2.61 mg/l in 6 patients with persistence of previous clinical infectious symptoms, respectively. The modified HPLC method is robust, highly reproducible and suited to monitor the concentration of teicoplanin. In critically ill Chinese patients, we should consider more appropriate loading doses and evaluate the relationship between teicoplanin trough concentration and the efficacy using microbiological and clinical parameters.

Determination of teicoplanin trough concentration target and appropriate total dose during the first 3 days: a retrospective study in patients with MRSA infections

An initial loading procedure has been recommended to enable teicoplanin to promptly reach an effective serum concentration for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to retrospectively evaluate the pharmacokinetics and pharmacodynamics of teicoplanin to determine the therapeutic target for the teicoplanin trough concentration and an appropriate dosing method during the first 3 days. The mean trough concentrations were 13.2 mg/L for patients with eradication of MRSA. Moreover, logistic regression analysis showed that the teicoplanin trough concentration was 13 mg/L to achieve MRSA eradication with a probability of 89.0%. The rates of achieving >or=13 mg/L in <or=24, 24-36 and >or=36 mg/kg (total dose during the first 3 days) groups were 9.1, 48.4 and 87.5%, respectively. These results suggest that the administration of >or=36 mg/kg during the first 3 days is appropriate to promptly obtain a trough concentration target of >or=13 mg/L for the initial treatment of MRSA infections.

Implementation and evaluation of a stochastic control strategy for individualizing teicoplanin dosage regimen.

A stochastic control strategy for individualizing teicoplanin dosing schedule in neutropenic patients is proposed and compared to the usual Bayesian approach based on the mode of the posterior density of the model parameters. Teicoplanin disposition is described by a bicompartmental model. Age, body weight, serum creatinine, white blood cell count, and sex can be included as covariates. Posterior density of model parameters is obtained by Bayes theorem under a discrete form from which the posterior density of teicoplanin trough concentrations are computed for any dosing schedule. Optimal maintenance dose is determined by minimizing the cost associated, through a logarithmic risk function, to the concentrations being outside the therapeutic range. In Monte Carlo simulation studies on 300 individuals, stochastic control was more accurate than, and equally precise as the usual Bayesian approach. Two-sample based predictions were not better than one-sample based ones. Inclusion of covariates in the model improved dramatically the performances of both strategies. A small retrospective study based on real data (n = 16 patients) shows that reasonable accuracy (bias of 0.7 mg/L) and precision (3 mg/L) in teicoplanin trough concentration prediction is obtained with both strategies provided that covariates are taken into account.