Therapeutic Drug Monitoring Of Teicoplanin Research Articles

Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots.

In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram-positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram-positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS). A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods. The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%-114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin. A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics.

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureusinfection.

This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

Accuracy of Therapeutic Drug Monitoring of Teicoplanin at the Onset of Febrile Neutropenia.

Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were -0.54, -0.25, and -0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/μL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/μL showed slightly inferior prediction accuracy.

Optimal Use and Need for Therapeutic Drug Monitoring of Teicoplanin in Children: A Systematic Review.

Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant Staphylococcus aureus. Despite some comparable advantages, there is no guideline or clinical recommendation for teicoplanin in the pediatric population, unlike vancomycin where abundant studies and the recently revised guideline on therapeutic drug level monitoring (TDM) exist. The systematic review was performed in accordance with the preferred reporting items for systematic reviews. Two authors (JSC and SHY) searched PubMed, Embase, and Cochrane Library databases using relevant terms independently. Fourteen studies were finally included with a total of 1,380 patients. TDM was available in 2,739 samples collected in the nine studies. Dosing regimens varied widely, and eight studies used recommended dosing regimens. Timing for measuring TDM was mostly 72-96 hours or longer after the initiation of the first dose, which was expected to be a steady-state. The majority of studies had target trough levels of 10 µg/mL or above. Three studies reported that the clinical efficacy and treatment success rate of teicoplanin was 71.4%, 87.5%, and 88%. Adverse events associated with teicoplanin use were described in six studies with a focus on renal and/or hepatic impairment. Except for one study, no significant relation was noted between the incidence of adverse events and trough concentration. Current evidence on teicoplanin trough levels in pediatric populations is insufficient due to heterogeneity. However, target trough levels with favorable clinical efficacy are achievable by recommended dosing regimen in the majority of patients.

Clinical practice guidelines for therapeutic drug monitoring of teicoplanin: a consensus review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring.

BackgroundOwing to its low risk of adverse effects, teicoplanin has been extensively used in patients with infections caused by MRSA. To promote the better management of patients receiving teicoplanin, we have updated the guidelines for therapeutic drug monitoring (TDM).MethodsThe guidelines were developed by a committee following the methodology handbook published by the Japanese Medical Information Distribution Service. Nine clinical questions were selected. The committee conducted a systematic review and meta-analysis to establish evidence-based recommendations for the target trough concentration (Cmin). An initial electronic database search returned 515 articles, and 97 articles qualified for a full review. Four and five studies were included for the efficacy evaluation of cut-off Cmin values of 15 and 20 mg/L, respectively.ResultsCompared with Cmin < 15 mg/L, a target Cmin value of 15–30 mg/L resulted in increased clinical efficacy in patients with non-complicated MRSA infections (OR = 2.68; 95% CI = 1.14–6.32) without an increase in adverse effects. Although there was insufficient evidence, target Cmin values of 20–40 mg/L were suggested in patients with complicated or serious MRSA infections. A 3 day loading regimen followed by maintenance treatment according to renal function was recommended to achieve the target trough concentrations. Because of the prolonged half-life of teicoplanin, measurement of the Cmin value on Day 4 before reaching steady state was recommended.ConclusionsThe new guideline recommendations indicate the target Cmin value for TDM and the dosage regimen to achieve this concentration and suggest practices for specific subpopulations.

Quantification of Teicoplanin Using the HPLC-UV Method for Clinical Applications in Critically Ill Patients in Korea.

A high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method has been used to quantify teicoplanin concentrations in human plasma. However, the limited analytical accuracy of previously bioanalytical methods for teicoplanin has given rise to uncertainty due to the use of an external standard. In this study, an internal standard (IS), polymyxin B, was applied to devise a precise, accurate, and feasible HPLC-UV method. The deproteinized plasma sample containing teicoplanin and an IS of acetonitrile was chromatographed on a C18 column with an acidic mobile phase consisting of NaH2PO4 buffer and acetonitrile (78:22, v/v) by isocratic elution and detection at 220 nm. The linearity was in the range 7.8–500 mg/L calculated by the ratio of the teicoplanin signal to the IS signal. This analytical method, validated by FDA guidelines with ICH Q2 (R1), was successfully applied to analyze the plasma samples of patients in the intensive care unit for treating serious resistant bacterial infectious diseases, such as those by methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The methods suggested the potential for use in routine clinical practice for therapeutic drug monitoring of teicoplanin, providing both improved accuracy and a wide range of linearity from lower than steady-state trough concentrations (10 mg/L) to much higher concentrations.

Teicoplanin Therapeutic Drug Monitoring and Treatment Outcomes in Children With Gram-Positive Infections.

This is a retrospective audit of teicoplanin dosing, drug-level monitoring, and outcomes in 29 children who received 31 courses of teicoplanin. Our study of noncritically ill children showed that the majority (35/43, 81%) of trough concentrations were within the therapeutic range (10-30 mg/L) contrasting previous studies in children. Overall, 21 of the 24 (88%) children with Gram-positive infections achieved cure.

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 teicoplanin in a patient with bloodstream infection by Enterococcus faecium

Objective： To analyze the blood concentration，efficacy and adverse drug reactions（ADRs） of teicoplanin in treatment of bloodstream infection by Enterococcus faecium.Methods： Changes in physiological and pathological indexes of the patient were closely followed and recorded，and the treatment regimen was adjusted according to the results of therapeutic drug monitoring（TDM） of teicoplanin.Results： In the light of the results of therapeutic drug monitoring of teicoplanin，bloodstream infection was cured，pathogenic microorganism was effectively eliminated and no ADRs occurred.Conclusion： With TDM，teicoplanin could be safely and effectively used in the treatment of blood stream infection.

Teicoplanin therapeutic drug monitoring (TDM) – excessive or essential?

Background: Teicoplanin is a glycopeptide antibiotic which is frequently used in preference to vancomycin because it does not require such regular TDM as the association between concentration and toxicity has not been fully established. TDM is however, recommended to help optimise therapy in some patients. In our hospital there was an observation of frequent sub-therapeutic levels which prompted an audit of TDM results. Methods: Retrospective review of TDM results August 2015- March 2017 at Homerton Hospital with analysis of dose, renal function, patients’ weight and type of infection. Results: We analysed 54 samples from 33 patients. The most common dose was 600 mg OD which equated to a mean dose of 8.68 mg/Kg with under-dosing in all weight groups but with lowest levels in the group between 110-120 Kg. A 24hr dosing regimen was the most common and other dosing regimens (48hrly or 72hrly) more frequently associated with sub-therapeutic levels. Overall, the mean level was 27.8 +/- 11.9 mg/L but 41% (n=22) of levels were sub-therapeutic for the type of infection treated including 4 patients with bacteraemia, 7 patients with bone and joint infections (n=10 samples) and 3 patients (n=6 samples) with prosthetic joint infections. There was only one patient with teicoplanin levels &gt;60 mg/L who was on treatment for a streptococcal endocarditis. She did not report any side effects. Conclusion: The current dosing regimen recommended by the BNF frequently results in sub-therapeutic levels. TDM is essential in managing complex infections to ensure therapeutic levels are achieved.

Interlaboratory analysis of teicoplanin plasma concentration assays among Chinese laboratories.

Teicoplanin is widely used for the treatment of infections caused by drug-resistant Gram-positive bacteria. Since there is a good correlation between trough levels and clinical outcome, therapeutic drug monitoring (TDM) is recommended to achieve better clinical curative effects. However, TDM of teicoplanin is not routine in China. So, a programme was initiated in 2017, including both HPLC method establishment and interlaboratory quality assessment, for the measurement of teicoplanin. A main centre and a quality control centre were set up in the study. An HPLC-based method of teicoplanin determination in plasma was developed by the main centre. Analysis was performed using a Waters Symmetry C18 column (250mm×4.6mm, 5µm). The mobile phase was NaH2 PO4 (0.01mol/L) and acetonitrile (75:25 v/v; pH 3.3), with a flow rate of 1.0mL/min and a detection wavelength of 215nm. Piperacillin sodium was selected as an internal standard (IS). Twenty-six additional TDM centres were then recruited to adopt this method. Then, all the centres were asked to take part in a quality control assessment evaluated by the quality control centre. For all TDM centres, linearity of teicoplanin concentration ranges was between 3.125 and 100µg/mL. Intraday and interday accuracies ranged from 87.1% to 118.4%. Intraday and interday precision ranged from 0.3% to 13.8%. Therapeutic drug monitoring centres all passed inter-room quality assessment. All samples tested met the acceptance criteria. Then, 542 samples were collected. Patients with sub-optimal (≤10mg/L) plasma teicoplanin concentrations constituted 42% of the total study population. For the first time, a simple, rapid and accurate HPLC method for determining teicoplanin levels was successfully applied to therapeutic drug monitoring in clinical practice for twenty-seven TDM centres in China. The results demonstrated excellent interlaboratory agreement for teicoplanin testing and provide support for clinical laboratory quality management and results inter-accreditation.

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.

Therapeutic Drug Monitoring of Teicoplanin in Children

Therapeutic Drug Monitoring of Teicoplanin in Children

Therapeutic drug monitoring of teicoplanin using an LC–MS/MS method: Analysis of 421 measurements in a naturalistic clinical setting

Teicoplanin is a glycopeptide antibiotic used for treatment of severe Gram-positive bacterial infection. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for therapeutic drug monitoring (TDM) of teicoplanin and to review our clinical experience.We established an LC–MS/MS method to analyze serum concentration of teicoplanin using simple protein precipitation with a 5 min run time for each sample. The linearity, lower limit of quantitation, detection accuracy, precision, carryover, matrix effect, and extraction recovery were evaluated. From September 2014 to June 2017, a total of 421 serum teicoplanin concentrations was measured in 223 patients. We collected demographic and clinical data, medication history, and laboratory findings through retrospective review of medical records.The LC–MS/MS method was linear for serum teicoplanin concentrations in the range of 12.0–89.0 μg/mL. The intra- and inter-assay precisions were below CV 7.5%. The accuracy was less than ±10% bias. The lower limit of quantification was 0.2 μg/mL. The extraction recovery ranged from 88.8% to 96.6%. Of 421 measurements, 87 (20.7%) were subtherapeutic (< 10 μg/mL), and four (0.9%) were above the toxic threshold (≥ 60 μg/mL). Serum teicoplanin concentration was measured once in 140 patients (63%), and multiple measurements were completed for the others (83 patients, 37%). Intra-patient variability in teicoplanin concentration was found (CV 33%, range 2–94%).Our simple and rapid LC–MS/MS method was successfully applied in TDM of teicoplanin in clinical practice. Such TDM of teicoplanin may be useful for individualized dose adjustment.

Therapeutic Drug Monitoring of Teicoplanin in Haematological Malignancy Patients with Febrile Neutropenia and Optimizing Dosage Regimens.

This study used high-performance liquid chromatography to measure 202 teicoplanin plasma trough concentrations (Cmin ) in 114 haematological malignancy patients with febrile neutropenia. Patients were divided into two groups according to the mean initial dose (MID) over the first 3 days of treatment: (i) MID = 533.33 mg/day (loading dose group, 400 mg q12h for three doses followed by 400 mg qd, n = 62) and (ii) MID < 533.33 mg/day (unloaded or underloaded group, n = 52). During the first 3 days after treatment, the overall Cmin was higher in group 1 than in group 2 (10.96 ± 5.44 mg/L versus 6.31 ± 3.73 mg/L, mean ± S.D.; p = 0.002), as was the qualifying rate of Cmin > 10 mg/L (54.5% versus 11.1%, p = 0.001), and the probability of Cmin < 5 mg/L was lower in group 1 than in group 2 (13.6% versus 40.7%, p = 0.037). After 3 days, the average Cmin and qualifying rates did not differ significantly between the two groups, and the average Cmin was <10 mg/L in both groups. Binary logistic regression analysis revealed that creatinine clearance (p = 0.004) and MID (p = 0.010) could affect Cmin during the first 3 days of treatment and that age (p = 0.022) only could affect Cmin after 3 days. In conclusion, it is necessary to apply loading dose to achieve teicoplanin Cmin > 10 mg/L rapidly and, from a pharmacokinetic/pharmacodynamic perspective, 600 mg is recommended as loading and maintenance dose for these patients when AUC24 /minimum inhibitory concentration > 345.

Measurement of Teicoplanin Concentration With Liquid Chromatography-Tandem Mass Spectrometry Method Demonstrates the Usefulness of Therapeutic Drug Monitoring in Hematologic Patient Populations.

Teicoplanin is a glycopeptide antibiotic that has become increasingly popular with the spread of methicillin-resistant Staphylococcus aureus. The aim of the study was to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for teicoplanin, and analyze trough teicoplanin concentrations achieved in patients with hematological diseases. The UHPLC-MS/MS method for teicoplanin was developed, validated, and applied in a retrospective analysis of trough plasma teicoplanin concentrations from 305 patients receiving standard dose, and 17 patients receiving therapeutic drug monitoring (TDM)-guided individualized dose. The linear range was 3.9-52.9 mg/L. The imprecision was less than 12%, the limits of detection and quantification were less than 0.13 and 0.72 mg/L, respectively. The sample carry-over and ion suppression were insignificant. In the standard dose group, the median teicoplanin concentrations were 7.5 mg/L (days 3-5) and 8.9 mg/L (on days 6-8); and the proportion of trough levels achieving ≥10 mg/L was 20% (days 3-5) and 38% (days 6-8), respectively. In the TDM-guided individualized dose group, median teicoplanin concentration was higher (16.9 mg/L), and the proportion of trough levels ≥10 mg/L was also higher (77%) when compared with the standard dose group. Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups.

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

Background: Teicoplanin is a glycopeptide antibiotic currently used for the treatment of methicillin-resistant Staphylococcus aureus. The need for therapeutic drug monitoring of teicoplanin has been increasingly highlighted as important. It is generally accepted that whereas a plasma trough concentration (C_min) of ≥10 mg/L is appropriate for the majority of infections, it should exceed 20 mg/L for severe infections. The target C_min of teicoplanin in patients with febrile neutropenia (FN) has not been reported. The aim of this study was to estimate the target C_min for the treatment of FN in patients with hematological malignancy. Methods: In this retrospective, single-center, observational cohort study, the records of 52 hospitalized patients with hematological malignancy who were treated with teicoplanin for FN due to bacteriologically documented or presumptive gram-positive infections were analyzed. Results: A significant difference in the first C_min of teicoplanin was observed between the response and nonresponse groups in patients with bacteremia. The areas under the receiver operating characteristic curves were 0.80 for clinical efficacy. The cut-off value of teicoplanin C_min on days 4-6 was 15.2 mg/L (sensitivity 80.0%, specificity 75.0%). Conclusions: The authors propose a target teicoplanin C_min of ≥15.2 mg/L for FN in patients with hematological malignancy.

Direct injection LC-MS/MS method for the determination of teicoplanin in human plasma.

A direct injection-based, simple, accurate, and robust LC-MS/MS method was developed and validated for the determination of teicoplanin in human plasma. Patient plasma samples were diluted in an aqueous buffer prior to injection into the LC-MS/MS system. Chromatographic separation was achieved using a Cadenza HS-C18 column and a gradient mixture of acetonitrile-water (both containing 0.1% formic acid) as the mobile phase at a flow rate of 0.5mL/min. The analytes were detected in multiple reaction monitoring mode with positive ion electrospray ionization. The concentration of teicoplanin was determined as the sum of six components (A3-1, A2-1, A2-2, A2-3, A2-4, and A2-5). The calibration curve was linear over a concentration range of 1-50mg/L, which covered the clinically accepted trough and therapeutic plasma levels. The intra- and inter-day precision and accuracy values were both less than 15%. This validated method was successfully applied to therapeutic drug monitoring of teicoplanin in routine clinical practice. Thus, we expect it to be useful for the determination of teicoplanin concentration in human plasma.

Is Therapeutic Drug Monitoring of Teicoplanin Useful?

Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by beta-lactam-resistant gram-positive organisms [1]. Teicoplanin, a glycopeptide antibiotic, has a lower possibility than vancomycin to cause renal toxicity, and causes fewer anaphylactoid reactions [2]. Teicoplanin has been found to be comparable to vancomycin in efficacy [1]. As teicoplanin can be administered once daily intramuscularly as well as intravenously, it can be used for outpatient therapy of methicillin-resistant staphylococcal infections [1]. Teicoplanin completely excreted unchanged in the urine by glomerular filtration, and doses should be reduced appropriately in patients with renal dysfunction. Its pharmacokinetics include a prolonged terminal half-life of 150 to 180 h, which is important during long-term therapy [1]. Usual dose and dosing interval of teicoplanin for IV injection or infusion consist initially 400 mg every 12 hours for 3 doses and subsequently 200 mg once daily (400 mg once daily for severe infections) [1, 3]. Higher doses are recommended in patients over 85 kg, or in severe burns or methicillin-resistant Staphylococcus aureus (MRSA) infection [1, 3]. For streptococcal endocarditis, initially 6 mg/kg every 12 hours for 3 doses, then 6 mg/kg once daily are typical [1, 3]. For enterococcal endocarditis, initially 10 mg/kg every 12 hours for 3 doses, then 10 mg/kg once daily are standard. For child, initially 10 mg/kg every 12 hours for 3 doses, subsequently 6 mg/kg once daily (10 mg/kg once daily for severe infections or in neutropenia) is a typical regimen [1, 3]. Vancomycin level monitoring is common in the hospitals with increasing minimal inhibitory concentration (MIC) of S. aureus (MIC creep) [1]. For complicated infections (bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia) and for infections caused by strains with MICs of >1 µg/mL, trough levels of 15 to 20 µg/mL are recommended [1]. Larger vancomycin doses are associated with increased nephrotoxicity [1], and monitoring of vancomycin trough serum levels is recommended in the view of avoiding nephrotoxicity [4]. Therapeutic drug monitoring (TDM) of teicoplanin is not routine because of the lack of evidence for dose-related adverse effects of teicoplanin [3]. However, measuring of teicoplanin plasma concentrations may help to optimize therapy in some patients. Data of teicoplainin TDM are largely lacking [1]. Harding et al. [5] reported the probability of successful treatment increased with mean pre-dose (trough) serum concentration of teicoplanin and reported that a mean daily dose of 4 mg/kg was associated with treatment failure when compared to a mean daily dose of 6 mg/kg [5]. Also, Harding et al. [5] suggested successful treatment of S. aureus septicemia with teicoplanin requires trough plasma teicoplanin concentration of >10 mg/L as a result of simulation. According to previous reports, higher trough concentrations > 20 mg/L and > 30 mg/L of teicoplanin are considered to be needed for MRSA endocardtis and osteomyelitis, respectively [6, 7]. Nah et al. [8] investigated the TDM of teicoplanin in clinical setting with Korean patients. They reported that there is the suboptimal concentration (< 10 mg/L) of plasma teicoplanin level in nearly half of the study patients in spite of the majority of the patients received loading dose as recommended (400 mg every 12 hours for three times), and emphasized the importance of loading dose and routine TDM of teicoplanin [8]. This article focused the roles of TDM for the optimal efficacy of therapeutic drug, not for avoiding adverse effects of a drug. An area under curve (AUC)/MIC value of ≥400 was associated with a successful outcome with human pharmacodynamic study for vancomycin [9]. The vancomycin target was identified in patients with pulmonary infections [9]. However, established pharmacodynamic targets were not available for teicoplanin [10]. An AUC/MIC value of teicoplanin to Staphylococcus considered important pharmacodynamics parameter [10]. There is no information about MIC values of pathogens and AUC/MIC values and a peak concentrations in the study by Nah et al. [8]. The TDM for vancomycin therapy has been shown to be a cost-effective procedure [11]. However, cost effective study of teicoplanin TDM is still largely lacking. Nah et al. [8] reported the first study about teicoplanin TDM in Korea, which emphasize the importance of loading dose and TDM of teicoplanin. The limitations of this study include that the association between plasma concentrations of teicoplanin and clinical therapeutic effects are not evaluated. We can expect the usefulness of teicoplanin TDM in the same respect of vancomycin TDM. However, we are currently in need of data of pharmacokinetics, clinical pharmacodynamics and TDM of teicoplanin in clinical setting, because of its current significant role for anti-MRSA treatment.

Development of new software (Ver. 2.0) based on the Bayesian estimation utilized in the therapeutic drug monitoring of teicoplanin, a glycopeptide antibiotic

We developed a new software (Ver. 2.0) based on the Bayesian estimation utilized in the therapeutic drug monitoring (TDM) of teicoplanin, a glycopeptide antibiotic, for the estimation of individual pharmacokinetic parameters. Individual pharmacokinetic parameters were calculated by a least squares methods, MULTI2 (BAYES), and a two-compartment model with population pharmacokinetic parameters in adult patients in Japan was adopted. The predicted teicoplanin concentrations in patients were similar to the observed concentrations, suggesting that the software predicts with acceptable precision. This new software is now available in clinical practice.