Loading Dose Of Teicoplanin Research Articles

Audit project on the appropriateness of teicoplanin prescribing in Milton Keynes University Hospital (MKUH)

Abstract Introduction Teicoplanin is the Trust’s preferred glycopeptide antibiotic compared to vancomycin due to the once-daily dosing, less toxic side effects and monitoring requirements1. Teicoplanin dosing regimen is weight-dependent, including loading and maintenance doses adjusted according to creatinine clearance (CrCl) from Day 52. As antimicrobial resistance emergence continues to be a public health concern, appropriate teicoplanin use is vital to avoid treatment failure in line with antimicrobial stewardship3. Aim and Standards To assess teicoplanin prescribing compliance with the Trust guideline. 100% compliance was expected for the following standards: 1. Teicoplanin is prescribed for an approved indication according to Trust guideline or by a Consultant Microbiologist. 2. Loading dose of teicoplanin is prescribed for treatment initiation. 3. Appropriate teicoplanin loading dose is prescribed based on actual body weight (ABW) and indication. 4. Appropriate teicoplanin maintenance dose is prescribed until Day 4 based on ABW and indication. 5. Appropriate teicoplanin maintenance dose is prescribed from Day 5 onwards based on CrCl, ABW and indication. Method This study did not require ethics approval. To assess audit feasibility, a pilot was done looking at teicoplanin prescriptions and clinical notes against the audit standards. CrCl was calculated where appropriate. Retrospective data of 18 teicoplanin prescriptions between 08/11/2022-14/11/2022 were extracted from the Electronic Prescribing and Medicines Administration (EPMA) system onto an Excel data collection spreadsheet. No changes were made to the data collection tool. One month’s data between 11/10/2022-07/11/2022 were further extracted and process was repeated. Paediatric patients and indications for surgical prophylaxis and Clostridioides difficile infection were excluded. Results 88 patients were included in the study. 90% (n=79) of teicoplanin prescriptions were prescribed for an indication approved on the Trust’s antimicrobial guideline or by a Consultant Microbiologist. Teicoplanin loading dose was prescribed for 82% (n=71) of patients. 1 patient was excluded as loading dose was administered in another hospital. 46% (n=40) of patients were prescribed the appropriate teicoplanin loading dose. 60% (n=34) of the 57 patients who continued teicoplanin up until Day 4 were prescribed the appropriate teicoplanin maintenance dose. 56% (n=22) of the 39 patients treated with teicoplanin past Day 4 were prescribed the appropriate teicoplanin maintenance dose. None of the 5 standards were met. Conclusion The results indicate inappropriate teicoplanin prescribing against the current Trust guideline which need improvement. Training with prescribers on utilising the EPMA’s pre-populated teicoplanin dose prescription function alongside encouraging pledges to be an Antibiotic Guardian are recommended during their induction. This would help avoid prescription errors and reduce antimicrobial resistance development. The data collected did not subdivide patients under specific specialities, which could highlight areas where training should be focused on. This limitation should be addressed when the re-audit due in 1 years’ time is carried out, to evaluate the changes implemented.

Trends in teicoplanin loading dose implementation from 2010 to 2019 and evaluation of safety and efficacy factors: a retrospective cohort study based on a Japanese administrative claims database

BackgroundThe loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration.MethodsA Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury.ResultsA total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury.ConclusionThus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.

Safety of high loading doses of teicoplanin: POSY-TEICO, a prospective, multicentre, observational study

Teicoplanin is used for treating infections caused by Gram-positive bacteria. The POSY-TEICO study assessed the safety of a high loading dose (HLD) of teicoplanin (12mg/kg twice daily) in a real-world setting. This prospective study was conducted across six countries in Europe and enrolled adults prescribed HLD of teicoplanin between 2016-2019. The primary objective was to determine the incidence of nephrotoxicity following HLD of teicoplanin over loading dose period. An independent clinical adjudication committee (ICAC) assessed all study outcomes related to nephrotoxicity. The study included 300 patients (males, 68.3%), with a mean age of 63.1 years and median teicoplanin treatment duration of 16 days (interquartile range: 9-38). Number of patients with bone and joint infection, infective endocarditis, and other severe infections was 176, 36, and 80, respectively. During loading dose period, 41 (13.8%) patients received 3 HLDs and 246 (82.8%) received ≥4 HLDs. Overall, 28 (11.0%) patients (95%CI, 7.4-15.5) experienced nephrotoxicity during loading and 10 (6.9%) patients (95%CI, 3.4-12.4) during maintenance dose periods. Number of patients who experienced nephrotoxicity certainly or possibly related to teicoplanin according to the ICAC was 20 (7.9%; 95%CI, 4.9-11.9), 8 (5.6%; 95%CI, 2.4-10.7) and 33 (12.4%; 95%CI, 8.7-16.9) across three study periods. HLD of teicoplanin had an acceptable safety profile in patients treated for bone and joint infection, infective endocarditis, and other severe infections and no increased risk of nephrotoxicity was observed. However, patients should be closely monitored when HLDs are administered.

Enhanced loading dose of teicoplanin for three days is required to achieve a target trough concentration of 20 μg/mL in patients receiving continuous venovenous haemodiafiltration with a low flow rate

IntroductionBecause of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 μg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. MethodsThe study was conducted in patients undergoing CVVHDF with a flow rate of <20 mg/kg/h who were treated with teicoplanin. We adopted three loading dose regimens for the initial 3 days: the conventional regimen, a high-dose regimen (four doses of 10 mg/kg), and an enhanced regimen (four doses of 12 mg/kg). The initial Cmin was obtained at 72 h after the first dose. ResultsOverall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03–317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01–0.44) were independent predictors of the achievement of Cmin ≥ 20 μg/mL. ConclusionsAn enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.

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.

Evaluation of Teicoplanin Trough Values After the Recommended Loading Dose in Children With Associated Safety Analysis.

This study evaluated whether the recommended teicoplanin loading dose (3 loading doses of 10 mg/kg every 12 hours) achieves a 15-30 μg/mL trough levels in 26 children (2-16 years). In addition, we examined the incidences of renal impairment and hepatic dysfunction in children treated with teicoplanin. This retrospective study was conducted between October 2008 and March 2014. The percentage of patients with a trough level <10 and <15 μg/mL were 15.4% (4/26) and 46.2% (12/26), respectively. There were significant correlations between age and concentration/cumulative loading dose (C/D) ratio (P = 0.045), serum creatinine and C/D ratio (P < 0.001) and estimated glomerular filtration rate and C/D ratio (P = 0.005). Serum creatinine was significantly lower when trough levels were <15 μg/mL compared with ≥15 μg/mL. The incidences of renal impairment and hepatic dysfunction were 2.3% and 5.8%, respectively, with no significant difference between <20 and ≥20 μg/mL trough-level groups. The recommended loading dose may be insufficient to achieve 15-30 μg/mL in children with normal renal function. In addition, the target trough level ≥20 μg/mL for deep-seated infections seems to be safe in children.

A simplified chart for determining the initial loading dose of teicoplanin in critically ill patients.

A simplified chart to determine the initial loading dose of teicoplanin (TEIC chart) for achieving the target trough concentration was developed. The aim of the present study was to evaluate the usefulness of this chart in critically ill patients. The initial loading dose and maintenance dose to achieve a target trough concentration ≥10 μg/mL on day 4 was determined using the teicoplanin TDM software and presented in a TEIC chart. The dosage of teicoplanin, including the loading dose for the first 2 days and the maintenance dose thereafter, was selected from the chart (chart method, N = 41) or calculated using TDM software (software method, N = 39). The performance rate of initial loading of teicoplanin increased from 83.0% to 100% after the TEIC chart was introduced (P = 0.016). The TEIC chart significantly reduced the time required for determining the initial loading dose compared with the use of software (1.9±0.6 min vs. 29.7±13.8 min, P < 0.001). No significant differences were observed in the rates of achieving a target level ≥10 μg/mL (P = 0.766). The TEIC chart enables a simple, rapid, and reliable determination of teicoplanin dosage.

Clinical Pharmacology of Teicoplanin in Neonates: Effects and Pharmacokinetics

Teicoplanin is a glycoside antibiotic which consists of five closely related glycopeptide antibiotics with similar antibacterial properties to vancomycin that were first isolated in 1976. Teicoplanin is active against many gram-positive anaerobe microorganisms and is particularly potent against clostridium species. It is also active against most Listeria, enterococci and staphylococci including methicillin-resistant strains. Nonviridans and viridans streptococci, Streptococcus pneumoniae, and enterococci are inhibited by teicoplanin. Teicoplanin has been used to treat a wide variety of infections, including osteomyelitis and endocarditis caused by methicillin-resistant and methicillin-susceptible staphylococci, streptococci, and enterococci. Teicoplanin has a spectrum of antimicrobial action similar to vancomycin, but teicoplanin has some advantages in that it only needs to be given once a day, does not need to be given as slowly as vancomycin and can be given by intramuscular injection. Teicoplanin cannot be given by mouth. Teicoplanin is excreted unchanged in the urine. The half-life of teicoplanin is 100 hours in adults and 21/2 days in children. Teicoplanin has a large distribution volume and long half-life and a loading dose is recommended. In infants, the loading dose of teicoplanin is 16 mg/kg administered intravenously followed by 8 mg/kg once daily. The target trough concentration of teicoplanin ranges from 15 to 30 µg/ml. The incidence of hepatic dysfunction, renal impairment and thrombocytopenia is 14.8%, 20%, and 14%, respectively, when the serum teicoplanin concentrations range from < 20 µg/ml and ≥ 20 µg/ml. The aim of this study is to review the effects and the pharmacokinetics of teicoplanin in neonates.

Change of teicoplanin loading dose requirement for incremental increases of systemic inflammatory response syndrome score in the setting of sepsis.

Background Target trough concentrations are recommended for teicoplanin (TEIC) to minimize its adverse effects and to maximize efficacy in sepsis caused by grampositive cocci, including methicillin-resistant Staphylococcus aureus infection. However, optimal doses to attain proper trough values in patients with sepsis have not yet been well established for TEIC. Objective This study investigated whether the systemic inflammatory response syndrome (SIRS) score could predict the pharmacokinetics of TEIC in patients with sepsis. Setting This study was conducted at Fukuoka University Hospital in Japan. Methods We retrospectively reviewed the records of patients using TEIC between April 2012 and March 2015. SIRS positive was defined as infection with a SIRS score ≥2. Estimates of pharmacokinetic parameters were calculated using a Bayesian method. Creatinine clearance rates were estimated by the Cockcroft-Gault formula (eCcr). Main outcome measure Change of TEIC loading dose requirement for incremental increases of SIRS score. Results In total, 133 patients were enrolled: 50 non-SIRS patients and 83 patients with SIRS. The TEIC plasma trough concentration was significantly lower in SIRS than non-SIRS patients (15.7±7.1 vs. 20.1±8.6μg/mL; P<0.01), although there was no significant difference in the loading dose administered. Moreover, SIRS scores were increasingly predictive of eCcr and TEIC clearance in a stepwise manner. To achieve the target trough concentration (15-30μg/mL), the optimal doses required in non-SIRS versus SIRS patients were 12-24 versus 18-30mg/kg/day, respectively, during the first 48h. Conclusions These findings suggest that the pharmacokinetics of TEIC are altered in SIRS patients, who required higher doses than non-SIRS patients to achieve the target trough concentration. We suggest that the SIRS score can become a new modality to determine the initial TEIC loading dose.

Retrospective study of teicoplanin loading regimen that rapidly achieves target 15-30μg/mL serum trough concentration.

There are several studies of assessment for teicoplanin loading dose regimen. However, the optimal loading dose achieving the target range 15-30μg/mL has been still unclear. We investigated the probability of target attachment as teicoplanin concentration 15-30μg/mL at the 3rd day after teicoplanin therapy started, clinical efficacy and safety in retrospective study. In total, 42 patients treated with teicoplanin from January 2010 to July 2014 at Aichi Medical University Hospital were divided into three groups; group 1 (about 40mg/kg for 2 days), group 2 (about 35mg/kg for 2 days) and group 3 (about 30mg/kg for 2 days; the previous regimen). The probability of target attachment as teicoplanin concentration, efficacy and toxicity were compared among three groups. The proportion of patients achieving the target range was 100% in group 1, 57.9% in group 2, and 38.9% in group 3 (p=0.05). The percentage of patients that showed hepatotoxicity and nephrotoxicity was not different from three groups (hepatotoxicity: group 1, 20%; group 2, 21.1%; group 3, 16.7%: p=0.48; nephrotoxicity: group 1, 0%; group 2, 5.3%; group 3, 16.7%: p=0.38). Finally, there were not significant differences of clinical efficacy among three regimens, but CRP 4-7 day after teicoplanin therapy in group 1 and group 2 exhibited a significant lower value, compared with group 3. We suggested that 35-40mg/kg for 2 days as a loading does would be needed for the early achieving target range (15-30μg/mL) and improvement of infection.

Development of Initial Loading Procedure for Teicoplanin in Critically Ill Patients with Severe Infections

Methicillin-resistant Staphylococcus aureus (MRSA) is now endemic in many hospitals. Infection with MRSA is more frequent in the intensive care unit (ICU) than in general wards. Therefore, appropriate treatments for MRSA infections will lead to good outcomes in the ICU. Teicoplanin is an anti-MRSA agent. Recently, it was recommended at a new target trough concentration of 15-30 µg/mL. However, the initial loading procedure for teicoplanin to allow it to reach the target concentration promptly remains uncertain. Therefore, this study aimed to determine the appropriate initial loading procedure for teicoplanin in critically ill patients with severe infections. We performed a retrospective study in patients given teicoplanin in the ICU in order to determine the initial loading procedure to promptly reach the target trough concentration. We then evaluated the trough concentration on the third day after commencement of teicoplanin therapy. The mean loading dose and trough concentration were 11.5±1.0 mg/kg and 18.9±5.9 µg/mL, respectively. A correlation (r=0.45, p=0.046) was shown between teicoplanin loading dose and trough concentration. The correlation equation was trough concentration=2.563·loading dose -10.672. In the cases of 11.0 and 15.0 mg/kg for the loading dose, respectively, trough concentrations were 17.5 and 27.8 µg/mL. We suggested that an initial loading dose of 11-15 mg/kg every 12 h for 3 doses should be administered to promptly achieve the target trough concentration of 15-30 µg/mL on the third day after commencement of teicoplanin therapy in the ICU.

Loading Dose Required to Achieve Rapid Therapeutic Teicoplanin Trough Plasma Concentration in Patients with Multidrug‐Resistant Gram‐Positive Infections

Teicoplanin is an antibiotic drug prescribed for the treatment of multidrug-resistant Gram-positive infections. However, there is currently no consensus as to the optimal teicoplanin loading dose. The objective of this study was to compare plasma concentrations of teicoplanin in patients with multidrug-resistant Gram-positive infections after the administration of two different loading doses. Two groups of patients were infused intravenously with four loading doses of 6mg/kg body-weight (group A, n=12) or 12mg/kg body-weight (group B, n=11). The first three loading doses were administered at 12-hr intervals, and the fourth was given 24hr after the third dose. Maintenance doses of 6mg/kg were administered every day, every other day or every third day depending on the individual's creatinine clearance, and teicoplanin trough plasma concentrations were monitored. Only samples obtained on the same day for both groups were compared statistically. A higher percentage of group B patients achieved the desired therapeutic concentration of teicoplanin (C(min.) ≥10mg/L) on days2 and 3 (90.0% and 100%, respectively) compared with patients in group A (18.2% and 16.7%, respectively) (p<0.001). In addition, more patients in group B achieved therapeutic concentrations from days2 through 12. In conclusion, despite limitations in drawing definitive conclusions because of a relatively small sample size and variability in renal impairment among patients, our findings suggest that a teicoplanin loading dose of 12mg/kg body-weight results in a safe and rapid attainment of therapeutic trough plasma concentrations. This regimen may enhance treatment efficacy.

Significance of individual adjustment of initial loading dosage of teicoplanin based on population pharmacokinetics

An initial loading dose of teicoplanin is required to reach the optimal trough concentration (≥10 μg/mL) rapidly. To attain the optimal teicoplanin concentration efficiently, an individual loading dose regimen based on population pharmacokinetics, in which the target trough concentration was set to 15 μg/mL, was defined. Among 70 patients, 33 patients received the individual loading dose regimen, 33 patients received the conventional loading dose regimen (200 mg or 400 mg every 12 h on Day 1 followed by 200 mg once daily) and 4 patients received no loading dose. The proportion of patients showing an optimal plasma concentration was 88% in the individual loading dose regimen but only 33% in the conventional loading dose regimen. No patient without a loading dose showed the optimal concentration. Both total loading dose and plasma concentration were significantly ( P < 0.001) higher in the individual loading dose group than in the conventional loading dose group. Notably, the trough concentration was almost constant in patients with individual loading doses ranging from 800 mg to 1800 mg. These findings suggest that individual adjustment of the initial loading dose of teicoplanin is potentially useful to attain the optimal concentration rapidly.

Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis

The optimum teicoplanin loading dose and duration of therapy required for rapid attainment of a therapeutic trough plasma concentration ( C min) (≥10 mg/L for serious Gram-positive infections and ≥20 mg/L for deep-seated infections) are not known. In this open-label, multicentre, observational study, teicoplanin levels were determined following administration of loading doses of 6 mg/kg every 12 h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised patients with suspected or diagnosed Gram-positive infections. C min levels for the first 4 days of treatment were collected 15 min prior to drug administration. Levels were determined with an Abbott TDx ®/FLx ® Analyzer and Seradyn Teicoplanin Innofluor Assay Kit. The two target trough values (≥10 mg/L and ≥20 mg/L) were only achieved by Day 4 in the once-daily group ( n = 34; mean 9.55 mg/L, 95% confidence interval (CI) 8.17–10.94 mg/L) and in the twice-daily group ( n = 40; mean 21.8 mg/L, 95% CI 17.21–26.39 mg/L), respectively. However, the mean C min in the twice-daily group was ≥10 mg/L (11.03 mg/L) by Day 2. To achieve rapid therapeutic C min concentrations targeted for the majority of serious Gram-positive infections, we recommend teicoplanin loading doses of 6 mg/kg every 12 h for 48 h followed by once-daily for infections other than infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter infections, higher loading doses might be warranted to reach rapid steady-state concentrations.

The effect of multifactorial, multidisciplinary educational interventions on appropriate use of teicoplanin

The aim of this study was to determine the effect of multifactorial, multidisciplinary educational interventions over a 3-year period on the appropriate use of teicoplanin. Teicoplanin was considered a valid surrogate marker of good antibiotic use in clinical practice owing to its peculiar pharmacokinetics (i.e. necessity for an initial loading dose regardless of the patient's renal function for early achievement of optimal exposure, namely C min ≥ 10 mg/L) and to the opportunity of comparing current routine therapeutic drug monitoring (TDM) results with those of a historical retrospective study. A significantly higher proportion of patients received appropriate loading doses of teicoplanin in the present prospective study than in the retrospective study, both when considered as a whole (66.6% versus 38.6%, respectively; P < 0.001) or when stratified according to the degree of estimated renal function (78.4% versus 60.4% for creatinine clearance (CL Cr) >50 mL/min; 59.8% versus 26.8% for CL Cr 20–50 mL/min; and 27.7% versus 5.5% for CL Cr <20 mL/min). The highest adherence was observed in haematological wards (97.7%). The percentages of patients with teicoplanin C min ≥ 10 mg/L during the treatment period in the present and retrospective study, respectively, were: 61.4% versus 3.2% on Day 2; 88% versus 35% on Day 4; 94% versus 70% on Day 7; and 99% versus 90% on Day 11. Our findings suggest that continuous application of a multifactorial educational programme including active TDM may be efficacious in improving and maintaining over time the appropriate use in a hospital setting of a theoretically difficult-to-use drug such as teicoplanin.

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level

Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10-15 microg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 microg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 microg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 x (MID; mg) - 0.057 x creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.

Teicoplanin therapeutic drug monitoring in critically ill patients: a retrospective study emphasizing the importance of a loading dose.

Data obtained as part of our routine drug monitoring of teicoplanin therapy (therapeutic drug monitoring, TDM) in adult critically ill patients being treated for suspected or documented Gram-positive multiresistant infections were assessed, retrospectively. Data were available for 202 patients (146 male, 56 female; age 58 +/- 16 years) with a total number of 829 teicoplanin trough plasma levels (C(min)) assessed. The percentage of patients with adequate teicoplanin concentrations (C(min) >/= 10 mg/L) during the treatment period substantially increased from 3.2% on day 2, to 35%, 70%, 90% and approximately 95% on days 4, 7, 11 and 15, respectively. The findings suggest that optimal teicoplanin therapy was achieved only after at least 4, and probably 7, days of therapy in most cases, mainly because of a failure to use an appropriate loading dose. Among the possible causes for the reluctance to use a loading dose, concern over the potential nephrotoxicity of teicoplanin was a major factor. We conclude that loading doses of teicoplanin (6 mg/kg every 12 h for at least three doses) must be considered mandatory in all patients, regardless of their renal function, to enable optimal drug concentrations to be achieved early in the treatment period. Subsequently, TDM is important to ensure that dose regimens are optimized to the individual requirements of the patients.

Use of Teicoplanin in Preterm Neonates with Staphylococcal Late-Onset Neonatal Sepsis

Objective: To study the clinical pharmacology of teicoplanin in babies admitted to a newborn intensive care unit, by monitoring serum levels, efficacy and potential side effects. Methods: An open, nonrandomized descriptive study was performed in the neonatal intensive and high care unit of the Universtiy Hospital Maastricht, The Neterlands. Twenty-three preterm neonates, gestational age ranging from 26 to 32 weeks (median 28.4 weeks), postnatal age from 5 to 47 days, and birth weight from 570 to 1,740 g, presenting with (suspected) late onset septicemia, were studied. Of 21 culture-proven septicemias, 20 were caused by staphylococci. The teicoplanin loading dose was 15 mg/kg i.v., followed by a maintenance dose of 8 mg/kg every 24 h. Intravenous gentamicin was also administered pending blood culture. Serum teicoplanin concentrations were measured by fluorescence polarization immunoassay. Clinical and microbiological cure/failure rates were determined and possible side effects were monitored. Results: The study of individual pharmacokinetics during multiple-dose intravenous infusions was rendered impossible by apparently inaccurate dosing. Peak (30 min after end of the infusion) and trough teicoplanin levels were stable throughout the study and averaged 27.8 (interquartile range 23.7–32.9) and 12.3 (interquartile range 9.1–16.8) mg/l, respectively. The microbiological and clinical cure rates were 90% in gram-positive septicemia. There was no apparent toxicity. Conclusions: Inaccurate drug administration was a problem in this study, making a multidose pharmacokinetic study impossible. It is possible that inaccurate drug administration and not current dosage guidelines yielded trough levels below 10 mg/l in 57 (32%) of 176 instances. This pharmaceutical aspect clearly warrants further study. However, microbiological and clinical cure rates were high in gram-positive septicemias. No side effects attributable to teicoplanin therapy were encountered.