Pharmacokinetics of Teicoplanin in An ICU Population of Children and Infants

Lukas, John C.; Karikas, Georgios; Gazouli, Maria; Kalabalikis, P; Hatzis, Tassos; Macheras, Panos

doi:10.1023/b:pham.0000048198.56873.d8

Cited by 23 publications

(30 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They showed that volume of distribution was higher in neonates than in children (0.6 versus 0.54 liter/kg body weight), and clearance was higher in older children than in neonates (0.028 versus 0.016 liter/h/kg). Finally, Lukas et al (24) conducted a population PK analysis in 20 infants and children (4 months to 10 years of age) in the intensive-care unit, showing differences among two identified subpopulations separated around 12 months of age. In younger infants (Ͻ12 months), 92% of concentrations were at target minimum levels (10 mg/liter) versus 65% of concentrations in older children (Ն12 months).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Teicoplanin in Children

Ramos-Martín

Paulus

Siner

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. 2). A significant rise in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulasenegative staphylococci (CoNS) has led to increased use of glycopeptides in the last decade (3, 4). Both vancomycin and teicoplanin are used for treatment of invasive infections caused by Gram-positive organisms, especially those that are resistant to ␤-lactam antibiotics (5, 6). The currently recommended regimen for teicoplanin in adults is 3 loading doses of 400 mg every 12 hours followed by a maintenance dose of 400 mg/day. In contrast, children receive 3 loading doses of 10 mg/kg of body weight every 12 hours followed by a maintenance dose of 10 mg/kg daily (7). However, there is a relative paucity of information to justify these regimens in children and even less information to identify optimal dosing strategies.Regulatory authorities such as the European Medicines Agency (EMA) have developed strategies to facilitate the safe and effective use of medicines in neonates and children (8). EMA supports the extrapolation of information from adults to children provided there are adequate safety data in the latter and the pharmacodynamics can reasonably assumed to be the same in both populations. This approach requires the development of robust population pharmacokinetic (PK) models in both adults and children, which facilitates the design of regimens that enable drug exposures in both populations to be matched (8).Teicoplanin is largely used without routinely measuring concentrations in the majority of pediatric patients. In our pediatric hospital setting, we have observed anecdotal cases of clinical failures with teicoplanin therapy and have observed "MIC creep" for CoNS with MICs at the breakpoint (4 mg/ liter) (unpublished data). To further investigate the clinical pharmacology of teicoplanin and to provide an insight into effective regimens for children, we performed a population PK study. The specific objectives of this study were to (i) describe the population PK of teicoplanin in children in a hospital setting, (ii) explore the percentage of patients attaining a predose minimum concentration (C min ) of Ͼ10 mg/liter, (iii) define the area under the concentration-time curve (AUC) distributions follo...

show abstract

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Teicoplanin in Children

Ramos-Martín

Paulus

Siner

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…This dosing relies on a priori knowledge of the PK parameters of tobramycin. However, there are different PK representations in the literature for aminoglycosides, namely for monocompartmental [22][23][24][25] and bicompartmental [11,12,26,27] disposition models. Some authors suggest that the use of literature values for dose adjustment across different populations is not appropriate and that the PKs for each group should be determined separately, always the target PD [6].…”

Section: Discussionmentioning

confidence: 99%

“…For the residual variance or within-subject variability (WSV), proportional or mixed (proportional and additive) models were tested. These methods have been described previously [11,12].…”

Section: Population Pk Analysismentioning

confidence: 99%

Bicompartmental kinetics of tobramycin analysed with a wide range of covariates

Inclan

Súárez

Calvo

et al. 2005

International Journal of Antimicrobial Agents

Self Cite

View full text Add to dashboard Cite

“…Three prospective studies describe teicoplanin PK in critically ill children with ages ranging from 7 days to a maximum of 12 years old [18,58,59]. Doses used in studies varied, with 2 studies [58,59] using 3 loading doses of 10 mg/ kg teicoplanin every 12 h and afterwards a maintenance dose of 10 mg/kg every 24 h. The study by Lukas et al was designed as a randomized controlled trial where patients in the other study arm received a higher maintenance dose of 15 mg/kg every 24 h [58]. One study, by Reed et al, used lower daily doses of 6 mg/kg in patients undergoing cardiac or head surgery, without information on whether a loading dose was given [18].…”

Section: Teicoplaninmentioning

confidence: 99%

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

View full text Add to dashboard Cite

Background Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults. Methods Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life. Results 50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles. Conclusion The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.

show abstract

Pharmacokinetics of Teicoplanin in An ICU Population of Children and Infants

Abstract: Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.

Cited by 23 publications

References 15 publications

Population Pharmacokinetics of Teicoplanin in Children

Population Pharmacokinetics of Teicoplanin in Children

Bicompartmental kinetics of tobramycin analysed with a wide range of covariates

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Contact Info

Product

Resources

About