Gentamicin Pharmacokinetics and Monitoring in Pediatric Patients with Febrile Neutropenia

Bialkowski, Sabina; Staatz, C. E.; Clark, Julia; Lawson, Rachael; Hennig, Stefanie

doi:10.1097/ftd.0000000000000341.

Cited by 12 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this group of patients, children's body composition and the PK of gentamicin are affected by chemotherapy and pathological changes such as presence of fever, decreased muscle mass, increased renal clearance and malnutrition . Both gentamicin Cl and Vd were reported to be increased in paediatric patients with cancer . On the other hand, Llanos‐Paez et al demonstrated that typical gentamicin Cl in oncology patients (0.08 L/h/kg) was lower compared to non‐oncology children of a similar age receiving gentamicin intramuscularly (0.10 L/h/kg).…”

Section: Discussionmentioning

confidence: 99%

A review of population pharmacokinetic models of gentamicin in paediatric patients

2019

View full text Add to dashboard Cite

What is known and objectives Gentamicin is often used for the treatment of Gram‐negative infections. Due to pharmacokinetic variability in paediatric patients, appropriate dosing of gentamicin in the paediatric population is challenging. This article reviews published population pharmacokinetic models of gentamicin in paediatric patients, identifies covariates that significantly influence gentamicin pharmacokinetics, and determines whether there is a consensus on proposed dosing for intravenous gentamicin in this population. Methods The PubMed database was searched for articles published until the end of 2017. If the articles described population pharmacokinetic models of gentamicin in the paediatric population (after intravenous administration of gentamicin), the following data were extracted: type of study, year of publication, population characteristics and number of patients, gentamicin dosing, total number of gentamicin (serum and/or plasma) concentrations, type of population modelling approach, developed model with pharmacokinetic parameters and covariates included. Results and discussion In most of the studies, one‐ or two‐compartment modelling was applied. The mean estimated gentamicin clearance for newborns, infants and the complete paediatric population was 0.048, 0.13 and 0.067 L/h/kg, respectively, and the mean predicted volume of distribution was 0.475, 0.35 and 0.33 L/kg, respectively. The values reflect differences in body composition and kidney maturation within the different paediatric populations. Gentamicin pharmacokinetics were most influenced by age, body size and renal function. What is new and conclusion Based on our review, the authors agree on a prolonged dosing interval for preterm and term newborns (up to 48 hours). However, there was no agreement on proposed dosing with respect to gestational age. In general, the proposed daily doses were lower compared to those initially applied for preterm newborns and comparable to those for term newborns. For infants and children, the dosing interval remained unchanged (24 hours), but the proposed daily doses were higher than actually applied. When differences in the paediatric population are considered and an appropriate population PK model with applicable covariates is applied, dosing can be individualized. In the future, studies of gentamicin pharmacokinetics in paediatric patients should focus on currently underestimated covariates, such as fat‐free mass, concomitantly administered drugs, body temperature and critical illness because these can change gentamicin PK considerably. Consequently, different dosing is required and TDM becomes even more important.

show abstract

Section: Discussionmentioning

confidence: 99%

A review of population pharmacokinetic models of gentamicin in paediatric patients

2019

View full text Add to dashboard Cite

show abstract

“…Second, a 1-compartment model was selected. Also for other aminoglycosides in pediatric neutropenic fever, individual PK calculations using a 1-compartment model have been used [32]. For amikacin, both 1-and 2compartment models have been published in neonates and/or children [7,17].…”

Section: Discussionmentioning

confidence: 99%

Covariates of amikacin disposition in a large pediatric oncology cohort

Dewandel¹,

Allegaert²,

Renard³

et al. 2021

View full text Add to dashboard Cite

Objective: Amikacin pharmacokinetics (PK) in children displays large variability due to maturational and disease-related covariates. The objective was to explore amikacin PK in a large pediatric oncology cohort, taking into account within-patient changes.Methods: Clinical data and amikacin therapeutic drug monitoring (TDM) observations were collected retrospectively from children with oncology diagnosis receiving amikacin during febrile neutropenia. Individual amikacin PK parameters were calculated using a onecompartment model with instantaneous input and first-order output. To explore covariates of clearance (Cl) and volume of distribution (Vd), linear mixed models were used, modelling a random effect for patient to account for clustering due to repeated measurements.Results: Based on 188 amikacin treatment episodes in 114 patients, median (interquartile range) amikacin Cl was 1.37 (1.05; 2.46) L/h and Vd 7.98 (5.66; 12.73) L. Height and creatinemia were significant covariates for Cl (marginal R² 71.1%), while weight, height and creatinemia determined Vd (marginal R² 59.5%). Conclusions:We described extensive variability of amikacin PK in a large cohort of pediatric oncology patients, including within-patient changes across treatment episodes. Maturational covariates and creatinemia determined amikacin Cl and Vd, while primary non-maturational covariates were not significant. Our observations, based on combined clinical and PK data in children with oncology diagnoses, can be useful to feed dosing software programs to improve drug exposure in special populations.

show abstract

“…This limits the exposure of children to gentamicin in cases where an appropriate indication for use is lacking, not only important in reducing unnecessary toxicity associated with the use of gentamicin, but also in reducing the development of antibiotic resistance over the long term. Although there has been considerable improvement in practice following the guideline change, there may continue to be a number of admissions where gentamicin dosage may be suboptimal, potentially contributing to an increased risk of nephrotoxicity and ototoxicity. Results on gentamicin dosing and TDM in this patient cohort have been previously reported .…”

Section: Discussionmentioning

confidence: 99%

“…Although there has been considerable improvement in practice following the guideline change, there may continue to be a number of admissions where gentamicin dosage may be suboptimal, potentially contributing to an increased risk of nephrotoxicity and ototoxicity. Results on gentamicin dosing and TDM in this patient cohort have been previously reported . Information on gentamicin toxicity events such as ototoxicity and nephrotoxicity or the frequency of admissions where piperacillin/tazobactam was in appropriate empiric monotherapy was not collected as part of this study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial stewardship in paediatric oncology: Impact on optimising gentamicin use in febrile neutropenia

Hennig

Staatz

Natanek

et al. 2017

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

Gentamicin Pharmacokinetics and Monitoring in Pediatric Patients with Febrile Neutropenia

Abstract: Based on a log-linear method of analysis, current dosing seems to be consistently producing gentamicin exposure below predefined pharmacokinetic targets, suggesting that an increase in the recommended starting dose of gentamicin may be required.

Cited by 12 publications

References 27 publications

A review of population pharmacokinetic models of gentamicin in paediatric patients

A review of population pharmacokinetic models of gentamicin in paediatric patients

Covariates of amikacin disposition in a large pediatric oncology cohort

Antimicrobial stewardship in paediatric oncology: Impact on optimising gentamicin use in febrile neutropenia

Contact Info

Product

Resources

About