Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study
Abstract Background Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentr...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Pediatrics |
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| Online Access: | http://link.springer.com/article/10.1186/s12887-019-1676-3 |
| _version_ | 1818596045545799680 |
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| author | Monique Bergenwall Sandra A. N. Walker Marion Elligsen Dolores C. Iaboni Carla Findlater Winnie Seto Eugene Ng |
| author_facet | Monique Bergenwall Sandra A. N. Walker Marion Elligsen Dolores C. Iaboni Carla Findlater Winnie Seto Eugene Ng |
| author_sort | Monique Bergenwall |
| collection | DOAJ |
| description | Abstract Background Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentration attainment for conventional and extended-interval dosing (EID) regimens. Methods Patient demographics and steady-state gentamicin concentration data were retrospectively collected for 60 neonates with no renal impairment admitted to a level III neonatal intensive care unit. Mean pharmacokinetics were calculated and multiple linear regression was performed to determine significant covariates of clearance (L/h) and volume of distribution (L). Classification and regression tree (CART) analysis identified breakpoints for significant covariates. Monte Carlo Simulation (MCS) was used to determine optimal dosing recommendations for each CART-identified sub-group. Results Gentamicin clearance and volume of distribution were significantly associated with weight at gentamicin initiation. CART-identified breakpoints for weight at gentamicin initiation were: ≤ 850 g, 851-1200 g, and > 1200 g. MCS identified that a conventional dose of gentamicin 3.5 mg/kg given every 48 h or an EID of 8-9 mg/kg administered every 72 h in neonates weighing ≤ 850 g, and every 24 and 48 h, respectively, in neonates weighing 851-1200 g, provided the best probability of attaining conventional (peak: 5-10 mg/L and trough: ≤ 2 mg/L) and EID targets (peak:12-20 mg/L, trough:≤ 0.5 mg/L). Insufficient sample size in the > 1200 g neonatal group precluded further investigation of this weight category. Conclusions This study provides initial gentamicin dosing recommendations that optimize target attainment for conventional and EID regimens in neonates weighing ≤ 1200 g. Prospective validation and empiric dose optimization for neonates > 1200 g is needed. |
| first_indexed | 2024-12-16T11:25:40Z |
| format | Article |
| id | doaj.art-33ee4286a0be4de487657d7d4f251140 |
| institution | Directory Open Access Journal |
| issn | 1471-2431 |
| language | English |
| last_indexed | 2024-12-16T11:25:40Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj.art-33ee4286a0be4de487657d7d4f2511402022-12-21T22:33:22ZengBMCBMC Pediatrics1471-24312019-09-0119111310.1186/s12887-019-1676-3Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective studyMonique Bergenwall0Sandra A. N. Walker1Marion Elligsen2Dolores C. Iaboni3Carla Findlater4Winnie Seto5Eugene Ng6Department of Pharmacy, Sunnybrook Health Sciences CentreDepartment of Pharmacy, Sunnybrook Health Sciences CentreDepartment of Pharmacy, Sunnybrook Health Sciences CentreWomen and Babies Program, Sunnybrook Health Sciences CentreWomen and Babies Program, Sunnybrook Health Sciences CentreLeslie L. Dan Faculty of Pharmacy, University of TorontoWomen and Babies Program, Sunnybrook Health Sciences CentreAbstract Background Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentration attainment for conventional and extended-interval dosing (EID) regimens. Methods Patient demographics and steady-state gentamicin concentration data were retrospectively collected for 60 neonates with no renal impairment admitted to a level III neonatal intensive care unit. Mean pharmacokinetics were calculated and multiple linear regression was performed to determine significant covariates of clearance (L/h) and volume of distribution (L). Classification and regression tree (CART) analysis identified breakpoints for significant covariates. Monte Carlo Simulation (MCS) was used to determine optimal dosing recommendations for each CART-identified sub-group. Results Gentamicin clearance and volume of distribution were significantly associated with weight at gentamicin initiation. CART-identified breakpoints for weight at gentamicin initiation were: ≤ 850 g, 851-1200 g, and > 1200 g. MCS identified that a conventional dose of gentamicin 3.5 mg/kg given every 48 h or an EID of 8-9 mg/kg administered every 72 h in neonates weighing ≤ 850 g, and every 24 and 48 h, respectively, in neonates weighing 851-1200 g, provided the best probability of attaining conventional (peak: 5-10 mg/L and trough: ≤ 2 mg/L) and EID targets (peak:12-20 mg/L, trough:≤ 0.5 mg/L). Insufficient sample size in the > 1200 g neonatal group precluded further investigation of this weight category. Conclusions This study provides initial gentamicin dosing recommendations that optimize target attainment for conventional and EID regimens in neonates weighing ≤ 1200 g. Prospective validation and empiric dose optimization for neonates > 1200 g is needed.http://link.springer.com/article/10.1186/s12887-019-1676-3NeonateGentamicinPharmacokineticsTraditional dosing, extended-interval dosing, Monte Carlo simulation |
| spellingShingle | Monique Bergenwall Sandra A. N. Walker Marion Elligsen Dolores C. Iaboni Carla Findlater Winnie Seto Eugene Ng Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study BMC Pediatrics Neonate Gentamicin Pharmacokinetics Traditional dosing, extended-interval dosing, Monte Carlo simulation |
| title | Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study |
| title_full | Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study |
| title_fullStr | Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study |
| title_full_unstemmed | Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study |
| title_short | Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation – a retrospective study |
| title_sort | optimizing gentamicin conventional and extended interval dosing in neonates using monte carlo simulation a retrospective study |
| topic | Neonate Gentamicin Pharmacokinetics Traditional dosing, extended-interval dosing, Monte Carlo simulation |
| url | http://link.springer.com/article/10.1186/s12887-019-1676-3 |
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