Vancomycin Pharmacokinetics in Preterm Infants

Machado, José Kleber Kobol; Feferbaum, Rubens; Kobayashi, Celia Etsuco; Sanches, Cristina; Santos, Sílvia Regina Cavani Jorge

doi:10.1590/s1807-59322007000400006

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…In contrast, vancomycin clearance is significantly lower in neonates compared with adults after correcting for body surface area (27). When expressed in ml/min/kg, the clearance estimates are lowest in the most preterm neonates (0.98 ml/min/kg) (15). In addition, Table 4 illustrates that there is at least a 2- to 3-fold difference in vancomycin clearance within the neonatal age range, which in part reflects maturation and other renal functions that are related to co-morbidity characteristics in neonates (12-27).…”

Section: Resultsmentioning

confidence: 99%

Clinical pharmacokinetics of vancomycin in the neonate: a review

Pacifici¹,

Allegaert²

2012

Clinics

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Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates.

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Section: Resultsmentioning

confidence: 99%

Clinical pharmacokinetics of vancomycin in the neonate: a review

Pacifici¹,

Allegaert²

2012

Clinics

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“…It is known that vancomycin pharmacokinetics is affected by the immaturity of the renal function of preterm infants and drug half-life and clearance are even higher in preterm newborns due to the high percentage of body water, especially during the first postnatal week. 26 , 27 …”

Section: Discussionmentioning

confidence: 99%

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Romanelli

Anchieta

Fernandes

et al. 2016

The Brazilian Journal of Infectious Diseases

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Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m(2)/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m(2)/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m(2)/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p<0.001). A dose of 27mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

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“…Consequently, adequate antimicrobial therapy including the optimal dosage based on drug plasma monitoring contributes significantly to a desired outcome and obviously to reduce the risk of bacterial resistance in patients with life-threatening infections, such as those that occur in critically ill, including burn patients and pre-term infants. 7,21 Increases on daily dose to reach adequate serum levels have been documented in adult burn and non-burn patients. It was reported previously that vancomycin dosing 2g daily must be prescribed to adult critically ill patients with creatinine clearance lower than 60 mL/min; while for patients with augmented renal function, corresponding doses must be increased to 3 g daily for aged higher than 65 years or to 3-4 g a day for young adult patients, serum creatinine 1mg/dL.…”

Section: Vancomycin Dosing Adjustment Is Required For Drug Effectiven...mentioning

confidence: 99%

Vancomycin and meropenem serum monitoring for target attainment by PK/PD approach as an effective tool in the battle against nosocomial pathogens in septic pediatric burn patients

Camargo¹,

Silva²,

Silva³

et al. 2022

PPIJ

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Introduction:Optimizing antimicrobial prescription for severe infections is a challenge in Intensive Care Units for critically ill patients to improve clinical outcome. Aim of the study was to evaluate drug effectiveness in septic pediatric burn patients undergoing combined therapy with vancomycin and meropenem.Methods: Pediatric septic burn patients receiving vancomycin and meropenem combined therapy were included (7F/10M). Characteristics of patient's population, expressed by minimum/maximum values were: 3.1/11.2 yrs; 12/44 kg; 11/75% TBSA; SCr: 0.15/0.47 mg/dL; 10/36 days in ICU, 21/45 days hospitalization for 15 patients. Drug serum measurements were done by liquid chromatography. Pharmacokinetic changes were investigated. Pharmacokinetic-pharmacodynamics (PK/PD) target recommended for vancomycin is AUC ss 0-24 /MIC>400; while the PK/PD meropenem target considered is 100%f∆T>MIC.Results: Target attainment (PTA) MIC 1 mg/L gram-positive strains was reached in 48% with vancomycin Set 1 empiric dose 40-60mg/kg daily 1hr-intermittent infusion (10-15mg/kg q6h); then, optimization of drug therapy was done Set 2 by dose adjustment patient bedside up to 102 mg/kg/day with cure for all patients. Meropenem effectiveness was reached against gram-negative susceptible strains up to MIC 2 mg/L and coverage was extended up to MIC 4 mg/L against strains of intermediate susceptibility due to the extended 3hrs-infusion. Then, meropenem coverage was guaranteed for all patients up to MIC 4 mg/L by recommended dose for ICU pediatric septic patients (40mg/kg q8h) after the extended infusion, to avoid mutant's selection of Klebsiella pneumoniae or Pseudomonas aeruginosa, intermediate susceptibility. Conclusion:A combined therapy with vancomycin -meropenem improves the effectiveness against infections in burn pediatric patients. Vancomycin dose adjustments must be done in real time by PK/PD approach based on serum levels permitting an earlier intervention of ICU Medical Team to reach the desired clinical outcome against nosocomial infections in septic pediatric burn patients and contributes also to avoid the bacterial resistance.

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Vancomycin Pharmacokinetics in Preterm Infants

Cited by 11 publications

References 20 publications

Clinical pharmacokinetics of vancomycin in the neonate: a review

Clinical pharmacokinetics of vancomycin in the neonate: a review

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Vancomycin and meropenem serum monitoring for target attainment by PK/PD approach as an effective tool in the battle against nosocomial pathogens in septic pediatric burn patients

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