How to use vancomycin optimally in neonates: remaining questions

Jacqz-Aigrain, Évelyne; Leroux, Stéphanie; Zhao, Wei; Anker, John N. van den; Sharland, Mike

doi:10.1586/17512433.2015.1060124

Cited by 30 publications

(43 citation statements)

References 90 publications

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“…Obviously, the developmental toxicity, e.g., ototoxicity, could not be evaluated in our study, and a long-term safety study of vancomycin in neonates is required (16). Despite the limitation of the use of creatinine concentration as a surrogate of nephrotoxicity in neonates, it allows us to compare the incidences of nephrotoxicity with those in previously published studies (4,7).…”

Section: Discussionmentioning

confidence: 99%

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Leroux

Jacqz-Aigrain

Biran

et al. 2016

Antimicrob Agents Chemother

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N eonatal bacterial sepsis, exacerbated by neonatal immunodeficiency (1), remains a major cause of mortality and morbidity in newborns (2). Vancomycin is widely used for the treatment of late-onset sepsis caused by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci in neonatal intensive care units (NICUs) (3); however, the clinical use of vancomycin is still hampered by its narrow therapeutic index and high pharmacokinetic variability (4). Indeed, de Hoog et al. reported that vancomycin clearance and half-life varied between 0.63 and 1.4 ml/ kg/min and between 3.5 and 10 h in neonates, respectively (4). The common adverse effects of vancomycin are nephrotoxicity and ototoxicity; however, it has been shown that neonates tolerated vancomycin better than adults. Safety data for a high dosing regimen and long-term follow-up are still lacking.The pharmacokinetic modeling approach is often applied to evaluate and optimize antimicrobial therapy in neonates (5). To date, vancomycin is one of the best-studied antimicrobials, and numerous studies have been conducted to characterize its pharmacokinetic parameters and to identify individual factors influencing variability (6). However, the clinical application of modelbased personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a patient-tailored dose of vancomycin in neonates. Model-based patient-tailored dose of vancomycin. Special training was conducted in each NICU. We first informed the staff of the clinical pharmacology of vancomycin, its pharmacokinetic variability, and a large variation of dosage schedules currently used. We then explained the principles of individual dosage adaptation and how we developed the Excel dosing calculator using the results from our published population pharmacokinetic model (6). MATERIALS AND METHODS Neonates receiving vancomycin as a continuous infusion in one of threeIn order to calculate the patient-tailored dosing of vancomycin for each neonate, neonatologists had to enter four patient covariates in the calculator, including birth weight (in grams), current weight (in grams), postnatal age (PNA; in days), and serum creatinine concentration (in micromoles per liter) measured within 48 h of starting vancomycin treatment. The developed calculator was locked, and no other information was required. The patient-tailored dose is calculated automatically by using the following pharmacokinetic equations.Maintenance dose ϭ Target concentration ϫ CL ϫ 24 hwhere the loading dose is in milligrams, the maintenance dose is in milligrams per 24 h, the target concentration is in milligrams per liter, V (vol-

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Section: Discussionmentioning

confidence: 99%

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Leroux

Jacqz-Aigrain

Biran

et al. 2016

Antimicrob Agents Chemother

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“…The PPK model found for this specific subpopulation is described in Table . NeonatesIn neonates, vancomycin is the first choice for late‐onset sepsis treatment. However, prescribing the right dose and dosing regimen remains a challenge in neonatal intensive care units . The high degree of pharmacokinetic variability in neonates makes TDM essential to ensure adequate therapeutic exposure and prevent adverse renal outcomes …”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…However, prescribing the right dose and dosing regimen remains a challenge in neonatal intensive care units. 52 The high degree of pharmacokinetic variability in neonates makes TDM essential to ensure adequate therapeutic exposure 53 and prevent adverse renal outcomes. 54 When using TDM in neonates the basic rules apply.…”

Section: (B) Neonatesmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

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Vancomycin is a fundamental antibiotic in the management of severe Gram‐positive infections. Inappropriate vancomycin dosing is associated with therapeutic failure, bacterial resistance and toxicity. Therapeutic drug monitoring (TDM) is acknowledged as an important part of the vancomycin therapy management, at least in specific patient subpopulations, but implementation in clinical practice has been difficult because there are no consensus and agglutinator documents. The aims of the present work are to present an overview of the current knowledge on vancomycin TDM and population pharmacokinetic (PPK) models relevant to specific patient subpopulations. Based on three published international guidelines (American, Japanese and Chinese) on vancomycin TDM and a bibliographic review on available PPK models for vancomycin in distinct subpopulations, an analysis of evidence was carried out and the current knowledge on this topic was summarized. The results of this work can be useful to redirect research efforts to address the detected knowledge gaps. Currently, TDM of vancomycin presents a moderate level of evidence and practical recommendations with great robustness in neonates, pediatric and patients with renal impairment. However, it is important to investigate in other subpopulations known to present altered vancomycin pharmacokinetics (eg neurosurgical, oncological and cystic fibrosis patients), where evidence is still unsufficient.

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“…aureus is prevalent [5]. Although it has been used for >50 years, the dosing regimen remains a challenge in NICU [29] and also for this antibiotic the use in clinical practice results variable [9]. In our NICUs, 36% of prescriptions resulted off-label as regards frequency: every 18 -24 h in preterm infants < 30 weeks (as partially suggested by ISN guide and BNFC), while data sheets generically reports every 8 -12 h based only on postnatal age.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Use in a Cohort of Extremely Low Birth Weight Neonates: Focus on Off-Label Uses and Prescription Behaviour

Cuzzolin¹,

Agostino²

2018

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Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.

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How to use vancomycin optimally in neonates: remaining questions

Cited by 30 publications

References 90 publications

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Antibiotic Use in a Cohort of Extremely Low Birth Weight Neonates: Focus on Off-Label Uses and Prescription Behaviour

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