Once‐Daily Gentamicin Dosing in Pediatric Patients Without Cystic Fibrosis

McDade, Erin; Wagner, Jeffrey L.; Moffett, Brady S.; Palazzi, Debra L.

doi:10.1592/phco.30.3.248

Cited by 17 publications

(19 citation statements)

References 24 publications

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“…Current dosing recommendations are 4–5 mg/kg every 24 hours for infants <3 months and 9.5 mg/kg every 24 hours in infants from 3 months to 2 years of age. 48 We recommend using these updated doses as an initial dose in infants on ECMO, followed by TDM at 2 and 8–12 hours after the infusion to guide further dosing. A decreased initial dose may be considered for neonates who are <3.5 kg.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature

Sherwin

Heath

Watt

2016

Clinical Therapeutics

121

120

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Purpose Extracorporeal Membrane Oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO, and are associated with a mortality of greater than 50%.1 Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO, because the ECMO circuit can alter drug pharmacokinetics. This review assessed the current literature for pharmacokinetic data and subsequent dosing recommendations for anti-infective drugs in patients on ECMO. Methods We searched the PubMed and EMBASE databases (1965 to February 2016) and included case reports, case series, or studies that provided pharmacokinetic data for anti-infective drugs including antibiotics, antifungals, and antivirals being used to treat patients of all age groups on ECMO. Pharmacokinetic parameters and dosing recommendations based on these data are presented. Findings The majority of data on this topic come from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution (V) due to ECMO and therefore, higher doses are needed initially. More adult data is now emerging, but with a predominance of case reports and case series without comparison to critically ill controls. The available pharmacokinetic analyses do suggest that V and clearance (CL) are unchanged in the adult population and therefore dosing recommendations largely remain unchanged. There are a lack of data in children >1 year of age. The data support the importance of therapeutic drug monitoring (TDM) when available in this population of patients. Implications This review found reasonably robust dosing recommendations for some drugs and scant or no data for other important anti-infectives. In order to better determine optimal dosing on ECMO, a systematic approach is needed. Approaches that combine ex vivo ECMO experiments, animal studies, specialized pharmacokinetic modeling, and human clinical trials are being developed.

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature

Sherwin

Heath

Watt

2016

Clinical Therapeutics

121

120

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“…Although organizational protocols vary, patients with CF of all ages typically receive 10 to 12 mg/kg once daily of tobramycin, whereas patients without CF are usually given lower doses of 7 to 8 mg/ kg once daily (Lexi-Comp, 2015;Nicolau et al, 1995;Prescott & Nagel, 2010;Smyth et al, 2005;Young et al, 2013a). Higher doses closer to those reserved for CF may be given to younger children without CF who also have a higher Vd than older patients (McDade, Wagner, Moffett, & Palazzi, 2010;Lexi-Comp, 2015). Tobramycin and gentamicin doses are interchangeable, but the typical starting dose of amikacin in persons with CF is 30 mg/kg once daily (Prescott & Nagel, 2010).…”

Section: Eliminationmentioning

confidence: 99%

Infectious Diseases Pharmacotherapy for Children With Cystic Fibrosis

Molloy¹,

Nichols²

2015

Journal of Pediatric Health Care

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Cystic fibrosis (CF) affects several organs, most notably the lungs, which become predisposed to infections with potentially severe consequences. Because of physiologic changes and infection characteristics, unique approaches to antimicrobial agent selection, dosing, and administration are needed. To provide optimal acute and long-term care, pediatric health care providers must be aware of these patient features and common approaches to antimicrobial therapy in CF, which can differ significantly from those of other infectious diseases. The purpose of this article is to review common respiratory pathogens, pharmacology of commonly used antimicrobial agents, and unique pharmacokinetics and dosing strategies often used when treating children with CF.

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“…18 In a pooled estimate of once-daily aminoglycoside therapy in pediatric patients 3 months to 18 years of age, the Vd and Ke were 0.24 ± 0.08 and 0.32 ± 0.06, respectively, resulting in a recommendation of gentamicin 7 mg/kg dose in children 8 to18 years. 12 Notably, this recommendation comes from a study using gentamicin, but tobramycin is generally considered equivalent with regard to pharmacokinetic and dosage recommendations. 20 As shown in Table 2, our patient had a larger Vd and similar or greater Ke than was reported in studies from non-CF patients, indicating that a treatment approach similar to that for a CF patient was warranted.…”

Section: Discussionmentioning

confidence: 99%

“…6,10,11 In pediatric patients greater than 8 years of age without CF, the recommended tobramycin dose is 4.5 to 7.5 mg/kg/day. 12,13 In pediatric patients with CF, a tobramycin dose of at least 10 mg/ kg/day is required to achieve the same 24-hour area under the curve (AUC 0-24h ) as is achieved with a non-CF child. 11,14 The different dosage requirements are thought to be due to the increased volume of distribution (Vd) and clearance of aminoglycosides in CF patients.…”

Section: Introductionmentioning

confidence: 99%

Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

Higgins

Noda

Stultz³

2018

The Journal of Pediatric Pharmacology and Therapeutics

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The pharmacokinetics of tobramycin in patients with ciliary dyskinesia have not been previously reported. A 10-year-old female patient with primary ciliary dyskinesia was admitted to the general pediatrics floor with an acute respiratory exacerbation after several months of worsening lung function that was unresponsive to oral antibiotics. Extrapolating from cystic fibrosis dosing regimens, she was given intravenous tobramycin 320 mg (10.3 mg/kg/day) on admission as a result of concern for a Pseudomonas aeruginosa infection. Two-point pharmacokinetic monitoring revealed a maximum serum concentration (Cmax) of 18.9 mg/L and a 24-hour area under the curve (AUC 0-24hr) of 58.8 (mg × hr)/L, as well as a volume of distribution (Vd) of 0.5 L/kg and an elimination rate (Ke) of 0.34 hr −1. After a dosage increase to tobramycin 400 mg (12.8 mg/ kg/day), pharmacokinetic parameters on 2 assessments were as follows: Vd 0.37 to 0.39 L/kg, Ke 0.33 to 0.39 hr −1 , Cmax 27.8 to 28.7 mg/L, and AUC 0-24h 78.4 to 89.4 (mg × hr)/L. This was the first case report of aminoglycoside pharmacokinetics in a patient with ciliary dyskinesia. The administration of larger doses (up to 12.8 mg/kg/day) of extended-interval tobramycin, similar to the treatment recommendation of at least 10 mg/kg/day for cystic fibrosis patients, was necessary in this patient to achieve serum concentrations that were appropriate for treatment. ABBREVIATIONS AUC 0-24hr , 24-hour approximate area under the curve; BUN, blood urea nitrogen; C 1 , concentration 1; C 2 , concentration 2; CF, cystic fibrosis; Cmax, maximum serum concentration; Cmin, minimum serum concentration; Cpeak, concentration at end of the infusion; Ctrough, concentration 24 hours after the start of the infusion; FEV 1 , forced expiratory volume in the first second; Ke, elimination rate constant; MIC, minimum inhibitory concentration; PAE, post-antibiotic effect; PCD, primary ciliary dyskinesia; SCr, serum creatinine; t 1 , concentration 1 time after start of the infusion (hr); t 2 concentration 2 time after start of the infusion (hr); tinfusion, duration of infusion (hr); Vd, volume of distribution

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Once‐Daily Gentamicin Dosing in Pediatric Patients Without Cystic Fibrosis

Abstract: Age was the primary factor in determining the once-daily dose of gentamicin in our pediatric population. Further prospective research is necessary to determine the safety and efficacy of these age-based, once-daily doses for gentamicin.

Cited by 17 publications

References 24 publications

Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature

Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature

Infectious Diseases Pharmacotherapy for Children With Cystic Fibrosis

Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

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