Extended interval aminoglycoside dosing: from concept to clinic

Maglio, Dana; Nightingale, Charles H.; Nicolau, David P.

doi:10.1016/s0924-8579(02)00030-4

Cited by 45 publications

(35 citation statements)

References 57 publications

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“…5 Studies in humans and laboratory animals have shown that a once-daily administration of aminoglycosides is more effective, decreases the emergence of resistant isolates, and results in similar or less nephrotoxicity than multiple daily dosing. 22,23 Such a dosing scheme has been investigated with gentamicin in adult horses with no evidence of nephrotoxicity. 24 In a recent study, once-daily amikacin was administered to 7 healthy equine neonates at a dosage of 21 mg/kg for 10 days with no apparent nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Once‐Daily Amikacin in Healthy Foals and Therapeutic Drug Monitoring in Hospitalized Equine Neonates

Bucki

Giguère

Macpherson

et al. 2004

Veterinary Internal Medicne

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The objectives of this study were to investigate the pharmacokinetics of once-daily amikacin in healthy neonates, to determine amikacin concentrations in hospitalized foals, and to determine the minimum inhibitory concentrations (MICs) of amikacin against gram-negative isolates from blood cultures in septic foals. Median half-life, clearance, and volume of distribution of amikacin in healthy 2-to 3-day-old foals after administration of an intravenous bolus of amikacin (25 mg/kg) were 5.07 hours (4.86-5.45 hours), 1.82 mL/min/kg (1.35-1.97 mL/min/kg), and 0.785 L/kg (0.638-0.862 L/kg), respectively. Statistically significant (P Ͻ.05) decreases in area under the curve (14% decrease), mean residence time (19% decrease), and C 24h plasma amikacin concentrations (29% decrease) occurred between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C 0.5h ) were significantly higher (P ϭ .02) than those of hospitalized foals. Sepsis, prematurity, and hypoxemia did not alter amikacin concentrations. The MIC at which 90% of all gram-negative isolates from equine neonatal blood cultures were inhibited by amikacin was 4 g/mL, suggesting that amikacin C 0.5h of 40 g/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C 0.5h Ն40 g/mL was significantly higher (P Ͻ.0001) in hospitalized foals receiving a dose of amikacin at 25 mg/kg (22/24 or 92%) than in foals receiving a dose at 21 mg/kg (9/25 or 36%), whereas no difference was found in the proportion of foals with C 24h concentrations Ն3 g/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once-daily amikacin in equine neonates.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Once‐Daily Amikacin in Healthy Foals and Therapeutic Drug Monitoring in Hospitalized Equine Neonates

Bucki

Giguère

Macpherson

et al. 2004

Veterinary Internal Medicne

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“…The extended-interval method of aminoglycosides has been used in 75% of U.S. hospitals since 2002 [24,25]. Young and Mangum [7] suggest a gentamicin dose of 5 mg/ kg every 48 h during the first week of life, when the gestational age is ≤29 weeks, a dose of 4.5 mg/kg every 36 h, during the first week of life, when the gestational age is 30 to 34 weeks and a daily dose of 4 mg/kg when the gestational age is ≥35 weeks.…”

Section: Gentamicinmentioning

confidence: 99%

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

Pacifici

2008

Eur J Clin Pharmacol

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Background Sepsis is common in neonates and is a major cause of morbidity and mortality. Sixty percent of preterm neonates receive at least one antibiotic, and 43% of the antibiotics administered to these neonates are aminoglycosides. The clearance (Cl), serum half-life (t 1/2 ), and volume of distribution (Vd) of aminoglycosides change during the neonatal life, and the pharmacokinetics of aminoglycosides need to be studied in neonates in order to optimise therapy with these drugs. Objective The aim of this work is to review the published data on the pharmacokinetics of aminoglycosides in order to provide a critical analysis of the literature that can be a useful tool in the hands of physicians. Methods The bibliographic search was performed electronically using PubMed, as the search engine, through July 11th, 2008. Firstly, a Medline search was performed with the keywords "pharmacokinetics of aminoglycosides in neonates" with the limit of "human". Other Medline searches were performed with the keywords "pharmacokinetics of … in neonates" followed by the name of the aminoglycosides: amikacin, gentamicin, netilmicin and tobramycin. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum (Thomson Healthcare, 2007) was consulted. Results The aminoglycosides are mainly eliminated by the kidney, and their elimination rates are reduced at birth. As a consequence Cl is reduced and t 1/2 is prolonged in the neonate as compared to more mature infants. The high body-water content of the neonate results in a large Vd of aminoglycosides as these drugs are fairly water soluble. Postnatal development is an important factor in the maturation of the neonate, and as postnatal age proceeds, Cl of aminoglycosides increases. Conclusion The maturation of the kidney governs the pharmacokinetics of aminoglycosides in the infant. Cl and t 1/2 are influenced by development, and this must be taken into consideration when planning a dosage regimen with aminoglycosides in the neonate. Aminoglycosides are fairly water soluble, and the larger water content of neonates yields a larger Vd in these patients.

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“…Like all aminoglycosides, amininosidine exhibits a concentration dependent bactericical activity and maintenance of drug concentration at levels above minimum inhibitory concentration for a long period between doses does not seem to positively affect bacterial death rate. Furthermore, it has been suggested that even non-detectable levels of aminoglycoside antimicrobials are responsible for a post-antibiotic effect against susceptible microorganisms (Isaksson et al, 1988;Maglio et al, 2002). If the same principles apply to L. infantum, the dosing regimen that has been employed in this study may be promising for the treatment of CanL and warrants evaluation in clinical trials.…”

Section: Discussionmentioning

confidence: 92%