One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates

Rao, Shripada; Srinivasjois, Ravisha; Hagan, R. D.; Ahmed, Mohmed

doi:10.1002/14651858.cd005091.pub2

Cited by 38 publications

(22 citation statements)

References 54 publications

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“…This is in agreement with previously published data [4,13,14]. Lower C peak could potentially impair the efficacy, due to failure in achieving desired ratio of the C peak and minimum inhibitory concentration (MIC).…”

Section: Discussionsupporting

confidence: 92%

“…Results of some studies indicate that the administration of gentamicin once daily causes minor discrepancies in minimal (C trough ) and/or maximal (C peak ) concentrations from the desired therapeutic range. Based on the results of a number of studies, the use of gentamicin by oncedaily regimen in neonates was as effective and safe as traditional dosing [4,5], whereas Croes et al showed restricted nephro-and cochleo-toxicity with preserved efficacy upon administration of aminoglycosides once daily [6].…”

Section: Introductionmentioning

confidence: 99%

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Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates

Vučićević

Rakonjac

Janković³

et al. 2014

Open Medicine

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AbstractGentamicin is readily used for suspected or proven sepsis in neonates, yet it shows considerable inter-individual pharmacokinetic variability, which limits achievements of therapeutic levels. Hence, the aim of this study was to compare peak and trough gentamicin concentrations according to dosing regimen, to evaluate pharmacokinetic parameters, and to consider adjustments of dosing regimen. Babies with infection were treated with 1 h infusion, and daily dose of 5 or 7.5 mg/kg depending on the age. Patients were randomized into two groups: I — dosing interval 12 h (n=8), II — 24 h (n=11). Two steady-state blood samples were obtained. Pharmacokinetic parameters were calculated using one-compartment model. The results showed a difference (p<0.05) in peak gentamicin concentrations between the groups, and tendency of lower trough levels in the group II. Calculated pharmacokinetic parameters included the volume of distribution (Vd) 0.52±0.47 l/kg, clearance (CL) 0.055±0.036 l/hkg and a half-life (t1/2) of 6.89±3.21 h. Based on the method for dosing regimen adjustments, there was a need to extend dosing interval to 36 h in 6 patients

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates

Vučićević

Rakonjac

Janković³

et al. 2014

Open Medicine

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“…Gentamicin is considered a valuable drug for treating sepsis and Pseudomonas infections, but the high dosages required can induce ototoxicity and nephrotoxicity. 36,37 Therefore, controlled release of gentamicin may decrease undesirable side effects. Furthermore, nanoparticle and microparticle preparations have the potential to be used in aerosol delivery and may enhance the therapeutic effectiveness and dose control of this and other aminoglycosides for treating pulmonary infections.…”

Section: Resultsmentioning

confidence: 99%

Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection

Abdelghany¹,

Quinn²,

Ingram³

et al. 2012

IJN

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Abstract:Gentamicin is an aminoglycoside antibiotic commonly used for treating Pseudomonas infections, but its use is limited by a relatively short half-life. In this investigation, developed a controlled-release gentamicin formulation using poly(lactide-co-glycolide) (PLGA) nanoparticles. We demonstrate that entrapment of the hydrophilic drug into a hydrophobic PLGA polymer can be improved by increasing the pH of the formulation, reducing the hydrophilicity of the drug and thus enhancing entrapment, achieving levels of up to 22.4 µg/mg PLGA. Under standard incubation conditions, these particles exhibited controlled release of gentamicin for up to 16 days. These particles were tested against both planktonic and biofilm cultures of P. aeruginosa PA01 in vitro, as well as in a 96-hour peritoneal murine infection model. In this model, the particles elicited significantly improved antimicrobial effects as determined by lower plasma and peritoneal lavage colony-forming units and corresponding reductions of the surrogate inflammatory indicators interleukin-6 and myeloperoxidase compared to free drug administration by 96 hours. These data highlight that the controlled release of gentamicin may be applicable for treating Pseudomonas infections.

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“…It is possible that many of the antibiotics approved for use in neonates have been licensed for so long that the emergence of bacterial resistance is being observed or suspected, underpinning the tendency to move to off-license alternatives. daily dosing of the total daily dose, with a reduced lower risk of toxicity [38,39]. Similarly, amoxicillin, licensed in children at a recommended dose of 40-50 mg/kg/day, proved to be effective against Streptococcus pneumoniae strains with relative resistance to penicillin when used at higher dose (80-90 mg/kg/day) without concomitant increase in the incidence of adverse events [40,41].…”

Section: Discussionmentioning

confidence: 99%