Aminoglycoside extended interval dosing in neonates is safe and effective: A meta-analysis

Eirik Nestaas ^1*, Hans-Jacob Bangstad ², Leiv Sandvik ³ and Karl-Olaf Wathne ²

¹ Department of Paediatrics, Hospital of Vestfold - Tnsberg, Norway, Norway
² Department of Paediatrics, UllevÅl University Hospital, Norway, Norway
³ Center for Clinical Research, UllevÅl University Hospital, Norway, Norway

^* To whom correspondence should be addressed. E-mail: eirikpda{at}start.no.

Accepted 19 January 2005

Abstract

Objectives:To review the evidence from controlled clinical trials of neonates given equal daily aminoglycoside dose as extended interval dosing (dosage interval typically 24 hrs in term and 36-48 hrs in immature neonates) compared to traditional dosing (dosage interval typically 8-12 hrs in term and 12-24 hrs in immature neonates). Design:Systematic review and meta-analysis of controlled trials found in electronic databases, trial registers and references in reviews and selected trials. Settings:The selected trials were blinded and assessed for methodological quality. Each trials own predefined criteria for treatment failure, nephrotoxicity, ototoxicity and therapeutic serum drug levels were used. Subjects:Controlled trials of neonatal aminoglycoside therapy in which equal aminoglycoside daily dose were given at traditional and extended dosage intervals. Main outcome measures:Serum drug levels outside the therapeutic range. Treatment failure and toxicity. Results:Sixteen trials involving 823 neonates met the inclusion criteria for the systematic review. Twelve trials involving 698 neonates were included in the meta- analysis of the pharmacokinetics. Compared to traditional dosing, extended interval dosing was associated with a significantly lower risk for both peak (summary risk ratio 0.50, 95% confidence interval 0.26 to 0,94) and trough (0.36, 0.25 to 0.56) serum drug levels outside the therapeutic range. Accurate information on treatment failure was obtained in nine trials involving 555 neonates. One trial reported treatment failure. In this trial two neonates in the traditional dosing group did not respond to therapy within 72 hrs. Nephrotoxicity was investigated in 589 neonates in twelve trials and ototoxicity in 210 neonates in four trials with no significant differences between the two dosing regimens. Conclusions:Extended interval dosing of aminoglycosides in neonates is safe and effective, with a reduced risk for serum drug levels outside the therapeutic range.

Keywords: aminoglycoside, meta-analysis, neonates, sepsis

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