Evaluation of an Extended-Interval Gentamicin Dosing Protocol Specifically
in Neonates  33 Weeks Gestational Age
Jennifer L. Thomas, Master of Physician Assistant Student; LaDonna S. Hale, Pharm.D
Wichita State University, Dept of Physician Assistant & Wesley Medical Center, Wichita, KS
Problem
Summary of Literature Evaluating EID in Neonates
Gentamicin is a commonly used antibiotic in the neonatal intensive care
unit (NICU). Extended-interval dosing (EID) is the standard of care in
adults nationwide due to ample evidence demonstrating that achieving
appropriate antibiotic levels early in treatment improves effectiveness
and reduces risk of gentamicin-induced nephrotoxicity and reduces
treatment and monitoring costs. Unfortunately, only a limited number of
studies have been conducted in neonates and these have included only
small numbers of very premature neonates (GA ≤ 33 weeks). Because
gentamicin has variable effects in different populations, data cannot
simply be extrapolated to all neonate populations.
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Purpose
This study evaluated the adoption of a simplified, weight-based, EID
gentamicin protocol in neonates with a GA  33 weeks, and its impact
on sub-therapeutic peaks, elevated troughs, and simplification of dosing
and monitoring as compared to a traditional, gestational-age based,
weight-based, multiple daily dose (MDD) protocol.
published studies is difficult as different EID protocols were used and
many excluded infants with low birth weights or low GA.
Since this was not a randomized, controlled trial, results may be more
applicable to a “real world” clinical setting. For example, routine
verification of dosage and level timing was not performed, unless an
unusual level was obtained. There were instances in each group,
although no pattern was noted, where the protocol was not followed
completely. This may also be typical in the clinical setting.
Although this EID protocol provided better appropriateness of levels and
simplification of dosing / monitoring, protocol revisions may reduce the
Results
Data were collected on 123 patients in the MDD group, and 98 in the EID
group. Average GA, gender, average birth wt, and length of stay were
similar between groups. The percentage of infants with at least 1 sub-
The purpose of this study included the following primary outcomes:
Results
2) Simplification of Dosing and Monitoring: mean number of
doses/patient and per day, percentage of patients requiring dosage
adjustments, mean number of levels/patient, and percentage of
patients receiving non-standard dosing frequencies (q18 or q36).
Methods
therapeutic peak was significantly lower for the EID group (7% vs. 20%,
p< 0.001); however the percentage of babies with at least 1 elevated
trough was similar between groups (15% vs. 19%, p=0.219). The
average number of peaks obtained per patient was lower in the EID
group (1.360.69 vs. 1.761.38, p=0.006) as was the average number of
troughs obtained per patient (1.4  0.77 vs. 1.91  1.45, p = 0.001). As
expected, the average number of doses administered per day was also
lower in the EID group (1.23  0.70 vs. 1.47  1.20, p = 0.016).
Conclusions
Setting: Wesley Medical Center, a tertiary-care referral center
licensed for 760 beds with a 36-bed, level-III, NICU
Study population: This study evaluated all infants with GA  33
weeks receiving gentamicin 1-year before EID protocol implementation
in Jan 2002, and 1-year after, Mar 2002 to Feb 2003. The desired
trough for these protocols was < 2.0 mcg/ml and the desired peak was
5 – 12 mcg/ml.
Study design: Retrospective, non-blinded, chart review
Old Dosing Protocol
Other comparative studies have shown EID to be superior to MDD in
providing appropriate levels. To directly compare our results to other
number of elevated troughs. Further extension of the dosing interval,
perhaps to q48h, may reduce the percentage of elevated troughs.
Main Outcomes
1) Appropriateness of Levels: percentage of patients with a low peak,
percentage with an elevated trough, and mean peak/trough.
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Discussion
In this very premature neonate population, GA ≤ 33 weeks, this
simplified, weight-based, EID gentamicin protocol appeared to provide
optimal therapeutic levels requiring fewer serum measurements and
fewer doses administered per day as compared to a traditional
gestational-age and weight-based, MDD protocol This research project
contributes to the limited knowledge base of extended-interval gentamicin
dosing in the very premature neonatal population.
New Dosing Protocol
References
Approved by WSU Institutional Review Board & Wesley
Medical Center Institutional Review Board.
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