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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.
This study evaluated the adoption of a simplified, weight-based, EID gentamicin protocol in neonates with a GA
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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.
The purpose of this study included the following primary outcomes:
: percentage of patients with a low peak, percentage with an elevated trough, and mean peak/trough.
: 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).
•
Other
have shown EID to be superior to MDD in providing appropriate levels. To directly compare our results to other published studies is difficult as different EID protocols were used and many excluded infants with low birth weights or low GA.
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Since this was not a randomized, controlled trial, results may be more
. 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.
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Although this EID protocol provided better appropriateness of levels and simplification of dosing / monitoring, protocol revisions may reduce the number of elevated troughs. Further
may reduce the percentage of elevated troughs.
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 subtherapeutic 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
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0.69 vs. 1.76
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1.38, p=0.006) as was the average number of troughs obtained per patient (1.4
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0.77 vs. 1.91
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1.45, p = 0.001). As expected, the average number of doses administered per day was also lower in the EID group (1.23
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0.70 vs. 1.47
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1.20, p = 0.016).
Wesley Medical Center, a tertiary-care referral center licensed for 760 beds with a 36-bed, level-III, NICU
This study evaluated all infants with GA
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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.
Retrospective, non-blinded, chart review
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.
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