Setting: Wesley Medical Center, a tertiary-care referral center licensed for 760 beds with a 36-bed, level-III, NICUStudy 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

• Other comparative studies 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.

• 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

number of elevated troughs. Further extension of the dosing interval,

perhaps to q48h, may reduce the percentage of elevated troughs.

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.

• Ali MZ, et al. Clin Infect Dis. 1997; 24:796-809.• Agarwal, et al. J Perinatol. 2002; 22:268-74.• Chuck SK, et al. Clin Infect Dis. 2000; 30:433-39.• Davies MW, et al. J Paediatr Child Health. 1998; 35:577-80.• DiCenzo, et al. Pharmacotherapy. 2003; 23:585-91.• Edson RS, et al. Mayo Clin Proc. 1999; 74:519-28.• Hale LS, et al. Am J Health-Syst Pharm. 2005; 62:1613-6.• Hansen, et al. J Perinatol. 2003; 23:635-9.• Hayani, et al. J Pediatr. 1997; 131:76-80. • Hitt CM, et al. Pharmacotherapy. 1997; 17:810 - 4.• Knoderer CA, et al. Pharmacotherapy. 2003; 23:44-56.• Lanao, et al. J Antimicrobial Chemother. 2004; 54:193-8.•Langlass, et al. Am J Health-Syst Pharm. 1999;56:440-3

Evaluation of an Extended-Interval Gentamicin Dosing Protocol Specifically Evaluation of an Extended-Interval Gentamicin Dosing Protocol Specifically in Neonates in Neonates 33 Weeks Gestational Age 33 Weeks Gestational Age

Jennifer L. Thomas, Master of Physician Assistant Student; LaDonna S. Hale, Pharm.DWichita State University, Dept of Physician Assistant & Wesley Medical Center, Wichita, KS

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.

The purpose of this study included the following primary outcomes:

1)Appropriateness of Levels: percentage of patients with a low peak, percentage with an elevated trough, and mean peak/trough.

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).

Approved by WSU Institutional Review Board & Wesley Medical Center Institutional Review Board.

ConclusionsConclusions

References

DiscussionDiscussionProblemProblem

MethodsMethods

Summary of Literature Evaluating EID in NeonatesSummary of Literature Evaluating EID in Neonates

ResultsResults

•Lundergan, et al. Pediatrics. 1999; 103:1228-34.• Moore RD, et al. J Infect Dis. 1987; 155:93-9.• Murry KR, et al. Pharmacotherapy. 1999; 19:1252-60.• Ohler, et al. Am J Perinatol 2000; 17:285-90.• Preston SL, et al. Pharmacotherapy. 1995; 15:297-316.• Raveh D, et al. QJM. 2002; 95:291-7.• Rougier F, et al. Antimicrobial Agents Chemother. 2003; 47:1010-6.• Rybak MJ, et al. Antimicrobial Agents Chemother. 1999; 43:1549-55.• Skopnik H, et al. Arch Dis Child. 1992; 67:57-61• Thureen, et al. Pediatrics. 1999; 103:594-8. • Turnidge J. Infect Dis Clin North Am. 2003; 17:503 - 28.• Young TE, et al. Neofax 2003. 16th ed. Raleigh, NC: Acorn Publishing, Inc; 2003.

New Dosing ProtocolNew Dosing Protocol

PurposePurposeThis 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.

Main OutcomesMain Outcomes

Old Dosing ProtocolOld Dosing Protocol

ResultsResultsData 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-

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 (1.360.69 vs. 1.761.38, 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).