Gentamicin is an aminoglycoside antibiotic commonly used to treat early and late onset neonatal sepsis. It is effective against many gram-negative bacteria. Gentamicin is administered intravenously over 30 minutes, with dosage and interval depending on gestational and postnatal age. Therapeutic drug monitoring includes checking peak and trough levels. Adverse effects include nephrotoxicity and ototoxicity. Research is exploring using gentamicin to suppress cystic fibrosis mutations. Gentamicin use in the NICU requires careful monitoring and coordination between the medical team and nursing staff.

1. GENTAMICIN
A Clinical Profile for Use in the
Neonatal ICU
By Patricia Pennywell
MSNE 5356 Advanced Pharmacology
Lamar University

2. Gentamicin: An
Aminoglycoside
In spite of the potential for toxicities related to
aminoglycosides, GENTAMICIN remains a
major drug of choice for the treatment of both
early and late onset sepsis in the neonate.

3. Neonatal Sepsis
• Early onset sepsis occurs in the first week of
life in 8 to 10 of every 1000 births
• Mortality of 10-20% for all infected neonates
• Symptoms include respiratory distress,
cardiovascular instability, temperature
instability, hypoglycemia, metabolic acidosis,
feeding intolerance, and altered CNS status
• Primary bacteria involved are E. coli and
Group B streptococcus

4. Uses for Gentamicin
in Neonates
Initial treatment of neonates with suspected
bacterial sepsis or meningitis
Used in combination with Ampicillin
Effective against gram negative organisms
including:
Pseudomonas aeruginosa
Escherichia coli
Klebsiella species

5. Dosage and Dosing Intervals
Dose range is from 2.5-5 mg/kg/day
Dosing interval depends on gestational and
chronological age
The chart below defines appropriate dosages
and dosing intervals:
Truven Health Analytics. Micromedex Neonatal Essentials. 2015. Web.
PMA
(weeks)
Postnatal
(days)
Dose
(mg/kg)
Interval
(hours)
<29
0 to 7
8 to 28
>29
5
4
4
48
36
24
30 to 34 0 to 7
>8
4.5
4
36
24
<35 ALL 4 24

6. Method of Administration
• Infuse over 30 minutes
• Incompatible with Amphotericin B,
Ampicillin, Furosemide, Heparin (if
>1unit/ml), and Indomethacin
• Compatible with D5W, D10W, NS, and
Dextrose/AA solutions and Fat Emulsion

7. Pharmacokinetics
Absorption: remains in the vascular
interstitial spaces. Higher body
water content the 1st week of
life may cause higher doses to
be needed to achieve optimal
drug levels.
Metabolism: does not significantly bind to
plasma proteins. Penetrates bacterial cell
wall to bind with the 30s subunit of the bacterial
ribosome to prevent polypeptide synthesis in the
bacteria.

8. Pharmacokinetics
• Distribution: Volume of distribution is increased
the 1st week of life. Dose may need to be adjusted.
Drug is distributed via vascular system.
• Excretion: Almost exclusively done by the
kidneys. Efficiency of excretion is dependent on
the glomerular filtration rate which is greater
decreased in the neonate. This causes re-
absorption of drug into vascular system and
increased levels of accumulation.

9. Monitoring Therapeutic Levels
Monitor serum levels with third dose:
*Peak: 5 to 12 mg/ml
*Trough: <2 mg/ml
Administer other antibiotics at least one hour
before or one hour after gentamicin dose (to
avoid reduced gentamicin efficacy)
Adjust doses for renal impairment
Peak: 30 minutes following a 30 minute infusion
Trough: 30 minutes prior to next dose

10. Adverse Effects
• Hypomagnesemia
• Electrolyte wasting
• Neuromuscular blockade
• Ototoxicity (associated with high peak levels),
tinnitis, and hearing loss (irreversible)
• Nephrotoxicity with proteinuria (associated
with high trough levels), reduced GFR,
elevated serum creatinine

11. Drug Interactions
Do not give gentamicin and other
ototoxic or nephrotoxic drugs
together. This will increase the
risk of toxicity.
Though gentamicin is synergistic with
ampicillin, it is inactivated by ampicillin
if they are infused together.
Wait at least an hour between infusions
and flush IV line well.

12. What’s the buzz in
pharmacogenomics?
Cystic fibrosis is an autosomal recessive disease that
causes excess mucous production in the lungs,
gastrointestinal tract and other body systems. This
mucous build-up can harbor bacteria and lead to serious
lung infections. CF is caused by a mutation leading to the
formation of the defective protein, CFTR (cystic fibrosis
transmembrane conductance regulator). Researchers have
found that gentamicin suppresses the mutation process so
that a normal functioning CFTR can be formed. Studies
are still in progress to validate these findings and find
useful applications without causing nephrotoxicity.

13. Application to the NICU Practice
Setting
• Institution of daily rounding on intensive and some
intermediate acuity patients that includes the neonatologists,
neonatal nurse practitioners, primary nurses, and clinical
pediatric pharmacist.
• Education of nursing staff to include the following:
--Reporting urine output and critical lab
values to MD/NNP
--Communicating weight changes to MD/
NNP and pharmacist.
--Strictly adhere to dosing schedule, flush IV lines
well, give antibiotics on time.
--Draw peaks and troughs as ordered.

14. References
• Arcangelo, V.P. and Walden, A.M. (2013). Pharmacotherapeutics for advanced
practice: A practical approach (3rd ed.). Philadelphia, PA: Lippincott Williams &
Wilkins.
• Clancy, J.P., et al. (2001). Evidence that systemic gentamicin suppresses premature
stop mutations in patients with cystic fibrosis. American Journal of Respiratory
Critical Care. 163(7), 1683-92.
• Inhibition of Protein Synthesis by Antibiotics. BioFiles 2006.
http://www.sigmaaldrich.com/technical-documents/articles/biofiles/inhibition-of-
protein.html#sthash.bQckiD9K.dpuf. Web.
• Koren, G. (1997). Therapeutic drug monitoring principles in the neonate. Clinical
Chemistry. 43(1), 222-227.
• Truven Analytics. Micromedex NeoFax Essentials (2015). Web.
• Verklan, M.T. and Walden, M. (2010). Neonatal Intensive Care Nursing (4th ed.).
St. Louis, MO: Saunders.
• Wallace, S.M. and Chan, L. (1985). Evidence that Systemic Gentamicin Suppresses
Premature Stop Mutations in Patients with Cystic Fibrosis. University of Alabama
at Birmingham Children’s Hospital. Birmingham, AL and University of Mississippi
Department of Pediatrics. Jackson,MS.