USE OF A LOADING DOSE FOR GENTAMICIN IN TREATING SEPSIS IN CRITICALLY ILL NEONATES
Date
1992-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
In the past decade, progress in neonatology has
resulted in the survival of smaller premature infants who
are predisposed to sepsis. Gentamicin has been used as a
first line agent in the treatment of neonatal sepsis for
almost two decades. Neonatal gentamicin regimens which
provide appropriate steady-state serum concentrations have
been developed based on the pharmacokinetic characteristics
of gentamicin in the neonate. Since the development of
these regimens, it has become increasingly clear that early
attainment of therapeutic peak serum concentrations (i.e.,
≥5 µg/mL) is an important determinant of clinical response.
The present study was designed to evaluate the use of a
4.0 mg/kg loading dose of gentamicin for treating sepsis in
neonates. For the 26 patients studied, the initial peak
serum concentration was ≥5 µg/mL in all 13 patients who
received the loading dose but in only 5 of the control
group. Three of the 8 patients in the control group who had
not achieved a serum concentration of ≥5 µg/mL with the
first dose did not achieve a serum concentration of ≥5 µg/mL
within 24 hours of initiating therapy. Patients in the
control group who did not achieve an initial serum
concentration ≥5 µg/mL were those <2500 g and ≤34 weeks
gestational age.
In the present investigation, the mean Vd (L/kg) was
ii0.72 (SD 0.88), 0.62 (SD 0.44) and 0.53 (SD 0.24) for the
VLBW, the LBW and the normal birthweight categories
respectively. The mean Vd in patients in the normal weight
category was significantly smaller than in the VLBW group.
However, Vd (L/kg) was not significantly correlated (r=-
0.232, p>0.05) with birthweight. The mean Vd in patients
≤34 weeks gestational age (n=16) (0.67 L/kg, SD 0.13 L/kg)
was significantly larger than in infants >34 weeks
gestational age (0.52 L/kg, SD 0.10 L/kg). However, there
was no significant correlation between Vd and gestational
age.
The mean kd values in the three body weight categories
were significantly different: VLBW 0.044 h-1, (SD 0.011 W I,
n=6), LBW 0.07011-1 (SD 0.011511'1, n=10), normal weight
0.104h-1 (SD 0.024h-1, n=10). The kd was positively correlated
with birthweight (r=0.788, p=0.0001).
Infants ≤34 weeks gestational age had a significantly
smaller elimination rate constant (mean 0.064 if% SD 0.022
h-1, n=16) than did infants >34 weeks gestational age (mean
0.092 h.% SD 0.024 h.% n=10).
Results of this study indicate that a loading dose of 4
mg/kg would be most beneficial in younger, smaller infants;
it would provide little additional benefit to normal
birthweight infants delivered at term. However, safe use of
a loading dose must also be linked to choice of appropriate
dosing intervals.
Description
Keywords
Neonatology, Septicemia, Gentamicin
Citation
Degree
Master of Science (M.Sc.)
Department
Pharmacy and Nutrition
Program
Pharmacy