In Vitro Antibacterial Activity of Amikacin, a New Aminoglycoside, Against Clinical Bacterial Isolates from Children MELVIN
A
(BBK8)* antibiotic
MIKACIN
side
‘‘-
mycin
A
tivity vantage
to
with
similar
kanamycin of activity
aeruginosa.1’2’34 not appear nificantly,5
It
gentamicin.6 amikacin
aminoglycofrom kana-
antibacterial
and against
ac-
the added Pseudonionas
is water
ad-
soluble,
to displace and its ototoxic
toxic potentials to be less than
does
bilirubin sigand nephro-
are preliminarily reported those of kanamycin and The
and
identical
is an derived
with
pharmacokinetics kanamycin are
a serum
of almost
half-life
of
both drugs.7’8 Because and the development
for
mycin-
and
negative a study in vitro
bacteria in hospital populations, was undertaken to evaluate the efficacy of amikacin against clini-
cal bacterial tients.
Materials
and
Recent obtained Children’s ing
to
isolates
of these of kanaGram-
from
pediatric
pa-
Methods
standard
methods
microbiology
teria
maintained
were
carbenicillin, lexin, 30;
in
use
in
laboratory. in
pure
the
culture
Department Montreal
McGill University-Montreal pital Research Institute, *
Bristol
246
Laboratories,
of
Pediatrics
at
(Infectious
Children’s
Hospital Children’s Montreal, Canada.
Syracuse,
N.Y.
13201.
dilution
and Hos-
Canada
in micrograms, 10; gentamicin, tobramycin, 10; 10;
test
All
bacteria
was
were
grown
broth
except
cocci
which
were
Hewitt night
broth. broth
A 10 culture
oculum in the mum inhibitory
cepha-
performed
defined
as
tests agar,
The lution
Lilly
except
for
and the
Lot The
Journal
dilu-
Mueller-
susceptibility
for the in pure amikacin,
GMC-2M-651;
S11-36-3H;
surface
agar on
gentamicin
Lot
of
on the
companies:
Lot Bristol
Miniwas
concentration
powders supplied
*73F1050;
Todd-
tests. (MIC)
streptococci for which sheep blood was added agar base.
following
tol Lot Schering sulfate,
in
performed
antibiotic tests were
in
strepto-
dilution of this overwas used as the in-
lowest
were
testing of fibrinated Mueller-Hinton
for
agar dilution concentration
the
the et
overnight
incubated
drug exhibiting no growth of the agar. Both the disk diffusion
the From the Diseases),
potencies, amikacin, 30;
50; streptomycin, oxacillin, 1.
and
agar
Hinton
Bac-
Montreal,
as previously described, employing replicate inoculation method of Steers
tion
clinical bacterial isolates were from children at the Montreal Hospital and identified accord-
diagnostic
of calipers. Disk were as follows: 10; kanamycin,
The
M.D.
diffusion tests were performed to the method of Barry et al.#{176} sizes were measured by means
Mueller-Hinton
2 hours properties
gentamicin-resistant
4#{176}C.Disk according Disk zone
al.9
about
I. MARKS.
73F505; disodium of Clinical
5% to
dethe
agar form
diby Bris-
sulfate, kanamycin tobramycin, carbeniPharmacology
ANTIBACTERIAL
ACTIVITY
OF
TABLE Results
of Disk
Diffusion
Sensitivities
No.of strains
Bacteria
tested
Salmonella
92
Klebsiella
43
Enterobacter
No.
11
12
13
of
14
Proteus
25 42
2
2
5
3
4
4
#{149}
S
0)
2
7
1
.78
S 2
#{149}
1.
Correlation
tests
for
amikacin
22
23
11
23
12
7
9
2
16
1
2
1
11
1
2
7
83
2
1
3
12
3
-
4
24
25
10
4143
26
16
27
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
S
#{149}
#{149}
S
2
#{149}
S
S
13
8
12
12
S
S
S
S
S
S
19
of
agar
BDH
strains coli
Lot
20
g/ml Figure (all
S
S
24
25
26
strep-
#73F-57;
(mm)
disk
diffusion
g)
sensitivity
values
(all
80
-a -c
C 0
60
40
a E
20 K ANA
.195
.39
78
1.56
3.12
6.25
MIC
248
Fig.
4. Susceptibility
four
antibiotics
(method
of
42 clinical as in Fig.
isolates
MY (IN
12.5
25
50
100
>100
&g/m
of
Pseudomona.s
aer-uginosa
to
2). The
Journal
of
Clinical
Pharmacology
ANTIBACTERIAL
ACTIViTY
OF
AMIKACIZi
K,
0
C
a)
C
>
0
0 D
E
.195
.39
.78
1.56
3.12
6.25
MIC
Fig.
5.
Susceptibility
antibiotics
(method
of 42 clinical as in Fig.
25
12.5
50
100
Ag/ml
isolates
of
Kiebsiella
pneumoniae
to
four
2).
100#{149}
-D 4)
80-
-a -C
0
C
60
In
C
4) >
40
0 fl
0
20
E
.195
.39
.78
1.56
MIC Fig.
6.
staphylococci were resistant was
with several
cloxacillin Seven tested
but
II for
tg/ml 36 strains
streptococcus, foecalis, and were
coccus to
faecalis g/ml 1975
strains pattern
resistant
strains
of the
g/ml
and
six,
were also sensitive
The present susceptibility
50
100
to four
,iLg/ml
12.5
strains
were
also
50
species
and
Four
Discussion
amikacin. were
kanamycin,
amikacin.
A beta-hemolytic
streptomycin,
of Salomenalla
to
ten strains of Streptococcus 16 strains of D. pneumoniae; to
25
were
to 3.12
gentamicin.
sensitive
tg/ml
to
1.56
penicillin
G.
to
three to 3.12 g/m1. are presented in Table
of group
isolates
albus;
were
sensitive
resistant
100
April,
strains
and results
some The
Staphylococcus
strains of Enterobacter with amikacin; four
to 1.56 Additional
all
(method
tested, while to kanamycin.
similar
however,
of 96 clinical as in Fig. 2).
Susceptibility
antibiotics
12.5
3.12
pg/mi
study has confirmed of a wide variety of
negative bacteria to the new aminoglycoside amikacin.4 This includes Escherichia coli, Proteus species, Kiebsiella pneunoniae,
Salmonella
Strepto-
spp., and Pseudonwnas dition, the susceptibility
resistant
aureus
g/ml
the Gram-
and
demonstrated
spp.,
In
ad-
of Staphylococcus
Staphylococcus in vitro.
Enterobacter
aeru1ginosa.
albus The
has
been
Gram-positive 249
MARKS
TABLE of Agar
Summary
Dilution
Sensitivities Total strains
Bacteria Streptococcus (Group
pneum.oniae
Diplococcus were
the
and
use
separate resistant This has been
Amikacin
similar
to
of
that Proteus
tive than Pseudomonas
Both
against
The however, cm is
gentamicin more ac-
was less than Pseudomonas and
genta-
cloxacillin, in
that
of
addition,
amikacin
was of
N-acetylation.12 Preliminary
1
vitro
for
thought
amikacin
to be to
in
vivo
ac-
due
to the
inactivation
by
studies
and
isolates
ceptibility parison by the
examined to
with disk
Proteus
fifty-eight
from
amikacin a number diffusion
species,
were
a
the
clinical
children’s
hos-
antibiotic
sus-
for
(BB-K8) in comof other antibiotics and agar dilution
methods. The wide of amikacin against teria was confirmed;
spectrum of Gram-negative it included Kiebsiella
highly
activity bacE. coli,
pneumoniae,
Enterobacter aeruginosa.
species, Staphylo-
sensitive,
Gram-positive sistant. A
disk
effectively tive bacteria
separated resistant in a standard
The MacKay Bristol edged.
but
bacteria tested zone diameter
other
were of 10
disk
remm
from sensidiffusion
mdi-
technical and the Laboratories
assistance of Miss Elaine support and cooperation of are gratefully acknowl-
References 1.
Bodey,
G.
studies
and have
in
Acknowledgment
of Gramby Price
0-adenylylation,
useful
test.
kanamycin;
gentamicin-
strains been noted
was
hundred were
cocci
genta-
significant
against has
8
urinary tract infections.13 are in progress to fully clinical usefulness of this
Salmonella species, and Pseudomonas
although
described
0-phosphorylation,
250
Escherichia
Staphylococcus,
In
resistance
30
Summary
pital
genta-
the spectrum is wider as amikaalso active against Pseudomonas
and
>100
antibiotic.
Four
isolates of The activity
amikacin against
paralleled
of
of
100
amikacin
of studies the
bacterial
active than amikacin Amikacin was highly
and tobramycin-resistant negative bacteria et al.’1
activity
kanamycin
activity
aeruginosa.
tivity
exhibited and
somewhat less so than micin, and tobramycin. amikacin
strains. present
and
that
therapy Other evaluate new
to
sensitive in the
hand, both significantly
were more Salmonella.
g/ml.
diameter
kanamycin against and Klebsiella.
aeruginosa.
active
zone
species
other were
cated
suggested
kanamycin
of gentamicin and that of tobramycin micin against
50
have
from confirmed
as well.
On the amikacin
(jg/ml)
16
to con-
under disk
study
coli. and
MIC
2
Strep-
insensitive
amikacin
of a 10-mm
for
50
5
Streptococcus
Washington4
micin
having
to Amikacin
16
and
uniformly of
Yu
strains
10
pneumoniae,
pyogenes,
centrations
of
36
Diplococcus
faccalis
No.
Bacteria
pyo genes
faecalis
tococcus
of Gram-Positive
no. of tested
A)
Streptococcu.s
bacteria
II
antibiotic.
2.
4:186 Karney,
P.,
of
and
of Journal
D.:
a new
Antimicrob.
(1973). W., Holmes,
Comparison The
Stewart,
BB-K8,
Agents
K. five of
K.,
In
Cheinother.
and
Turck,
aminocyclitol
Clinical
vitro
aminoglycoside
Pharmacology
M.: anti-
ANTIBACTERIAL biotics and 3.
4.
in
vitro
against
Pseudomonas.
ACTIVITY
Enterobacteriaceae Antimicrob.
Agents
Chemother. 3:338 (1973). Young, L. S., and Hewitt, W. L.: Activity of five aminoglycoside antibiotics in vitro against gram-negative bacilli and Staph ylococcus aureus. Antimicrob. Agents Chemother. 4:617 (1973). Yu, P. K. W., and Washington, J. A., II: Comparative
in
vitro
activity
of
aminoglycoside antibiotics: BB-K8, mycin and gentamicin. Antimicrob.
Chemother. 5. 6.
C., observations.
Dupont,
Reiffenstein,
8.
April,
Ctin. Barry,
1975
10.
11.
three kanaAgents
C.,
Holmes,
H., and studies
S. W.,
Bierwagen,
of
amikacin
Phar,n. Therap. A. L., Garcia, F.,
and 15:610 and
L.
single-disk
antibiotic pathogens.
53:149 (1970). Steers, E., Foltz, Inocula replicating
for
test-
of rapidlyClin. Pathot.
E.
13.
5:143
Brzezinska,
M.,
zymes
E.:
which
kanamycin carrying Chenwther. King, W. Therapy
Clinical science Agents D.C.,
Montreal,
(1974).
and
Davies,
J.:
phosphorylate
Two
neomycin
in Escherichia factors. Antimicrob. 3:266 (1973). W., and Cox, C. of Urinary Tract
coli
B
and Pharmacologic Conference on and Sept.
Reprint requests treal Children’s D.:
method
susceptibility Amer. J.
L., and Graves, B. S.: apparatus of routine testing of bacterial susceptibility to antibiotics. Antibiot. Cheinother. 9:307 (1959). Price, K. B., Pursiano, P. A., DeFuria,
Chemother.
kanamycin. (1974).
Thrupp,
improved
D., and Wright, G. B.: Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics. Antimicrob. Agents
Hotten-
M.
An
M.
unpublished
with BB-K8, a new semisynthetic aminoglycoside antibiotic. J. Antibiot. 26:94 (1973). Cabana, B. E., and Taggart, J. G.: Comparative pharmacokinetics of BB-K8 and kanamycin in dogs and humans. Antimicrob. Agents Chemother. 3:478 (1973). Clarke, J. T., Libke, H. D., Regamey, C. and Kirby, W. M.: Comparative pharma-
cokinetics 9.
I.,
AMIKACIN
ing the growing
12. J.
dorf, G. Ototoxicity
7.
4:133 (1973). and Marks, M.
OF
Quebec
H3H
B.: BB-K8 Infections:
Washington,
Melvin 2300 1P3,
strains Agents
Studies. InterAntimicrobial
Chemotherapy. 1973.
to: Dr. Hospital,
enand
I. Marks, Tupper
MonStreet,
Canada.
251