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

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4:133 (1973). and Marks, M.

OF

Quebec

H3H

B.: BB-K8 Infections:

Washington,

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MonStreet,

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251