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Title THERAPEUTIC TREATMENTS IN CANINE DISTEMPER WITH CHLOROMYCETIN AND AUREOMYCIN

Author(s) NAKAMURA, Ryoichi; SONODA, Mitsuo; TOO, Kimehiko; KIKUCHI, Tetsuo; NISHIOKA, Naruhito

Citation Japanese Journal of Veterinary Research, 2(2), 65-72

Issue Date 1954-08-20

DOI 10.14943/jjvr.2.2.65

Doc URL http://hdl.handle.net/2115/1655

Type bulletin (article)

File Information KJ00002372873.pdf

Instructions for use

Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP


THERAPEUTIC TREATMENTS IN CANINE DISTEMPER
WITH CHLOROMYCETIN AND AUREOMYCIN

Ryoichi NAKA:\fUHA, lVlitsuo SONODA, Kimehiko Too,


Tetsuo KIKUCHI and Naruhito NISHIOKA
Laboratory of Internal Medicine, Faculty of
Veterinary Medicine, Hokkaido University,
Sapporo, Japan
(Received for publication, June 2, 1954)

I:NTHODl;(;TION

It is already known that chloromycetin and aureomycin are not only extremely
active against Gram-negative microorganisms, but also against certain Gram-positive
microorganisms, rickettsiae, viruses and certain protozoa. So they possess a wide
range of activity against the various pathogens. They are now well established
as effective chemotherapeutic agents for m~my infectious diseases of animals.
Many authors U ,2,5, H.l!I,:~O) have found that, when these antibiotics were administered
per orally, they were very effective against disturbances caused by the secondary
infections in canine distemper, but were not beneficial in nervous type disturbances.
There have been published only few reports in Japan of therapeutic experiments
using chloromycetin(15,lS) and aureomycin(!),1(;l in complicated canine distemper. The
results of treatments were not found to be so effective in nervous type diseases
as were reported in foreign papers. With the basic studies(l,o.7, e, IT) on the thera-
peutic blood levels in chloromycetin and aureomycin treatments, it seems that
they are to be used orally ]5 to 50 mg/kg of body weight respectively divided to
3 or 4 times per day.
The present workers used these antibiotics for 35 dogs which showed
clinically canine distemper with almost always what seemed to be com-
plicated secondary infections. Workers attempted to investigate the
clinical, hematological, bacteriological, parasitological and the pathological
changes in the course of their study of these cases.

MATJ~HIALfi A.:-oD METHODS

For 15 cases chloromycetin therapy was carried out and for 20 cases aureo-
mycin therapy. Ages were 1 to ]2 months with a mean of 5.6 months. Body
weights were 8 to :)2 kg with a mean of 14.4 kg. Conditions of diseases were
severe in almost all cases. In the first diagnosis, high temperature, poor or loss
of appetite, depression, emaciation, anemia of mucous membranes, palpitation, cardiac

Jap. J. Vet. Res., Vol. 2, No.2, 1954


66 NAKAMURA, R. et al.

disturbance, nasal catarrh, pneumonia, gastroenteritis, conjunctivitis, pustular


dermatitis and nervous disturbance were found respectively.
The dosage schedules of both antibiotics ranged· from 20 to 50 mg/kg of body
weight. They were administered orally in divided doses 4 times per day for 1 to
6 days and the aureomycin ointment was used topically. As additional treatments,
glucose~5%)-ringer liquors and cardiotonicums were injected subcutaneously.
Further, stomachia and digestiva were given orally in gastroenteritis and sinapism
packing was applied to the case of pneumonia.

RESULTS OF EXl'J~l{DIENTH

From the clinical findings, patients were classified as suffering


respiratory, digestive and the nervous type sicknesses.

1. Respiratory Type Crable 1)


Fifteen cases (43 ;;;':;) were found of the respiratory type; the characteristic
symptoms were catarrhal pneumonia which was associated with high temperature,
conjunctivitis, increase in breathing or dyspnea and catarrhal rhinitis.
TABLE 1. Treatment of Respiratory Type in Canine Distemper
~---~-.-~--- - ------~,-~~--- ---------- - - - - - - - - - - - - - - -.. ------- - - - - --- - - - - - -
REMARK- DOSE DAYS
DOG. AGE BODY SEVERI- ABLE PER FOR
TOTAL
GR. SPEC. WEIGHT TY OF DOSES COURSE
No. (Mon.) (kg) DISEASE SYMP- DAY ADMI-
TOMS (mg/kg) NIST. (g) (days)

1 Sheph. 7 19 Slight P.G.C. 20 3 1.14 6


$:I 2 Setter 9 13 Severe P.C.D. 20 5 1.56 7
'';::;
Q)
~
3 Ainu 8 21 " P.C. 20 4 1.68 6
>.
4 Mongr. 7 13 " P. C. D. 30 2 0.78 2

J
-------
I 5

8
Sheph.
6* Setter
7 Sheph.
12

-- --- ------

Mongr.
4
5

9
32
11
25
----------

10
.--------
"
"
"

Severe
--- -
P.G.C.
P.C.K.
P.G.C.
---,._------

P.G.C.
_.
30
30
30
---

20
. ---
3
3
5

4
--
2.88
0.99
6.25
5
15
8
-.--------~----~

080 6

j
9 Sheph. 6 20 Slight p.e.D. 25 2 1.00 3

'5 10 Mongr. 8 14 Severe P.G.C. 25 3 1.05 5


>. 11 She ph. 4 12 Slight P.C.K. 25 2 0.60 5

~r
" 8 27 Severe P.G. 25 2 1.35 5
~ 13 " 6 20 " P.G.C.D. 50 2 2.00 5
14 " 6 20 " P.C. 50 2 2.00 6
15 " 4 11 " B. G. D. 50 2 1.10 3
------- - - - -

Note: B (Bronchial catarrh), C (Conjunctivitis), D (Pustular dermatitis),


G (Gastroenteritis), K (Keratitis), P (Catarrhal pneumonia).
No.6 died but the other dogs recovered.
Therap eutic Treatm ents in Canine Distem per with ChlO1'ornycetin
and Aureom ycin 67

Seven dogs were subjec ted to chloro myceti n therap y. When chloro
myceti n was
admin istered with a mean of 28.6 mg/kg of body weigh t per
day for 2 to [) days,
the suitab le sympt omatic treatm ents were conduc ted in accord ance
with the severi ty
of the diseases. Gener al condit ions im proved at 24 to 48 hours
and () dogs re-
covere d in 2 to 7 days, but 1 dog died in 15 days.
Aureo mycin was used for the other 8 dogs; the condit ions before
treatm ents
were almos t identic al with chloro myceti n group. Aureo mycin
was admin istered
with a mean of B:3.7 mg/kg of body weigh t per day for 2
to 4 days and the
sympt omatic treatm ents were made as in the chloro myceti n group.
All recove red
at :3 to 6 days after treatm ents.

2. Nervo us Type Cfable 2)


Fourte en cases (40/;) were clinically recogn ized as nervou s
type sickne sses.
The majori ty of patien ts in this type, sympt omatic epilepsia,
tic or signs of en-
cephal itis were associ ated with catarrh al pneum onia or gastro
enterit is. With the
except ion of antibio tic treatm ents sympt omatic therap y was carried
on.
Chloro myceti n was used for 6 dogs with a mean of :)7.5 mg/kg
of body weigh t
per day for 2 to ;3 days. Three dogs died in :{ to 8 days,
while in the other :)
TABLE 2. Treatm ent of Nervou s Type in Canine Disternper
-"- ~-- - - -- -- -- --- - - - - - - - - --- -- -. - --. - - - - --.- - - - - - - - -- - ----._- - - - - - " - - , - - - - --,--"- - --- - ---- --- --

DOG AGE BODY REMARKABLE DOSE PER DAYS FOR TOTAL


GR. SPEC. WEIGHT DAY COURSE
No. (mon.) (kg) SYMPTOMS (mg/kg ) ADMINIST. DOSES
------
~-
(gt__ J~ays)
16 Mongr. 6 15 P.G.C . 25
r:::: 3 1.125 9
'.0 17 Ainu 4 8 P.G.C. 30
(]) 3 0.72 8
e.l
>, 18 Mongr. 6 8 P.G.C. 30 3
8 0.72 4
....0 19 Akita 3 9 G.C.E . 30 2 0.54 8
0
:a
0
20 Sheph. 4 8 G.E. 50 3 1.20 12
21 Ainu 4 10 E. 50
~-----------
3 1.50 3
------- ----~
- -- -- --- - ------- - ----._------- ---- - - - - - - - - - - -
22 Monge. 6 9 B. E. 20 1 0.18 2
23 Sheph. 2 8.5 P.G.GE . 20 4

'II
0.68 5
24 Spitts 1 3 E. 20 2 0.12 3
25 Sheph. 7 26 G.C.E . 25 6 ~:L90
0
10
(])
.... 26 " 4 12 P.G.CE . 25 4 1.20 5
::l
<lj 27 " 3 10 P.G.CE . 25 6 1.50 10
28 Mongr. 4 12 G.E. 30 2 0.72 2
29 Sheph. 3 10 P.C.E. 30 5 2.50 6
- ----- ---~--
--- -----~---
-

Note: B (Bronc hial catarrh ), C (Conju nctiviti s), D (Pustu lar dermat
itis),
E (Sympt omatic epileps ia), G (Gastro enterit is), P (Catarr hal pneumo
nia).
The severit y of disease of Nos. 16-29 was serious . Nos. 18, 19,21 -29 died and
Nos. 16, 17 & 20 recove red but remain ed tic.
NAKAMURA, R. et al.
68
s and the y re-
vou s sym pto ms exc ept ing tic dis app ear ed in 8 to ]2 day
dogs, ner s wit h a me an of
cin was adm inis tere d to 8 dog
cov ere d good hea lth. Au reo my efic ial res ults wer e
per day for 1 to 6 day s. Ben
26.8 mg /kg of bod y wei ght
to 10 day s.
not obt ain ed and all died in 2

3. Dig esti ve Typ e (Ta ble 3)


prin cip ally in-
esti ve typ e sick nes ses we re fou nd in 6 dog s (17 %). The y
Dig ctiv itis and pus tula r
h ass oci ated pne um oni a, con jun
dic ated gas troe nte riti s, but wit
der mat itis . y wei ght per day
d for 2 dog s 30 mg /kg of bod
Chl oro my ceti n was adm inis tere per day for 2 to
use d for 4 dog s 20 to 30 mg /kg
for 4 day s and aur eom yci n was in the oth er
'Th e sym pto ma tic trea tme nts wer e also giv en as was don e
5 day s. all rec ove red in 3
e slig ht afte r 1 to 2 day s and
2 gro ups . The dise ase s bec am
to 6 day s.
TABLE 3. Tre atm ent of Digesti
ve Type in Canine Dis tem per
--------- REMARK- DOSE DAYS TOTAL
AGE BODY SEVERI- ABLE PER FOR COURSE
DOG
SPECIES WE IGH T TY OF SYM P- DAY ADMI- DOSES
GR. (mo n.) (kg) DISEASE (mg /kg) NIST. (g) (day s)
No. TOMS
s:: 30 4 1.80 4
3 15 Slig ht G. C. D.
b"il { 30 Kar ahu to
f-<~ 30 4 0.66 4
Sev ere G.P .c.
~ 8' 31 Mo ngr el 4 5.5

r
0
----.~
----

20 5 1.20 6
8 12 Sev ere G. C. K.
2 Mo ngr el 3
G. R. 20 2 0.60
8 15 Slig ht
» 33 Set tre
"5
S
6 18 " G. 25 2 0.90 4
g 34 Poi nter
1.56 5
~ G.C . 30 2
She phe rd 6 26 "
< 35
), K (Ke rati tis) ,
derm atit is), G (Ga stro ente ritis
Not e: C (Co njun ctiv itis) , D (Pu stul ar
tarr hal rhin itis) .
P (Ca tarr hal pne umo nia) , R (Ca
* All the anim als reco vere d.
tme nt
4. Top ica l Use of Au reo my cin Oin
ma titis and
y-f ive dog s hav ing con jun ctiv itis , 6 dog s hav ing pus tula r der
Tw ent yci n oin tme nt.
loy ed for trea tme nt wit h aur eom
8 dog s hav ing ker atit is wer e emp the y had com ple tely
the oph tha lmi c and der ma tic app lica tion s in the se pat ien ts,
By
4 day s.
rec ove red resp ecti vel y in 2 to

Hem ato log ical Fin din gs (Ta ble


4)
5.
de of the find-
re obs erv ed and com par ison s ma
The hem ato log ical cha nge s we in tab le 4,
bef ore trea tme nts and tho se of term ina tion s. As ind icat ed
ing s as of eom yci n gro up for
wer e use d and 17 dog s in aur
8 dog s in chl oro my ceti n gro up
the hem ato log ical exa min atio ns.
Therap eutic Treatm ents in Canine Distem per 'with Chloro mycetin
and AU1'eomycin 69

Before treatm ents anemi a and leucoc ytosis were appare nt


in severe cases.
Especi ally neutro philes increa sed in paralle l to leucoc yte numbe
rs and eosino philes
showe d a remar kable decrea se or disapp earanc e. These hemato
logica l finding s
were gradua lly altered to norma l condit ions in paralle l with
the advanc e of the
treatm ents in cured cases. The variati ons of neutro philes and
eosino philes have
impor tant signifi cation in observ ing the severi ty of diseas
es or knowi ng their
progno sis.
TABLE 4.
Hemato logical Findin gs
CASE TIME OF ERYTH. LEUC O.- - - ---~-PERCENTAGE IN LEUCOCYTES
-----
GR. TERMIN. EXAMI - N eut.
Nos. NA'rION (Mill.) (Thous.) - -------------------
Met. Rod. Seg. Total Ly. Mon. Eos. Bas.
s:: f Before 495.4 13.2 1.0 12.9 58.7 72.6
'.g Recove r 5 . treatm . 6.9 10.1 0.5

S
~
>. l Termin . 591.6 12.5 1.7 15.4 53.2 70.3 14.1 13.6 1.7
o~ Before
o Death 3 .[ treatm . 296.3 21.1 4.8 70.0 74.8 14.0 8.1
6 lTermi n. 381.0 27.2 7.3 80.7 87.7 5.5 7.1
J Before 524.3 13.6
s:: 1.9 58.7 60.6 32.7
.~ Recove r 11 . treatm . 3.8 2.8
>.
S
l
Termin . 657.5 11.5 2.4 55.3 57.7 31.6 4.0 6.5
o Before
0)
~
6 ; treatm . 362.0 14.0 4.1 70.7 74.8 23.1 1.8 0.3
::l Death
~
l
Termin . 373.1 15.2 1.7 83.7 88.4 4.4 7.2

TABLE 5. Bacteriological and Parasit ologica l Findin gs


FECES (Case Nos.) _!'l"AS~LPI~HA~G~j~~~!'ios.)~
DISEASE'S CASE Before
GROUP Termin al Before Termin al
TYPE Treatm ent
Nos. . - - - - - " " - -
C
1
P
6+(1*) 3+ 6+(1*) 2+
~
C
Time
P
Treatm ent
.-"---.

C
1+
P C
Time
P -- -
s:: Resp. 7
'.:;3
0) ll- 4- 1- 5·· 6-
~
>, f6+(P<*) 3+ 6+ (P<>:<)
a0 Nerv. 6 2+ 2+ 1+ 1+
0
~ l 3- 4- 4- 5- 5-
:c f2,:<>:<+ 1+ F+ 2+(1*)
U Digest. 2
l 1- 1--
---~----
.-------

f8+(2*)
-

Resp. 2+ 8+ (27:) 3+ 1+
8
s::
.~
>.
t 6- 3- 7-
a0 f6+ (l.:t) 1+ 8+(1*) 4+
Nerv. 8
0)
~ l2- 7- 4+
::l
< Digest. 4 f4+ 1+ 2+ 2+ 1+ 1+
l 3- 2- 2- 3- 3-
--------
-~~----
.~--------."---~
-- - - - - ----
Note: C (E. coli), P (Proteus)' 7: (Toxocara canis), ** (Dipyli dium caninu m).
70 NAKAM URA, R.. et al.

6. Bacter iologic al and Parasi tologic al Findin gs (Table 5)


group in gastro -
There being suspicions of second ary infecti ons by Salmonella
of all dogs. As
enterit is, bacter iologic al invest igation s were made on the feces
coli and proteu s groups by
indica ted in table 5, there were found in high degree
On the simila r
direct and enrich ment cultur es in the before and after treatm ents.
rganis ms were
exami nation s perfor med on the nasal discha rges both these microo
nella group could not
found, but they were much less than in the feces. Salmo
be found at all.
eggs of Toxo-
In the parasit ologic al findings for the feces of all dogs, parasi tic
of the hosts
cara canis in 5 and of Dipyli dium caninu m in 1 were found. Each
is.
of these parasi tic eggs was severe ly affecte d with gastro enterit

7. Pathol ogical Findin gs


obtain ed follow-
In autops y findings of 5 corpse s in nervou s type there were
of ventri cles in 5
ing pathol ogical chang es: Catarr hal pneum onia and dilatat ion
of spinal cord and
respec tively; gastro enterit is, anemi a of whole body, conges tion
ahl cystiti s and
interst itial nephri tis in 3 respec tively; acute myocarditis, catarr
fatty degen eration of liver respec tively in 1.

DISCU&~ION

tin
From the above prese nted data, clinical trials with chloro myce
have
or aureo mycin again st the patien ts excep t for the nervo us type
toms
derno nstrat ed the effect ivene ss of these antibi otics. Sever al symp
dary In-
found in the mater ials used were consi dered due to the secon
fectio ns.
most
and other workers(R,21) report ed AI. bronchisepticus to be the
FERRy( :l,4)
specie s of strepto cocci,
freque ntly isolate d organi sm, furthe r they stated that
Recen tly HSIUNG
staphylococci and even E. coli or S. enteri tidis were found.
specie s of strepto cocci were the
et al. stated that Micr. pyogenes var. albus and
discha rges from
comm onest organi sms found in serous and mucop urulen t ocular
dogs affecte d with distem per.
na-
In the prese nt biological studie s, befor e treatm ents and termi
prote us
tions for feces and nasal disch arges , there were found coli and
s of the
group s, but other micro organ isms were not found. The result
n1ethods
prese nt exam inatio ns are consi dered to be influe nced by the
tin and
of cultu res. It will be thoug ht from the data that chloro myce
in the
aureo mycin were not very effect ive for 2 of the group s found
prese nt classifications.
and enceph a-
Fourte en nervou s patien ts showe d marke d sympt omatic epilep sia
Aureom ycin 71
TheTapeutic l'rcatm ents 'in Canine DistempeT with Chloromycetin and

nervou s sympt oms


litic signs. From many years ago, it has been accept ed that if
and the mortal ity is
appear in canine distem per there are on therap eutic agents
been discov ered up to
high. Thera peutic metho ds in nervou s distem per have not
date.
tible to these
On the other hand, it is said that many of the viruse s are suscep
to be effecti ve in infecti ons where the
antibiotics,(l!),~o.:,~) but they do not appea r
distem per viruse s
viruse s are very small. HEAGA N and BRUCK NER report ed that the
rment of electro n
are round and have a mean diame ter of 21 m.u by direct measu
ible to inhibit the
microg raphs. On the basis of their study it may be imposs
activit y of the distem per virus by chloro mycet in and aureom ycin.

SlJ~I:\IAHY

d
The worke rs tried to make thera peuti c exper iment s in comp licate
aureo -
canin e distem per with oral adulin istrati oll of chloro myce tin and
s.
mycin. The result s thus obtain ed may be summ arized as follow
the
1. Chlor omyc etin was an effect ive agent in contro lling
It was
secon dary pneum onia and gastro enter itis of canin e distem per.
mg/k g
admin istere d at the rate of 25 to 50 mg/k g with a mean of 30.3
5 days.
of body weigh t in divide d doses to 4 times per day for 2 to
dary
2. Aureo mycin was also an effect ive agent for the secon
dosag e
invad ers in canin e disten lper as was chloro myce tin. The
mg/k g of
sched ules range d from 25 to 50 mg/k g with a ll1ean of 31.3
body weigh t divid ed into 4 times per day for 2 to 5 days.
the
3. Chlor omyc etin and aureo nlycin have no effect ivene ss for
nt ex-
nervo us type of canin e distem per insofa r as shown in the prese
perim ents.
for
4. Topical use of aureo mycin ointm ent 1 or 2 times per day
pustu lar
2 to 4 days has a dram atic value for conju nctivi tis and
derm atitis accom panyi ng canin e distem per.
is
5. For the treatm ents in comp licate d canin e distem per, there
neede d also sympt Olnat ic therap ies.
there
6. By MULLEl t and S. S. media in feces and nasal disch arges
no patho -
were found coli and prote us group s which seeme d to have
gens; other micro organ isms were not found . Resea rches on the
clinic.
secon dary invad ers using other cultu res are now in progr ess in our
es
7. Varie ties of hema tologi cal findings, espec ially in neutr ophil
sever ity
and eosinophiles, have impo rtant signif icance in obser ving the
of diseas es and to make prong noses .
72 NAKAMURA, R. et al.

The author s would like to expres s their cordial gratitu de to


Prof. YAMAGIWA, Prof.
HIRATO and"to Prof. MIURA who provide d the patholo gical or
bacteri ologica l finding s and
many other kindly advices . Furthe r they are gratefu l to Sankyo
, Takeda and Lederle Co.
Ltd., who willing ly supplie d drugs.

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(1952)].
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