TERRAMYCIN IN CHRONIC AMOEBIC

DYSENTERY

By NAJIB KHAN

Physician Incfiarge, Tata Main Hospital, Jamshedpur

Anderson and Hansen (1950) reviewed the

recent position of chemotherapy of amoebiasis. Of the various substances obtained from plants, even among synthetic drugs, emetine remains

prominent, but as a therapeutic agent suffers

from severe limitations. Useful synthetics are tri-and pentavalent arsenicals and the

halogenated oxyquinolines and chloroquine (4- aminoqunoline). Several antibiotics have lately been tried. The response of amoebic intestinal

infection to aureomycin encouraged the use of

terramycin in this refractory and prolonged infection. ?

,

- ?

Most and Van Assendelft (1950) in America

were among the first to report on the effect of

terramycin in acute amoebic dysentery, which

526 THE INDIAN MEDICAL GAZETTE [Sept., 1954

they found completely effective in 21 of their 22 cases. In a further paper (1951) they also

reported results in 54 cases and pointed out that the optimal dosage is 2 Gm. a day for 10 days. Crosnier et al (1951) from France also reported treatment of acute amoebic dysentery with terra- mycin using 3 Gm. daily for 5 days and then 2 Gm. daily for a similar period.

Noor-El-Din (1950) in Egypt treated 9 pa-

tients of chronic amoebic dysentery in relapse with terramycin. With the dosage of 15 Gm.

over a period of 5 days he found that amoebae disappeared in an average period of 2 to 4 days, associated tenesmus improved in 3 days, though diarrhoea lasted a little longer.

At that phase I started a trial of terramycin in those cases of chronic amoebic dysentery who 'had proved refractory to other forms of treat- ment. This report covers 10 patients in whom Entamoeba histolytica vegetative forms had been demonstrated in the stools and also who were

proven to be chronic not only by frequent | relapses but also from sigmoidoscope examina- tion of Uie colonic mucosal ulcers. All the

patients were kept in hospital where every ,

stool passed was inspected and periodic sigmoid- | oscopy done. j

Case I

D., male aged 43 years. Admitted on 15. 3. 52 with the history of chronic dysentery off and

on for previous 20 years. In the past hacl had several courses of emetine, retention enema, E.B.I, and many other drugs.

At the time of admission he had been in his

present relapse for 6 days and was passing 7- 9 stools daily. The stools were loose and con-

tained frank blood and mucus. Microscopic examination of stool revealed vegetative forms of E. histolytica. Sigmoidoscope examination revealed chronic ulceration of the colon with

deep dirty based ulcers scattered throughout.

He was given terramycin 0.5 Gm. four-hourly for 2 days, six-hourly on the 3rd and 4th day, after which the dose was cut down to 0.25 Gm.

four-hourly, and on the 6th day reduced to

six-hourly, which he received for 3 days. Total dose 14.5 Gm. over 8 days. From the 2nd day the stools were semiformed

and from the 6th day they were formed. E. histolytica disappeared from the 3rd day of treatment and no blood or mucus was visible

microscopically from the 4th day onwards.

Sigmoidoscopy on the 4th day after commen- cement of treatment showed ulcers to be clean-

looking with healthy bases; on the 6th day?

ulcers appeared to be filling up and on the 9th

day only redness was left over the sites of the

ulccrs. Has remained under surveillance and has kep; fit.

Case 11

S.K.C., male aged 37. Admitted to the hos-

pital on 19. 4. 52 with history of dysentery off

and on for the past 10 years. Had been hospi-

talized 4 times and had had many injections and pills orally. The present attack had lasted for 15 days when lie was passing on the average 7 motions a day with frank blood and mucus.

On admission he appeared greatly emaciated and weighed 86 lbs. He was afebrile and not

anaemic. Stool revealed E. kistolygica vegeta- tive forms and sigmoidoscope examination showed chronic amoebic ulcers with dirty gr^ bases with dark hair-like slough and undermined edges.

Terramycin was given 0.5 Gm. to start with and 0.25 Gm. four-hourly for 6 days when ^

was reduced to six-hourly and continued fQl

another 4 days. Total 13.25 gms. over 10 day5'

On the day of commencement of treatment the stool showed blood stained mucus with hai'db any faecal matter; on the next day, the stool consisted of small faecal matter with blood and mucus; on the 3rd and 4th days stool Wa

watery with blood and mucus; on the 5th a11(' 6th days stool was semiformed but blood

mucus were still present, and on the 7th da>

stool was formed and there were no blood and mucus. E. histolytica disappeared from the

stool from the 4th day onwards.

Sigmoidoscopic examination on the 3rd day treatment showed that the bases of the ulce17

were clean and margins fresh-looking; on ^lC

6th day ulcers appeared to be healing and on 9th day mucosa appeared to be healthy only some colouration left over the site 0

ulcers.

Case III

C. R., male aged 35 years. Admitted to

hospital on 30. 6. 52 with history of chron^ dysentery off and on for 5?6 years, and

h9

been taking entero-vioform tablets off and ol1'

Present relapse of his trouble had proved m?rC

Sep t.. 1954] TERRAMYCIN IN DYSENTERY : NAJIB KHAN 527

?kstinate than before and had lasted for a week ^'hen he was passing 2-3 semiformed stools

claily with blood and mucus. On admission he

appeared to be fairly well but had sallow com- l^exion. Microscopic examination revealed E.

histolytica vegetative form. Sigmoidoscope; lamination revealed chronic amoebiasis ulcers

dark hair-like slough adhering to the bases ?* the ulcers.

He was given terramycin which was started 1)1 the dosage of 0.25 Gm. four-hourly for 4

and six-hourly for 3 days. Total dose 9

over 7 days.

Siools were semiformed and contained blood

mucus till the 5th day of treatment when

?sy were formed but contained blood and mucus

jvhich continued till the 7th day when stool was lealthy. E. histolytica disappeared from the

st?ol on the 3rd day of treatment.

Sigmoidoscope examination on the 4th day of ^reatment revealed the colonic ulcers to be

^ean-looking and on the 7th day mucosa appear- healthy though still had redness over the

^lcer sites, which redness disappeared after 2

^ays.

. ^ 9 days in hospital the patient's weight had

Creased from 117 lbs. on admission to 122 lbs

Case IV

S., male aged 56. Admitted to hospital on ? 52. with history of loose motions periodi-

cally witli irritation round the anal margin and ^reat deal of distension. The trouble had

Parted with an attack of amoebic dysentery in 930 when he was treated with emetine and re- gion enema. Been treating himself with

etltero-vioform for his attacks. The present ^tack of loose motions had started 2 months

Garlier and was more resistant than the previous SlI*iilar attacks. He was passing 3 semiformed "tools daily without any blood or mucus visible

^acroscopically. ?Microscopic examination of the stool showed

? histolytica vegetative forms and blood and

Ucus. Sigmoidoscopic examination revealed

C'lronic amoebic ulcers of punched out type but unhealthy granulating base.

?He was given terramycin 0.5 Gm. six-hourly ?r 4 days and 0.25 Gm. six-hourly for subse- ClUent 3 days. Total 11 Gm. over 7 days.

^he stools were normal on the 3rd day micros- >ically as well as macroscopically and E.

histolytica was seen only on the 2nd day. Sigmoidoscopic examination on the 7th day showed ulcers to have healed.

Case V

K., female aged 38 years. Seen on 17. 8. 52

when she had history of dyspeptic symptoms and periodic attacks of diarrhoea for many

years. Stool examination had often revealed

E. histolytica. She was once given, 3 years

earlier, Diodoquin and E.B.I. A year earlier she had been given a course of aureomycin with

only temporary relief.

Present attack had started a week earlier

when she was passing daily 4-6 semiformed

stools with blood and mucus. Microscopic examination revealed E. histolytica vegetative forms. Sigmoidoscopic examination revealed

chronic amoebic ulcers.

She was given terramycin 0.5 Gm. six-hourly for 3 days, and 0.25 Gm. six-hourly for subse- quent 4 days. Total 10 Gm. over 7 days. Her

stools were normal on the 3rd day and no E. histolytica was seen, but on the 5th day onwards she developed diarrhoea and distension which

passed off a day after terramycin was stopped. ' Sigmoidoscopic examination showed healed

; mucosa on the 7th day.

Case VI

D., male aged 36; admitted on 19.8.52 with

history of chronic dysentery of 4 years' dura- tion. Has had admission in two hospitals and given emetine, retention enemas, E.B.I., etc., etc. The present attack started a month pre-

viously when he was passing formed stools but with blood and mucus, and defecation was

accompanied by griping pain. He was at work

and had really got accustomed to his bowel

troubles. Stool on examination showed E.

histolytica and sigmoidoscopy revealed chronic ulcers with shagy hair-like slough adhering to base.

He was given terramycin 0.5 Gm. six-

hourly for 4 days and 0.25 Gm. for the same

period. Total terramycin given was 12 Gm. over 8 days. His abdominal pain disappeared on the 3rd day and stools were free of E.

histolytica on the same day but blood and

mucus continued till the 6th day. Sigmoidos- copic examination on the 4th day showed ulcers to be clean and on the 7th day only redness left on the site of the old ulcers.

528 THE INDIAN MEDICAL GAZETTE [Sept., 1954

Case VII

B., male aged 54 years ; admitted on 5. 9. 52

with history of having had dysentery 10 years earlier and since then irregular bowel action

and great deal of abdominal distension. The

present attack of loose motions had lasted 2

days. Stool showed microscopic mucus and

blood and revealed E. histolytica vegetative form and sigmoidoscopy showed chronic type of amoebic ulcers with dirty base and under-

mind edges.

He was given the same dose of terramycin as Case VI. E. histolytica could not be seen

from the 3rd day when his stools were also

normal. Sigmoidoscopy showed on the 4th day clean ulcer and on 8th day healed ulcers.

Case VIII

M., male aged 45 years; admitted on 5. 10. 52 with history of dysentery 1 year previously and irregular motions since then; but he had

paid little attention to that and had taken entero-vioform tablets off and on. He started

fever 10 days before admission for which he

he received sulphadiazine and penicillin but

without effect.

On admission he was feverish and appeared toxemic and emaciated ; temperature, ranged between 99 and 101 ?F. He had liver 1"

below the costal margin, which was tender on

deep palpation. The movements of the liver

upward were diminished clinically. Blood slide

was negative for malarial parasite, and he had moderate leucocytosis (12,400) with polymorph neutrophils 72%. The stools were 'semiformed

and revealed microscopic blood, mucus and

E. histolytica. Sigmoidoscopy revealed chron- ic amoebic ulceration. He was given terra-

mycin on the same schedule as for cases nos.

6 & 7. The stools became normal on the 4th

day and no E. histolytica could be found after the 3rd day. Sigmoidoscopy showed healing ulcers on the 4th day and healed ulcers on the 7th daj^.

However, his pyrexia continued though daily maximum was 100?F. His liver tenderness

and enlargement were not affected by terra-

mycin. He was, therefore, started on chloro-

quin on the 6th day. His temperature became normal after 5 days on chloroquin and liver

was not palpable after further 6 days.

Case IX

N., male aged 39 years. Admitted on 8. 11-^ with a history of dysentery off and on for

past 6 months. Had had aureomyein at thc

beginning of his trouble which had cured hifl1

temporarily. Had had many other medicine' but was troubled by irregular bowel action-" alternate constipation and diarrhoea.

On admission he was passing semifonne^ stools with only microscopic blood and inde-

finite exaduate. Sigmoidoscopy showed chr?'

nic ulceration with granulating base and un-

dermined edges. Swarb from the ulcers taken

through the sigmoidoscope revealed E. histo-

lytica vegetative form.

He was given terramycin 0.5 Gm. six-hourl) for 3 days and 0.25 Gm. six-hourly for sub'

sequent 4 days. Total 10 Gm. over 7 day0.

From the 7th day onwards the stools we*''

normal. Sigmoidoscopy on the 4th day show? clean ulcer and on the 8th day healed ulcer-

Case X

K., male aged 48 years. Admitted on

July, 1953 with history of dysentery of ^

attacks in the past year and also dysentery '

years and 4 years earlier. The present attac

went on for about a month and he

passing 4-5 stools a day with mucus but 110

blood. Microscopic examination of stoo3

showed indefinite exduate. Sigmoidoscopy ,e

vealed chronic ulcers and swab from the ulce

showed E. histolytica vegetative form.

was given the same dose of terramycin as

case IX. Stools were normal on the ^ !

day. Sigmoidoscopy on the 4th day reveal healing ulcers and on the 7th day healed ulcC''

Discussion

In the ten patients the total dosage of terl3, mycin varies from 9 Gm. to 14.5 Gm. W Gm. (1), 13.25 Gm. (1), 12 Gm. (3), 11 G^' (1), 10 Gm. (3) and 9 Gm. (1)]; the

dosage from 1.5 Gm. to 3 Gm. to start with 2?4 days and 1 Gm. a day to finish with ^ 3?4 days. The period of treatment vai"ie

from 7 to 10 days, 5 receiving treatment 1

7 days, 4 for 8 days ; only the 1st patiel1 was given 10 days' treatment. The dos^ ̂

of terramycin has been progressively decree ̂ since the first case, the reason being the c?~

of the drug.

Sept.. 1954] TERRAMYCIN IN DYSENTERY : NA.JIB KHAN .

529

All the 10 patients responded to treatment; histolytica disappearing from the stools

between 2 and 6 days and stools becoming nor- mal jn 3 to 7 days. Sigmoidoscopy showed

^rty chronic ulcers changed into healthy ul-

Cers after 3 to 5 days, and the ulcers healed

after 7?9 days.

There was no serious toxic effect of terra-

'"ycin, but 2 patients complained of abdominal

^tension and 2 of nausea and in one patient diarrhoea set in towards the end of terramy- Un treatment but it subsided a day after ter-

^mycin was stopped. Those patients who

lad distension of the abdomen prior to treat.-

lllent were quickly relieved by terramycin. ^Ile patient who had amoebic dysentery, res-

ided to the latter condition but failed to

8how any benefit to his liver, for which clilo-

r?ciuin proved successful.

Of the 10 patients described here 8 have

^'er> followed for 1 year and 2 for nearly 2 years. ^ those followed, only one (No. 5) .

has had

"Ccasional loose motions but repeated stools

Qxainined have failed to elicit E. histolytica, and S le has not been submitted to sigmoidoscopy.

Since this study Thorris & Kessel (1953) from the Institute of Medical Research at

Papeete, Tahito, have reported successful treat- ment of 50 patients of intestinal amoebiasis

using 2 Gm. a day of terramycin for 3 days and 2.5 Gm. daily for 7 days. With this plan pain and diarrhoea ceased after 2 to 8 days; and at the end of the treatment 100 per cent., 1 month later 97 per cent., at the end of 6

months 87 per cent, of the patients had nega- tive stools.

In this connection the work of W. R. .Tones

of the I.C.I. Research Laboratories at YVimin-

slow, Lancashire, is significant as he found I hat-

using experimental amoebic infection of rats

terramycin was effective at 10 mg/Kgm given twice daily for 2 days. (Personal Communi-

cation) .

The effective dosage of terramycin found by Jones is 10 mg/Kg. given twice daily. The

dosages of 2 Gm. a day used in the cases, in

majority of the patients described is equal to

40 mg/Kg.

A Synopsical Table of Treatment of Amoebic Dysentery with Terramycin

Terramycin. StooL.

Total E. histolytica Normal Sigmoidoscopy. Dose Gm. Days. disappearance. stools. Healing Days.

Days. Days.

0.5 Gm. 4-hrly. 2 days. " 6 ? ? ?

0.25 ? 4 ? 1 days. 14.5 8 3rd 4th 9th

?, 4 ,, 3 da}^s.

0.5 Gm. stat. 0.25 "

4-hrly. 6 days 13.25 10 4th 7th 9th "

6 ? 4 ?

0.25Gm. 4-hrly. 6 days. 6 ? 4 ? 9.0 7 3rd 4th 7th

0.5 Gm. 6-hrly. 4 days. 0.25 ?? 3 ? 11 7 2nd 3rd 7th

5 0.5 Gm. 6-lirly. 3 days. 0.25 ? 4. ? 10 7 3rd 4th 7th

12 8 6th 3rd 7th

7 0.5 Gm. 6-hrly. 4 days. 12 8 3rd 3rd Sth

o' 0.25 " 4 ? 12 8 3rd 3rd Sth

12 8 3rd 4 th 7th

1q' 0.5 Gm. 6-hrly. 4 days. 10 7 X 5th 8th ' 0.25 "

? 4 ? 10 7 X 4th Sth

530 THE INDIAN MEDICAL GAZETTE [Sept., 1954

Summary A report of treatment with terramycin of 10

patients of chronic amoebic dysentery who

were refractory to several other drugs is given. Terramycin appeared to be more effective than

any other single drug or combination of drugs. The dosage recommended is 0.5 Gm. six-hourly for 3-4 days and 0.25 Gm. six-hourly for 4 days.

My thanks are due to sister Raj an for her

great interest in this study and Dr. R. M. Suri for his help. I am indebted to Messrs. Chas.

Pfizer <fc Co. who kindly supplied terramycin used in this study free of charge.

REFERENCES

Anderson, H. H., and Pharmacol. Rev., 2, 399.

Hansel, E. L. (1950).

Crcsiner, R., et al. Bull. Mem. Soc. Med. llosp. (1951). Paris, 67, 875.

Most, H., and Van Ann. New York Acad. Sci., Assendelft, F. (1950). 53, 427.

Idem (1951). Amer. J. Trop. Med., 31, 284.

Noor El Din (1950) .. ./. Roy. Egyptian Med.

.4ssoc., 34, 150.

Thooris, G. C., and Presse Med., 61, 705.

Kessel. J. F. (1953).

BIBLIOGRAPHY

Jones, W. R. (1946) .. Ann. Trop. Med. and

Parasit., 40, 150.