COLLARGOL: CLINICAL
ON
EXPERIMENTS ITS ANTISEPTIC ACTION.
M. Fortescue-Brickdale,
J.
Registrar (From
REVIEW OF SOME OF ITS
A
APPLICATIONS, WITH
the
and
Pathologist
Bacteriological
to the
M.D.
M.A.,
Royal Hospital for
Oxon.,
Sick Children and
Women, Bristol.
Research Laboratory, University
College, Bristol.)
The purpose of the present article is to review and criticise the results obtained by the internal use of silver in diseases which may
broadly The
cations.
be said to cases
belong
hereafter
of conditions this
variety underlying or as
to the group of bacterial intoxi-
to be
quoted
has been
drug
will show in what
employed,
but
a
the
indication has in all been the presence, either proved assumed, of bacteria and their products in the system. Silver an
antiseptic
Dresden,
who in
was
brought
1897
made
a
into
prominence by Crede of on the subject to
communication
Congress of Medicine at Moscow. He first (citrate and lactate) as wound dressings, and later employed the substance known as collargol, which he thought had a direct antiseptic action in internal diseases. I propose now to give a short account of the physical and physiological properties of this substance, then a description of the mode of its application, a summary of the clinical results, and lastly an account of the experimental evidence as to its utility. the International
used salts of silver
22
Vol. XXI.
No. 82.
338
DR.
J. M. FORTESCUE-BRICKDALE
Physical Properties.?Collargol (an allotropic modification of silver) is a blackish brittle substance with a slight metallic lustre, capable of forming an opaque black liquid when rubbed Weaker up with distilled water up to a proportion of 1 in 25. in and all leave an irridescent solutions are light brown colour, film
on
drying.
well in the dark, " solution."
It is not very especially if
stable, but a
is said to
keep fairly
little albumin is added to the
Physiological Properties.?Brunner
states that
leucocytosis injection, which attains its maximum in twenty-four hours, and has disappeared at the end of two days. Beyer states that in rabbits (after the injection of large doses) collargol may be found in the blood in eight to ten hours; he also found it in various organs eight or It was excreted mainly by the intestine, and nine days later. find it in the kidney, he considers that it is did not he although
is established six hours after
an
a
intravenous
also eliminated in that way. Blood retains the colloid silver in solution remarkably well, and prevents its precipitation or conversion into the ordinary metallic form. All observers agree that it is
rapidly eliminated,
and that
no
poisonous symptoms
ever occur.
Methods of
Application.?Collargol
has been
employed
in
veterinary medicine. For internal use in infective diseases two forms are prepared: (1) An ointment containing
human and
15 per cent, of the drug, a few grams of which are rubbed into the carefully cleaned healthy skin once a day or oftener; (2) A
freshly prepared, as required, from the solid intravenous injection. The strength of this solution is usually 1 per cent., 5 or 10 cc. (sometimes more) being injected once a day, or at intervals of two or three days.
solution
to
substance
be
for
Clinical Results.?I have been able to collect forty-four cases from the literature in which a clinical account, sufficiently full I shall divide them into five for critical purposes, is given. classes, for practical purposes, as follows :? I. Cases in which other treatment was given which may be credited with the results (six cases):?
fairly
with recovery.
In-
1.
Netter.
unction +
Rheumatic
salicylates.
pericarditis
ON
"
COLLARGOL.
339
A case diagnosed as general tuberculosis, Brainerd. subacute symptoms suggestive of meningitis. Improvement began after one month. Inunctions + very careful hygiene, tonics, etc. A choroidal tubercle vanished during 2.
with
treatment.
Injections
Anthrax.
3. Fischer. ment of
+ usual
pustule.
surgical
treat-
Recovery. Old standing tuberculous knee, clearing up 4. Muller. quickly under injections. Although not mentioned, accessory
is certain, as patient was removed from bad surinto hospital. Cerebro-spinal meningitis. Lumbar puncture 5. Netter.
treatment
roundings
+ inunctions. 6. Dvoretzki.
Inunctions + usual
Furunculosis.
surgical
treatment.
II. Cases in which
cases)
a
doubt exists
to the
as
diagnosis (four
:?
Netter. Broncho-pneumonia, which cleared up (pneuPhthisis subsequently diagnosed (although tubercle bacilli were never found) owing to signs of cavitation at one 1.
mococcal).
apex. 2.
Meier.
Case
operated
on
for mastoid disease.
After
remained high, but fell in three days (inunctions). Lateral sinus thrombosis was diagnosed. 3. Haase. Amputation with post operative fever. Stump appeared healthy. Temperature fell after one injection. Septicaemia diagnosed. Fractured pelvis and other injuries. Eight 4. Crede. weeks after injury rigors occurred, which ceased after two
operation temperature
injections.
Septic peritonitis diagnosed.
III. Cases in which the influence of collargol nature of the case, doubtful (five cases) :? 1.
2.
initial
Pneumococcal
Netter.
day (inunctions). Netter.
Enteric in
(inunctions).
3. Dvoretzki. An
(apparently during injections. 5. Netter.
child
Erysipelas.
unctions. 4. Crede.
a
Crisis
pneumonia. (no
"
widal
Temperature normal
symptoms.
"
in
Recovery
is, from on
done).
sixth
Severe
nineteen
after
the
three
days in-
case of phthisis, in which only) improvement occurred after
advanced
one
week
Scarlet fever.
A
case
severe
with recovery
(inunctions). IV. Cases in which
collargol
was
inert
(eighteen cases):?
1-6. Strohmayer. Puerperal fever. pyaemia Two recovered under energetic
Three
surgical
died of treatment.
dr.
34-0
j.
m.
fortescue-brickdale
One case in which temNo effect observed after inunctions. perature rose after the inunctions were discontinued, though they had no marked effect otherwise. Death from general
peritonitis.
7-8. Strohmayer.
9. Strohmayer. 10. 11.
quently
Streptococcal
empyema.
Glandular abscesses after scarlet.
Strohmayer. Strohmayer.
Furunculosis (yielded to incisions Popliteal abscess. Amputation
easily). subse-
necessary.
Middle ear suppuration after scarlet Death. Tuberculous meningitis. 13-18. Netter. (These cases not reported, but Netter states that inunctions were inert.) 12.
Strohmayer.
fever. are
V. Cases
favourably
influenced
cases):? 1-3. S. S.
Jones.
by collargol (seventeen
Septic endometritis;
Polak.
Septic
These cases Parametritis. The general (toxaemic) occurred after delivery or abortion. Adequate stimulant treatment, etc. symptoms were severe.
endometritis
Heinsheimer.
;
only was local treatment discontinued when begun. In all the inunctions were frequent at first (more frequent than in Strohmayer's cases), and improveIn none was there direct evidence of general ment rapid. In
Jones'
inunctions
case
were
septicaemia
or
pyaemia.
Empyema. Complete aspiration impos4. Witthauer. sible. Rapid recovery under inunctions (12 days). In Furunculosis. four and Werler. 5-9. Dvoretzki In one local local treatment failed till inunctions were begun. treatment not mentioned. In these symptoms Klotz and Wenkelbach. 10-12. certainly pointed to septic endocarditis. A fall of temperature and general improvement followed a few days' treatment with S. pyogenes albus said to have been isolated from injections. blood in one case, but this organism is practically always due to a contamination of the culture. Perinephric abscess. Operation. Wound 13. Netter. healed five days after removal of tube. A case which had resisted 14. Niessen. Chronic arthritis. No more attacks of pain occurred treatment for some time. A peculiar organism isolated from after twenty daily inunctions. blood, but not proved to be aetiological. 15. Dvoretzki. Osteomyelitis. Six months' history of pain and discharge. Complicated by enteritis. Improvement in general condition after a week (inunctions). Acute rheumatism, with pleuritic effusion and 16. Crede. pericarditis. Ordinary treatment had failed, but improvement Patient then got occurred after two injections (48 hours). worse, but after three injections (10 days) convalescence was established.
ON
COLLARGOL.
34-1
Extensive gangrene. Incisions had been 17. Crede. General symptoms improved, and temperature fell after made. each injection. are
For critical purposes the first fifteen cases (Classes I.?III.) obviously useless. In the remainder, seventeen are favour-
able to the
six
cases, a
which
cases,
sible)
efficiency of collargol are
It
seems
therefore, collargol had temperature.
reduction of
have influenced
a
but
unreported,
unfavourable.
are
and
clear that in about half the seen
in
has it been proved
to
influence?principally
an
In
eighteen (including Netter's being negative are admis-
no case
general pysemic
or
septicemic condition,
of Wenkelbach's, in which there were emboli a septic had have which may origin. In the pysemic case recorded by Strohmayer, in which the temperature rose after except in
the
one case
inunctions
symptoms
were
Experimental action
ments of the two
during
their
Evidence.?Crede in
Brown in America
inhibitory
discontinued,
had occurred
on
have the
proved
growth
no
amelioration
of the
application. Germany
and Bolton and
that various metals have
of bacterio in vitro.
last-named observers
are
The
an
experi-
remarkably exact and the metals according
Crede has classified very fully reported. to their inhibitory power, silver standing fourth
on his list. The method adopted is to place a piece of metal on the surface of an inoculated Petri dish and observe the ring round it, on which Crede states that a piece of silver few or no colonies appear.
wound is
gradually absorbed, whereas this aseptic wound. I have only been able to of animal experiments. find two accounts Beyer inoculated two rabbits with anthrax, and injected one subcutaneously and Both the other intravenously with a large dose of collargol. placed
on
a
septic
does not occur on an
recovered, but he makes no mention of a control animal. Trommsdorff calculated the dose of collargol for rabbits at He injected twenty-one rabbits in all, using ?oo25-,oo59 gm.
organisms of swine erysipelas and swine fever. The injections were given once or twice daily, and were begun in different animals either immediately or six, twelve, twenty-four Ten animals received aud thirty-six hours after inoculation. ten times the amount of collargol their weight assigned to them. the
DR.
342
J. Mf FORTESCUE-BRICKDALE
weighed on an average 2,500 gms. Control animals and his results in every case were negative. were used, I have been unable to find details of any test tube experiThe animals
the actual germicidal power of collargol, though it is stated to have inhibited S. pyogenes aureus, a fairly resistant organism, in solutions of *05 per cent, to *oi per cent. With a ments as to
view
the effect of
collargol as an antiseptic, I have allowed to following experiments at the Bacteriological Laboratory of University College by the kindness of Professor Stanley Kent:? to
testing
been
A stock solution
(50
Crede's directions, and the
the
carry out
dark at
were
all of
which
room
cent.) was prepared according carefully kept in a stoppered bottle per
to
in
The cultivations of bacteria
temperature.
hours' growth, except those of anthrax, broth cultivations of 16-18 hours' growth. This
twenty-four
were
practically prevented the collargol has more effect
formation of spores. on
Crede states that
less virulent strains of cocci.
It is
noted, therefore, that my cultivations were prepared from ordinary laboratory strains of no especial virulence. Broth
to be
tubes
were
prepared containing
4
cc.
each,
to
which
1
cc.
of
strength of the latter being required point. These broth and collargol tubes were then inoculated with the organisms, incubated at 37? C. for twenty-four hours and examined. The stronger solutions were so opaque that no growth (if present) could be seen. Coverslip preparations were therefore necessary; in weaker solutions these were also made to test the purity of
solutions of collaigol varied to
bring
the growth. 1
per
was
The results cent,
were as
follows:?
No
collargol.
S. pyogenes aureus, ?1
the
added,
the total to the
or
of
growth
B.
anthracis,
strep, pyogenes.
collargol. No growth of strep, pyogenes. Occasionally slight growth of B. anthracis and S. per
cent,
pyogenes
aureus.
collargol. No growth of strep, pyogenes. Growth of B. anthracis and S. pyogenes aureus.
?05 per cent,
?03 per cent,
collargol.
No
growth
ox
strep, pyogenes.
ON
of B.
Growth
in
(except
one
all three Over
?addition
anthracis
343
and
S.
aureus
pyogenes
case).
and
per cent,
?02
COLLARGOL.
*oi
per
cent,
Growth of
collargol.
organisms.
In seventy tubes were inoculated in this series. this, four glycerine Agar plates were prepared and
to
mixed cultivation of streptococcus pyogenes staphylococcus pyogenes aureus. After twenty-four hours' growth at 370 C., a solution of collargol was poured over the
inoculated with
a
and
plate, and further incubation for twenty-four 370 C. allowed. At the end of this time the surface of Agar had become softened, and from the supernatant
surface of the
hours the
at
liquid
broth tubes
inoculated and incubated in the
were
The results with
manner.
different
strengths
of
same
collargol
were :? 1
per cent,
*5
?05 In has
collargol,
,,
,,
j>
>>
>>
>>
>>
of *5 per cent, and
bactericidal effect
on
strep, pyogenes
grow
In
of
living blood plasma
collargol
is
S. pyogenes
inversely
act; and
amount
Crede,
as
solution. and bactericidal power broth cultivation medium.
inhibitory
than in
a
approximate
estimate
antiseptics varies of albumin in the medium in which
noted
above,
states that metals
than non-virulent
virulent cultivations less regard to the amount of of intravenous
organisms
per cent., and B. anthracis will
shown that the power of all
has
with the
an
the
probably less
Behring they
under, collargol or
hours' exposure ; both these
after
twenty-four freely in solutions of -02 always grow in a -05 per cent,
aureus
>} >>
solutions, therefore,
no
growth. growth of both organisms.
no
readily collargol can
injections.
be
The
ones.
inhibit With
in solution in the blood,
only
in the
case
made,
and that
only
right ventricle in an average the weight of silver, therefore,
man contains about 100 cc.; carried into it with each pulse wave represents the percentage It is solution it will pump into the pulmonary circulation. possible to inject 1 cc. of solution per pulse beat, and this in
COLLARGOL.
344 most
therefore
pumped
At the outset of its
cent.
the
would represent -oi gm. collargol. The percentageout by the right ventricle would be *oi per
cases
strength
of
delicate
through the body, therefore, certainly be insufficient to inhibit
course
would
collargol organism
such as streptococcus pyogenes. The general conclusions which may therefore be drawn the action of collargol are as follows :?
even a
(1)
as
to.
collargol has never been introduced into the body sufficiently large quantities to produce an antiseptic solution in the mass of the blood.
That in
(2)
effect
(3)
That
as
artificial
on
far
effect in
That
a
as
the above
proved
caemia in
(4)
strongly against its having septicaemia in rabbits.
That the evidence is
cases
cases
of
show it has
any
not had any
general pyaemia
septi-
or
man.
fall of temperature and
condition
improvement
in the
sometimes comparable general produced by antipyretics and hydrotherapy has been, observed in some cases of general toxaemia, but that in half the recorded
proved
to
cases
that
admissible
as
evidence it.
inert.
REFERENCES. Crede.?Berl. klin. Wchnschr., 1901, xxxviii. 941. Beyer.?Miinchen. vied. Wchnschr., 1902, xlix. 331. Brunner.?Quoted by Beyer. Netter.?Bull. Soc. med d. Hop., Dec., 1902. Brainerd.?South Calif. Pract., August, 1900. Fischer.?-Miinchen. med. Wchnschr., 1901, xlviii. 1879. Muller.?Berl. klin. Wchnschr., March 13th, 1902. Dvoretzki.?Therap. Monatshr., 1900, No. 3. Meier.?Munchen. med. Wchnschr., 1899, xlvi. 1411. Haase.?Ibid., 1902, xlix. 331 (discussion). Strohmayer.?Ibid., 1900, xlvii. 1064. S. S. Jones.?Obstetrics, Feb. 2nd, 1899.
Polak.?Pcst-Graduate, 1900, xv. 475. Heinsheimer.?Allg. med. Centr.-Ztg., 1900, No. 49. Witthauer.?Diakonissen Anstalt. Halle a. S., 1900. Klotz.?Deutsche med. Wchnschr., 1902, 524.
Wenkelbach.?Schmidt's Jarhb., cclxxii. 162. Niessen.?Wien. med. Wchnschr., 1899, Nos. 44 and 45. Bolton.?Tr. Assoc. Am. Physicians, 1894, ix. 174. Bolton & Brown.?Ibid., 1897, x*i- 4^8Trommsdorff.?Munchen. med. Wchnschr, 1902, xlix. 1300.
ON
EXPERIMENTS ITS ANTISEPTIC ACTION.
M. Fortescue-Brickdale,
J.
Registrar (From
REVIEW OF SOME OF ITS
A
APPLICATIONS, WITH
the
and
Pathologist
Bacteriological
to the
M.D.
M.A.,
Royal Hospital for
Oxon.,
Sick Children and
Women, Bristol.
Research Laboratory, University
College, Bristol.)
The purpose of the present article is to review and criticise the results obtained by the internal use of silver in diseases which may
broadly The
cations.
be said to cases
belong
hereafter
of conditions this
variety underlying or as
to the group of bacterial intoxi-
to be
quoted
has been
drug
will show in what
employed,
but
a
the
indication has in all been the presence, either proved assumed, of bacteria and their products in the system. Silver an
antiseptic
Dresden,
who in
was
brought
1897
made
a
into
prominence by Crede of on the subject to
communication
Congress of Medicine at Moscow. He first (citrate and lactate) as wound dressings, and later employed the substance known as collargol, which he thought had a direct antiseptic action in internal diseases. I propose now to give a short account of the physical and physiological properties of this substance, then a description of the mode of its application, a summary of the clinical results, and lastly an account of the experimental evidence as to its utility. the International
used salts of silver
22
Vol. XXI.
No. 82.
338
DR.
J. M. FORTESCUE-BRICKDALE
Physical Properties.?Collargol (an allotropic modification of silver) is a blackish brittle substance with a slight metallic lustre, capable of forming an opaque black liquid when rubbed Weaker up with distilled water up to a proportion of 1 in 25. in and all leave an irridescent solutions are light brown colour, film
on
drying.
well in the dark, " solution."
It is not very especially if
stable, but a
is said to
keep fairly
little albumin is added to the
Physiological Properties.?Brunner
states that
leucocytosis injection, which attains its maximum in twenty-four hours, and has disappeared at the end of two days. Beyer states that in rabbits (after the injection of large doses) collargol may be found in the blood in eight to ten hours; he also found it in various organs eight or It was excreted mainly by the intestine, and nine days later. find it in the kidney, he considers that it is did not he although
is established six hours after
an
a
intravenous
also eliminated in that way. Blood retains the colloid silver in solution remarkably well, and prevents its precipitation or conversion into the ordinary metallic form. All observers agree that it is
rapidly eliminated,
and that
no
poisonous symptoms
ever occur.
Methods of
Application.?Collargol
has been
employed
in
veterinary medicine. For internal use in infective diseases two forms are prepared: (1) An ointment containing
human and
15 per cent, of the drug, a few grams of which are rubbed into the carefully cleaned healthy skin once a day or oftener; (2) A
freshly prepared, as required, from the solid intravenous injection. The strength of this solution is usually 1 per cent., 5 or 10 cc. (sometimes more) being injected once a day, or at intervals of two or three days.
solution
to
substance
be
for
Clinical Results.?I have been able to collect forty-four cases from the literature in which a clinical account, sufficiently full I shall divide them into five for critical purposes, is given. classes, for practical purposes, as follows :? I. Cases in which other treatment was given which may be credited with the results (six cases):?
fairly
with recovery.
In-
1.
Netter.
unction +
Rheumatic
salicylates.
pericarditis
ON
"
COLLARGOL.
339
A case diagnosed as general tuberculosis, Brainerd. subacute symptoms suggestive of meningitis. Improvement began after one month. Inunctions + very careful hygiene, tonics, etc. A choroidal tubercle vanished during 2.
with
treatment.
Injections
Anthrax.
3. Fischer. ment of
+ usual
pustule.
surgical
treat-
Recovery. Old standing tuberculous knee, clearing up 4. Muller. quickly under injections. Although not mentioned, accessory
is certain, as patient was removed from bad surinto hospital. Cerebro-spinal meningitis. Lumbar puncture 5. Netter.
treatment
roundings
+ inunctions. 6. Dvoretzki.
Inunctions + usual
Furunculosis.
surgical
treatment.
II. Cases in which
cases)
a
doubt exists
to the
as
diagnosis (four
:?
Netter. Broncho-pneumonia, which cleared up (pneuPhthisis subsequently diagnosed (although tubercle bacilli were never found) owing to signs of cavitation at one 1.
mococcal).
apex. 2.
Meier.
Case
operated
on
for mastoid disease.
After
remained high, but fell in three days (inunctions). Lateral sinus thrombosis was diagnosed. 3. Haase. Amputation with post operative fever. Stump appeared healthy. Temperature fell after one injection. Septicaemia diagnosed. Fractured pelvis and other injuries. Eight 4. Crede. weeks after injury rigors occurred, which ceased after two
operation temperature
injections.
Septic peritonitis diagnosed.
III. Cases in which the influence of collargol nature of the case, doubtful (five cases) :? 1.
2.
initial
Pneumococcal
Netter.
day (inunctions). Netter.
Enteric in
(inunctions).
3. Dvoretzki. An
(apparently during injections. 5. Netter.
child
Erysipelas.
unctions. 4. Crede.
a
Crisis
pneumonia. (no
"
widal
Temperature normal
symptoms.
"
in
Recovery
is, from on
done).
sixth
Severe
nineteen
after
the
three
days in-
case of phthisis, in which only) improvement occurred after
advanced
one
week
Scarlet fever.
A
case
severe
with recovery
(inunctions). IV. Cases in which
collargol
was
inert
(eighteen cases):?
1-6. Strohmayer. Puerperal fever. pyaemia Two recovered under energetic
Three
surgical
died of treatment.
dr.
34-0
j.
m.
fortescue-brickdale
One case in which temNo effect observed after inunctions. perature rose after the inunctions were discontinued, though they had no marked effect otherwise. Death from general
peritonitis.
7-8. Strohmayer.
9. Strohmayer. 10. 11.
quently
Streptococcal
empyema.
Glandular abscesses after scarlet.
Strohmayer. Strohmayer.
Furunculosis (yielded to incisions Popliteal abscess. Amputation
easily). subse-
necessary.
Middle ear suppuration after scarlet Death. Tuberculous meningitis. 13-18. Netter. (These cases not reported, but Netter states that inunctions were inert.) 12.
Strohmayer.
fever. are
V. Cases
favourably
influenced
cases):? 1-3. S. S.
Jones.
by collargol (seventeen
Septic endometritis;
Polak.
Septic
These cases Parametritis. The general (toxaemic) occurred after delivery or abortion. Adequate stimulant treatment, etc. symptoms were severe.
endometritis
Heinsheimer.
;
only was local treatment discontinued when begun. In all the inunctions were frequent at first (more frequent than in Strohmayer's cases), and improveIn none was there direct evidence of general ment rapid. In
Jones'
inunctions
case
were
septicaemia
or
pyaemia.
Empyema. Complete aspiration impos4. Witthauer. sible. Rapid recovery under inunctions (12 days). In Furunculosis. four and Werler. 5-9. Dvoretzki In one local local treatment failed till inunctions were begun. treatment not mentioned. In these symptoms Klotz and Wenkelbach. 10-12. certainly pointed to septic endocarditis. A fall of temperature and general improvement followed a few days' treatment with S. pyogenes albus said to have been isolated from injections. blood in one case, but this organism is practically always due to a contamination of the culture. Perinephric abscess. Operation. Wound 13. Netter. healed five days after removal of tube. A case which had resisted 14. Niessen. Chronic arthritis. No more attacks of pain occurred treatment for some time. A peculiar organism isolated from after twenty daily inunctions. blood, but not proved to be aetiological. 15. Dvoretzki. Osteomyelitis. Six months' history of pain and discharge. Complicated by enteritis. Improvement in general condition after a week (inunctions). Acute rheumatism, with pleuritic effusion and 16. Crede. pericarditis. Ordinary treatment had failed, but improvement Patient then got occurred after two injections (48 hours). worse, but after three injections (10 days) convalescence was established.
ON
COLLARGOL.
34-1
Extensive gangrene. Incisions had been 17. Crede. General symptoms improved, and temperature fell after made. each injection. are
For critical purposes the first fifteen cases (Classes I.?III.) obviously useless. In the remainder, seventeen are favour-
able to the
six
cases, a
which
cases,
sible)
efficiency of collargol are
It
seems
therefore, collargol had temperature.
reduction of
have influenced
a
but
unreported,
unfavourable.
are
and
clear that in about half the seen
in
has it been proved
to
influence?principally
an
In
eighteen (including Netter's being negative are admis-
no case
general pysemic
or
septicemic condition,
of Wenkelbach's, in which there were emboli a septic had have which may origin. In the pysemic case recorded by Strohmayer, in which the temperature rose after except in
the
one case
inunctions
symptoms
were
Experimental action
ments of the two
during
their
Evidence.?Crede in
Brown in America
inhibitory
discontinued,
had occurred
on
have the
proved
growth
no
amelioration
of the
application. Germany
and Bolton and
that various metals have
of bacterio in vitro.
last-named observers
are
The
an
experi-
remarkably exact and the metals according
Crede has classified very fully reported. to their inhibitory power, silver standing fourth
on his list. The method adopted is to place a piece of metal on the surface of an inoculated Petri dish and observe the ring round it, on which Crede states that a piece of silver few or no colonies appear.
wound is
gradually absorbed, whereas this aseptic wound. I have only been able to of animal experiments. find two accounts Beyer inoculated two rabbits with anthrax, and injected one subcutaneously and Both the other intravenously with a large dose of collargol. placed
on
a
septic
does not occur on an
recovered, but he makes no mention of a control animal. Trommsdorff calculated the dose of collargol for rabbits at He injected twenty-one rabbits in all, using ?oo25-,oo59 gm.
organisms of swine erysipelas and swine fever. The injections were given once or twice daily, and were begun in different animals either immediately or six, twelve, twenty-four Ten animals received aud thirty-six hours after inoculation. ten times the amount of collargol their weight assigned to them. the
DR.
342
J. Mf FORTESCUE-BRICKDALE
weighed on an average 2,500 gms. Control animals and his results in every case were negative. were used, I have been unable to find details of any test tube experiThe animals
the actual germicidal power of collargol, though it is stated to have inhibited S. pyogenes aureus, a fairly resistant organism, in solutions of *05 per cent, to *oi per cent. With a ments as to
view
the effect of
collargol as an antiseptic, I have allowed to following experiments at the Bacteriological Laboratory of University College by the kindness of Professor Stanley Kent:? to
testing
been
A stock solution
(50
Crede's directions, and the
the
carry out
dark at
were
all of
which
room
cent.) was prepared according carefully kept in a stoppered bottle per
to
in
The cultivations of bacteria
temperature.
hours' growth, except those of anthrax, broth cultivations of 16-18 hours' growth. This
twenty-four
were
practically prevented the collargol has more effect
formation of spores. on
Crede states that
less virulent strains of cocci.
It is
noted, therefore, that my cultivations were prepared from ordinary laboratory strains of no especial virulence. Broth
to be
tubes
were
prepared containing
4
cc.
each,
to
which
1
cc.
of
strength of the latter being required point. These broth and collargol tubes were then inoculated with the organisms, incubated at 37? C. for twenty-four hours and examined. The stronger solutions were so opaque that no growth (if present) could be seen. Coverslip preparations were therefore necessary; in weaker solutions these were also made to test the purity of
solutions of collaigol varied to
bring
the growth. 1
per
was
The results cent,
were as
follows:?
No
collargol.
S. pyogenes aureus, ?1
the
added,
the total to the
or
of
growth
B.
anthracis,
strep, pyogenes.
collargol. No growth of strep, pyogenes. Occasionally slight growth of B. anthracis and S. per
cent,
pyogenes
aureus.
collargol. No growth of strep, pyogenes. Growth of B. anthracis and S. pyogenes aureus.
?05 per cent,
?03 per cent,
collargol.
No
growth
ox
strep, pyogenes.
ON
of B.
Growth
in
(except
one
all three Over
?addition
anthracis
343
and
S.
aureus
pyogenes
case).
and
per cent,
?02
COLLARGOL.
*oi
per
cent,
Growth of
collargol.
organisms.
In seventy tubes were inoculated in this series. this, four glycerine Agar plates were prepared and
to
mixed cultivation of streptococcus pyogenes staphylococcus pyogenes aureus. After twenty-four hours' growth at 370 C., a solution of collargol was poured over the
inoculated with
a
and
plate, and further incubation for twenty-four 370 C. allowed. At the end of this time the surface of Agar had become softened, and from the supernatant
surface of the
hours the
at
liquid
broth tubes
inoculated and incubated in the
were
The results with
manner.
different
strengths
of
same
collargol
were :? 1
per cent,
*5
?05 In has
collargol,
,,
,,
j>
>>
>>
>>
>>
of *5 per cent, and
bactericidal effect
on
strep, pyogenes
grow
In
of
living blood plasma
collargol
is
S. pyogenes
inversely
act; and
amount
Crede,
as
solution. and bactericidal power broth cultivation medium.
inhibitory
than in
a
approximate
estimate
antiseptics varies of albumin in the medium in which
noted
above,
states that metals
than non-virulent
virulent cultivations less regard to the amount of of intravenous
organisms
per cent., and B. anthracis will
shown that the power of all
has
with the
an
the
probably less
Behring they
under, collargol or
hours' exposure ; both these
after
twenty-four freely in solutions of -02 always grow in a -05 per cent,
aureus
>} >>
solutions, therefore,
no
growth. growth of both organisms.
no
readily collargol can
injections.
be
The
ones.
inhibit With
in solution in the blood,
only
in the
case
made,
and that
only
right ventricle in an average the weight of silver, therefore,
man contains about 100 cc.; carried into it with each pulse wave represents the percentage It is solution it will pump into the pulmonary circulation. possible to inject 1 cc. of solution per pulse beat, and this in
COLLARGOL.
344 most
therefore
pumped
At the outset of its
cent.
the
would represent -oi gm. collargol. The percentageout by the right ventricle would be *oi per
cases
strength
of
delicate
through the body, therefore, certainly be insufficient to inhibit
course
would
collargol organism
such as streptococcus pyogenes. The general conclusions which may therefore be drawn the action of collargol are as follows :?
even a
(1)
as
to.
collargol has never been introduced into the body sufficiently large quantities to produce an antiseptic solution in the mass of the blood.
That in
(2)
effect
(3)
That
as
artificial
on
far
effect in
That
a
as
the above
proved
caemia in
(4)
strongly against its having septicaemia in rabbits.
That the evidence is
cases
cases
of
show it has
any
not had any
general pyaemia
septi-
or
man.
fall of temperature and
condition
improvement
in the
sometimes comparable general produced by antipyretics and hydrotherapy has been, observed in some cases of general toxaemia, but that in half the recorded
proved
to
cases
that
admissible
as
evidence it.
inert.
REFERENCES. Crede.?Berl. klin. Wchnschr., 1901, xxxviii. 941. Beyer.?Miinchen. vied. Wchnschr., 1902, xlix. 331. Brunner.?Quoted by Beyer. Netter.?Bull. Soc. med d. Hop., Dec., 1902. Brainerd.?South Calif. Pract., August, 1900. Fischer.?-Miinchen. med. Wchnschr., 1901, xlviii. 1879. Muller.?Berl. klin. Wchnschr., March 13th, 1902. Dvoretzki.?Therap. Monatshr., 1900, No. 3. Meier.?Munchen. med. Wchnschr., 1899, xlvi. 1411. Haase.?Ibid., 1902, xlix. 331 (discussion). Strohmayer.?Ibid., 1900, xlvii. 1064. S. S. Jones.?Obstetrics, Feb. 2nd, 1899.
Polak.?Pcst-Graduate, 1900, xv. 475. Heinsheimer.?Allg. med. Centr.-Ztg., 1900, No. 49. Witthauer.?Diakonissen Anstalt. Halle a. S., 1900. Klotz.?Deutsche med. Wchnschr., 1902, 524.
Wenkelbach.?Schmidt's Jarhb., cclxxii. 162. Niessen.?Wien. med. Wchnschr., 1899, Nos. 44 and 45. Bolton.?Tr. Assoc. Am. Physicians, 1894, ix. 174. Bolton & Brown.?Ibid., 1897, x*i- 4^8Trommsdorff.?Munchen. med. Wchnschr, 1902, xlix. 1300.
