Alexander Fleming (1881-1955)

On streptococcal infections of septic wounds at base hospital.

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THE LANCET,] DR. H. J. B. FRY: CERTAIN ORGANISMS ISOLATED FROM INFLUENZA CASES. [JULY 12,1919

51

broth or glucose broth. It has also the great merit that the
number of streptococci in the circulating blood can be
determined. The technique is as follows :—

1 c.cm. of blood from the suspected septicæmic case is
added to about 5 c.cm. of water. The blood will thus be
laked and the clotting power diminished, so that it can
readily be carried back to the laboratory before coagulation
takes place. It is then mixed with about 20 c.cm. of agar at
47°C., poured into a Petri dish, allowed to set, and incubated.
In 24 hours the colonies can easily be seen.

Minced meat medium, such as is commonly used in the
cultivation of anaerobes, furnishes a better fluid medium for
blood culture in these surgical cases than does broth, glucose
broth, or citrated broth. In several cases we have obtained
growths of streptococcus from the blood in this medium
when they failed to develop in the broth cultures. It has
the advantage that anaerobes, if present, will also develop.

The figure represents a plate made from 1 c.cm. of blood
from a patient with septicæmia following a flesh wound in
the thigh. It shows very many more streptococci than are
snally present in the blood. Two days after the specimen
was taken the patient died, and the autopsy showed, in
addition to a septic thigh wound, abscesses in the hand,
wrist both elbows, neck, and a very large abscess in the
buttock. The specimen of blood was taken immediately the
orderlies had finished washing the patient, during which
process he must of necessity have been considerably dis-
turbed, and it seems probable that the large number of
streptococci in the blood was due rather to this disturbance
than to their growth in the blood stream.

It is unlikely, also, that the small number of streptococci
present in the blood stream in the ordinary case of septi-
cæmia would be able to flourish in that situation, as the serum
of these patients show by Sir Almroth Wright’s sero-culture
method a very much enhanced bactericidal power to Strepto-
coccus pyogenes.4 (The bactericidal power of normal serum
to this microbe is practically nil.)

So far as we know, streptococci are destroyed in the body
by three agencies: (1) bactericidal power of the serum;
(2) direct bactericidal power of the leucocytes (without
phagocytosis); (3) phagocytosis due to the combined action
of the serum (opsonic power) and leucocytes. In strepto-
coccal septicæmia these are changed from the normal as
follows.

1. Bactericidal power of the serum. (This, as stated above,
is increased.)

2. Direct bactericidal power of the leucocytes.—It has been
shown5 that living leucocytes have the power of destroying
streptococci without ingesting them. This power of the
leucocytes is apparently unaltered in septicæmia cases
except that as there is always a leucocytosis in these cases
the power is more manifest.

3. Phagocytosis.—In some cases of septicæmia the serum
has lost completely or almost completely its opsonic power
(and also its complementing power). The phagocytic power
of the leucocytes is not diminished.

It would appear from these observations that, as a rule, it
is not the circulating blood which is at fault in cases of
streptococcal septicæmia, and in all probability we have to
look for some deficiency in the local protective mechanism
which allows access of the streptococci to the blood stream.
It would seem to follow, also, that for the successful treat-
ment of a case of septicæmia the most essential element
would be the thorough local treatment of the infected focus.

It has been observed that when an infection has become
circumscribed by the collection of leucocytes in the walls
of the wound and by the other factors which operate
locally in this connexion, it is very difficult to graft a
serious streptococcal infection on the wound. It follows
from this that the utmost care should be taken in the first
few days after the injury to keep out the streptococcus
and to avoid any treatment which will inhibit the defensive
processes developing.. In the after-treatment fresh tissue
should only be opened up when there is a very urgent
necessity.

In conclusion, we wish to express our thanks to Major M.
Sinclair and our other surgical colleagues for permitting us
to make observations on patients under their care; to
Captain L. Colebrook for permission to use some of his
experimental work; and to the Medical Research Committee
tor supplying us with apparatus which made the work easier.

____________________________________________________
4 For this observation we are indebted to Captain L. Colebrook.
5 Wright, Fleming, and Colebrook, THE LANCET, 1918, i., 831.

                                              NOTE ON

CERTAIN ORGANISMS ISOLATED FROM
                CASES OF INFLUENZA.

                 BY H. J. B. FRY, M.D. OXON.,
                        CAPTAIN, R.A.M.C. (T.).

IN the course of investigation of material derived from
cases of influenza during the three waves of the present
epidemic, when searching for Pfeiffer’s bacillus, Gram-
negative, “Pfeiffer-like” bacilli were frequently isolated.
They were not, however, hæmophilic, and grew rapidly and
readily on ordinary agar. They have been isolated from
sputum, post-mortem material, and in blood culture. The
organisms derived from the latter source deserve further
description.

They were isolated from the blood of two German prisoners,
out of four cases examined, at the commencement of the
third wave of the epidemic in February, 1919. The camp
to which the prisoners had belonged had escaped the two
previous waves, but was overwhelmed by the present one, a
large proportion of the prisoners being severely attacked.

The organism was obtained in 2 per cent. glucose
and appeared in 24 hours in the blood culture, as round or
oval Gram-negative “yeast-like” bodies, 3–5μ long by 2–4μ
broad. Subculture to agar produced, nob the above organisms
but Gram-negative bacilli, varying in size from coccal or
cocco-bacillary forms to short filaments. The “ yeast-like”
bodies rapidly disappeared from the blood culture, and were
replaced by clumps of Gram-negative bacilli, in the neigh-
bourhood of which could be seen, in some cases, Gram-
negative amorphous masses, resembling the ruptured envelopes
of the above-mentioned “ yeast-like” bodies.

         Characters of Organism : Pathogenesis.

The bacilli were pure in subculture, and had the following
morphological and cultural characters:—

Morphology and cultural characters.—Small non-sporing
bacilli, often grouped in parallel, or as diplo-bacilli, 1-2μ in
length, but varying in size from coccal forms to short fila-
ments. The smaller forms are actively, but the larger forms
are feebly, motile. They are Gram-negative but not acid-
fast. Polar staining is not usually present. They are aerobic
and grow rapidly and well on agar, forming a whitish-grey
moist growth of circular, slightly flattened colonies, about
0·5 mm. in diameter. Viewed by transmitted light, the
colonies are translucent and slightly iridescent. In stab-
culture on gelatin there is a white growth, confined to the
needle track, without extension on the surface, and the
gelatin is not liquefied. Broth is rendered turbid, with a
flocculent, whitish, stringy deposit.

The fermentation reactions are as follows: Acid pro-
duction but no gas in dextrose, maltose, and mannite. No
change in lactose, cane-sugar. salicin, or inulin. Litmus
milk is first rendered faintly acid and then becomes strongly
alkaline, without any clotting. Neutral-red broth is rendered
alkaline. There is a fairly well-marked indol reaction after
48 hours’ growth in peptone water. Stalactite growth was
not obtained in butter-fat broth.

Grown on 6 per cent. salt agar, numerous yeast-like forms
were obtained resembling those obtained in the blood
culture, together with filamentous, curved, and swollen
forms. The organism resists heating to 65° C. for 30 minutes,
but is killed at a temperature of 60° C. for 1 hour.

Pathogenesis.—The organism was highly pathogenic to the
rat and guinea-pig. 0·25 c.cm. of a saline emulsion of a
24-hour agar culture by intrathoracic injection killed a white
rat in 17 hours. The lesions produced were ecchymoses and
hæmorrhagic extravasations on the surfaces of both lungs,
which were congested and œdematous. The heart was
engorged and filled with clot. The organism was recovered
in pure culture from heart, lungs, and spleen.

A similar dose by intrathoracic injection killed a guinea-
pig in five days, causing a slight caseous nodule at the site
of inoculation, sero-purulent effusions into both pleural sacs,
and lobular pneumonia with hæmorrhages in both lungs.
The bronchial glands were greatly enlarged and showed
caseous nodules. The heart was dilated and filled with
clot. The organism was recovered in pure culture from, the
pleural effusion, lungs, heart blood, tracheal mucus, and
spleen. By intraperitoneal inoculation death was caused

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