2
Treatment of Strangles with Sulphanilamide
doubt that they have a direct effect on
bacterial metabolism (inhibition of an
essential enzyme reaction) leading to
bacteriostasis and that the phagocytic
cells of the body are the actual killing
agents. This effect was nicely shown by
Gay and Clark [1937] in the case of an
experimental streptococcus empyema in
rabbits. The phagocytic cells themselves
are unharmed by concentrations of the
drug which are active against bacteria.
McIntosh and Whitby [1939] have shown
that the drugs are not simple germicides,
although, as Colebrook, Buttle and
O'Meara [1936] had pointed out for sul-
phanilamide, the drug is bactericidal on
small numbers of hæmolytic streptococci
in culture medium and in blood. It is also
known that they are not immediately
active in vitro or in vivo; they are active
on highly virulent organisms and those
in the logarithmic phase of growth, and
there is a quantitative relationship
between effective dose and the number
of bacteria attacked. Further, it is
decided that the drugs do not neutralize
toxins, they do not stimulate the activity
of leucocytes nor influence the production
or quality of specific immune bodies. The
compounds are easily diffusible in the
body and are very effective in a medium
which is a poor one for the organism, e. g.
urine or blood. On the other hand, as
Fleming [1941] has shown, pus inhibits
the action of sulphanilamide, so that it
should not be used on grossly septic
wounds.
The sulphonamide drugs which are
chiefly in use at the present time are
sulphanilamide, sulphapyridine (M & B
693) and sulphathiazole. Sulphanilamide
is capable of dealing with most hæmolytic
streptococcus infections, is active against
Cl. welchii, meningococci, gonococci, Bact.
coli and Proteus, but is relatively inactive
against staphylococci and pneumococci.
Sulphapyridine is active against hæmolytic
streptococci, pneumococci and Cl. welchii
and has some action against staphylococci
and Cl. septicum. Sulphathiazole is not
only active against hæmolytic streptococci
but is also definitely better than the other
two against staphylococcus infections.
Finally, it is to be noted that among bac-
teria belonging to susceptible species
drug-resistant strains are sometimes met
with. An apposite illustration of this was
recently reported by Hendry [1942]. A
horse undergoing immunization with group
A hæmolytic streptococci developed a
streptococcus septicæmia and died in spite
of 10 days treatment with sulphanilamide.
The streptococci isolated from the blood
of the animal, the day before its death
were considerably more resistant to sul-
phanilamide by in vitro tests than were
the organisms used for immunization.
Since the early days when prontosil
was found to be efficient in reducing the
mortality in human puerperal fever, it has
become apparent that the sulphonamides
are of value in a number of other human
infections, streptococcal and otherwise,
particularly the more acute class of
disease. However, their efficacy has not
been proved in all cases, e.g. French
[1939] in a series of painstaking and
controlled observations was unable to
demonstrate any useful action in scarlet
fever.
All careful practitioners realize that
the drug should be given as early as
possible, in full dosage, at proper inter-
vals, and for a sufficient length of time,
say up to 10 days. Continuation without
an interval beyond this time may lead to
leucopenia and anæmia. If relapses
appear, dosing should be recommended.
Water intake should be restricted and
medicines containing sulphur withheld.
It is good practice if possible to make
periodic estimations of the sulphonamide
concentration in the blood, since the rate
of absorption and excretion varies some-
what in different individuals. Bazeley,
Jokobowicz and Splatt [1940] give a
convenient dosage table for horses. Thus,
to attain a concentration of sulphanila-
mide of 5 mg. per cent in the blood, a
horse weighing 1000 lb. would require 90
gm. the first day and 60 gm. on subsequent
days. For a 750 lb. horse the amounts