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The treatment of meningitis due to hemolytic streptococcus with sulfanilamide
THE TREATMENT OF MENINGITIS DUE TO HEMOLYTIC STREPTOCOCCUS W I T H SULFANILAMIDE NELLES SILVERTHORNE,
M.B.,
AND A L A N BROWN,
M.D., F.R.C.P. (C.)
TORONTO, ONTARIO
following communication presents the results of the treatment T HE of nine patients suffering from meningitis due to hemolytic streptococcus with sulfanilamide. No attempt is made to review the extensive literature on the subject of sulfanilamide therapy. CLINICAL DATA
From 1924 to 1936, ninety-three patients suffering from meningitis due to hemolytic streptococcus have been admitted to the Hospital for Sick Children, Toronto. This series of cases was treated either by spinal drainage, intravenous glucose-saline injections, scarlet fever antitoxin, and mastoidectomy when it was indicated, or by some combination of these methods. In this group of cases there was one recovery. From this patient a culture of hemolytic streptococcus was obtained from the cerebrospinal fluid on only one occasion. The treatment used in this case was daily spinal puncture and drainage. During 1937 nine cases of streptococcic meningitis have been treated with disodium-4-sulphamidophenyl-2azo-7-acetyl-amino-l-hydroxynaphthalene 3:6-disulphonate (prontosil) and para-aminobenzenesulphonamide (prontylin) or both, as well as with a continuous intravenous injection of glucose-saline, daily spinal puncture with drainage, and mastoidectomy in patients suffering from mastoid disease. Table I summarizes the results obtained. COMMENT
Probably the most efficient test of a therapeutic agent is to observe its effects in patients suffering from a disease which usually has a case fatality of from 95 to ]00 per cent. Before the use of sulfanilamide, of a total of ninety-three patients with streptococcic meningitis in our series, only one recovered. The recovery of this patient may not have been unusual since on only one occasion was a culture of the spinal fluid reported positive. In our series of five recovered patients, four showed the presence of hemolytic streptococcus in culture from the spinal fluid on three or more occasions. Previously such cases treated by other methods, in our experience, have resulted fatally. Although, as stated in an article on influenzal meningitis,1 continuous intravenous injection of fluids facilitates more adequate spinal drainage, we believe that the use F r o m the w a r d s and laboratories of the Hospital for Sick Children, Toronto, the D e p a r t m e n t of Paediatrics and the Connaught Laboratories, University of Toronto. 504
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THE JOURNAL OF PEDIATRICS
of sulfanilamide in patients with streptococcic meningitis, secondary to mastoid disease, was mainly responsible for their recovery. In the group of nine eases it may be significant that the four patients who died were the youngest of the group. In addition to meningeal involvement there was a septicemia in two of them. It is our belief that the use of sulfanilamide has not favorably affected the most critically ill patients. There were no alarming effects produced as a result of the administration of the drug. Cyanosis was noted in all of our patients receiving prontylin in large doses, but this subsided within a few days after the drug had been discontinued. An increased respiratory rate was noted occasionally, but it was not a disturbing symptom. There have been no sequelae in four of the patients whom we have been able to reexamine. Dr. Frieda Fraser of the Connaught Laboratory has examined four of the cerebrospinal fluid strains isolated and fomid that they are all hemolytic streptococci of group A (Lancefield). SUlVs1Y[ARY
1. From 1924 to ]936, ninety-three patients suffering from meningitis due to hemolytic streptococcus have been admitted to hospital. These patients were treated by one of the following procedures, or by a combination of them: namely, spinal drainage, intravenous glucose-saline injections, scarlet fever antitoxin, and mastoidectomy when indicated. In this group there was on]y one recovery. 2. Nine patients with streptococcic meningitis during 1937 have been treated with sulfanilamide, a continuous intravenous injection of glucosesaline and daily spinal puncture with drainage. ~astoidectomy was performed in six of the nine patients in whom mastoiditis was present. F i v e of these nine patients have recovered. 3. It is our belief that sulfanilamide has been chiefly responsible for the satisfactory outcome in our patients suffering from streptococcic meningitis secondary to mastoid disease. The authors wish to thank the staff of the Ear, :Nose and Throat Service of the Hospital for Sick Children for their cooperation~ assistance, and suggestions in the treatment of these patients. Also we are indebted to Dr. :Bradley of this service for permission to include Case 7 in our series. We also wish to thank Dr. Leonard Colebrook for his help and suggestions in the treatment in Case 3.
REFERENCE 1. Silvertherne, NeHes, Frase~ Donald T., and Snellin~ Char]es, E.: J. PEOIAT. i0: 228,1937.
M.B.,
AND A L A N BROWN,
M.D., F.R.C.P. (C.)
TORONTO, ONTARIO
following communication presents the results of the treatment T HE of nine patients suffering from meningitis due to hemolytic streptococcus with sulfanilamide. No attempt is made to review the extensive literature on the subject of sulfanilamide therapy. CLINICAL DATA
From 1924 to 1936, ninety-three patients suffering from meningitis due to hemolytic streptococcus have been admitted to the Hospital for Sick Children, Toronto. This series of cases was treated either by spinal drainage, intravenous glucose-saline injections, scarlet fever antitoxin, and mastoidectomy when it was indicated, or by some combination of these methods. In this group of cases there was one recovery. From this patient a culture of hemolytic streptococcus was obtained from the cerebrospinal fluid on only one occasion. The treatment used in this case was daily spinal puncture and drainage. During 1937 nine cases of streptococcic meningitis have been treated with disodium-4-sulphamidophenyl-2azo-7-acetyl-amino-l-hydroxynaphthalene 3:6-disulphonate (prontosil) and para-aminobenzenesulphonamide (prontylin) or both, as well as with a continuous intravenous injection of glucose-saline, daily spinal puncture with drainage, and mastoidectomy in patients suffering from mastoid disease. Table I summarizes the results obtained. COMMENT
Probably the most efficient test of a therapeutic agent is to observe its effects in patients suffering from a disease which usually has a case fatality of from 95 to ]00 per cent. Before the use of sulfanilamide, of a total of ninety-three patients with streptococcic meningitis in our series, only one recovered. The recovery of this patient may not have been unusual since on only one occasion was a culture of the spinal fluid reported positive. In our series of five recovered patients, four showed the presence of hemolytic streptococcus in culture from the spinal fluid on three or more occasions. Previously such cases treated by other methods, in our experience, have resulted fatally. Although, as stated in an article on influenzal meningitis,1 continuous intravenous injection of fluids facilitates more adequate spinal drainage, we believe that the use F r o m the w a r d s and laboratories of the Hospital for Sick Children, Toronto, the D e p a r t m e n t of Paediatrics and the Connaught Laboratories, University of Toronto. 504
SILVEI~TEORINE
AND
BI~OWN:
SULFANILAMIDE
IN
MENINGITIS
Si
505
J
r |
L~
Do 9
o .+_
~
9 ,o
r
~
.Q
F
9
,
it0
i!! g
oo1~
0 Q 0
I ~ ~g
~g
oo
r~
L~
o
N
mN~ N~m o
9
N N
N N
I
=
=
=
:i =
k
~2
506
THE JOURNAL OF PEDIATRICS
of sulfanilamide in patients with streptococcic meningitis, secondary to mastoid disease, was mainly responsible for their recovery. In the group of nine eases it may be significant that the four patients who died were the youngest of the group. In addition to meningeal involvement there was a septicemia in two of them. It is our belief that the use of sulfanilamide has not favorably affected the most critically ill patients. There were no alarming effects produced as a result of the administration of the drug. Cyanosis was noted in all of our patients receiving prontylin in large doses, but this subsided within a few days after the drug had been discontinued. An increased respiratory rate was noted occasionally, but it was not a disturbing symptom. There have been no sequelae in four of the patients whom we have been able to reexamine. Dr. Frieda Fraser of the Connaught Laboratory has examined four of the cerebrospinal fluid strains isolated and fomid that they are all hemolytic streptococci of group A (Lancefield). SUlVs1Y[ARY
1. From 1924 to ]936, ninety-three patients suffering from meningitis due to hemolytic streptococcus have been admitted to hospital. These patients were treated by one of the following procedures, or by a combination of them: namely, spinal drainage, intravenous glucose-saline injections, scarlet fever antitoxin, and mastoidectomy when indicated. In this group there was on]y one recovery. 2. Nine patients with streptococcic meningitis during 1937 have been treated with sulfanilamide, a continuous intravenous injection of glucosesaline and daily spinal puncture with drainage. ~astoidectomy was performed in six of the nine patients in whom mastoiditis was present. F i v e of these nine patients have recovered. 3. It is our belief that sulfanilamide has been chiefly responsible for the satisfactory outcome in our patients suffering from streptococcic meningitis secondary to mastoid disease. The authors wish to thank the staff of the Ear, :Nose and Throat Service of the Hospital for Sick Children for their cooperation~ assistance, and suggestions in the treatment of these patients. Also we are indebted to Dr. :Bradley of this service for permission to include Case 7 in our series. We also wish to thank Dr. Leonard Colebrook for his help and suggestions in the treatment in Case 3.
REFERENCE 1. Silvertherne, NeHes, Frase~ Donald T., and Snellin~ Char]es, E.: J. PEOIAT. i0: 228,1937.