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The serum treatment of meningococcic meningitis
T H E S E R U M T R E A T M E N T O F MENINGOCOCCIC M E N I N G I T I S CHAaLES J. LESLIE, M.D., AND ADOLPH G. DE SANCTIS, M.D. NEW YORK, N. Y. D E R A B L E interest in the problem of meningococcic infections C OhasN S Ibeen stimulated recently by the development of new methods of treatment. The demonstration by Ferry* in 1931 of a meningoeoccus exotoxin and the therapeutic use of an antitoxin by t t o y n e f Fisk, a Lindsey and others 4 gave rise to a number of interesting questions. The introduction of sulfanilamide also promises to bring a valuable addition to our therapeutic resources. The use of antitoxin brings up several problems, the chief of which are (1) the question of the superiority of antitoxin over antibacterial serum and (2) the advisability of supplanting intraspinal methods of treatment in meningitis by intravenous injections alone. Hoyne 5 has recently abandoned the intraspinal route in t h e r a p y and states that in most cases the exclusive use of intravenous antitoxin is the method of choice. I n the present paper we will attempt to evaluate the efficacy of antibacterial serum a t t h e present time. This paper forms a supplement to that of Wright, De Sanetis and Shcplar G from this service in 1929. It is based on a study of 75 cases treated with antibacterial serum during the period from January, 1929, to October, 1937. The experience with these cases leads us to b e both critical in our judgment of the accepted method of treatment, and cautious of abandoning it for those perhaps less effective. We are able to show that, when a potent antibacterial serum is properly used, the results are good. In fact, during the last five years we have had no reason to change our methods. T E C H ~ I Q U E OF TREATMENT
On admission a routine blood culture is taken. If a marked peteehial eruption be present, smears and cultures are made of these lesions. A spinal puncture is then done, and specimens of fluid are removed for the following routine examinations: (1) cell count and globulin content; (2) stained smear for bacteria; (3) culture; and (4) sugar and lactic acid content. I f the fluid proves to be cloudy, intraspinal sermn is given at once. As much spinal fluid as possible is drained off, and 20 c.c. of New York City antimeningocoecus serum is introduced by gravity. One intraspinal dose of 20 e.e. of serum is given every calendar day thereafter, u n t i l the patient shows definite clinical improvement and F r o m the . D e p a r t m e n t of Pedia t ri c s , New Y ork P o s t G r a d u a t e lV[edical School, Columbia University. 83
84
THE
JOURNAL
OF PEDIATRICS
the culture, chemistry, and cell count of the spinal fluid show a r e t u r n to normal. Two Consecutive negative cultures are obtained before the serum is stopped. I f the patient is v e r y toxic, a second i n t r a s p i n a l dose of serum is occasionally given during the first twenty-four hours. I f the patient shows evidence of much intraeranial pressure, a second spinal drainage m a y be done during a day, without giving more serum. I t is generally better not to drain until six or eight hours a f t e r the previous serum injection. I n t r a v e n o u s serum is not given unless extreme toxicity, rash and fever indicate bacteriemia. I f given, the dose is 20 to 40 c.c. of serum diluted with equal p a r t s of n o r m a l saline. Doses are repeated only on persistenee of bacteriemia, in such eases generally twice dMly. I n t r a m u s c u l a r s e r u m is given only when an intravenous injection is indicated and a vein is not available. The sera we have used have been those m a d e by the New York City and the New York State Boards of tIeaRh. The New York City serum is now used routinely. I f i m p r o v e m e n t does not occur with this a f t e r f o u r or five days, a change is made to New Y o r k State serum. I n this series there was no m a r k e d advantage with one or the other. Both sera, as f a r a s we know, have been practically the same since 1928. We have not used commercial sera or antitoxin. I n t r e a t i n g our eases in this fashion, we have used in all 491 doses of serum, an average of 6.8 doses per ease and an average of 130 c.c. per case. I n t r a v e n o u s serum was used only in 11 eases and intramuscular injections in seven. W h e n used, these routes were employed generally only once or twice. This was not the procedure in 2 eases of bacteriemia without meningitis not included in the present series. These eases were treated intravenously, a p p r o x i m a t e l y with 40 c.c. of serum p e r day for six days. E a c h had an uneventful recovery. RESULTS
Our 75 cases comprise an age range of f r o m 1 month to 11 years wittl an average age in the entire group of 3.7 years. The average age in the f a t a l cases was 2 years. I n general the patients had been ill 41/~ days before admission. There were 15 deaths in the 75 cases, a m o r t a l i t y of 20 p e r cent. I t is interesting to note t h a t in 7 of the 15 f a t a l cases there were serious complications not due to the meningocoeeus. We feel t h a t these conditions are worthy of mention : 1. Bronchopneumonia with hemolytic streptococcus bacteriemia. 2. Massive consolidation of the right l u n g with staphylococcus empyema, t t y d r o u r e t e r and atrophic r i g h t kidney. This case also showed a hemolytic streptococcus in the v e n t r i c u l a r fluid.
L E S L I E A N D DE SAI~CTIS :
1VIENINGOCOCCIC IVLENINGITIS
~5
3. Bilateral mastoiditis and questionable superimposed pneumocoeeus meningitis. 4. Bilateral bronehopneumonia. 5. Bullous impetigo with bilateral suppurative otitis media. 6. L o b a r pneumonia with pneumoeoccus iridocyclitis. 7. Previous bronehopneumonia of three weeks' duration. I t is obvious t h a t most of these children might well have died in spite of any t y p e of antimeningococeus therapy. I n the 8 uncomplicated f a t a l cases 3 patients died within forty-eight hours a f t e r admission, one o~ them without the diagnosis having been nlade. I t seems therefore t h a t the gross mortality figure of 20 per cent does not give an entirely accurate picture of the results of treatment. Excluding the forty-eighthour deaths, the total mortality was 16 per cent. I f one would be allowed a little more latitude in statistics and exclude those cases with unusual multiple complications, the mortality rate more closely approaches 10 p e r cent. We noted in the patients who recovered twelve instances of complications due to meningocoecus, eight of which were permanent. They are as follows : 1. Two cases of hydrocephalus with mental impairment. 2. Three cases of h'idoeyclitis with p e r m a n e n t blindness; two of these were bilateral. 3. One case of bilateral optic atrophy. 4. One case of bilateral nerve deafness. 5. One case of bilateral iritis with recovery. 6. One case of bilateral optic nel~ritis with recovery. 7. One case of strabismus. 8. Two cases of arthritis with complete recovery. I t is of interest to note t h a t 5 of the 8 p e r m a n e n t sequelae occurred in 1929, 2 in ]931, and the last in ]935. I n this connection we observe that the greatest incidence, mortality, and severity of the disease occurred during the years ~929 to 1932. In this period there were 49 cases with a death rate of 24.5 p e r cent. Since 1933 we have h a d 26 eases with a m o r t a l i t y of a p p r o x i m a t e l y 13 p e r cent. There have been no deaths in the last 20 cases t r e a t e d with serum. SUMMARY
Our results closely approximate the figures reported by NeaF in 1933. Her series comprised 302 cases with 57 deaths, a rate of 18.3 per cent. A series of cases summarized recently by Bolduan s at Bellevue Hospital also show a comparable moI~tality. He reported 191 cases f r o m 1928 to 1937 with 26 p e r cent deaths. F r o m 1929 to 1932 there were 138 cases with 30 per cent mortality. F r o m 1933 to 1937 there were 53 cases with 15 per cent mortalRy. Taking the greater n u m b e r of his cases into consideration, the results are quite similar to ours.
86
THE
J O U R N A L OF P E D I A T R I C S
The fatality rate in our cases is strikingly lower t h a n in H o y n e ' s series of 211 cases treated with antiserum, where the death rate was 45.9 per cent. I t also compares favorably with a series of 278 cases treated by Sehwentker, 9 of Baltimore, where the death rate was 30 per cent. Other authors r e p o r t e d much higher m o r t a l i t y rates in different parts of the country. These figures have been quoted as high as 62 to 80 p e r cent (TuckerS~ F u r t h e r m o r e , the m o r t a l i t y rates of our serum-treated cases and those of Neal and Bolduan a p p e a r to compare f a v o r a b l y with H o y n e ' s series of antitoxin treated cases. The latter group comprises 85 cases with a m o r t a l i t y of 23.5 per cent. There seems to be little to choose between the efficacy of antitoxin as used by t I o y n e and others (Hodges and Shields, 11 T u c k e r / ~ and others) and the antibacterial serum as used b y Neal~ Bolduan, a n d ourselves. We are somewhat at a loss to explain why their m o r t a l i t y with serumtreated cases is so m u c h higher t h a n ours. As f a r as the t r e a t m e n t of meningococcus cases with New York City serum is concerned, we feel that the procedure is of considerable value. I t is evident, however, t h a t there is still room for improvement. I t appears t h a t the low m o r t a l i t y in the past few cases might v e r y welt be due to a decreased virulence of the infecting organism. The mortality of the first four years of our series was almost twice as high as for the latter period; yet both the serum and the method of t r e a t m e n t were the same. This was also noted by Bolduan. I t goes without saying t h a t early diagnosis is of prime importance. Our patients who died h a d been ill on the average one day longer before admission t h a n those who recovered. I t m a y well be that delay in treatment, even for such a short time, has a great bearing on the outcome. Potent serum must be used. This is not such an obvious point as one might as first suppose, and it m a y in p a r t explain some of the higher mortality rates in serum-treated cases. There are at present, unfortunately, no laboratory methods which will indicate the clinical potency of a serum in a given case. De Sanetis and Sheplar showed clearly t h a t the only reliable test of the serum is its t h e r a p e u t i c effect. Agglutination titers have no relation to clinical potency. I t is of p r i m e importance that the serum used be obtained f r o m the strain of bacteria which is causing the case u n d e r treatment. I t is also of importance that the serum not be made f r o m bacterial strains which have been so long on laboratory media as to have dhninished their antigenic properties. In the clinical handling of the case if one does not obtain satisfactory improvement within a period of a few days, another b r a n d of serum should be used. We arc strongly of the opinion t h a t intraspinal administration of serum is essential. This, however, should not be done at too frequent intervals. I n our eases a single daily injection of 20 c.c. has been most
LESLIE AND DE SANCTIS:
MENINGOCOCCIC MENINGITIS
~7
effective. More frequent injections offer no advantage. This is borne out by the fact that Bolduan's cases Were treated on the average twice as frequently as ours (every twelve hours), yet the results were Mmost identical. Neal has the impression that more frequent injections may have a deleterious effect. There are some, chiefly Hoyne, who maintain that meningitis is a phase of a generalized meningoeoecus infection, the most important lesion being baeteriemia with toxemia from bacterial products. Bacteriemia has not been a prominent feature of our cases. Routine blood cultures were done on 41 patients, of which only 11 were positive. Five
of these 41 patients died. Of the 5 patients who died, 2 had baeteriemia, and 3 had not. Neal also reports only 3 positive blood cultures in 43 early eases. 12 Furthermore, when bacteriemia was present, it was generally transient and r a r e l y persisted beyond the second day of treatment. There are a few eases in which baeteriemia does occur without meningeal involvement or with a v e r y mild meningitis. We had three eases of this type not included in the present series. In the great majority of cases it would seem that the massive infection of the central nervous system is of paramount importance, while bacteriemia is coincidental and not of p r i m a r y importance. Certainly a very conspicuous aspect of the patholog~y is the thick, obstructive, fibrinoplastic exudate involving the meninges. It is also true that the most feared sequelae of the disease are those involving the brain and cranial neiwes, namely, obstructive hydrocephalus, mental deterioration, optic atrophy, iridoeyclitis, and nerve deafness. We would therefore hesitate to abandon intraspinal t h e r a p y in favor of an exclusively intravenous type of treatment, whether antitoxin or antibacterial serum were the therapeutic agent in use. We have had only slight personal experience with the use of sulfanilamide in treating meningoeoeeie meningitis. The first ease in which we used this agent as the sole method of treatment resulted in fatality. As we had previously treated 18 consecutive eases successfully with serum, we were discouraged from continuing the sulfanilamide as the sole therapeutic agent. W e have, however, used this material in conjunction with serum in a few eases not included here. We have been unable to note ans~ striking effect attributable to this drug. The number of eases, however, has been too small to w a r r a n t definite conclusions. Sehwentker reports 330 cases, 52 of which were treated solely with sulfanilamide, the remainder being treated with serum. H e had very much better success with sulfanilamide, the mortality rate being 15 per cent, whereas in the serum-treated cases it was 30 per cent. While this is an interesting series of cases, the superiority of sulfanilamide is not conclusively proved. Sehwentker himself pointed out that the cases treated with sulfanilamide were those occurring after that particular epidemic had been on the decline, a fact which would tend to produce
88
THE JOURNAL OF PEDIATRICS
lowered mortality, no matter what the treatment. In the second place, complete control is lacking in that alternate cases were not used. While not conclusive, the results of sulfanilamide are striking, and the treatment obviously warrants further t r i a l I t evidently has a beneficial effect upon meningococcus infections and its administration simplifies the treatment of meningitis. I t is possible that this may be the method whereby the number of intraspinal treatments may ultimately be reduced. Although sulfanilamide itself may be introduced into the spinal canal in solution, a concentration of the drug can be maintMned in the spinal fluid by 0ral administration alone. While, at the present time, we feel that antibacterial sermn properly used is the method of choice, we hope that a more thorough trim of sulfanilamide will be forthcoming in order to definitely determine its usefulness. We can see no objection to combining sulfanilamide with serum treatment. CONCLUSIONS
Meningoeoccic infections in children can be treated effectively with antibacterial serum. Intraspinal administration of serum is essential except in cases of bacteriemia without meningeal involvement. The conservative method of therapy discussed is the method of choice. Repeated intravenous injections of serum are indicated only in persistent cases of bacteriemia. Intramuscular serum injection is very rarely indicated. REFERENCES ]. 2. 3. 4. 5. 6. 7. 8. 9. 10. ]L 12.
Ferry, Iq. S., Norton, J. F., and Steele, A. It.: J. Immunol. 21: 293, 1931. tIoyne, A. L.: J. A. M. A. 104: 980, 1935; J. A. IV[. A. 107: 478, 1936. Fisk, C. J . : J. Iowa M. Soe. 26: 307, 1936. Lindsey, 1K ]~I., Johnson, G. L., and Greening, W . P . : J. 01dahoma iVL A. 29: 283, 1936. I-Ioyne~ A. I~.: Nebraska 1VJC.g. 21: 321, 1936. Wright, L S., De San~tis, A. ~., and Sheptar, A . E . : Am. J. Dis. Child. 38: 730, 1929. Neal, ft. B. : :New York State J. ivied. 33: 94, 1933. Boiduan, .Nils : Personal communication. Sehwentker, ]~. F. : Personal communication. Tucker, W. It. : Illinois M. J. 71: 328, 1937. Hodges, F. H., and Shields, C.: K e n t u c k y M. J. 35: 46% 1937. Nea], Y. B.: 1V[ed. Clin. North America 19: 751, 7935.
On admission a routine blood culture is taken. If a marked peteehial eruption be present, smears and cultures are made of these lesions. A spinal puncture is then done, and specimens of fluid are removed for the following routine examinations: (1) cell count and globulin content; (2) stained smear for bacteria; (3) culture; and (4) sugar and lactic acid content. I f the fluid proves to be cloudy, intraspinal sermn is given at once. As much spinal fluid as possible is drained off, and 20 c.c. of New York City antimeningocoecus serum is introduced by gravity. One intraspinal dose of 20 e.e. of serum is given every calendar day thereafter, u n t i l the patient shows definite clinical improvement and F r o m the . D e p a r t m e n t of Pedia t ri c s , New Y ork P o s t G r a d u a t e lV[edical School, Columbia University. 83
84
THE
JOURNAL
OF PEDIATRICS
the culture, chemistry, and cell count of the spinal fluid show a r e t u r n to normal. Two Consecutive negative cultures are obtained before the serum is stopped. I f the patient is v e r y toxic, a second i n t r a s p i n a l dose of serum is occasionally given during the first twenty-four hours. I f the patient shows evidence of much intraeranial pressure, a second spinal drainage m a y be done during a day, without giving more serum. I t is generally better not to drain until six or eight hours a f t e r the previous serum injection. I n t r a v e n o u s serum is not given unless extreme toxicity, rash and fever indicate bacteriemia. I f given, the dose is 20 to 40 c.c. of serum diluted with equal p a r t s of n o r m a l saline. Doses are repeated only on persistenee of bacteriemia, in such eases generally twice dMly. I n t r a m u s c u l a r s e r u m is given only when an intravenous injection is indicated and a vein is not available. The sera we have used have been those m a d e by the New York City and the New York State Boards of tIeaRh. The New York City serum is now used routinely. I f i m p r o v e m e n t does not occur with this a f t e r f o u r or five days, a change is made to New Y o r k State serum. I n this series there was no m a r k e d advantage with one or the other. Both sera, as f a r a s we know, have been practically the same since 1928. We have not used commercial sera or antitoxin. I n t r e a t i n g our eases in this fashion, we have used in all 491 doses of serum, an average of 6.8 doses per ease and an average of 130 c.c. per case. I n t r a v e n o u s serum was used only in 11 eases and intramuscular injections in seven. W h e n used, these routes were employed generally only once or twice. This was not the procedure in 2 eases of bacteriemia without meningitis not included in the present series. These eases were treated intravenously, a p p r o x i m a t e l y with 40 c.c. of serum p e r day for six days. E a c h had an uneventful recovery. RESULTS
Our 75 cases comprise an age range of f r o m 1 month to 11 years wittl an average age in the entire group of 3.7 years. The average age in the f a t a l cases was 2 years. I n general the patients had been ill 41/~ days before admission. There were 15 deaths in the 75 cases, a m o r t a l i t y of 20 p e r cent. I t is interesting to note t h a t in 7 of the 15 f a t a l cases there were serious complications not due to the meningocoeeus. We feel t h a t these conditions are worthy of mention : 1. Bronchopneumonia with hemolytic streptococcus bacteriemia. 2. Massive consolidation of the right l u n g with staphylococcus empyema, t t y d r o u r e t e r and atrophic r i g h t kidney. This case also showed a hemolytic streptococcus in the v e n t r i c u l a r fluid.
L E S L I E A N D DE SAI~CTIS :
1VIENINGOCOCCIC IVLENINGITIS
~5
3. Bilateral mastoiditis and questionable superimposed pneumocoeeus meningitis. 4. Bilateral bronehopneumonia. 5. Bullous impetigo with bilateral suppurative otitis media. 6. L o b a r pneumonia with pneumoeoccus iridocyclitis. 7. Previous bronehopneumonia of three weeks' duration. I t is obvious t h a t most of these children might well have died in spite of any t y p e of antimeningococeus therapy. I n the 8 uncomplicated f a t a l cases 3 patients died within forty-eight hours a f t e r admission, one o~ them without the diagnosis having been nlade. I t seems therefore t h a t the gross mortality figure of 20 per cent does not give an entirely accurate picture of the results of treatment. Excluding the forty-eighthour deaths, the total mortality was 16 per cent. I f one would be allowed a little more latitude in statistics and exclude those cases with unusual multiple complications, the mortality rate more closely approaches 10 p e r cent. We noted in the patients who recovered twelve instances of complications due to meningocoecus, eight of which were permanent. They are as follows : 1. Two cases of hydrocephalus with mental impairment. 2. Three cases of h'idoeyclitis with p e r m a n e n t blindness; two of these were bilateral. 3. One case of bilateral optic atrophy. 4. One case of bilateral nerve deafness. 5. One case of bilateral iritis with recovery. 6. One case of bilateral optic nel~ritis with recovery. 7. One case of strabismus. 8. Two cases of arthritis with complete recovery. I t is of interest to note t h a t 5 of the 8 p e r m a n e n t sequelae occurred in 1929, 2 in ]931, and the last in ]935. I n this connection we observe that the greatest incidence, mortality, and severity of the disease occurred during the years ~929 to 1932. In this period there were 49 cases with a death rate of 24.5 p e r cent. Since 1933 we have h a d 26 eases with a m o r t a l i t y of a p p r o x i m a t e l y 13 p e r cent. There have been no deaths in the last 20 cases t r e a t e d with serum. SUMMARY
Our results closely approximate the figures reported by NeaF in 1933. Her series comprised 302 cases with 57 deaths, a rate of 18.3 per cent. A series of cases summarized recently by Bolduan s at Bellevue Hospital also show a comparable moI~tality. He reported 191 cases f r o m 1928 to 1937 with 26 p e r cent deaths. F r o m 1929 to 1932 there were 138 cases with 30 per cent mortality. F r o m 1933 to 1937 there were 53 cases with 15 per cent mortalRy. Taking the greater n u m b e r of his cases into consideration, the results are quite similar to ours.
86
THE
J O U R N A L OF P E D I A T R I C S
The fatality rate in our cases is strikingly lower t h a n in H o y n e ' s series of 211 cases treated with antiserum, where the death rate was 45.9 per cent. I t also compares favorably with a series of 278 cases treated by Sehwentker, 9 of Baltimore, where the death rate was 30 per cent. Other authors r e p o r t e d much higher m o r t a l i t y rates in different parts of the country. These figures have been quoted as high as 62 to 80 p e r cent (TuckerS~ F u r t h e r m o r e , the m o r t a l i t y rates of our serum-treated cases and those of Neal and Bolduan a p p e a r to compare f a v o r a b l y with H o y n e ' s series of antitoxin treated cases. The latter group comprises 85 cases with a m o r t a l i t y of 23.5 per cent. There seems to be little to choose between the efficacy of antitoxin as used by t I o y n e and others (Hodges and Shields, 11 T u c k e r / ~ and others) and the antibacterial serum as used b y Neal~ Bolduan, a n d ourselves. We are somewhat at a loss to explain why their m o r t a l i t y with serumtreated cases is so m u c h higher t h a n ours. As f a r as the t r e a t m e n t of meningococcus cases with New York City serum is concerned, we feel that the procedure is of considerable value. I t is evident, however, t h a t there is still room for improvement. I t appears t h a t the low m o r t a l i t y in the past few cases might v e r y welt be due to a decreased virulence of the infecting organism. The mortality of the first four years of our series was almost twice as high as for the latter period; yet both the serum and the method of t r e a t m e n t were the same. This was also noted by Bolduan. I t goes without saying t h a t early diagnosis is of prime importance. Our patients who died h a d been ill on the average one day longer before admission t h a n those who recovered. I t m a y well be that delay in treatment, even for such a short time, has a great bearing on the outcome. Potent serum must be used. This is not such an obvious point as one might as first suppose, and it m a y in p a r t explain some of the higher mortality rates in serum-treated cases. There are at present, unfortunately, no laboratory methods which will indicate the clinical potency of a serum in a given case. De Sanetis and Sheplar showed clearly t h a t the only reliable test of the serum is its t h e r a p e u t i c effect. Agglutination titers have no relation to clinical potency. I t is of p r i m e importance that the serum used be obtained f r o m the strain of bacteria which is causing the case u n d e r treatment. I t is also of importance that the serum not be made f r o m bacterial strains which have been so long on laboratory media as to have dhninished their antigenic properties. In the clinical handling of the case if one does not obtain satisfactory improvement within a period of a few days, another b r a n d of serum should be used. We arc strongly of the opinion t h a t intraspinal administration of serum is essential. This, however, should not be done at too frequent intervals. I n our eases a single daily injection of 20 c.c. has been most
LESLIE AND DE SANCTIS:
MENINGOCOCCIC MENINGITIS
~7
effective. More frequent injections offer no advantage. This is borne out by the fact that Bolduan's cases Were treated on the average twice as frequently as ours (every twelve hours), yet the results were Mmost identical. Neal has the impression that more frequent injections may have a deleterious effect. There are some, chiefly Hoyne, who maintain that meningitis is a phase of a generalized meningoeoecus infection, the most important lesion being baeteriemia with toxemia from bacterial products. Bacteriemia has not been a prominent feature of our cases. Routine blood cultures were done on 41 patients, of which only 11 were positive. Five
of these 41 patients died. Of the 5 patients who died, 2 had baeteriemia, and 3 had not. Neal also reports only 3 positive blood cultures in 43 early eases. 12 Furthermore, when bacteriemia was present, it was generally transient and r a r e l y persisted beyond the second day of treatment. There are a few eases in which baeteriemia does occur without meningeal involvement or with a v e r y mild meningitis. We had three eases of this type not included in the present series. In the great majority of cases it would seem that the massive infection of the central nervous system is of paramount importance, while bacteriemia is coincidental and not of p r i m a r y importance. Certainly a very conspicuous aspect of the patholog~y is the thick, obstructive, fibrinoplastic exudate involving the meninges. It is also true that the most feared sequelae of the disease are those involving the brain and cranial neiwes, namely, obstructive hydrocephalus, mental deterioration, optic atrophy, iridoeyclitis, and nerve deafness. We would therefore hesitate to abandon intraspinal t h e r a p y in favor of an exclusively intravenous type of treatment, whether antitoxin or antibacterial serum were the therapeutic agent in use. We have had only slight personal experience with the use of sulfanilamide in treating meningoeoeeie meningitis. The first ease in which we used this agent as the sole method of treatment resulted in fatality. As we had previously treated 18 consecutive eases successfully with serum, we were discouraged from continuing the sulfanilamide as the sole therapeutic agent. W e have, however, used this material in conjunction with serum in a few eases not included here. We have been unable to note ans~ striking effect attributable to this drug. The number of eases, however, has been too small to w a r r a n t definite conclusions. Sehwentker reports 330 cases, 52 of which were treated solely with sulfanilamide, the remainder being treated with serum. H e had very much better success with sulfanilamide, the mortality rate being 15 per cent, whereas in the serum-treated cases it was 30 per cent. While this is an interesting series of cases, the superiority of sulfanilamide is not conclusively proved. Sehwentker himself pointed out that the cases treated with sulfanilamide were those occurring after that particular epidemic had been on the decline, a fact which would tend to produce
88
THE JOURNAL OF PEDIATRICS
lowered mortality, no matter what the treatment. In the second place, complete control is lacking in that alternate cases were not used. While not conclusive, the results of sulfanilamide are striking, and the treatment obviously warrants further t r i a l I t evidently has a beneficial effect upon meningococcus infections and its administration simplifies the treatment of meningitis. I t is possible that this may be the method whereby the number of intraspinal treatments may ultimately be reduced. Although sulfanilamide itself may be introduced into the spinal canal in solution, a concentration of the drug can be maintMned in the spinal fluid by 0ral administration alone. While, at the present time, we feel that antibacterial sermn properly used is the method of choice, we hope that a more thorough trim of sulfanilamide will be forthcoming in order to definitely determine its usefulness. We can see no objection to combining sulfanilamide with serum treatment. CONCLUSIONS
Meningoeoccic infections in children can be treated effectively with antibacterial serum. Intraspinal administration of serum is essential except in cases of bacteriemia without meningeal involvement. The conservative method of therapy discussed is the method of choice. Repeated intravenous injections of serum are indicated only in persistent cases of bacteriemia. Intramuscular serum injection is very rarely indicated. REFERENCES ]. 2. 3. 4. 5. 6. 7. 8. 9. 10. ]L 12.
Ferry, Iq. S., Norton, J. F., and Steele, A. It.: J. Immunol. 21: 293, 1931. tIoyne, A. L.: J. A. M. A. 104: 980, 1935; J. A. IV[. A. 107: 478, 1936. Fisk, C. J . : J. Iowa M. Soe. 26: 307, 1936. Lindsey, 1K ]~I., Johnson, G. L., and Greening, W . P . : J. 01dahoma iVL A. 29: 283, 1936. I-Ioyne~ A. I~.: Nebraska 1VJC.g. 21: 321, 1936. Wright, L S., De San~tis, A. ~., and Sheptar, A . E . : Am. J. Dis. Child. 38: 730, 1929. Neal, ft. B. : :New York State J. ivied. 33: 94, 1933. Boiduan, .Nils : Personal communication. Sehwentker, ]~. F. : Personal communication. Tucker, W. It. : Illinois M. J. 71: 328, 1937. Hodges, F. H., and Shields, C.: K e n t u c k y M. J. 35: 46% 1937. Nea], Y. B.: 1V[ed. Clin. North America 19: 751, 7935.