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Diagnosis and Treatment of Secondary Anaerobic Infections of Kidney Wounds1
DIAGNOSIS AND TREATMENT OF SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUNDS 1 CHARLES PIERRE MATHE
The diagnosis and treatment of anaerobic infection of lumbar wounds following operative interference on the kidney offers quite a problem to the kidney surgeon. Two types of this uncommon wound infection are encountered: (1) the acute rapidly fatal gas gangrene type necessitating immediate heroic measures and (2) the more mild chronic type of persistent infection requiring less heroic but equally technical care. The acute fulminating type is well recognized; it occurred rather often in wounds during the World War, occasionally takes place after operations on the abdomen and extremities and is a common complication of traumatizing wounds resulting from automobile and train accidents. Gas gangrene infection of the wound is readily recognized by the sudden onset of emphysematous infiltration of the tissues, bronze induration and hemorrhagic phlyctena of the skin, is accompanied by extreme prostration and grave general symptoms often terminating rapidly in death. This type demands immediate surgical resection of the affected area as well as intelligent administration of serum therapy. The second type of chronic insidious infection offers a greater problem for diagnosis and is recognized only by expert bacteriological examination. Both types are amenable to sere-therapy in conjunction with surgical treatment and good results will be in proportion to the correct local and general administration of properly selected antigens in proper doses. Having recently observed a spectacular cure of a persistent mixed anaerobic and aerobic infection of a kidney wound following nephropexy and sympathectomy which was achieved by general and local administration of a specially prepared undenatured antigen, I present the following case: Miss H. J., a schoolteacher, aged 59, entered St. Mary's Hospital April 6, 1936, for surgical relief of infected hydronephrosis secondary to ptosis and torsion of the right kidney. For the past 2 years she had been suffering from pain in the right abdomen, frequent urination, nycturia, high blood pressure and insomnia. In March 1935, a number of polypi of the bladder neck and a caruncle of the urethra were removed by fulguration. At this time complete 1 Read before the Section on Urology of the California Medical Association, Pasadena, May 11, 1938.
488
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
489
urological investigation revealed marked ptosis, torsion and staphylococcal pyelonephritis of the right kidney. A number of ureteral dilatations and pelvic lavages were made but failed to improve drainage or to eradicate chronic infection of the right kidney. The heart presented myocarditis. Blood pressure: systolic 210, diastolic 120. Examination of blood revealed hemoglobin 96 per cent, erythrocytes 4,900,000; leucocytes 13,400 and the differential count showed small lymphocytes 15, monocytes 1, neutrophiles 83 and eosinophiles 1. The urine was found to be slightly turbid, of acid reaction, with a specific gravity of 1,005, albumen positive and sugar negative. Microscopical examination revealed a few uric acid crystals, leucocytes 6 to 10 to H.D.F. and staphylococci. Palpation of the abdomen revealed a tender, fixed, low kidney presenting third degree ptosis. On April 7, 1936, sympathectomy and nephropexy of the right kidney were performed according to the author's technique. Following the operation the febrile reaction which was first considered as part of the usual postoperative reaction persisted. Every day the fever would vary from 100° to 101.8°. The rubber tissue drain which had been inserted in the kidney wound and brought out through the upper end of the skin incision was customarily removed about 1 cm. each day and was entirely withdrawn 9 days after the operation at which time the silk skin stitches were also removed. On April 15, the patient developed a severe sore throat. Bacteriological examination of smears taken from the throat showed spirilla, fusiform bacilli and pus cells. The throat infection responded to treatment by topical application of silver nitrate. The kidney wound had become swollen and indurated and saline compresses were applied. Five daily 2 gram doses of uretone were administered intravenously. The wound was exposed to heat and to the air. As the fever persisted it was thought that the patient might be suffering from an exacerbation of pyelonephritis in the right kidney caused by the handling of the kidney necessary to perform the nephropexy and sympathectomy. On May 7, lavage of the right kidney was performed, at which time B. coli were recovered from the bladder and right kidp.ey. The kidney wound was then opened in such a manner that the upper and lower portions were connected by an underlying sinus which was irrigated with boric acid solution by means of a catheter. On May 12, the entire wound was opened up, liberating a slight amount of sero-sanguinous exudate. The temperature receded and thereafter varied between 98.2° and 99°. The wound was irrigated with Dakin's solution and packed with gauze soaked in the well-known bismuth iodoform ointment. Heliotherapy was now employed. In spite of all these measures the low grade temperature persisted and on May 24 exploration of the wound revealed that a pocket had formed in the iliac fossa which connected with the lumbar incision. The sinus leading to this pocket was opened again liberating some sero-sanguinous material and
490
CHARLES PIERRE
MATHE
wide drainage was established. On June 1, 1936, a recheck pyelogram revealed that the right kidney had been placed high up in normal position and perfect drainage had been established (figs. 1 and 2) . The urine collected from the right kidney and bladder revealed staphylococci. It was felt that the source of the patient's infection was in the incision rather than in the kidney itself therefore it was decided to make a thorough exploration of the kidney wound under general anesthesia. This was performed on June 4 and examination of the wound revealed 3 connecting sinus tracts in the anterior abdominal wall (figs. 3 and 4). The first tract extended below the rectus muscle to the midline; the second tract extended under the subcutaneous fascia, across the midline to the upper left abdominal quadrant and the third tract extended subcutaneously to the right costal margin. All 3 tracts ended blindly. The blind ends were opened and the entire tracts were packed with iodoform gauze. No free pus was obtained. On June 11 roentgenograms of the abdomen were made and revealed no connection of these sinuses with the abdominal cavity. On June 13 a blood transfusion consisting of 750 cc of whole blood was administered. In spite of drainage of the wounds, kidney lavage, the use of urinary antiseptics and blood transfusion, the infection continued and fever persisted. Cultures taken by Dr. Elmer Smith, pathologist of St. Mary's Hospital, revealed Staphylococcus aureus. We realized that we were dealing with a bacteriological problem due to an anaerobic infection of the kidney wound and on the advice of Professor Karl Meyer, Dr. A. P . Krueger, of the Bacteriological Department of the University of California, was asked to make a detailed bacteriological study of this unusual infection. He identified an anaerobic streptococcus as well as the Staphylococcus aureus previously observed. While waiting for him to prepare undenatured antigens a number of injections of citrated whole blood obtained from donors immunized by a long course of injections of Staphylococcus aureus and mixed streptococcic undenatured bacterial antigens were given intramuscularly. In administering the immunized blood and specially prepared antigens all of Dr. Krueger's suggestions were meticulously carried out. Two forms of antigens were prepared from the Staphylococcus and the Streptococcus for general and local immunization. For general immunization 2 undenatured antigens of different strengths were made and were given intradermally and subcutaneously every other day. The intradermal dose of 0.1 cc of dilute antigen (No. 1) was repeated but not increased every other day. The subcutaneous dose was increased every other treatment until the patient received 0.5 cc which was found to be the maintenance dose i.e., that producing clinical improvement without reaction to the patient. When this was obtained the more concentrated antigen (No. 2) was administered repeating the procedure and dosage as for the dilute antigen No. 1. For local immunization a specially prepared
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
491
FIG.2
FIG.
3
FIG. 1. Pyelogram taken in vertical position demonstrating third degree ptosis, torsion and early hydronephrosis of right kidney. FIG. 2. Vertical pyelogram taken 1 month after nephropexy and sympathetectomy showing fixation of right kidney in perfect anatomical position and regression of hydronephrosis. Lateral to kidney one notes an opaque shadow due to bismuth that had been injected into infected wound pocket. FIG. 3. Roentgenogram demonstrating renal wound with its pockets and connecting sinus tracts in anterior abdominal wall. Course of these tracts formed by anaerobic infection is well shown by indwelling rubber tubes. FIG. 4. Schematic illustration showing infected renal wound and its connecting pockets and sinus tracts.
antigen was injected daily in all pockets and sinuses making up the wound for the purpose of inducing local immunization alternately with SO per cent hydro-
--------- ------ - ~ - -
492
---·
------·----- - - -
CHARLES PIERRE MATHE
gen peroxide solution. Immediately following the intradermal, subcutaneous and local application of the antigen, marked improvement in the kidney wound was observed. The temperature promptly receded and although it occasionally went up to 99° it became normal on July 4, 2½ weeks after the institution of antigen therapy. The patient left the hospital on July 10. The sinus tracts had healed and the original lumbar wound with its extension into the iliac fossa was rapidly closing. On July 24, 1936, the entire wound had healed. The patient returned to her occupation as a schoolteacher and recheck examination on February 17, 1938, revealed marked reduction of blood pressure, the systolic now being 158 and diastolic 110 !!! She is enjoying good health and the urine has remained free from infection.
Problems of diagnosis. The acute fulminating type of gas gangrene of kidney wounds caused by the Vibrion Septique of Pasteur and the Welch bacillus in combination with each other and with associated anerobes and aerobes presents clinical forms which are readily recognized. Three different types of emphysematous gas gangrene were described by M. Weinberg in 1923. He was the pioneer in this field and successfully worked out its sero-therapy based on employing a combined serum made from the different anaerobes and aerobes found to be present in the infected wound. This method of employing polyvolent sera was found to be most successful in combating gas gangrene. The first clinical form is characterized by emphysematous infiltration of the wound, the appearance of bronze induration of the skin and hemorrhagic phlyctena. The second type consists of extensive and progressive edema of the wound (so-called white edema). The third form is characterized by enormous gas infiltration with gangrene of the wound. A putrid odor is usually present however in some cases it may be lacking. In all 3 forms the general condition of the patient is grave. He presents extreme prostration, pallor of the face, rapid, weak, irregular pulse and other signs of extreme intoxication which often rapidly terminate in death. Bacteriological examination of the wound employing the proper anaerobic culture medium will reveal the offending organisms. The chronic insidious type of anaerobic infection of kidney wounds offers a greater problem for diagnosis. One is often deceived as the induration of the wound which is encountered at the onset is ordinarily ascribed to the usual postoperative swelling and induration of the tissues. The inflammatory process does not undergo suppuration and has a tendency to form blind pockets and sinuses as was observed in our case. In opening these a sero-sanguinous exudate and not free pus is en-
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
493
countered. However associated aerobic pus-producing organisms which sometimes live in symbiosis might result in pus formation. The offend~ ing anaerobes are often missed if one employs the methods of culture generally used in our present day hospitals. Cultures should be made on proper anaerobic media preferably by a bacteriologist who has had wide experience in the cultivation of anaerobes. When one encounters an infection which resists the usual forms of local treatment one should suspect anaerobic infection and make the proper bacteriological examination by virtue of which scientific sero-therapy can be added to surgical treatment. Treatment. The treatment of emphysematous gas gangrene consists of surgical resection of the affected area and sero-therapy. In employing sero-therapy best results are obtained by employing a serum specially prepared from the 5 commonly known infecting anaerobes in combination with that obtained from associated aerobes. In skilled hands the results obtained by the use of sero-therapy are good and one must take cognizance of the excellent results obtained by Weinberg during the World War who reported 19 cu.res in 24 extremely grave cases of gas gangrene and 50 cures in 60 treated cases of pseudo-grave gas infection. He observed that successful results are in direct proportion to the number of specific serums prepared from the following 5 anaerobes that have been identified as the causative organisms in the production of gas gangrene, viz: Vibrion Septique, Welch Bacillus, B. Histolyticus, B. Sporogenes, and B. Oedematus. He advises that 100 cc of the combined serum be injected subcutaneously through a fine needle taking one and a half hours for the injection. When one encounters emphysematous gangrene of a kidney wound one should make an injection ofpolyvalent serum immediately. Surgical resection should also be carried out at once and in order to expedite matters the serum might be injected during the operation while the patient is under anesthesia. We have observ~d 1 case of extensive gangrene of a kidney wound extending to and involving the scrotum which was relieved by surgical resection, drainage and the employment of Professor Weinberg's polyvalent anaerobic serum obtained from the Pasteur Institute in Paris in 1930. We have also witnessed 2 other cases of fatal gas gangrene and although they did not involve the lumbar wound, they are of sufficient interest to mention in passing. One patient seen with Dr. George Oviedo on whom prostatectomy had been performed the day before in a hospital in which we are not regularly doing work succumbed from gas gangrene of the thigh fol-
494
CHARLES PIERRE MATHE
lowing a hypodermic injection in a room that had just been occupied by a patient who had died of gas gangrene. The second patient, also one of our prostatics who had been relieved by transurethral resection, succumbed from gas gangrene of the thigh 36 hours after amputation of the lower extremity by a general surgeon for gangrene secondary to obliterative endarteritis. Treatment of the more benign chronic type of anaerobic infection of kidney wounds consists of surgical drainage as well as sero-therapy which is well exemplified by the management of our particular case in which infection was found to be due to the Staphylococcus aureus and to an anaerobic streptococcus. The patient showed absolutely no capacity to react against this rather overwhelming infection and on the advice of Dr. A. P. Krueger, immunity was established by supplying her with some preformed immune bodies. Blood was obtained from donors who had been immunized by a long course of injections of Staphylococcus aureus and mixed streptococcal undenatured bacterial antigens. This blood was citrated and inj'ected intramuscularly with the idea of producing local deposits of antibodies in the recipient's tissues. From these deposits a constant flow of anti-bodies into the blood stream enabled the patient to regain some degree of tissue reactivity so that she could suqsequently respond to injections of antigen, thereby developing an active immunity. Two forms of autogenous undenatured bacterial antigens specially prepared by Dr. Krueger from the Staphylococcus aureus and the streptococcus were utilized. Krueger, Cutler, Vaughan and others have shown that in employing antigen therapy the immune response to native cell proteins is more effective and quite different to that exhibited toward denatured cell proteins . . Therefore undenatured antigens were obtained by Dr. Krueger by making mass cultures of the organisms by growing them in Roux flasks. The cells were harvested in Locke's solution and were washed in order to free them from non-specific media proteins. These were ground in the special Krueger mechanical roll mill and the intact cells were removed by ultrafiltration through an acetic collodion membrane. The ultrafiltrate contains the unaltered cell constituents in 2 phases (1) the soluble phase and (2) the colloidal phase. The ultrafiltrate was prepared in 2 dilutions for hypodermic administration with the idea of developing general immunity. An aliquot of the ultrafiltrate was prepared in 1 per cent peptone solution for local immunization and was used directly in all the sinuses and pockets of the wound. The advantages of the undenatured bacterial antigens is that they do 1+ot
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
495
produce non-specific reactions, they contain no unnecessary medium proteins or metabolites, their activity is specific and they are rapidly dissolved in body fluids. In addition to sero-therapy all pockets should be drained and blind sinuses opened up. These should be injected with antigen according to the method of local immunity discovered by Besredka and bathed with peroxide of hydrogen which has a beneficial effect in inhibiting the growth of anaerobes. CONCLUSIONS
A case of overwhelming infection of a kidney wound following nephropexy and sympathectomy due to an anaerobic streptococcus as well as to the Staphylococcus aureus is reported. This infection resisted all forms of treatment including compressing, surgical drainage, lavage with commonly used antiseptic solutions, local and general use of chemotherapy, etc. The anaerobic nature of the infection was diagnosed by special culture. Prompt cure followed the institution of sero-therapy. This consisted of establishing the patient's tissue reactivity to antigen therapy to be used later by supplying her with intramuscular injections of preformed immune bodies contained in blood secured from donors previously immunized by a long course of injections of undenatured antigen obtained from the above mentioned offending organisms. Spectacular cure followed the intradermal, subcutaneous and local injection of undenatured bacterial antigens. Anaerobic infections of kidney wounds present an immunological as well as a surgical problem and its cure is best obtained by the cooperation of the surgeon with the bacteriologist.
450 Sutter Street, San Francisco, Calif. REFERENCES BESREDKA, A.: Immunisation Locale. Masson and Cie., Paris, 1925. CUTLER, 0 .: Immune reactions to acid treated bacteria. J. Infect. Dis., 44: 203, 1929. KRUEGER, A. P. : New type of roll mill for maceration of tissues and bacteria under aseptic conditions. J. Infect. Dis., 63: 185, 1933. KREUGER, A. P .: A method for the preparation of bacterial antigens. J. Infect. Dis., 63: 237, 1933. KREUGER, A. P.: The preparation of a graded series of ultrafilters and measurements of their pore sizes. J. Gen. Physiol., 13: 409, 1930. VAUGHAN, V. C.: A study of bacterial cells. Tr. A. Am. Physicians, 17: 327, 1902. WEINBERG, M.: Le Serum Antigangreneux et Son Emploi en Therapeutique. Soc. Gle. d'Imp. et d'Edit., Paris, 1923.
The diagnosis and treatment of anaerobic infection of lumbar wounds following operative interference on the kidney offers quite a problem to the kidney surgeon. Two types of this uncommon wound infection are encountered: (1) the acute rapidly fatal gas gangrene type necessitating immediate heroic measures and (2) the more mild chronic type of persistent infection requiring less heroic but equally technical care. The acute fulminating type is well recognized; it occurred rather often in wounds during the World War, occasionally takes place after operations on the abdomen and extremities and is a common complication of traumatizing wounds resulting from automobile and train accidents. Gas gangrene infection of the wound is readily recognized by the sudden onset of emphysematous infiltration of the tissues, bronze induration and hemorrhagic phlyctena of the skin, is accompanied by extreme prostration and grave general symptoms often terminating rapidly in death. This type demands immediate surgical resection of the affected area as well as intelligent administration of serum therapy. The second type of chronic insidious infection offers a greater problem for diagnosis and is recognized only by expert bacteriological examination. Both types are amenable to sere-therapy in conjunction with surgical treatment and good results will be in proportion to the correct local and general administration of properly selected antigens in proper doses. Having recently observed a spectacular cure of a persistent mixed anaerobic and aerobic infection of a kidney wound following nephropexy and sympathectomy which was achieved by general and local administration of a specially prepared undenatured antigen, I present the following case: Miss H. J., a schoolteacher, aged 59, entered St. Mary's Hospital April 6, 1936, for surgical relief of infected hydronephrosis secondary to ptosis and torsion of the right kidney. For the past 2 years she had been suffering from pain in the right abdomen, frequent urination, nycturia, high blood pressure and insomnia. In March 1935, a number of polypi of the bladder neck and a caruncle of the urethra were removed by fulguration. At this time complete 1 Read before the Section on Urology of the California Medical Association, Pasadena, May 11, 1938.
488
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
489
urological investigation revealed marked ptosis, torsion and staphylococcal pyelonephritis of the right kidney. A number of ureteral dilatations and pelvic lavages were made but failed to improve drainage or to eradicate chronic infection of the right kidney. The heart presented myocarditis. Blood pressure: systolic 210, diastolic 120. Examination of blood revealed hemoglobin 96 per cent, erythrocytes 4,900,000; leucocytes 13,400 and the differential count showed small lymphocytes 15, monocytes 1, neutrophiles 83 and eosinophiles 1. The urine was found to be slightly turbid, of acid reaction, with a specific gravity of 1,005, albumen positive and sugar negative. Microscopical examination revealed a few uric acid crystals, leucocytes 6 to 10 to H.D.F. and staphylococci. Palpation of the abdomen revealed a tender, fixed, low kidney presenting third degree ptosis. On April 7, 1936, sympathectomy and nephropexy of the right kidney were performed according to the author's technique. Following the operation the febrile reaction which was first considered as part of the usual postoperative reaction persisted. Every day the fever would vary from 100° to 101.8°. The rubber tissue drain which had been inserted in the kidney wound and brought out through the upper end of the skin incision was customarily removed about 1 cm. each day and was entirely withdrawn 9 days after the operation at which time the silk skin stitches were also removed. On April 15, the patient developed a severe sore throat. Bacteriological examination of smears taken from the throat showed spirilla, fusiform bacilli and pus cells. The throat infection responded to treatment by topical application of silver nitrate. The kidney wound had become swollen and indurated and saline compresses were applied. Five daily 2 gram doses of uretone were administered intravenously. The wound was exposed to heat and to the air. As the fever persisted it was thought that the patient might be suffering from an exacerbation of pyelonephritis in the right kidney caused by the handling of the kidney necessary to perform the nephropexy and sympathectomy. On May 7, lavage of the right kidney was performed, at which time B. coli were recovered from the bladder and right kidp.ey. The kidney wound was then opened in such a manner that the upper and lower portions were connected by an underlying sinus which was irrigated with boric acid solution by means of a catheter. On May 12, the entire wound was opened up, liberating a slight amount of sero-sanguinous exudate. The temperature receded and thereafter varied between 98.2° and 99°. The wound was irrigated with Dakin's solution and packed with gauze soaked in the well-known bismuth iodoform ointment. Heliotherapy was now employed. In spite of all these measures the low grade temperature persisted and on May 24 exploration of the wound revealed that a pocket had formed in the iliac fossa which connected with the lumbar incision. The sinus leading to this pocket was opened again liberating some sero-sanguinous material and
490
CHARLES PIERRE
MATHE
wide drainage was established. On June 1, 1936, a recheck pyelogram revealed that the right kidney had been placed high up in normal position and perfect drainage had been established (figs. 1 and 2) . The urine collected from the right kidney and bladder revealed staphylococci. It was felt that the source of the patient's infection was in the incision rather than in the kidney itself therefore it was decided to make a thorough exploration of the kidney wound under general anesthesia. This was performed on June 4 and examination of the wound revealed 3 connecting sinus tracts in the anterior abdominal wall (figs. 3 and 4). The first tract extended below the rectus muscle to the midline; the second tract extended under the subcutaneous fascia, across the midline to the upper left abdominal quadrant and the third tract extended subcutaneously to the right costal margin. All 3 tracts ended blindly. The blind ends were opened and the entire tracts were packed with iodoform gauze. No free pus was obtained. On June 11 roentgenograms of the abdomen were made and revealed no connection of these sinuses with the abdominal cavity. On June 13 a blood transfusion consisting of 750 cc of whole blood was administered. In spite of drainage of the wounds, kidney lavage, the use of urinary antiseptics and blood transfusion, the infection continued and fever persisted. Cultures taken by Dr. Elmer Smith, pathologist of St. Mary's Hospital, revealed Staphylococcus aureus. We realized that we were dealing with a bacteriological problem due to an anaerobic infection of the kidney wound and on the advice of Professor Karl Meyer, Dr. A. P . Krueger, of the Bacteriological Department of the University of California, was asked to make a detailed bacteriological study of this unusual infection. He identified an anaerobic streptococcus as well as the Staphylococcus aureus previously observed. While waiting for him to prepare undenatured antigens a number of injections of citrated whole blood obtained from donors immunized by a long course of injections of Staphylococcus aureus and mixed streptococcic undenatured bacterial antigens were given intramuscularly. In administering the immunized blood and specially prepared antigens all of Dr. Krueger's suggestions were meticulously carried out. Two forms of antigens were prepared from the Staphylococcus and the Streptococcus for general and local immunization. For general immunization 2 undenatured antigens of different strengths were made and were given intradermally and subcutaneously every other day. The intradermal dose of 0.1 cc of dilute antigen (No. 1) was repeated but not increased every other day. The subcutaneous dose was increased every other treatment until the patient received 0.5 cc which was found to be the maintenance dose i.e., that producing clinical improvement without reaction to the patient. When this was obtained the more concentrated antigen (No. 2) was administered repeating the procedure and dosage as for the dilute antigen No. 1. For local immunization a specially prepared
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
491
FIG.2
FIG.
3
FIG. 1. Pyelogram taken in vertical position demonstrating third degree ptosis, torsion and early hydronephrosis of right kidney. FIG. 2. Vertical pyelogram taken 1 month after nephropexy and sympathetectomy showing fixation of right kidney in perfect anatomical position and regression of hydronephrosis. Lateral to kidney one notes an opaque shadow due to bismuth that had been injected into infected wound pocket. FIG. 3. Roentgenogram demonstrating renal wound with its pockets and connecting sinus tracts in anterior abdominal wall. Course of these tracts formed by anaerobic infection is well shown by indwelling rubber tubes. FIG. 4. Schematic illustration showing infected renal wound and its connecting pockets and sinus tracts.
antigen was injected daily in all pockets and sinuses making up the wound for the purpose of inducing local immunization alternately with SO per cent hydro-
--------- ------ - ~ - -
492
---·
------·----- - - -
CHARLES PIERRE MATHE
gen peroxide solution. Immediately following the intradermal, subcutaneous and local application of the antigen, marked improvement in the kidney wound was observed. The temperature promptly receded and although it occasionally went up to 99° it became normal on July 4, 2½ weeks after the institution of antigen therapy. The patient left the hospital on July 10. The sinus tracts had healed and the original lumbar wound with its extension into the iliac fossa was rapidly closing. On July 24, 1936, the entire wound had healed. The patient returned to her occupation as a schoolteacher and recheck examination on February 17, 1938, revealed marked reduction of blood pressure, the systolic now being 158 and diastolic 110 !!! She is enjoying good health and the urine has remained free from infection.
Problems of diagnosis. The acute fulminating type of gas gangrene of kidney wounds caused by the Vibrion Septique of Pasteur and the Welch bacillus in combination with each other and with associated anerobes and aerobes presents clinical forms which are readily recognized. Three different types of emphysematous gas gangrene were described by M. Weinberg in 1923. He was the pioneer in this field and successfully worked out its sero-therapy based on employing a combined serum made from the different anaerobes and aerobes found to be present in the infected wound. This method of employing polyvolent sera was found to be most successful in combating gas gangrene. The first clinical form is characterized by emphysematous infiltration of the wound, the appearance of bronze induration of the skin and hemorrhagic phlyctena. The second type consists of extensive and progressive edema of the wound (so-called white edema). The third form is characterized by enormous gas infiltration with gangrene of the wound. A putrid odor is usually present however in some cases it may be lacking. In all 3 forms the general condition of the patient is grave. He presents extreme prostration, pallor of the face, rapid, weak, irregular pulse and other signs of extreme intoxication which often rapidly terminate in death. Bacteriological examination of the wound employing the proper anaerobic culture medium will reveal the offending organisms. The chronic insidious type of anaerobic infection of kidney wounds offers a greater problem for diagnosis. One is often deceived as the induration of the wound which is encountered at the onset is ordinarily ascribed to the usual postoperative swelling and induration of the tissues. The inflammatory process does not undergo suppuration and has a tendency to form blind pockets and sinuses as was observed in our case. In opening these a sero-sanguinous exudate and not free pus is en-
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
493
countered. However associated aerobic pus-producing organisms which sometimes live in symbiosis might result in pus formation. The offend~ ing anaerobes are often missed if one employs the methods of culture generally used in our present day hospitals. Cultures should be made on proper anaerobic media preferably by a bacteriologist who has had wide experience in the cultivation of anaerobes. When one encounters an infection which resists the usual forms of local treatment one should suspect anaerobic infection and make the proper bacteriological examination by virtue of which scientific sero-therapy can be added to surgical treatment. Treatment. The treatment of emphysematous gas gangrene consists of surgical resection of the affected area and sero-therapy. In employing sero-therapy best results are obtained by employing a serum specially prepared from the 5 commonly known infecting anaerobes in combination with that obtained from associated aerobes. In skilled hands the results obtained by the use of sero-therapy are good and one must take cognizance of the excellent results obtained by Weinberg during the World War who reported 19 cu.res in 24 extremely grave cases of gas gangrene and 50 cures in 60 treated cases of pseudo-grave gas infection. He observed that successful results are in direct proportion to the number of specific serums prepared from the following 5 anaerobes that have been identified as the causative organisms in the production of gas gangrene, viz: Vibrion Septique, Welch Bacillus, B. Histolyticus, B. Sporogenes, and B. Oedematus. He advises that 100 cc of the combined serum be injected subcutaneously through a fine needle taking one and a half hours for the injection. When one encounters emphysematous gangrene of a kidney wound one should make an injection ofpolyvalent serum immediately. Surgical resection should also be carried out at once and in order to expedite matters the serum might be injected during the operation while the patient is under anesthesia. We have observ~d 1 case of extensive gangrene of a kidney wound extending to and involving the scrotum which was relieved by surgical resection, drainage and the employment of Professor Weinberg's polyvalent anaerobic serum obtained from the Pasteur Institute in Paris in 1930. We have also witnessed 2 other cases of fatal gas gangrene and although they did not involve the lumbar wound, they are of sufficient interest to mention in passing. One patient seen with Dr. George Oviedo on whom prostatectomy had been performed the day before in a hospital in which we are not regularly doing work succumbed from gas gangrene of the thigh fol-
494
CHARLES PIERRE MATHE
lowing a hypodermic injection in a room that had just been occupied by a patient who had died of gas gangrene. The second patient, also one of our prostatics who had been relieved by transurethral resection, succumbed from gas gangrene of the thigh 36 hours after amputation of the lower extremity by a general surgeon for gangrene secondary to obliterative endarteritis. Treatment of the more benign chronic type of anaerobic infection of kidney wounds consists of surgical drainage as well as sero-therapy which is well exemplified by the management of our particular case in which infection was found to be due to the Staphylococcus aureus and to an anaerobic streptococcus. The patient showed absolutely no capacity to react against this rather overwhelming infection and on the advice of Dr. A. P. Krueger, immunity was established by supplying her with some preformed immune bodies. Blood was obtained from donors who had been immunized by a long course of injections of Staphylococcus aureus and mixed streptococcal undenatured bacterial antigens. This blood was citrated and inj'ected intramuscularly with the idea of producing local deposits of antibodies in the recipient's tissues. From these deposits a constant flow of anti-bodies into the blood stream enabled the patient to regain some degree of tissue reactivity so that she could suqsequently respond to injections of antigen, thereby developing an active immunity. Two forms of autogenous undenatured bacterial antigens specially prepared by Dr. Krueger from the Staphylococcus aureus and the streptococcus were utilized. Krueger, Cutler, Vaughan and others have shown that in employing antigen therapy the immune response to native cell proteins is more effective and quite different to that exhibited toward denatured cell proteins . . Therefore undenatured antigens were obtained by Dr. Krueger by making mass cultures of the organisms by growing them in Roux flasks. The cells were harvested in Locke's solution and were washed in order to free them from non-specific media proteins. These were ground in the special Krueger mechanical roll mill and the intact cells were removed by ultrafiltration through an acetic collodion membrane. The ultrafiltrate contains the unaltered cell constituents in 2 phases (1) the soluble phase and (2) the colloidal phase. The ultrafiltrate was prepared in 2 dilutions for hypodermic administration with the idea of developing general immunity. An aliquot of the ultrafiltrate was prepared in 1 per cent peptone solution for local immunization and was used directly in all the sinuses and pockets of the wound. The advantages of the undenatured bacterial antigens is that they do 1+ot
SECONDARY ANAEROBIC INFECTIONS OF KIDNEY WOUND
495
produce non-specific reactions, they contain no unnecessary medium proteins or metabolites, their activity is specific and they are rapidly dissolved in body fluids. In addition to sero-therapy all pockets should be drained and blind sinuses opened up. These should be injected with antigen according to the method of local immunity discovered by Besredka and bathed with peroxide of hydrogen which has a beneficial effect in inhibiting the growth of anaerobes. CONCLUSIONS
A case of overwhelming infection of a kidney wound following nephropexy and sympathectomy due to an anaerobic streptococcus as well as to the Staphylococcus aureus is reported. This infection resisted all forms of treatment including compressing, surgical drainage, lavage with commonly used antiseptic solutions, local and general use of chemotherapy, etc. The anaerobic nature of the infection was diagnosed by special culture. Prompt cure followed the institution of sero-therapy. This consisted of establishing the patient's tissue reactivity to antigen therapy to be used later by supplying her with intramuscular injections of preformed immune bodies contained in blood secured from donors previously immunized by a long course of injections of undenatured antigen obtained from the above mentioned offending organisms. Spectacular cure followed the intradermal, subcutaneous and local injection of undenatured bacterial antigens. Anaerobic infections of kidney wounds present an immunological as well as a surgical problem and its cure is best obtained by the cooperation of the surgeon with the bacteriologist.
450 Sutter Street, San Francisco, Calif. REFERENCES BESREDKA, A.: Immunisation Locale. Masson and Cie., Paris, 1925. CUTLER, 0 .: Immune reactions to acid treated bacteria. J. Infect. Dis., 44: 203, 1929. KRUEGER, A. P. : New type of roll mill for maceration of tissues and bacteria under aseptic conditions. J. Infect. Dis., 63: 185, 1933. KREUGER, A. P .: A method for the preparation of bacterial antigens. J. Infect. Dis., 63: 237, 1933. KREUGER, A. P.: The preparation of a graded series of ultrafilters and measurements of their pore sizes. J. Gen. Physiol., 13: 409, 1930. VAUGHAN, V. C.: A study of bacterial cells. Tr. A. Am. Physicians, 17: 327, 1902. WEINBERG, M.: Le Serum Antigangreneux et Son Emploi en Therapeutique. Soc. Gle. d'Imp. et d'Edit., Paris, 1923.