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Subacute bacterial endocarditis successfully treated with aureomycin
Case Report Subacute
Bacterial Treated
Endocarditis
Successfully
with Aureomycin” SIDNEY 0.
HUGHES, M.D.
Philadelphia, Pennsylvania
A
first admitted to the Presbyterian Hospital on November 9, 1948, with fever and joint pains. Past medical history included tonsillectomy at the age of four, rheumatic fever ,with chorea at the age of five which persisted for a year and pneumonia at the age of nine. From nine to thirteen she had occasional bouts of fever and joint pain. She had had one chill in the summer of 1947 and had lost weight. On admission she appeared undernourished, was febrile and had an enlarged liver palpable 2 cm. below the costal margin. A grade II systolic murmur was heard at the third interspace to the left of the sternum. A soft, blowing, aortic diastolic murmur was heard transmitted to the same area. The left ankle was slightly swollen and tender. No petechiae were noted. Laboratory data revealed a hemoglobin of 8.5 gm., 58.2 per cent, red cell count 4.35 million, leukocyte count 10.25 thousand, with a normal ratio of cells. The sedimentation rate (Westergren) was 48 to 118 mm. in one hour. The urine gave a 2 plus reaction for albumin. Eleven blood cultures were sterile. Elec-
UREOMYCIN has proved effective in a wide variety of infecting agents. Besides many bacteria aureomycin has proved useful against protozoa and spirochetes, rickettsia, virus and viral-like agents such as pleuropneumonia organisms. An extensive review of the literature reveals a few reports of the use of aureomycin in subacute bacterial endocarditis with varied results. Long’ cites two cases of patients with subacute bacterial endocarditis caused by Streptococcus faecalis who were treated successfully and followed for four months while Brainerd2 treated two similar patients with only a temporary clinical response. Harvey3 reporting four cases obtained a favorable result in only one. Dowling4 collected two cases, and one of the patients recovered. Astler? reported two cases, one due to Str. faecalis, treated with a combination of aureomycin and chloramphenico1 with a clinical response, but the blood culture remained positive. The other case succumbed from embolic complications. Allen6 reports a case of a patient who died from ulceration through the septum. A recent case discussed in a clinico-pathologic responded clinically but the conference7 patient died of renal failure. It is the purpose of this article to report three cases successfully treated with aureomycin and followed for periods of seven, ten and four months.
were repeatedly essentially trocardiograms normal. The course was that of a long febrile illness with temperature varying between 99°F. and 101”~. and occasionally rising to 102”~. On the
fifteenth hospital day the spleen was palpable and on the forty-fifth and sixtieth days ecchymoses were noted on the plantar surface of the right first toe and right elbow, respectively. The murmurs varied from day to day and frequently the diastolic component could not be heard. On the forty-fifth day penicillin and carinamide were prescribed in doses of 1 million units a day and 15 gm. a day, respectively, for forty days. The temperature gradually came down to normal, the sedimentation rate dropped
CASE REPORTS The first and most striking case is that of a thirteen year old Italian girl who was CASE I.
* From the Medical Division, Presbyterian Hospital, Philadelphia,
402
AMERICAN
Pa.
JOURNAL
OF
MEDIClNE
Aureomycin in Subacute Bacterial Endocarditis-Hughes to 42 mm. in one hour and the diastolic murmur disappeared completely. She was discharged on the hundredth day. She was followed regularly in the outpatient department, was afebrile and gained weight until October, 1949, when further elevation of the sedimentation rate developed to 91 mm. in one hour and the basal diastolic murmur recurred. She was readmitted on October 13, 1949, to Presbyterian Hospital. On the second admission physical examination disclosed a normal temperature, slight tachycardia and the same murmurs that were presented on the first admission. The spleen and liver were not palpable and no petechiae were noted. Laboratory studies revealed a hemoglobin of 12.6 gm., 86 per cent, red cell count 3.9 million, leukocyte count 5.3 thousand with 61 per cent filamented neutrophils, 7 per cent non-filamented neutrophils, 1 per cent eosinophils and 29 per cent lymphocytes. Sedimentation rate was 77 mm. in one hour. The urine gave a 2 plus reaction for albumin. On the twelfth hospital day the patient had a chill and the temperature rose to 103”~. A coagulase-negative hemolytic staphylococcus albus was cultured from the blood and found in vitro to be markedly resistant to penicillin, slightly sensitive to streptomycin and markedly sensitive to aureomycin. Aureomycin was prescribed on the fifteenth hospital day in a dose of 500 mg. every four hours for twenty-four hours and 250 mg. every four hours thereafter. The temperature promptly returned to normal but on the twenty-first day she had a chill, rise in temperature and petechiae were found on the right conjunctiva. The aureomycin was increased to 500 mg. every four hours. The temperature returned to normal, five blood cultures were sterile and she was discharged on the fortyfifth hospital day to the Children’s Heart Hospital, Philadelphia. There she was given 250 mg. aureomycin every four hours for three additional weeks. Six blood cultures in the next two months were sterile; she was afebrile. In February, 1950, she was sent to the Philadelphia General Hospital for study because of a rising sedimentation rate. Blood cultures were repeatedly sterile, and she was thought to have had a reactivation of her rheumatic fever which had responded to bed rest and salicylates. At this writing ten months have elapsed since treatment. Repeated blood cultures have been sterile, she has remained afebrile, the diastolic MARCH,
1951
403
murmur has disappeared and the sedimentation rate is 48 mm. in one hour. CASE II. A sixty-nine year old white female was admitted November 27, 1949, to Preshyterian Hospital with the chief complaint of recurrent fever. The patient had no history of cardiac disease. She had pneumonia in August, 1949, which was followed by a persistent cough, low grade fever, tachycardia and intermittent left abdominal pain. She had lost 27 pounds and was becoming progressively weaker. Prior to admission she had received 15 million units of penicillin over twenty-five days, then 8 gm. of aureomycin during the next fifteen days, each of which had produced a temporary fall of temperature to normal. Physical examination on admission revealed blood pressure 120,/50, pulse 88. A blowing grade III systolic murmur was heard at the apex and transmitted to the axilla. The spleen was not palpable and no petechiae were noted. Pertinent laboratory findings were hemoglobin 10 gm., 72 per cent, red blood count 3.5 million, leukocyte count 5.3 thousand with 50 per cent filamented neutrophils, 16 per cent non-filamented neutrophils and 30 per cent lymphocytes. The sedimentation rate (Westergren) was 59 mm. in one hour. Three positive blood cultures were obtained for Streptococcus viridans. In vitro the organism was markedly resistant to penicillin, streptomycin and slightly sensitive to aureomycin. During the first seven days the temperature rose sharply in the evenings to as high as 103°F. Aureomycin was prescribed on the seventh day with an initial dose of 500 mg. followed by 250 mg. every eight hours. The temperature returned to normal until the seventeenth day when it reached 102°F. and a petechia was seen on her palate, Aureomycin was increased to 500 mg. every six hours. The temperature gradually returned to normal and remained so. The sedimentation rate dropped to 14 mm. in one hour. The tnurmur diminished in intensity. Three subsequent blood cultures were sterile and she was discharged on the forty-fourth day. Aureomycin was continued over forty-five days in a total dose of 18 gm. Seven months have since elapsed, the patient has gained weight, has been afebrile and the murmur has practically disappeared. A sixteen year old white female was to Presbyterian Hospital on May 3,
CASE III.
admitted
1950, for study. The patient was born with a congenital heart lesion but had no tnanifestation
Aureomycin in Subacute Bacterial Endocarditis--Hughes other than a murmur. She had gained weight and developed normally, and school health authorities had reported the murmur without any other defects. Her activities had been somewhat limited by her family doctor. Two months prior to admission she noted excessive fatigue and weight loss. Three weeks previous to admission she began having a daily rise in temperature to about 102'F. associated with a chilly sensation. She was treated for pneumonia with unknown amounts of penicillin and aureomycin. On admission her blood pressure was 130/65, pulse 120 and temperature 101”~. She appeared pale and showed signs of recent weight loss. There were rales and dullness to percussion present at the right lung base. Examination of the heart revealed no enlargement. A machinery murmur was heard loudest over the pulmonic area but transmitted over the entire upper chest. The spleen was not palpable and no petechiae were noted. Laboratory data included a red blood count of 4.5 million with 12 gm. hemoglobin. White blood count was 7.1 thousand with 51 per cent filamented and 22 per cent non&lamented neutrophils. Sedimentation rate (Westergren) was 91 mm. in one hour. Urinalysis was normal. Multiple agglutinations were negative. Chest x-ray showed enlargement of the pulmonary artery with no definite evidence of patent ductus or pulmonary stenosis. Bilateral basal bronchopneumonia was present. Electrocardiogram was interpreted as acute car pulmonale with toxic myocardial changes. Her temperature fluctuated from 100”~. to 104°F. and her symptoms persisted. On the fourth hospital day Str. viridans was isolated from the blood. The organism in vitro was resistant to penicillin, moderately sensitive to streptomycin and markedly sensitive to aureomycin which was prescribed in a dose of 1.5 gm. a day. She began feeling better and her temperature returned to normal. On the twentieth hospital day her chest x-ray showed almost complete clearing of the pneumonic process and the sedimentation rate had dropped to 26 mm. in one hour. On the twenty-first hospital day ligation of the patent ductus arteriosus was performed and the convalescence was uneventful. Aureomycin was continued postoperatively in a dose of 3 gm. a day for two weeks. She was dis-
charged on the thirty-fifth hospital day. Since that time two blood cultures have been sterile, she has gained weight and remained afebrile. COMMENTS In case I the organism, usually susceptible to penicillin, became markedly resistant and the patient relapsed despite large doses of penicillin. In the second case the organism in vitro was only slightly sensitive to aureomycin but the clinical and bacteriologic response was excellent. The third case is difficult to evaluate in that frequently ligation alone is adequate therapy. However, the patient did so well pre- and postoperatively that I believe the aureomycin could well have been a contributing factor. No toxic reactions to aureomycin were noted except moderate initial nausea. SUMMARY
Three cases of patients with subacute bacterial endocarditis successfully treated with aureomycin have been presented. All patients had been previously treated with penicillin and the gram-positive organisms were markedly resistant to penicillin. REFERENCES 1. LONG, P. H., SCHOENBACH, E. B., BLISS,E. A., BRYER, M. S. and CHANDLER,C. A. The experimental and clinical use of polymyxin, chloromycetin and aureomycin. California Med., IO: 157, 1949. 2. BRAINERD, H. D. What’s new in aureomycin and other antibiotics. California Med., 71: 9, 1949. 3. HARVEY, J. C., MIRICK, G. S. and SCHAUB, I. G. Clinical experience with aureomycin. 3, Clin. Investigation, 28: 987, 1949. 4. DOWLING, H. F., LEPPER, M. H., CALDWELL, E. R., JR., WHELTON, R. L. and BRICKHOUSE, R. L. Aureomycin in various infections. M. Ann. District Columbia, 18: 335, 1949. 5. ANTLER, V. B. and MORGAN, H. R. Some biologic complications of the prophylactic and therapeutic use of antibiotics. Univ. Mich. M. Bull., 16: 127,195O. 6. ALLEN, A. W. and RIECHER, H. H. Bacterial endocarditis caused by a hemoiytic staphylococcus albus. 3. Michigan M. Sot., 48: 1461, 1949. 7. Clinico-pathologic Conference. Penicillin-resistant subacute bacterial endocarditis. Am. 3. Med., 8: 794, 1950.
AMERICAN
JOURNAL
OF
MEDICINE
Bacterial Treated
Endocarditis
Successfully
with Aureomycin” SIDNEY 0.
HUGHES, M.D.
Philadelphia, Pennsylvania
A
first admitted to the Presbyterian Hospital on November 9, 1948, with fever and joint pains. Past medical history included tonsillectomy at the age of four, rheumatic fever ,with chorea at the age of five which persisted for a year and pneumonia at the age of nine. From nine to thirteen she had occasional bouts of fever and joint pain. She had had one chill in the summer of 1947 and had lost weight. On admission she appeared undernourished, was febrile and had an enlarged liver palpable 2 cm. below the costal margin. A grade II systolic murmur was heard at the third interspace to the left of the sternum. A soft, blowing, aortic diastolic murmur was heard transmitted to the same area. The left ankle was slightly swollen and tender. No petechiae were noted. Laboratory data revealed a hemoglobin of 8.5 gm., 58.2 per cent, red cell count 4.35 million, leukocyte count 10.25 thousand, with a normal ratio of cells. The sedimentation rate (Westergren) was 48 to 118 mm. in one hour. The urine gave a 2 plus reaction for albumin. Eleven blood cultures were sterile. Elec-
UREOMYCIN has proved effective in a wide variety of infecting agents. Besides many bacteria aureomycin has proved useful against protozoa and spirochetes, rickettsia, virus and viral-like agents such as pleuropneumonia organisms. An extensive review of the literature reveals a few reports of the use of aureomycin in subacute bacterial endocarditis with varied results. Long’ cites two cases of patients with subacute bacterial endocarditis caused by Streptococcus faecalis who were treated successfully and followed for four months while Brainerd2 treated two similar patients with only a temporary clinical response. Harvey3 reporting four cases obtained a favorable result in only one. Dowling4 collected two cases, and one of the patients recovered. Astler? reported two cases, one due to Str. faecalis, treated with a combination of aureomycin and chloramphenico1 with a clinical response, but the blood culture remained positive. The other case succumbed from embolic complications. Allen6 reports a case of a patient who died from ulceration through the septum. A recent case discussed in a clinico-pathologic responded clinically but the conference7 patient died of renal failure. It is the purpose of this article to report three cases successfully treated with aureomycin and followed for periods of seven, ten and four months.
were repeatedly essentially trocardiograms normal. The course was that of a long febrile illness with temperature varying between 99°F. and 101”~. and occasionally rising to 102”~. On the
fifteenth hospital day the spleen was palpable and on the forty-fifth and sixtieth days ecchymoses were noted on the plantar surface of the right first toe and right elbow, respectively. The murmurs varied from day to day and frequently the diastolic component could not be heard. On the forty-fifth day penicillin and carinamide were prescribed in doses of 1 million units a day and 15 gm. a day, respectively, for forty days. The temperature gradually came down to normal, the sedimentation rate dropped
CASE REPORTS The first and most striking case is that of a thirteen year old Italian girl who was CASE I.
* From the Medical Division, Presbyterian Hospital, Philadelphia,
402
AMERICAN
Pa.
JOURNAL
OF
MEDIClNE
Aureomycin in Subacute Bacterial Endocarditis-Hughes to 42 mm. in one hour and the diastolic murmur disappeared completely. She was discharged on the hundredth day. She was followed regularly in the outpatient department, was afebrile and gained weight until October, 1949, when further elevation of the sedimentation rate developed to 91 mm. in one hour and the basal diastolic murmur recurred. She was readmitted on October 13, 1949, to Presbyterian Hospital. On the second admission physical examination disclosed a normal temperature, slight tachycardia and the same murmurs that were presented on the first admission. The spleen and liver were not palpable and no petechiae were noted. Laboratory studies revealed a hemoglobin of 12.6 gm., 86 per cent, red cell count 3.9 million, leukocyte count 5.3 thousand with 61 per cent filamented neutrophils, 7 per cent non-filamented neutrophils, 1 per cent eosinophils and 29 per cent lymphocytes. Sedimentation rate was 77 mm. in one hour. The urine gave a 2 plus reaction for albumin. On the twelfth hospital day the patient had a chill and the temperature rose to 103”~. A coagulase-negative hemolytic staphylococcus albus was cultured from the blood and found in vitro to be markedly resistant to penicillin, slightly sensitive to streptomycin and markedly sensitive to aureomycin. Aureomycin was prescribed on the fifteenth hospital day in a dose of 500 mg. every four hours for twenty-four hours and 250 mg. every four hours thereafter. The temperature promptly returned to normal but on the twenty-first day she had a chill, rise in temperature and petechiae were found on the right conjunctiva. The aureomycin was increased to 500 mg. every four hours. The temperature returned to normal, five blood cultures were sterile and she was discharged on the fortyfifth hospital day to the Children’s Heart Hospital, Philadelphia. There she was given 250 mg. aureomycin every four hours for three additional weeks. Six blood cultures in the next two months were sterile; she was afebrile. In February, 1950, she was sent to the Philadelphia General Hospital for study because of a rising sedimentation rate. Blood cultures were repeatedly sterile, and she was thought to have had a reactivation of her rheumatic fever which had responded to bed rest and salicylates. At this writing ten months have elapsed since treatment. Repeated blood cultures have been sterile, she has remained afebrile, the diastolic MARCH,
1951
403
murmur has disappeared and the sedimentation rate is 48 mm. in one hour. CASE II. A sixty-nine year old white female was admitted November 27, 1949, to Preshyterian Hospital with the chief complaint of recurrent fever. The patient had no history of cardiac disease. She had pneumonia in August, 1949, which was followed by a persistent cough, low grade fever, tachycardia and intermittent left abdominal pain. She had lost 27 pounds and was becoming progressively weaker. Prior to admission she had received 15 million units of penicillin over twenty-five days, then 8 gm. of aureomycin during the next fifteen days, each of which had produced a temporary fall of temperature to normal. Physical examination on admission revealed blood pressure 120,/50, pulse 88. A blowing grade III systolic murmur was heard at the apex and transmitted to the axilla. The spleen was not palpable and no petechiae were noted. Pertinent laboratory findings were hemoglobin 10 gm., 72 per cent, red blood count 3.5 million, leukocyte count 5.3 thousand with 50 per cent filamented neutrophils, 16 per cent non-filamented neutrophils and 30 per cent lymphocytes. The sedimentation rate (Westergren) was 59 mm. in one hour. Three positive blood cultures were obtained for Streptococcus viridans. In vitro the organism was markedly resistant to penicillin, streptomycin and slightly sensitive to aureomycin. During the first seven days the temperature rose sharply in the evenings to as high as 103°F. Aureomycin was prescribed on the seventh day with an initial dose of 500 mg. followed by 250 mg. every eight hours. The temperature returned to normal until the seventeenth day when it reached 102°F. and a petechia was seen on her palate, Aureomycin was increased to 500 mg. every six hours. The temperature gradually returned to normal and remained so. The sedimentation rate dropped to 14 mm. in one hour. The tnurmur diminished in intensity. Three subsequent blood cultures were sterile and she was discharged on the forty-fourth day. Aureomycin was continued over forty-five days in a total dose of 18 gm. Seven months have since elapsed, the patient has gained weight, has been afebrile and the murmur has practically disappeared. A sixteen year old white female was to Presbyterian Hospital on May 3,
CASE III.
admitted
1950, for study. The patient was born with a congenital heart lesion but had no tnanifestation
Aureomycin in Subacute Bacterial Endocarditis--Hughes other than a murmur. She had gained weight and developed normally, and school health authorities had reported the murmur without any other defects. Her activities had been somewhat limited by her family doctor. Two months prior to admission she noted excessive fatigue and weight loss. Three weeks previous to admission she began having a daily rise in temperature to about 102'F. associated with a chilly sensation. She was treated for pneumonia with unknown amounts of penicillin and aureomycin. On admission her blood pressure was 130/65, pulse 120 and temperature 101”~. She appeared pale and showed signs of recent weight loss. There were rales and dullness to percussion present at the right lung base. Examination of the heart revealed no enlargement. A machinery murmur was heard loudest over the pulmonic area but transmitted over the entire upper chest. The spleen was not palpable and no petechiae were noted. Laboratory data included a red blood count of 4.5 million with 12 gm. hemoglobin. White blood count was 7.1 thousand with 51 per cent filamented and 22 per cent non&lamented neutrophils. Sedimentation rate (Westergren) was 91 mm. in one hour. Urinalysis was normal. Multiple agglutinations were negative. Chest x-ray showed enlargement of the pulmonary artery with no definite evidence of patent ductus or pulmonary stenosis. Bilateral basal bronchopneumonia was present. Electrocardiogram was interpreted as acute car pulmonale with toxic myocardial changes. Her temperature fluctuated from 100”~. to 104°F. and her symptoms persisted. On the fourth hospital day Str. viridans was isolated from the blood. The organism in vitro was resistant to penicillin, moderately sensitive to streptomycin and markedly sensitive to aureomycin which was prescribed in a dose of 1.5 gm. a day. She began feeling better and her temperature returned to normal. On the twentieth hospital day her chest x-ray showed almost complete clearing of the pneumonic process and the sedimentation rate had dropped to 26 mm. in one hour. On the twenty-first hospital day ligation of the patent ductus arteriosus was performed and the convalescence was uneventful. Aureomycin was continued postoperatively in a dose of 3 gm. a day for two weeks. She was dis-
charged on the thirty-fifth hospital day. Since that time two blood cultures have been sterile, she has gained weight and remained afebrile. COMMENTS In case I the organism, usually susceptible to penicillin, became markedly resistant and the patient relapsed despite large doses of penicillin. In the second case the organism in vitro was only slightly sensitive to aureomycin but the clinical and bacteriologic response was excellent. The third case is difficult to evaluate in that frequently ligation alone is adequate therapy. However, the patient did so well pre- and postoperatively that I believe the aureomycin could well have been a contributing factor. No toxic reactions to aureomycin were noted except moderate initial nausea. SUMMARY
Three cases of patients with subacute bacterial endocarditis successfully treated with aureomycin have been presented. All patients had been previously treated with penicillin and the gram-positive organisms were markedly resistant to penicillin. REFERENCES 1. LONG, P. H., SCHOENBACH, E. B., BLISS,E. A., BRYER, M. S. and CHANDLER,C. A. The experimental and clinical use of polymyxin, chloromycetin and aureomycin. California Med., IO: 157, 1949. 2. BRAINERD, H. D. What’s new in aureomycin and other antibiotics. California Med., 71: 9, 1949. 3. HARVEY, J. C., MIRICK, G. S. and SCHAUB, I. G. Clinical experience with aureomycin. 3, Clin. Investigation, 28: 987, 1949. 4. DOWLING, H. F., LEPPER, M. H., CALDWELL, E. R., JR., WHELTON, R. L. and BRICKHOUSE, R. L. Aureomycin in various infections. M. Ann. District Columbia, 18: 335, 1949. 5. ANTLER, V. B. and MORGAN, H. R. Some biologic complications of the prophylactic and therapeutic use of antibiotics. Univ. Mich. M. Bull., 16: 127,195O. 6. ALLEN, A. W. and RIECHER, H. H. Bacterial endocarditis caused by a hemoiytic staphylococcus albus. 3. Michigan M. Sot., 48: 1461, 1949. 7. Clinico-pathologic Conference. Penicillin-resistant subacute bacterial endocarditis. Am. 3. Med., 8: 794, 1950.
AMERICAN
JOURNAL
OF
MEDICINE