Group G Streptococcal Endocarditis EMILIO BOUZA, M.D., RICHARD D. MEYER, M.D., AND DAVID F. BUSCH, M.D.
Bouza, Emilio, Meyer, Richard D., and Busch, David F.: Group G streptococcal endocarditis. Am J Clin Pathol 70: 108-111, 1978. The group G streptococcus may be a more common human pathogen than previously recognized. A case of group G streptococcal endocarditis is reported and the 11 cases reported previously are reviewed. Group G endocarditis may have significant clinical and prognostic differences from endocarditis caused by the more commonly identified viridans or group D streptococci. Routine serologic grouping of betahemolytic streptococcal isolates from serious infections is warranted. (Key words: Streptococcus; Endocarditis; Streptococcus, Group G.)
From the Infectious Disease Section, Research and Medical Services, Veterans Administration, Wadsworth Hospital Center, and the Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California
Report of a Case A 63-year-old man was admitted to the Wadsworth V.A. Hospital May 14, 1976, with a history of fever, chills and occasional urinary frequency for four days. He denied chest pain, shortness of breath or recent dental or surgical manipulation. He had a history of rheumatic heart disease with mitral insufficiency and a grade II/VI systolic murmur, as well as alcoholic hepatic disease and adultonset diabetes mellitus, controlled by oral agents. On physical examination the patient was alert. The temperature was 40 C, pulse rate 100/min, respiratory rate 28/min, and blood pressure 180/80 mm Hg. The patient was edentulous and had several petechiae on the soft palate and the conjuntivae. The neck was supple. A harsh grade IV/V1 holosystolic murmur was heard at the apex and left sternal border, with radiation to the left axilla. The liver was felt 6 cm below the right costal margin (as on previous admissions); the spleen was not palpable. There were several subungual splinter hemorrhages. Under the tip of the left fifth finger was a 6 mm lesion which was tender, yellow and covered by intact Received February 28, 1977; received revised manuscript April 25, 1977; accepted for publication April 25, 1977. Dr. Bouza is a second-year fellow supported by a grant of The Del Amo Foundation. Address reprint requests to Dr. Meyer: Infectious Disease Section, (691/11 IF), Wadsworth V.A. Hospital, Los Angeles, California 90073.
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GROUP G STREPTOCOCCI, although rarely identified, have been implicated in a variety of animal and human infections, of which the most severe is endocarditis. Biochemical reactions, such as the hippurate test, may lead to confusion of group G with group B streptococci. Therefore, identification must be made serologically when this distinction is important, as in endocarditis. The present paper is a report of a case of group G streptococcal endocarditis and a review of the literature. There may be important diagnostic and prognostic differences between endocarditis due to group G and the more commonly seen viridans and group D streptococcal endocarditides.
epidermis. A well-delineated, erythematous, tender, spreading lesion was noticed on the dorsal aspect of the right foot and ankle on the second day of hospitalization. Complementary data on admission included: leukocyte count 13,500/cu mm, with 96% neutrophils and 4% lymphocytes. Hemoglobin was 13.6 g/dl. Urinalysis showed 3+ protein and 2+ glucose; there were many erythrocytes but no leukocytes or casts. Blood urea nitrogen was 13 mg/dl and blood glucose 250 mg/dl. The chest x-ray showed cardiomegaly but was unchanged from previous admissions. Six sets of blood cultures taken within 48 hours of admission grew beta-hemolytic streptococci. These were initially identified as group B on the basis of a negative bile esculin test, resistance to a bacitracin disk, absence of growth in 6.5% sodium chloride, and a positive hippurate test. Subsequently, identification as group G on the basis of the cell-wall carbohydrate antigen was made by Dr. William Martin at the University of California at Los Angeles Center for the Health Sciences and Dr. Richard Facklam at The Center for Disease Control in Atlanta, Georgia. The same organism was cultured from an aspirate of the lesion on the fifth finger. Sputum culture yielded a beta-hemolytic streptococcus of a group other than A, B, or D but not identified further. Cultures of urine and the aspirate of the border of the lesion of the right ankle were sterile. Results of tube-dilution susceptibility tests for the blood culture isolate were: penicillin, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) both less than 0.06 jiAg/ml: streptomycin MIC and MBC = 32 /xg/ml; gentamicin MIC = 4 /xg/ ml and MBC = 8 jug/ml. Ampicillin MIC and MBC were both less than 1 /xg/ml. Penicillin G (18 million units), oxacillin (12 g) and gentamicin (3 mg/kg) were administered by intermittent intravenous infusion on the first day. Oxacillin was discontinued the next day, when the organism was identified, and gentamicin two days later when results of susceptibility testing became available. The patient became afebrile within three days; all subsequent blood cultures were negative. Deterioration of both mental status and renal function occurred as the serum creatinine rose to 4.5 mg/dl (398 /umol/1). The patient became comatose, but there were no focal neurologic abnormalities. Lumbar puncture showed an opening pressure of 230 mm H 2 0 and yielded clear cerebrospinal fluid with normal protein and glucose and 16 leukocytes/cu mm (3 neutrophils and 13 mononuclear cells). Gram-stain, India ink preparation, and bacterial and fungal cultures were all negative. Computer-assisted axial tomography showed diffuse cerebral atrophy but no focal lesion. Electroencephalogram showed a diffuse low-voltage pattern. During the second week of hospitalization, serum complement (C3) was 36 mg/dl; when repeated ten days later it was 40 mg/dl (normal 55 to 120 mg/dl). Tests for antinuclear antibodies were negative. The antistreptolysin O titer was 200 Todd units. No eosinophilia was found in blood or urine.
109
CASE REPORTS
Vol. 70 • No. I
Table I. Cases of Streptococcus Group G Endocarditis Case
Reference Number
Patient's Age ( Y r . ) . Sex
Underlying Disease
Course
Valve Involved
Other Findings
—
—
—
Died
—
Died (4 weeks)
1
30
—, —
—
2
25
44. F
—
3
25
48, F
4
27
5
Mitral
None
Acute
Mitral
30, F
Septic abortion
Acute
Aortic
19
8. F
Congenital heart disease
Subacute
—
6
33
Acute
7
33
—.— —, —
— —
8
13
84. M
9
10
24, F
Rheumatic heart disease Mitral prosthesis
10
10
71, F
Cancer o f the breast
II
14
71, M
Aortic stenosis
Acute
Aortic
12
Present
63, M
Rheumatic heart disease Mitral insufficiency
Acute
Mitral
— — —
Subacute Acute
Aortic
Acute
M it ral
—
On the fourth hospital day, the mitral murmur changed in quality and became high-pitched. Echocardiogram showed calcification of the mitral valve without evidence of vegetations. Ten days later the echocardiogram was repeated and was unchanged. Serum creatinine was stable at 2 mg/dl (177 Atmol/I). The patient remained barely arousable. The penicillin doses were progressively reduced in consideration of the highly susceptible organism and the presence of renal failure. Yet on the eleventh and twelfth hospital days, serum penicillin levels were 400 fig/mi 45 minutes after infusion and 350 /ig/ml immediately prior to infusion. A cerebrospinal fluid penicillin level was 20 /xg/ml. Severe hypoglycemia (serum glucose 20-30 mg/100 ml) was documented during a period of six to eight hours on the sixteenth hospital day. Penicillin was discontinued on the 28th hospital day: on the 32nd hospital day fever and signs of right lower lobe consolidation developed. Gram stain of sputum showed gram-positive cocci in clusters. Despite treatment with cefazolin, the patient's condition did not improve. He died on the 36th hospital day. Permission for postmortem examination was denied.
Discussion Several reviews have shown that the majority of extrarespiratory streptococcal infections are caused by groups other than A. The strains isolated in one study were, in order of frequency, D, B, K, C, G, F and E.' 2 Clinical syndromes produced by these streptococci have included endocarditis, menigitis, purulent arthritis, puerperal sepsis and hepatic abscess. 28 In contrast, groups L through T have not been shown to be important human pathogens.'
—
Erysipelas
— — — — —
Treatment
— —
Died (12 days)
Sulfonamides
Died (5 weeks)
Sulfonamides
Died (3 months)
Sulfonamides
— —
— —
Died (7 weeks)
Sulfonamides and penicillin
Miscarriage: dilatation and curretage: generalized petechiae and purpura
Survived
Penicillin: removal of prosthetic valve
Postirradiation cutaneous ulcer on arm
Survived
Penicillin and streptomycin
— Erysipelas: embolic lesion
Died (more than a Penicillin and streptomycin year) Died (1 month)
Penicillin
Duma and associates studied 154 streptococcal blood culture isolates from 140 patients at the Massachusetts General Hospital."' Eighteen of these patients had endocarditis. More than 50% of the 154 isolates were of groups other than A or D, and more than half of these were considered clinically significant. A majority of the infections (66%) occurred in patients with other underlying diseases. Despite almost universal susceptibility of these streptococcal isolates to penicillin, the mortality rate for streptococcal bacteremia was 27%. In contrast, the seven patients with group G streptococcal bacteremia, including two who had endocarditis, all survived.' 1 ' Group G was added to the initial Lancefield classification2' in 193522 as the result of a survey of the streptococcal vaginal flora of healthy and infected peripartum women. Although initially considered non-pathogenic, 22 group G streptococci have since been isolated in cases of puerperal sepsis, endocarditis, various abscesses,7'"-2'"'-27 neonatal sepsis,1-4 primary peritonitis, 2 " pharyngitis and lymphadenitis, 1217 pyoderma, 2 empyema, 10 and vaginal infections. 7 Necrotizing dermatitis in animals and bovine mastitis have also been reported. "•'3-31 The 12 cases of group G streptococcal endocarditis reported to date are summarized in Table I. Cases due to group G are absent from the larger series of patients with endocarditis.a-23-29"12
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Acute
Course
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BOUZA, MEYER AND BUSCH
The 12 patients with group G streptococcal endocarditis reported to date (Table 1) ranged in age from 8 to 84 years. Two thirds were older than 44 years. Eight were female and four were male. Fever was a universal sign in this group. At the time of admission a heart murmur was present in all patients about whom this information was recorded with the exception of one patient in whom a murmur developed during the hospital course. Infection of the mitral valve was reported for four patients, the aortic valve was involved in three, and the involved valve was not indicated in five cases. Information concerning the portal of entry is limited. Two patients had apparent uterine foci. Although our patient and three others had possible cutaneous foci, a respiratory portal of entry cannot be excluded in these cases. Pneumonia was the initial event in the patient of the fifth case, who also had congenital heart disease. The course of group G streptococcal endocarditis was often aggressive, compared with the more commonly subacute course of endocarditis due to viridans or group D streptococci. Eight of the ten patients about whom we have data had an acute type of endocarditis. Four of the patients had underlying heart disease and another had cancer of the breast. In five other cases no information concerning underlying diseases is available. While some serologic groups of streptococci ap-
pear to infect certain individuals more frequently than others (e.g., group B in peripartum women, neonates, and diabetics: groups B, D, and G in patients undergoing genitourinary manipulations, and perhaps group G in patients with carcinoma)10 no such conclusion can be drawn from this series. Urinary sediment changes were described in two of the previously reported cases. In the fifth case, although urinalysis showed erythrocytes and the rheumatoid factor was positive, renal function remained normal. In Case 11, although urine was again abnormal, renal biopsy was essentially normal. Renal failure in association with this type of endocarditis has not been reported previously. Although several factors may have contributed to our patient's renal failure, the low level of serum complement suggests that an immunecomplex mechanism may have played an important role.14 Two of the 12 patients had severe neurologic manifestations. Patient 7 had aphasia and monoparesis of the right upper extremity. Our patient had diffuse neurologic involvement resulting in coma. Contributory factors may have included endocarditis with diffuse cerebral vasculitis, hypoglycemia and penicillin neurotoxicity.-" Information about the outcome of group G streptococcal endocarditis is available in ten of the 12 cases. Eight patients died. Of the five who received pencillin, three died. In addition to the present patient, one patient died of congestive heart failure a year after therapy,14 and one died as a result of aortic insufficiency after seven weeks of therapy.13 There is, however, no evidence that these three deaths were due to failure of penicillin to control bacteremia. In contrast, with enterococcal and viridans group streptococcal endocarditis, cure rates as high as 90% have been reported.1K Although the group G streptococci studied have been exquisitely susceptible to penicillin G in vitro, the apparently aggressive nature of this disease in the few patients reported to date may warrant the combined use of penicillin and an aminoglycoside in order to achieve a synergistic bactericidal effect. The possible prognostic differences between group G and most other streptococcal endocarditides and the occasional difficulty of identifying these organisms by biochemical testing suggest a need for more widespread attention to serologic grouping of streptococcal isolates recovered from the bloodstream in endocarditis and other serious infections. References 1. Baker CJ: Unusual occurrence of neonatal septicemia due to group G streptococcus. Pediatrics 53:568-570. 1974 2. Belcher DW. Afoakwa SN. Osei-Tulu E, et al: Non group A
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Group G streptococci are similar in many respects to those of groups A and B. Most strains are betahemolytic; gamma-hemolysis has rarely been reported. Group G organisms can be divided into a large-colony type (Streptococcus canis) and a "minute"-colony type (Streptococcus anginosus). At least three serologic subgroups of the large-colony type have been defined.30 Both colony types utilize glucose, levulose, galactose, maltose, saccharose, trehalose and dextrin. The large-colony type also utilizes starch and glycerol, whereas the "minute"-colony type does not. Because as many as a third of group G streptococci may be sensitive to bacitracin,13 this test is not reliable for differentiation of group G from group A. Identification should be made on the basis of the cell-wall carbohydrate (C) antigen. The terminal antigenic component of the group G carbohydrate, L rhamnose,8-9 is shared by group B streptococci and 5. pneumoniae, group XXIII."•'" This explains the antigenic cross reaction that sometimes occurs among these three organisms. However, after cross absorption the antisera are considered specific.8 The M12 antigenic substance has also been discovered in the wall of group G streptococci.24 Previously this was considered specific for group A and had been related to the nephritogenic potential of that group.
A.J.C.P. . July 1978
Vol. 70 • No. I
3. 4. 5.
6. 7. 8.
9. 10. 11. 12.
14.
15.
16.
17.
18.
streptococci in Ghanian patients with pyoderma (letter). Lancet 2:1032, 1975 Blount JG: Bacterial endocarditis. Am J Med 38:909-922, 1965 Brans YW: Group G streptococcal sepsis. Pediatrics 55:745746, 1975 Broome CV, Moellering RC, Watson BK: Clinical significance of Lancefield groups L - T streptococci isolated from blood and cerebrospinal fluid. J Infect Dis 133:382-392, 1976 Chionglo DT, Hayashi JA: Structural basis of group G streptococcal antigenicity. Arch Biochem Biophys 130:39-47, 1969 Colebrook L, Purdie AW: Treatment of 106 cases of puerperal fever by sulphanilamide. Lancet 2:1237-1242, 1937 Curtis SN, Krause RM: Immunochemical studies on the specific carbohydrate of group G Streptococci. J Exp Med 119:9971004, 1964 Curtis SN, Krause RM: Antigenic relationships between groups B and G streptococci. J Exp Med 120:629-637, 1964 Duma RJ, Weinberg AN, Mederek TF, et al: Streptococcal infections. Medicine 48:87-127, 1969 Eberhart J, Guss SB: Group G streptococci in the udders of a Pennsylvania dairy herd. JAVMA 157:1195-1199, 1970 Foley GE: Further observations on the occurrence of streptococci of groups other than A in human infection. N Engl J Med 237:809-811, 1947 Feingold DS, Stagg NL, Kunz LJ: Extra-respiratory streptococcal infections: Importance of the various serologic groups. N Engl J Med 275:356-361, 1966 Gutman RA, Striker GE, Gilliland BC, et al: The immunocomplex glomerulonephritis of bacterial endocarditis. Medicine 51:1-25. 1972 Hamilton CA, Stark DM: Occurrence and characterization of Lancefield group G streptococci in bovine mastitis. Am J Vet Res 31:397-398, 1970 Heidelberger M, Davie JM, Krause RM: Cross reactions of the group-specific polysaccharides of streptococcal groups B and G in anti-pneumococcal sera with special reference to type XX1I1 and its determinants. J Immunol 99:794-796, 1967 Hill HR, Caldwell GG, Wilson E, et al: Epidemic of pharyngitis due to streptococci of Lancefield group G. Lancet 2:371-374, 1969 Kaye D: Cure rates and prognosis. Infective Endocarditis. Edited by Kaye D. Baltimore, University Park Press, 1976, pp 201-211
111
19. Keith HM, Heilman FR: Subacute bacterial endocarditis due to hemolytic streptococci of Lancefield group G. Am J Dis Child 65:77-80, 1943 20. Khan AJ, Evans HE, Macabuhay MR, et al: Primary peritonitis due to group G streptococcus: A case report. Pediatrics 56: 1078-1079, 1975 21. Lancefield RC: A serological differentiation of human and other groups of hemolytic streptococci, J Exp Med 57:571-595. 1933 22. Lancefield RC. Hare R: The serological differentiation of pathogenic and nonpathogenic strains of hemolytic streptococci from parturient women. J Exp Med 61:335-349, 1935 23. Lerner PI. Weinstein L: Infective endocarditis in the antibiotic era. N Engl J Med 274:199-206, 259-266, 323-331. 388-393, 1965 24. Maxted WR, Potter EV: The presence of type 12 M-protein antigen in group G streptococci. J Gen Microbiol 49: 119-125, 1967 25. MacDonaldl: Fatal and severe human infections with haemolytic streptococci group G. Med J Aust 2:471-474, 1939 26. Raichle ME, Kutt H, Louis S. McDowell F: Neurotoxicity of intravenously administered penicillin G. Arch Neurol 25:232239, 1971 27. Ramsey AM, Gillespie M: Puerperal infection associated with haemolytic streptococci other than Lancefield's group A. J Obstet Gynecol Br Emp 48:569-585, 1941 28. Reinarz JA, Sanford JP: Human infections caused by non-group A or D streptococci. Medicine 44:81-96, 1965 29. Shinebourne EA, Cripps CM, Hayward GW, et al: Bacterial endocarditis 1956-1965: Analysis of clinical features and treatment in relation to prognosis and mortality. Br Heart J 31:536-542, 1969 30. Simmons RT, Keogh EV: Physiological characters and serological types of haemolytic streptococci of groups B, C and G from human sources. Aust J Exp Biol Med Sci 18:151-161, 1940 31. Stewart DD, Buck GE, McConnell EE, et al: An epizootic of necrotic dermatitis in laboratory mice caused by Lancefield group G streptococci. Lab Anim Sci 25:296-302, 1975 32. Tompsett R: Bacterial endocarditis. V. Changes in the clinical spectrum. Arch Intern Med 119:329-332, 1967 33. Uwaydah MM. Weinberg AN: Bacterial endocarditis: a changing pattern. N Engl J Med 273:1231-1235. 1965
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13.
CASE REPORTS
Bouza, Emilio, Meyer, Richard D., and Busch, David F.: Group G streptococcal endocarditis. Am J Clin Pathol 70: 108-111, 1978. The group G streptococcus may be a more common human pathogen than previously recognized. A case of group G streptococcal endocarditis is reported and the 11 cases reported previously are reviewed. Group G endocarditis may have significant clinical and prognostic differences from endocarditis caused by the more commonly identified viridans or group D streptococci. Routine serologic grouping of betahemolytic streptococcal isolates from serious infections is warranted. (Key words: Streptococcus; Endocarditis; Streptococcus, Group G.)
From the Infectious Disease Section, Research and Medical Services, Veterans Administration, Wadsworth Hospital Center, and the Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California
Report of a Case A 63-year-old man was admitted to the Wadsworth V.A. Hospital May 14, 1976, with a history of fever, chills and occasional urinary frequency for four days. He denied chest pain, shortness of breath or recent dental or surgical manipulation. He had a history of rheumatic heart disease with mitral insufficiency and a grade II/VI systolic murmur, as well as alcoholic hepatic disease and adultonset diabetes mellitus, controlled by oral agents. On physical examination the patient was alert. The temperature was 40 C, pulse rate 100/min, respiratory rate 28/min, and blood pressure 180/80 mm Hg. The patient was edentulous and had several petechiae on the soft palate and the conjuntivae. The neck was supple. A harsh grade IV/V1 holosystolic murmur was heard at the apex and left sternal border, with radiation to the left axilla. The liver was felt 6 cm below the right costal margin (as on previous admissions); the spleen was not palpable. There were several subungual splinter hemorrhages. Under the tip of the left fifth finger was a 6 mm lesion which was tender, yellow and covered by intact Received February 28, 1977; received revised manuscript April 25, 1977; accepted for publication April 25, 1977. Dr. Bouza is a second-year fellow supported by a grant of The Del Amo Foundation. Address reprint requests to Dr. Meyer: Infectious Disease Section, (691/11 IF), Wadsworth V.A. Hospital, Los Angeles, California 90073.
0002-9173/78/0700/0108 $00.60 © American Society of Clinical Pathologists
108
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GROUP G STREPTOCOCCI, although rarely identified, have been implicated in a variety of animal and human infections, of which the most severe is endocarditis. Biochemical reactions, such as the hippurate test, may lead to confusion of group G with group B streptococci. Therefore, identification must be made serologically when this distinction is important, as in endocarditis. The present paper is a report of a case of group G streptococcal endocarditis and a review of the literature. There may be important diagnostic and prognostic differences between endocarditis due to group G and the more commonly seen viridans and group D streptococcal endocarditides.
epidermis. A well-delineated, erythematous, tender, spreading lesion was noticed on the dorsal aspect of the right foot and ankle on the second day of hospitalization. Complementary data on admission included: leukocyte count 13,500/cu mm, with 96% neutrophils and 4% lymphocytes. Hemoglobin was 13.6 g/dl. Urinalysis showed 3+ protein and 2+ glucose; there were many erythrocytes but no leukocytes or casts. Blood urea nitrogen was 13 mg/dl and blood glucose 250 mg/dl. The chest x-ray showed cardiomegaly but was unchanged from previous admissions. Six sets of blood cultures taken within 48 hours of admission grew beta-hemolytic streptococci. These were initially identified as group B on the basis of a negative bile esculin test, resistance to a bacitracin disk, absence of growth in 6.5% sodium chloride, and a positive hippurate test. Subsequently, identification as group G on the basis of the cell-wall carbohydrate antigen was made by Dr. William Martin at the University of California at Los Angeles Center for the Health Sciences and Dr. Richard Facklam at The Center for Disease Control in Atlanta, Georgia. The same organism was cultured from an aspirate of the lesion on the fifth finger. Sputum culture yielded a beta-hemolytic streptococcus of a group other than A, B, or D but not identified further. Cultures of urine and the aspirate of the border of the lesion of the right ankle were sterile. Results of tube-dilution susceptibility tests for the blood culture isolate were: penicillin, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) both less than 0.06 jiAg/ml: streptomycin MIC and MBC = 32 /xg/ml; gentamicin MIC = 4 /xg/ ml and MBC = 8 jug/ml. Ampicillin MIC and MBC were both less than 1 /xg/ml. Penicillin G (18 million units), oxacillin (12 g) and gentamicin (3 mg/kg) were administered by intermittent intravenous infusion on the first day. Oxacillin was discontinued the next day, when the organism was identified, and gentamicin two days later when results of susceptibility testing became available. The patient became afebrile within three days; all subsequent blood cultures were negative. Deterioration of both mental status and renal function occurred as the serum creatinine rose to 4.5 mg/dl (398 /umol/1). The patient became comatose, but there were no focal neurologic abnormalities. Lumbar puncture showed an opening pressure of 230 mm H 2 0 and yielded clear cerebrospinal fluid with normal protein and glucose and 16 leukocytes/cu mm (3 neutrophils and 13 mononuclear cells). Gram-stain, India ink preparation, and bacterial and fungal cultures were all negative. Computer-assisted axial tomography showed diffuse cerebral atrophy but no focal lesion. Electroencephalogram showed a diffuse low-voltage pattern. During the second week of hospitalization, serum complement (C3) was 36 mg/dl; when repeated ten days later it was 40 mg/dl (normal 55 to 120 mg/dl). Tests for antinuclear antibodies were negative. The antistreptolysin O titer was 200 Todd units. No eosinophilia was found in blood or urine.
109
CASE REPORTS
Vol. 70 • No. I
Table I. Cases of Streptococcus Group G Endocarditis Case
Reference Number
Patient's Age ( Y r . ) . Sex
Underlying Disease
Course
Valve Involved
Other Findings
—
—
—
Died
—
Died (4 weeks)
1
30
—, —
—
2
25
44. F
—
3
25
48, F
4
27
5
Mitral
None
Acute
Mitral
30, F
Septic abortion
Acute
Aortic
19
8. F
Congenital heart disease
Subacute
—
6
33
Acute
7
33
—.— —, —
— —
8
13
84. M
9
10
24, F
Rheumatic heart disease Mitral prosthesis
10
10
71, F
Cancer o f the breast
II
14
71, M
Aortic stenosis
Acute
Aortic
12
Present
63, M
Rheumatic heart disease Mitral insufficiency
Acute
Mitral
— — —
Subacute Acute
Aortic
Acute
M it ral
—
On the fourth hospital day, the mitral murmur changed in quality and became high-pitched. Echocardiogram showed calcification of the mitral valve without evidence of vegetations. Ten days later the echocardiogram was repeated and was unchanged. Serum creatinine was stable at 2 mg/dl (177 Atmol/I). The patient remained barely arousable. The penicillin doses were progressively reduced in consideration of the highly susceptible organism and the presence of renal failure. Yet on the eleventh and twelfth hospital days, serum penicillin levels were 400 fig/mi 45 minutes after infusion and 350 /ig/ml immediately prior to infusion. A cerebrospinal fluid penicillin level was 20 /xg/ml. Severe hypoglycemia (serum glucose 20-30 mg/100 ml) was documented during a period of six to eight hours on the sixteenth hospital day. Penicillin was discontinued on the 28th hospital day: on the 32nd hospital day fever and signs of right lower lobe consolidation developed. Gram stain of sputum showed gram-positive cocci in clusters. Despite treatment with cefazolin, the patient's condition did not improve. He died on the 36th hospital day. Permission for postmortem examination was denied.
Discussion Several reviews have shown that the majority of extrarespiratory streptococcal infections are caused by groups other than A. The strains isolated in one study were, in order of frequency, D, B, K, C, G, F and E.' 2 Clinical syndromes produced by these streptococci have included endocarditis, menigitis, purulent arthritis, puerperal sepsis and hepatic abscess. 28 In contrast, groups L through T have not been shown to be important human pathogens.'
—
Erysipelas
— — — — —
Treatment
— —
Died (12 days)
Sulfonamides
Died (5 weeks)
Sulfonamides
Died (3 months)
Sulfonamides
— —
— —
Died (7 weeks)
Sulfonamides and penicillin
Miscarriage: dilatation and curretage: generalized petechiae and purpura
Survived
Penicillin: removal of prosthetic valve
Postirradiation cutaneous ulcer on arm
Survived
Penicillin and streptomycin
— Erysipelas: embolic lesion
Died (more than a Penicillin and streptomycin year) Died (1 month)
Penicillin
Duma and associates studied 154 streptococcal blood culture isolates from 140 patients at the Massachusetts General Hospital."' Eighteen of these patients had endocarditis. More than 50% of the 154 isolates were of groups other than A or D, and more than half of these were considered clinically significant. A majority of the infections (66%) occurred in patients with other underlying diseases. Despite almost universal susceptibility of these streptococcal isolates to penicillin, the mortality rate for streptococcal bacteremia was 27%. In contrast, the seven patients with group G streptococcal bacteremia, including two who had endocarditis, all survived.' 1 ' Group G was added to the initial Lancefield classification2' in 193522 as the result of a survey of the streptococcal vaginal flora of healthy and infected peripartum women. Although initially considered non-pathogenic, 22 group G streptococci have since been isolated in cases of puerperal sepsis, endocarditis, various abscesses,7'"-2'"'-27 neonatal sepsis,1-4 primary peritonitis, 2 " pharyngitis and lymphadenitis, 1217 pyoderma, 2 empyema, 10 and vaginal infections. 7 Necrotizing dermatitis in animals and bovine mastitis have also been reported. "•'3-31 The 12 cases of group G streptococcal endocarditis reported to date are summarized in Table I. Cases due to group G are absent from the larger series of patients with endocarditis.a-23-29"12
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Acute
Course
110
BOUZA, MEYER AND BUSCH
The 12 patients with group G streptococcal endocarditis reported to date (Table 1) ranged in age from 8 to 84 years. Two thirds were older than 44 years. Eight were female and four were male. Fever was a universal sign in this group. At the time of admission a heart murmur was present in all patients about whom this information was recorded with the exception of one patient in whom a murmur developed during the hospital course. Infection of the mitral valve was reported for four patients, the aortic valve was involved in three, and the involved valve was not indicated in five cases. Information concerning the portal of entry is limited. Two patients had apparent uterine foci. Although our patient and three others had possible cutaneous foci, a respiratory portal of entry cannot be excluded in these cases. Pneumonia was the initial event in the patient of the fifth case, who also had congenital heart disease. The course of group G streptococcal endocarditis was often aggressive, compared with the more commonly subacute course of endocarditis due to viridans or group D streptococci. Eight of the ten patients about whom we have data had an acute type of endocarditis. Four of the patients had underlying heart disease and another had cancer of the breast. In five other cases no information concerning underlying diseases is available. While some serologic groups of streptococci ap-
pear to infect certain individuals more frequently than others (e.g., group B in peripartum women, neonates, and diabetics: groups B, D, and G in patients undergoing genitourinary manipulations, and perhaps group G in patients with carcinoma)10 no such conclusion can be drawn from this series. Urinary sediment changes were described in two of the previously reported cases. In the fifth case, although urinalysis showed erythrocytes and the rheumatoid factor was positive, renal function remained normal. In Case 11, although urine was again abnormal, renal biopsy was essentially normal. Renal failure in association with this type of endocarditis has not been reported previously. Although several factors may have contributed to our patient's renal failure, the low level of serum complement suggests that an immunecomplex mechanism may have played an important role.14 Two of the 12 patients had severe neurologic manifestations. Patient 7 had aphasia and monoparesis of the right upper extremity. Our patient had diffuse neurologic involvement resulting in coma. Contributory factors may have included endocarditis with diffuse cerebral vasculitis, hypoglycemia and penicillin neurotoxicity.-" Information about the outcome of group G streptococcal endocarditis is available in ten of the 12 cases. Eight patients died. Of the five who received pencillin, three died. In addition to the present patient, one patient died of congestive heart failure a year after therapy,14 and one died as a result of aortic insufficiency after seven weeks of therapy.13 There is, however, no evidence that these three deaths were due to failure of penicillin to control bacteremia. In contrast, with enterococcal and viridans group streptococcal endocarditis, cure rates as high as 90% have been reported.1K Although the group G streptococci studied have been exquisitely susceptible to penicillin G in vitro, the apparently aggressive nature of this disease in the few patients reported to date may warrant the combined use of penicillin and an aminoglycoside in order to achieve a synergistic bactericidal effect. The possible prognostic differences between group G and most other streptococcal endocarditides and the occasional difficulty of identifying these organisms by biochemical testing suggest a need for more widespread attention to serologic grouping of streptococcal isolates recovered from the bloodstream in endocarditis and other serious infections. References 1. Baker CJ: Unusual occurrence of neonatal septicemia due to group G streptococcus. Pediatrics 53:568-570. 1974 2. Belcher DW. Afoakwa SN. Osei-Tulu E, et al: Non group A
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Group G streptococci are similar in many respects to those of groups A and B. Most strains are betahemolytic; gamma-hemolysis has rarely been reported. Group G organisms can be divided into a large-colony type (Streptococcus canis) and a "minute"-colony type (Streptococcus anginosus). At least three serologic subgroups of the large-colony type have been defined.30 Both colony types utilize glucose, levulose, galactose, maltose, saccharose, trehalose and dextrin. The large-colony type also utilizes starch and glycerol, whereas the "minute"-colony type does not. Because as many as a third of group G streptococci may be sensitive to bacitracin,13 this test is not reliable for differentiation of group G from group A. Identification should be made on the basis of the cell-wall carbohydrate (C) antigen. The terminal antigenic component of the group G carbohydrate, L rhamnose,8-9 is shared by group B streptococci and 5. pneumoniae, group XXIII."•'" This explains the antigenic cross reaction that sometimes occurs among these three organisms. However, after cross absorption the antisera are considered specific.8 The M12 antigenic substance has also been discovered in the wall of group G streptococci.24 Previously this was considered specific for group A and had been related to the nephritogenic potential of that group.
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streptococci in Ghanian patients with pyoderma (letter). Lancet 2:1032, 1975 Blount JG: Bacterial endocarditis. Am J Med 38:909-922, 1965 Brans YW: Group G streptococcal sepsis. Pediatrics 55:745746, 1975 Broome CV, Moellering RC, Watson BK: Clinical significance of Lancefield groups L - T streptococci isolated from blood and cerebrospinal fluid. J Infect Dis 133:382-392, 1976 Chionglo DT, Hayashi JA: Structural basis of group G streptococcal antigenicity. Arch Biochem Biophys 130:39-47, 1969 Colebrook L, Purdie AW: Treatment of 106 cases of puerperal fever by sulphanilamide. Lancet 2:1237-1242, 1937 Curtis SN, Krause RM: Immunochemical studies on the specific carbohydrate of group G Streptococci. J Exp Med 119:9971004, 1964 Curtis SN, Krause RM: Antigenic relationships between groups B and G streptococci. J Exp Med 120:629-637, 1964 Duma RJ, Weinberg AN, Mederek TF, et al: Streptococcal infections. Medicine 48:87-127, 1969 Eberhart J, Guss SB: Group G streptococci in the udders of a Pennsylvania dairy herd. JAVMA 157:1195-1199, 1970 Foley GE: Further observations on the occurrence of streptococci of groups other than A in human infection. N Engl J Med 237:809-811, 1947 Feingold DS, Stagg NL, Kunz LJ: Extra-respiratory streptococcal infections: Importance of the various serologic groups. N Engl J Med 275:356-361, 1966 Gutman RA, Striker GE, Gilliland BC, et al: The immunocomplex glomerulonephritis of bacterial endocarditis. Medicine 51:1-25. 1972 Hamilton CA, Stark DM: Occurrence and characterization of Lancefield group G streptococci in bovine mastitis. Am J Vet Res 31:397-398, 1970 Heidelberger M, Davie JM, Krause RM: Cross reactions of the group-specific polysaccharides of streptococcal groups B and G in anti-pneumococcal sera with special reference to type XX1I1 and its determinants. J Immunol 99:794-796, 1967 Hill HR, Caldwell GG, Wilson E, et al: Epidemic of pharyngitis due to streptococci of Lancefield group G. Lancet 2:371-374, 1969 Kaye D: Cure rates and prognosis. Infective Endocarditis. Edited by Kaye D. Baltimore, University Park Press, 1976, pp 201-211
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19. Keith HM, Heilman FR: Subacute bacterial endocarditis due to hemolytic streptococci of Lancefield group G. Am J Dis Child 65:77-80, 1943 20. Khan AJ, Evans HE, Macabuhay MR, et al: Primary peritonitis due to group G streptococcus: A case report. Pediatrics 56: 1078-1079, 1975 21. Lancefield RC: A serological differentiation of human and other groups of hemolytic streptococci, J Exp Med 57:571-595. 1933 22. Lancefield RC. Hare R: The serological differentiation of pathogenic and nonpathogenic strains of hemolytic streptococci from parturient women. J Exp Med 61:335-349, 1935 23. Lerner PI. Weinstein L: Infective endocarditis in the antibiotic era. N Engl J Med 274:199-206, 259-266, 323-331. 388-393, 1965 24. Maxted WR, Potter EV: The presence of type 12 M-protein antigen in group G streptococci. J Gen Microbiol 49: 119-125, 1967 25. MacDonaldl: Fatal and severe human infections with haemolytic streptococci group G. Med J Aust 2:471-474, 1939 26. Raichle ME, Kutt H, Louis S. McDowell F: Neurotoxicity of intravenously administered penicillin G. Arch Neurol 25:232239, 1971 27. Ramsey AM, Gillespie M: Puerperal infection associated with haemolytic streptococci other than Lancefield's group A. J Obstet Gynecol Br Emp 48:569-585, 1941 28. Reinarz JA, Sanford JP: Human infections caused by non-group A or D streptococci. Medicine 44:81-96, 1965 29. Shinebourne EA, Cripps CM, Hayward GW, et al: Bacterial endocarditis 1956-1965: Analysis of clinical features and treatment in relation to prognosis and mortality. Br Heart J 31:536-542, 1969 30. Simmons RT, Keogh EV: Physiological characters and serological types of haemolytic streptococci of groups B, C and G from human sources. Aust J Exp Biol Med Sci 18:151-161, 1940 31. Stewart DD, Buck GE, McConnell EE, et al: An epizootic of necrotic dermatitis in laboratory mice caused by Lancefield group G streptococci. Lab Anim Sci 25:296-302, 1975 32. Tompsett R: Bacterial endocarditis. V. Changes in the clinical spectrum. Arch Intern Med 119:329-332, 1967 33. Uwaydah MM. Weinberg AN: Bacterial endocarditis: a changing pattern. N Engl J Med 273:1231-1235. 1965
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CASE REPORTS
