Bacterial Endocarditis Caused by Oerskovia turbata L BARTH RELLER, M.D., F.A.C.P., GERRY L MADDOUX, M.D., MARK R. ECKMAN, M.D., and GEORGE PAPPAS, M.D., Denver, Colorado
Oerskovia turbata is a yellow, motile actinomycete, which before now has only been found in soil and has not been known to cause disease in man or animals. It was isolated from 29 cultures of blood taken during 6 months from an urban pensioner after homograft replacement of his aortic valve. The combination of ampicillin, sulfamethoxazole, and trimethoprim was lethal for O. turbata in vitro; however, antimicrobial therapy alone failed to eradicate the patient's infection. Cure was achieved after the infected homograft was replaced with a prosthetic aortic valve. Although the source of 0. turbata in this patient is unknown, sterilization of homograft valves with antimicrobial solutions is difficult. Moreover, environmental contamination during cardiopulmonary bypass is common. Oerskovia turbata is another opportunistic pathogen of man.
I N 1938 0rskov described a nocardioform bacterium found in Danish soil that was motile and produced a yellow pigment ( 1 ) . This organism, now called Oerskovia turbata, has not been recognized in infections of man or animals but has been isolated from soil in the United States and Europe (1-3). We report a case of endocarditis caused by O. turbata in a man whose aortic valve was replaced with a homograft heart valve because of severe aortic insufficiency associated with ankylosing spondylitis 20 years after ileal resections for regional enteritis. Case Report A 68-year-old urban pensioner entered Colorado General Hospital in July 1973 because of acute pulmonary edema. A grade 2/6 murmur of aortic insufficiency had been noted since 1964; however, his blood pressure had remained stable at 140/60 mm Hg. Part of his ileum had been resected 20 years earlier because of symptomatic Crohn's disease. He was being treated with 60 mg of prednisone each day for ankylosing spondylitis. Radiographs showed obliteration of both sacroiliac joints; he had histocompatibility antigen (HL-A) type W27. Evidence of inflammation included serum-iron, 14 fig per dl; iron-binding capacity, 209 fig per dl; and erythrocyte sedimentation rate, 54 mm/h. Four cultures of blood were negative. His cardiac failure improved after diuresis and he was discharged. One month later he was readmitted; a harsh, grade 4/6 diastolic murmur of aortic insufficiency was present. Owing to progressive cardiac failure he was treated for 6 weeks with parenteral ampicillin and gentamicin despite 12 negative blood cultures (Figure 1). In November 1973, after his blood pressure fell from 140/40 to 140/0 mm Hg, the patient's aortic • From the Departments of Medicine and Surgery, University of Colorado Medical Center, Denver, Colorado.
664
valve was replaced with a stented homograft valve that had been stored for 50 days in an antimicrobial solution, which contained nystatin, penicillin, polymyxin B, and streptomycin. The patient's valve showed no signs of infective endocarditis; however, there was fibrosis of the aortic valve cusps and aortic root with infiltration of lymphocytes as found by others in the aortitis of ankylosing spondylitis (4, 5). He went home well with no cardiac murmurs. The patient again entered the hospital in January 1974 after 4 days of fever and rigors. Physical examination showed an oral temperature of 40 °C, blood pressure of 150/70 mm Hg, splenomegaly, and a new grade 2/6 diastolic murmur. After 48 h, the first of 29 subsequently positive blood cultures grew a diphtheroid organism that was identified later as O. turbata by the Center for Disease Control. During the next 6 months treatment with several antimicrobials was tried without lasting success (Figure 1). Because of recurrent fever and positive blood cultures when antimicrobials were stopped, the patient's homograft valve was replaced with a Bjork-Shiley prosthetic aortic valve in July 1974. The patient was given sulfamethoxazole-trimethoprim, intravenously for 48 h after surgery; he was then treated with oral sulfamethoxazole-trimethoprim for 12 weeks, simultaneously with 6 weeks of parenteral ampicillin followed by 6 weeks of oral amoxicillin. Owing to the possibility of inhibition of folate metabolism in man by trimethoprim, the patient was given 400 fig of folinic acid each day (6). During antimicrobial therapy his serum contained 7 to 11 ng of folate per ml; these concentrations would not be expected to antagonize the effect of sulfamethoxazole-trimethoprim on O. turbata (7). Blood cultures during 3 months after therapy were all negative; the patient was asymptomatic 7 months after stopping all antimicrobials (Figure 1). His only medication was 800 mg of sulfinpyrazone each day to prevent platelet thrombi on his prosthetic valve (8). Microbiological Findings
All 29 positive blood cultures after placement of the homograft valve grew the same Gram-positive rods and cocci, which formed yellow colonies on subculture to sheep blood agar. Moreover, O. turbata was isolated from the resected homograft valve and the Gram-positive organisms were seen on microscopic examination of the valve itself and the attached vegetations. The biochemical reactions were typical of O. turbata (1-3); it produced acid from lactose and sucrose but not mannitol, and hydrolyzed casein but not tyrosine or xanthine. The organism was motile, not acid-fast, and had cell wall type VI, which contains major amounts of galactose ( 2 ) . Many antimicrobials were tested against O. turbata; no single agent showed enough activity to be successful in treating endocarditis. The most effective combination in vitro was ampicillin and sulfamethoxazole-trimethoprim {see Table 1). The initial isolates of O. turbata and those after each relapse and from the resected homograft valve Annals of Internal Medicine 83:664-666, 1975
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
Figure 1 . Summary of temperature, blood cultures, and antimicrobial and surgical therapy of patient with endocarditis caused by Oerskovia turbata. AMP = ampicillin; GM = gentamicin; PEN = penicillin; ERY = erythromycin; SMX = sulfamethoxazole; TMP = trimethoprim; AMOX = amoxicillin; IV = intravenous; IM = intramuscular; and PO = oral.
all showed the same antibiogram and degree of susceptibility. Concentrations of 10 or 50 ng of folinic acid per ml did not alter the susceptibility of O. turbata from this patient to sulfamethoxazole-trimethoprim in vitro. The patient's serum was assayed often for antibacterial activity. While receiving erythromycin and ampicillin, a 1:16 dilution of serum inhibited O. turbata but no bactericidal activity was present. Similarly sulfamethoxazoletrimethoprim was inhibitory at a 1:32 dilution of serum but did not kill the organism. On combined therapy with ampicillin and sulfamethoxazole-trimethoprim the patient's serum was inhibitory at a dilution of 1:32 or higher and bactericidal at a 1:8 dilution. Moreover, each antimicrobial was assayed separately and shown to be present in concentrations that exceeded the minimal lethal concentration required for O. turbata with the combination of ampicillin and sulfamethoxazole-trimethoprim (Table 1) (7). One week after stopping therapy the patient's serum showed no activity against his O. turbata. Discussion
This patient had a sequence of uncommon illnesses that makes him unique. Ankylosing spondylitis occurs in about 3% of all patients with regional enteritis (9); it occurs in one of six patients, such as ours, who have HL-A type W27 and Crohn's disease (10). The incidence of aortic insufficiency in patients with ankylosing spondylitis is about 8% (4, 5); there is one report of aortic insufficiency in a patient with ankylosing spondylitis and
regional enteritis (4). The aortitis and associated valvulitis of ankylosing spondylitis are progressive and result in free aortic regurgitation in half of patients within 7 years of the earliest evidence of valvulitis (5). Our patient had a blood pressure of 140/0 mm Hg before replacement of his uninfected aortic valve. The reported incidence of bacterial endocarditis after homograft replacement of the aortic valve varies from 2.6% to 15.1% (11, 12). Before this 0. turbata has been described only as a soil organism (1,3). The source of O. turbata in this patient must remain speculative. Three preoperative cultures of the involved homograft tissue were negative; however, seven previous valves harvested at the same medical center were discarded because of contamination with diphtheroids that were later identified as O. turbata. Moreover, homograft heart valves are not usually collected under sterile conditions and are exceedingly difficult to sterilize with antibiotics (12, 13). Microbial contamination occurs often during open heart surgery; diphtheroids are the most commonly isolated organism (14). Diphtheroid endocarditis is uncommon but does occur after prosthetic valve replacement (15). Cure of this patient after two bacteriologic relapses illustrates two principles of treatment of infective endocarditis. Successful medical therapy requires bactericidal concentrations of antimicrobials in serum that exceed the minimal lethal concentration of the infecting organism; patients with unresponsive infection need valve replace-
Table 1. Susceptibility of Oerskovia turbata to Antimicrobials Alone and in Combination and Concentrations of Antimicrobials Achieved in Patient's Serum Concentration of Antimicrobial
Minimal inhibitory concentration Minimal lethal concentration Serum (1 to 3 h after last dose)
Ampicillin
Sulfamethoxazole
Trimethoprim
32 32 36
5 >160 270
0.25 >8.0 6.6
Ampicillin/Sulfamethoxazole/Trimethoprim 4 8
5 10
0.25 0.5
Roller et al. • Oerskovia turbata Endocarditis
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
665
ment (16). Satisfactory inhibition of O. turbata was achieved with two courses of treatment and all 14 blood cultures during therapy were negative; however, fever and positive blood cultures occurred shortly after inhibitory therapy was stopped (Figure 1). Moreover, O. turbata was grown from the excised valve and from vegetations on the valve after grinding. In contrast none of the 6 blood cultures taken after replacement of the infected valve and bactericidal therapy was positive. The specific identification of O. turbata in this patient was important. Owing to the initial report of a diphtheroid, a common contaminant of blood cultures and open heart surgery (14, 15), inadequate therapy was given (Figure 1). Because O. turbata has only been isolated from soil, there was no precedent for choosing antimicrobial therapy. The relation of O. turbata to the genus Nocardia aided selection of possibly effective agents for testing. The techniques required for reliable assay of sulfamethoxazole and trimethoprim were used (7). The absence of antagonism of sulfamethoxazole-trimethoprim by folinic acid when tested against O. turbata in vitro made possible the prolonged high doses of sulfamethoxazole-trimethoprim required to achieve bactericidal synergism with ampicillin or amoxicillin without suppression of the bone marrow (6). Successful replacement of the infected valve was then possible during bactericidal antimicrobial coverage. When it occurs, relapse with the same organism is almost always within 2 months after stopping therapy (16). This patient seems cured. ACKNOWLEDGMENTS: The authors thank David B. Weeks for technical assistance; June Brown of the Mycology Branch, Laboratory Division, Center for Disease Control for identification of Oerskovia turbata; Hoffman-LaRoche, Inc. for providing amoxicillin and sulfamethoxazole-trimethoprim for intravenous use; and Jeanne R. Cleary for secretarial work. Presented in part on 2 May 1975 at the 75th Annual Meeting of the American Society for Microbiology, New York, New York. Received 19 May 1975; revision accepted 11 July 1975.
666
• Requests for reprints should be addressed to L. Barth Reller, M.D., Box B168, University of Colorado Medical Center, 4200 East 9th Avenue, Denver, CO 80220. References 1. ERIKSON D: Factors promoting cell division in a 'soft' mycelial type of Nocardia: Nocardia turbata n.sp. / Gen Microbiol 11: 198-208, 1954 2. PRAUSER H, LECHEVALIER MP, LECHEVALIER H: Description of
Oerskovia gen. n. to harbor 0rskov's motile Nocardia. Appl Microbiol 19:534, 1970 3. LECHEVALIER MP: Description of a new species, Oerskovia xanthineolytica, and emendation of Oerskovia Prauser et al. Int J Syst Bacteriol 22:260-264, 1972 4. KINSELLA TD, JOHNSON LG, SUTHERLAND RI: Cardiovascular
manifestations of ankylosing spondylitis. Can Med Assoc / 1 1 1 : 1309-1311, 1974 5. GRAHAM DC, SMYTHE HA: The carditis and aorititis of ankylosing spondylitis. Bull Rheum Dis 9:171-174, 1958 6. KAHN SB, FEIN SA, BRODSKY I: Effects of trimethoprim on
folate metabolism in man. Clin Pharmacol Ther 9:550-560, 1968 7. PAVILLARD ER: Treatment of nocardial infection with trimethoprim-sulphamethoxazole. Med J Aust l:(suppl) 65-69, 1973 8. WEILY HS, GENTON E: Altered platelet function in patients with prosthetic mitral valves: effects of sulfinpyrazone therapy. Circulation 42:967-972, 1970 9. ANSELL BM, WIGLEY RAD: Arthritic manifestations in regional enteritis. Ann Rheum Dis 23:64-72, 1964 10. MORRIS RI, METZGER AL, BLUESTONE R, et al: HI^A-W27—
a useful discriminator in the arthropathies of inflammatory bowel disease. N Engl J Med 290:1117-1119, 1974 11. CLARKSON PM, BARRATT-BOYES BG: Bacterial endocarditis following homograft replacement of the aortic valve. Circulation 42:987-991, 1970 12. MANHAS DR, MOHRI H, MERENDINO KA: Late results of beta-
propiolactone sterilized aortic homograft valves: a study of fifty-one patients followed up five to seven and a half years. Am J Surg 126:255-262, 1973 13. WATERWORTH PM, LOCKEY E, BERRY EM, et al: A critical in-
vestigation into the antibiotic sterilization of heart valve homografts. 77zorax 29:432-436, 1974 14. KLUGE RM, CALIA FM, MCLAUGHLIN JS, et al: Sources of
contamination in open heart surgery. JAMA 230:1415-1418, 1974 15. JACKSON G, SAUNDERS K: Prosthetic valve diphtheroid endocarditis treated with sodium fusidate and erythromycin. Br Heart J 35:931-936, 1973 16. OKIES JE, BRADSHAW MW, WILLIAMS TW JR: Valve replace-
ment in bacterial endocarditis. Chest 63:898-904, 1973
November 1975 • Annals of Internal Medicine • Volume 83 • Number 5
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
Oerskovia turbata is a yellow, motile actinomycete, which before now has only been found in soil and has not been known to cause disease in man or animals. It was isolated from 29 cultures of blood taken during 6 months from an urban pensioner after homograft replacement of his aortic valve. The combination of ampicillin, sulfamethoxazole, and trimethoprim was lethal for O. turbata in vitro; however, antimicrobial therapy alone failed to eradicate the patient's infection. Cure was achieved after the infected homograft was replaced with a prosthetic aortic valve. Although the source of 0. turbata in this patient is unknown, sterilization of homograft valves with antimicrobial solutions is difficult. Moreover, environmental contamination during cardiopulmonary bypass is common. Oerskovia turbata is another opportunistic pathogen of man.
I N 1938 0rskov described a nocardioform bacterium found in Danish soil that was motile and produced a yellow pigment ( 1 ) . This organism, now called Oerskovia turbata, has not been recognized in infections of man or animals but has been isolated from soil in the United States and Europe (1-3). We report a case of endocarditis caused by O. turbata in a man whose aortic valve was replaced with a homograft heart valve because of severe aortic insufficiency associated with ankylosing spondylitis 20 years after ileal resections for regional enteritis. Case Report A 68-year-old urban pensioner entered Colorado General Hospital in July 1973 because of acute pulmonary edema. A grade 2/6 murmur of aortic insufficiency had been noted since 1964; however, his blood pressure had remained stable at 140/60 mm Hg. Part of his ileum had been resected 20 years earlier because of symptomatic Crohn's disease. He was being treated with 60 mg of prednisone each day for ankylosing spondylitis. Radiographs showed obliteration of both sacroiliac joints; he had histocompatibility antigen (HL-A) type W27. Evidence of inflammation included serum-iron, 14 fig per dl; iron-binding capacity, 209 fig per dl; and erythrocyte sedimentation rate, 54 mm/h. Four cultures of blood were negative. His cardiac failure improved after diuresis and he was discharged. One month later he was readmitted; a harsh, grade 4/6 diastolic murmur of aortic insufficiency was present. Owing to progressive cardiac failure he was treated for 6 weeks with parenteral ampicillin and gentamicin despite 12 negative blood cultures (Figure 1). In November 1973, after his blood pressure fell from 140/40 to 140/0 mm Hg, the patient's aortic • From the Departments of Medicine and Surgery, University of Colorado Medical Center, Denver, Colorado.
664
valve was replaced with a stented homograft valve that had been stored for 50 days in an antimicrobial solution, which contained nystatin, penicillin, polymyxin B, and streptomycin. The patient's valve showed no signs of infective endocarditis; however, there was fibrosis of the aortic valve cusps and aortic root with infiltration of lymphocytes as found by others in the aortitis of ankylosing spondylitis (4, 5). He went home well with no cardiac murmurs. The patient again entered the hospital in January 1974 after 4 days of fever and rigors. Physical examination showed an oral temperature of 40 °C, blood pressure of 150/70 mm Hg, splenomegaly, and a new grade 2/6 diastolic murmur. After 48 h, the first of 29 subsequently positive blood cultures grew a diphtheroid organism that was identified later as O. turbata by the Center for Disease Control. During the next 6 months treatment with several antimicrobials was tried without lasting success (Figure 1). Because of recurrent fever and positive blood cultures when antimicrobials were stopped, the patient's homograft valve was replaced with a Bjork-Shiley prosthetic aortic valve in July 1974. The patient was given sulfamethoxazole-trimethoprim, intravenously for 48 h after surgery; he was then treated with oral sulfamethoxazole-trimethoprim for 12 weeks, simultaneously with 6 weeks of parenteral ampicillin followed by 6 weeks of oral amoxicillin. Owing to the possibility of inhibition of folate metabolism in man by trimethoprim, the patient was given 400 fig of folinic acid each day (6). During antimicrobial therapy his serum contained 7 to 11 ng of folate per ml; these concentrations would not be expected to antagonize the effect of sulfamethoxazole-trimethoprim on O. turbata (7). Blood cultures during 3 months after therapy were all negative; the patient was asymptomatic 7 months after stopping all antimicrobials (Figure 1). His only medication was 800 mg of sulfinpyrazone each day to prevent platelet thrombi on his prosthetic valve (8). Microbiological Findings
All 29 positive blood cultures after placement of the homograft valve grew the same Gram-positive rods and cocci, which formed yellow colonies on subculture to sheep blood agar. Moreover, O. turbata was isolated from the resected homograft valve and the Gram-positive organisms were seen on microscopic examination of the valve itself and the attached vegetations. The biochemical reactions were typical of O. turbata (1-3); it produced acid from lactose and sucrose but not mannitol, and hydrolyzed casein but not tyrosine or xanthine. The organism was motile, not acid-fast, and had cell wall type VI, which contains major amounts of galactose ( 2 ) . Many antimicrobials were tested against O. turbata; no single agent showed enough activity to be successful in treating endocarditis. The most effective combination in vitro was ampicillin and sulfamethoxazole-trimethoprim {see Table 1). The initial isolates of O. turbata and those after each relapse and from the resected homograft valve Annals of Internal Medicine 83:664-666, 1975
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
Figure 1 . Summary of temperature, blood cultures, and antimicrobial and surgical therapy of patient with endocarditis caused by Oerskovia turbata. AMP = ampicillin; GM = gentamicin; PEN = penicillin; ERY = erythromycin; SMX = sulfamethoxazole; TMP = trimethoprim; AMOX = amoxicillin; IV = intravenous; IM = intramuscular; and PO = oral.
all showed the same antibiogram and degree of susceptibility. Concentrations of 10 or 50 ng of folinic acid per ml did not alter the susceptibility of O. turbata from this patient to sulfamethoxazole-trimethoprim in vitro. The patient's serum was assayed often for antibacterial activity. While receiving erythromycin and ampicillin, a 1:16 dilution of serum inhibited O. turbata but no bactericidal activity was present. Similarly sulfamethoxazoletrimethoprim was inhibitory at a 1:32 dilution of serum but did not kill the organism. On combined therapy with ampicillin and sulfamethoxazole-trimethoprim the patient's serum was inhibitory at a dilution of 1:32 or higher and bactericidal at a 1:8 dilution. Moreover, each antimicrobial was assayed separately and shown to be present in concentrations that exceeded the minimal lethal concentration required for O. turbata with the combination of ampicillin and sulfamethoxazole-trimethoprim (Table 1) (7). One week after stopping therapy the patient's serum showed no activity against his O. turbata. Discussion
This patient had a sequence of uncommon illnesses that makes him unique. Ankylosing spondylitis occurs in about 3% of all patients with regional enteritis (9); it occurs in one of six patients, such as ours, who have HL-A type W27 and Crohn's disease (10). The incidence of aortic insufficiency in patients with ankylosing spondylitis is about 8% (4, 5); there is one report of aortic insufficiency in a patient with ankylosing spondylitis and
regional enteritis (4). The aortitis and associated valvulitis of ankylosing spondylitis are progressive and result in free aortic regurgitation in half of patients within 7 years of the earliest evidence of valvulitis (5). Our patient had a blood pressure of 140/0 mm Hg before replacement of his uninfected aortic valve. The reported incidence of bacterial endocarditis after homograft replacement of the aortic valve varies from 2.6% to 15.1% (11, 12). Before this 0. turbata has been described only as a soil organism (1,3). The source of O. turbata in this patient must remain speculative. Three preoperative cultures of the involved homograft tissue were negative; however, seven previous valves harvested at the same medical center were discarded because of contamination with diphtheroids that were later identified as O. turbata. Moreover, homograft heart valves are not usually collected under sterile conditions and are exceedingly difficult to sterilize with antibiotics (12, 13). Microbial contamination occurs often during open heart surgery; diphtheroids are the most commonly isolated organism (14). Diphtheroid endocarditis is uncommon but does occur after prosthetic valve replacement (15). Cure of this patient after two bacteriologic relapses illustrates two principles of treatment of infective endocarditis. Successful medical therapy requires bactericidal concentrations of antimicrobials in serum that exceed the minimal lethal concentration of the infecting organism; patients with unresponsive infection need valve replace-
Table 1. Susceptibility of Oerskovia turbata to Antimicrobials Alone and in Combination and Concentrations of Antimicrobials Achieved in Patient's Serum Concentration of Antimicrobial
Minimal inhibitory concentration Minimal lethal concentration Serum (1 to 3 h after last dose)
Ampicillin
Sulfamethoxazole
Trimethoprim
32 32 36
5 >160 270
0.25 >8.0 6.6
Ampicillin/Sulfamethoxazole/Trimethoprim 4 8
5 10
0.25 0.5
Roller et al. • Oerskovia turbata Endocarditis
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
665
ment (16). Satisfactory inhibition of O. turbata was achieved with two courses of treatment and all 14 blood cultures during therapy were negative; however, fever and positive blood cultures occurred shortly after inhibitory therapy was stopped (Figure 1). Moreover, O. turbata was grown from the excised valve and from vegetations on the valve after grinding. In contrast none of the 6 blood cultures taken after replacement of the infected valve and bactericidal therapy was positive. The specific identification of O. turbata in this patient was important. Owing to the initial report of a diphtheroid, a common contaminant of blood cultures and open heart surgery (14, 15), inadequate therapy was given (Figure 1). Because O. turbata has only been isolated from soil, there was no precedent for choosing antimicrobial therapy. The relation of O. turbata to the genus Nocardia aided selection of possibly effective agents for testing. The techniques required for reliable assay of sulfamethoxazole and trimethoprim were used (7). The absence of antagonism of sulfamethoxazole-trimethoprim by folinic acid when tested against O. turbata in vitro made possible the prolonged high doses of sulfamethoxazole-trimethoprim required to achieve bactericidal synergism with ampicillin or amoxicillin without suppression of the bone marrow (6). Successful replacement of the infected valve was then possible during bactericidal antimicrobial coverage. When it occurs, relapse with the same organism is almost always within 2 months after stopping therapy (16). This patient seems cured. ACKNOWLEDGMENTS: The authors thank David B. Weeks for technical assistance; June Brown of the Mycology Branch, Laboratory Division, Center for Disease Control for identification of Oerskovia turbata; Hoffman-LaRoche, Inc. for providing amoxicillin and sulfamethoxazole-trimethoprim for intravenous use; and Jeanne R. Cleary for secretarial work. Presented in part on 2 May 1975 at the 75th Annual Meeting of the American Society for Microbiology, New York, New York. Received 19 May 1975; revision accepted 11 July 1975.
666
• Requests for reprints should be addressed to L. Barth Reller, M.D., Box B168, University of Colorado Medical Center, 4200 East 9th Avenue, Denver, CO 80220. References 1. ERIKSON D: Factors promoting cell division in a 'soft' mycelial type of Nocardia: Nocardia turbata n.sp. / Gen Microbiol 11: 198-208, 1954 2. PRAUSER H, LECHEVALIER MP, LECHEVALIER H: Description of
Oerskovia gen. n. to harbor 0rskov's motile Nocardia. Appl Microbiol 19:534, 1970 3. LECHEVALIER MP: Description of a new species, Oerskovia xanthineolytica, and emendation of Oerskovia Prauser et al. Int J Syst Bacteriol 22:260-264, 1972 4. KINSELLA TD, JOHNSON LG, SUTHERLAND RI: Cardiovascular
manifestations of ankylosing spondylitis. Can Med Assoc / 1 1 1 : 1309-1311, 1974 5. GRAHAM DC, SMYTHE HA: The carditis and aorititis of ankylosing spondylitis. Bull Rheum Dis 9:171-174, 1958 6. KAHN SB, FEIN SA, BRODSKY I: Effects of trimethoprim on
folate metabolism in man. Clin Pharmacol Ther 9:550-560, 1968 7. PAVILLARD ER: Treatment of nocardial infection with trimethoprim-sulphamethoxazole. Med J Aust l:(suppl) 65-69, 1973 8. WEILY HS, GENTON E: Altered platelet function in patients with prosthetic mitral valves: effects of sulfinpyrazone therapy. Circulation 42:967-972, 1970 9. ANSELL BM, WIGLEY RAD: Arthritic manifestations in regional enteritis. Ann Rheum Dis 23:64-72, 1964 10. MORRIS RI, METZGER AL, BLUESTONE R, et al: HI^A-W27—
a useful discriminator in the arthropathies of inflammatory bowel disease. N Engl J Med 290:1117-1119, 1974 11. CLARKSON PM, BARRATT-BOYES BG: Bacterial endocarditis following homograft replacement of the aortic valve. Circulation 42:987-991, 1970 12. MANHAS DR, MOHRI H, MERENDINO KA: Late results of beta-
propiolactone sterilized aortic homograft valves: a study of fifty-one patients followed up five to seven and a half years. Am J Surg 126:255-262, 1973 13. WATERWORTH PM, LOCKEY E, BERRY EM, et al: A critical in-
vestigation into the antibiotic sterilization of heart valve homografts. 77zorax 29:432-436, 1974 14. KLUGE RM, CALIA FM, MCLAUGHLIN JS, et al: Sources of
contamination in open heart surgery. JAMA 230:1415-1418, 1974 15. JACKSON G, SAUNDERS K: Prosthetic valve diphtheroid endocarditis treated with sodium fusidate and erythromycin. Br Heart J 35:931-936, 1973 16. OKIES JE, BRADSHAW MW, WILLIAMS TW JR: Valve replace-
ment in bacterial endocarditis. Chest 63:898-904, 1973
November 1975 • Annals of Internal Medicine • Volume 83 • Number 5
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19503/ by a University of California San Diego User on 02/09/2017
