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Salmonella bacteremia in patients with prosthetic heart valves
Salmonella Bacteremia in Patients with Prosthetic Heart Valves
SALVADOR ALVAREZ-ELCORO,
M.D.
l
LUIS SOTO-RAMIREZ, M.D. MIGUEL MATEOS-MORA,
M.D.
Mexico City, Mexico
During 1982 and 1983, flve patients wfth prosthetic heart valves and documented Salmonella bacteremia were admitted to the lnstltuto National de Cardlologia in Mexico City. The clinical and mlcrobiologic features in this group of patients are described, as well as the therapeutic Implications when Salmonella bacteremla Is present in patlents with heart prostheses. None of the patients had evidence of infectious endocardltls; however, all received prolonged parenteral antimicrobial therapy for at least four weeks wlth amplclllln or chloramphenicol, with excellent cllnlcal response. Intravascular infection involving prosthetic valves or adjacent tissues is a serious complication of cardiovascular surgery [l-4]. Once valvular infection is established, eradication with antibiotics alone is extremely difficult. It is usually impossible to determine whether a patient has endocarditis or bacteremia from some other site [ 1,231. Frequently; the diagnosis is not established until disease is advanced or until postmortem examination is carried out. Arteritis and endocarditis are rare complications of salmonellosis [6,7]. A diagnostic and therapeutic dilemma arises when Salmonella bacteremia develops in a patient with an intracardiac prosthesis [6,8]. Salmonella endocarditis has been cured in a few cases by surgery in combination with antibiotics in patients with natural cardiac valves [ 6,9]. Only one report of endocarditis caused by Salmonella species in a patient with a prosthetic heart valve has been described [lo]. In an attempt to establish clinical and bacteriologic criteria that might help to resolve this dilemma, we describe herein five patients with prosthetic cardiac valves and Salmonella bacteremia observed at the lnstituto National de Cardiologia in Mexico City. PATIENTS AND METHODS Patients admitted at the lnstituto National de Cardiolog/a “lgnacio Chavez”
from June 1982 to June 1983 were selected when they had a prosthetic heart valve and culture evidence of the genus Salmonella. All patients in the series were seen in consultation during hospitalization by one or more of us. Salmonella was isoiated and identified by routine methods using serotyping (Salmonella test serum, Behringwerke AG). Antibiotic sensitivity was determined by the standard Kirby-Bauer technique [ 1 l] and, in most cases, by an antibiotic dilution method in broth. From the infectious Diseases and Medical MicrobiologySections, lnstitutoNational de Cardiologia“lgnacio Chavez,” Mexico City, Mexico. Manuscriptaccepted January19, 1984. Currentaddressandaddressfor reprintrequests: Division of Infectious Diseases, Veterans Administration Medical Center, Mountain Home, Tennessee37884. l
CASE REPORTS A summary of the five patients is presented in Table I. Patlent 1. A 29-year-old man with rheumatic heart disease and a mitral vahre prosthesis (Starr-Edwards)since 1989 was admitted with historyof chills and fever for two weeks. Findings on physical examination were normal except for a systolic murmur with normal prosthetic heart sounds. No peripheral stigmata of endocarditis were observed.
July 1984
The American Journal of Medlclne Volume 77
61
SALMONELLA BACTEREMIA IN PATIENTS WITH HEART PROSTHESES-ALVAREZ-ELCORO
TABLE I
ET AL
Summary of Clinical and Laboratory Features* Duration
Patlent Number
Blood Cullures
Age/Sex
Valve
1
29/M
Starr-Edwards
Salmonella
1/3+
2
23/F
Duramater
3
31/F
Duramater
Salmonella typhi Salmonella
BraunwaldCutter BjorkShilley
typhi Salmonella typhi Salmonella typhi
4
28/F
5
15/F
Therapy
of Therapy (weeks)
Cktal Activity
Minimal InhibitorY Csecentration
4
ND
ND
216
Ampicillin, chloramphenicol Ampicillin
4
1:16/1:126
9.4 CLg
616
Ampicillin
4
1:1/1:8
6.8 pg
616
Ampicillin, chloramphenicol Ampicillin
5
1:16/1:128
3.12 pg
4
1:2/1:64
3.12 pg
416
Echocardiographic results were negative in all patients, and all patients were cured. + Number of positive results per number of specimens cultured. l
The echocardiographic results were considered normal. One of the three blood cultures grew Salmonella. Administration of ampicillin was begun, but fever continued up to 39OC. New blood culture specimens were obtained and reportedly showed no growth. Chloramphenicol was administered, with excellent clinical response. He received a total of four weeks of chloramphenicol and remains well one year later. Patient 2. A 23-year-old woman with mitral stenosis and a cardiac prosthesis (Duramater) since 1978 was admitted with a one-week history of fever, shaking chills, night sweats, and joint pains. Findings on physical examination were normal except for hepatomegly. No stigmata of endocarditis were observed. Echocardiographic results were normal without evidence of vegetations. Two of the initial six blood cultures grew a gram-negative bacilli. Administration of gentamicin and cephalothin was begun, and when a Salmonella species was identified, ampicillin was given with excellent clinical improvement. Therapy was continued for four weeks. She was discharged and remains well 10 months later. Patlent 3. A 31-year-old woman with rheumatic heart disease with mitral stenosis and a valve prothesis (Duramater) since 1980 was admitted with fever and dysuria. She received oral ampicillin, with improvement of her urinary symptoms but remained febrile. Physical examination revealed normal prosthetic heart sounds and discrete hepatomegaly. Echocardiography revealed no vegetations. After blood culture specimens were obtained, she was given gentamicin and cephalothin. The six blood cultures grew Salmonella species. Ampicillin was given, and she remained febrile for four days and then became afebrile. New blood cultures showed no growth. Ampicillin was administered for a total of four weeks. She was discharged and remains asymptomatic nine months later. Patlent 4. A 28.year-old woman with rheumatic heart disease and mitral valve replacement (Braunwald-Cutter) in 1977, had history of probable infectious endocarditis in 1979 (with negative results of blood culture) treated with antibiotics alone for six weeks. She was admitted with history of nausea and vomiting,
82
July 19B4
The American Journal of Medicine
Volume 77
diarrhea, fever, and headache for one week. She was febrile (40°C), and the sclera were icteric. The prosthetic heart sounds were considered normal. Painful hepatomegaly 6 cm below the costal margin was palpated. No peripheral findings of endocarditis were observed. The white blood cell count was 3,100/mm3. The total bilirubin level was 10.5 mg/dl, with elevated serum glutamic oxaloacetic transaminase and alkaline phosphatase levels. Six blood cultures grew a gram-negative bacilli later identified as Salmonella typhi. Administration of ampicillin was begun, and she remained febrile with no growth on blood culture after six days of therapy. Chloramphenicol was given, with excellent clinical response and improvement of her general condition. She received a total of five weeks of chloramphenicol therapy and remains asymptomatic after three months. Patient 5. A 15year-old girl with rheumatic heart disease and mitral valve replacement (BjorkShilley) in February 1982 was admitted with a threeday history of fever and headache. Findings on admission physical examination were normal. She became afebrile without treatment, and blood cultures showed no growth. Two weeks later, sha had fever again, and four of the six blood culture specimens obtained grew Salmonella. Administration of ampicillin was begun, with excellent response. She received four weeks of treatment and remains asymptomatic two months later. COMMENTS
A diagnostic and therapeutic dilemma arises when bacteremia develops in a patient with an intracardiac prosthesis, especially in the early postoperative period. Sande and Johnson [l] suggested an approach for the resolution of this clinically important, difficult, and now quite common diagnostic challenge. They suggested, from their data, that the development of bacteremia shortly after implantation of a prosthetic valve in the heart should not always be interpreted as indicating infection in the prosthesis. Those patients with prosthetic valve infection had positive blood culture results
SALMONELLA BACTERl%IA IN PATtENTS WfTH HEART PROSTHESES-ALVAREZILCORO
ET AL
25 days or more after the operation, with gram-positive organisms, no obvious source for bacteremia, and new or changing mumurs. The group without proved valvular infection had earlier bacteremia, with gram-negative bacilli and obvious possible sources of bacteremia. Evidence of extracardiac sources of bacteremia such as sternal infection, the presence of intravenous catheters, pneumonia, or suppurative phlebitis makes involvement of the prosthetic valve quite unlikely. However, it should be clear that these criteria, singly or in any combination, will not always distinguish intracardiac from extracardiac infections. Even the detection of an infected area outside the heart does not always exclude intracardiac infection, because the peripheral lesion may be the source from which organisms may invade the circulation and colonize the prosthesis. The Salmonella are primarily intestinal pathogens. Cardiac complications of salmonellosis are uncommon, and endocarditis caused by Salmonella is a rare disease [6,9]. Most of the patients with documented Salmonella endocarditis were younger than 50 and had an underlying valvular disease. Antibiotic treatment has cured only four of the 32 previously described patients [6,9,12]. These poor results suggest that prompt diagnostic evaluation and an attempt at surgical excision of the lesion is worth consideration, despite the very limited experience to date with surgical therapy
in this disease, there is a predilection for previously diseased valves or endocardial surfaces, and several valves frequently are affected [9]. There was no evidence of valvular dysfunction in any of the patients in this group. The echocardiographic findings were also negative, and the favorable clinical response with sterile blood cultures after antibiotic therapy make this diagnosis highly unlikely. All of our patients received therapy for at least four weeks. We believe that when a person in a high-risk group has Salmonella bacteremia and negative results of diagnostic studies for valvular infection, prolonged parenteral antibiotic therapy is indicated because this could prevent or sterilize an early endothelial lesion. Chloramphenicol remains the drug of choice of typhoid fever. High-dose ampicillin, a bactericidal drug, was used as initial therapy in our patients, with negative findings on blood culture soon after treatment was begun. However, two patients remained febrile despite ampicillin therapy, and chloramphenicol was given with good clinical improvement. Antibiotics do prolong fecal excretion of Salmonella and do increase the frequency of resistant stool isolates [ 131. However, none of our patients had positive findings on stool culture during the acute illness or the post-therapy period.
[lOI.
We are very grateful to Dr. William R. McCabe for reviewing the article, and to Ms. Ana Mar/a Martinez for typing the manuscript.
None of our patients had clinical features of Salmonella endocarditis. When cardiac involvement occurs
ACKNOWLEDGMENT
REFERENCES 1.
2.
3. 4. 5. 6.
7.
Sande MA, Johnson WD: Sustained bacteremia in patients with prosthetic cardiac valves. N Engl J Med 1972; 286: 1067-1070. Weinstein L: Infected prosthetic valves. A diagnostic and therapeutic dilemma. N Engl J Med 1972; 286: 11081109. Wilson WB, Danielson GK, Giuliani ER, Geraci JE: Prosthetic valve endocardltis. Mayo Clin Proc 1982; 57: 155-161. Wilson WR, Jaumin PM: Prosthetic valve endocarditis. Ann Intern Med 1975; 82: 751-756. Dismukes WE, Karchmer AW: Prosthetic valve endocarditis, analysis of 38 cases. Circulation 1973; 48: 365-377. Cohen PS, O’Brien TF, Schoenbaum SC, Medeiros AA: The risk of endothellal infection In adults with Salmonella bacteremia. Brief reports. Ann Intern Med 1978; 89: 931-932. Meade RH, Moran JM: Salmonella arteritis. N Engl J Med 1969; 281: 310-312.
8. 9.
10.
11.
12.
13.
Weinstein L, Kaplan K: Salmonella aortitis in a patient with a Hufnagel valve. Circulation 1965; 31: 755-757. Scheider PJ, Nernoff J, Gold JA: Acute Salmonella endocarditis. Report of a case and review. Arch intern Med 1967; 120: 478-482. Yamamoto N, Magidson 0, Posner C, Mender AM, Zubiate P, Kay JH: Probable Salmonella endocarditis treated with prosthetic valve replacement. A case report. Surgery 1974; 76: 878-68 1. Bauer AW, Kirby WMM, Sherris JC, Turk M: Antlbiotlc susceptibility testing by a standard single disc method. Am J Clin Pathol 1966; 45: 492-496. Doraiswami S, Friedman SA, Kagan A: Salmonella endocarditis complicated by a myocardial abscess. Am J Cardiol 1970; 26: 104-105. Aserkoff B, Bennett JV: Effect of antibiotic therapy In acute salmonellosis on the fecal excretion of Salmonella. N Engl J Med 1969; 281: 636-640.
July 1984
The American Journal of Medicine
Volume 77
63
SALVADOR ALVAREZ-ELCORO,
M.D.
l
LUIS SOTO-RAMIREZ, M.D. MIGUEL MATEOS-MORA,
M.D.
Mexico City, Mexico
During 1982 and 1983, flve patients wfth prosthetic heart valves and documented Salmonella bacteremia were admitted to the lnstltuto National de Cardlologia in Mexico City. The clinical and mlcrobiologic features in this group of patients are described, as well as the therapeutic Implications when Salmonella bacteremla Is present in patlents with heart prostheses. None of the patients had evidence of infectious endocardltls; however, all received prolonged parenteral antimicrobial therapy for at least four weeks wlth amplclllln or chloramphenicol, with excellent cllnlcal response. Intravascular infection involving prosthetic valves or adjacent tissues is a serious complication of cardiovascular surgery [l-4]. Once valvular infection is established, eradication with antibiotics alone is extremely difficult. It is usually impossible to determine whether a patient has endocarditis or bacteremia from some other site [ 1,231. Frequently; the diagnosis is not established until disease is advanced or until postmortem examination is carried out. Arteritis and endocarditis are rare complications of salmonellosis [6,7]. A diagnostic and therapeutic dilemma arises when Salmonella bacteremia develops in a patient with an intracardiac prosthesis [6,8]. Salmonella endocarditis has been cured in a few cases by surgery in combination with antibiotics in patients with natural cardiac valves [ 6,9]. Only one report of endocarditis caused by Salmonella species in a patient with a prosthetic heart valve has been described [lo]. In an attempt to establish clinical and bacteriologic criteria that might help to resolve this dilemma, we describe herein five patients with prosthetic cardiac valves and Salmonella bacteremia observed at the lnstituto National de Cardiologia in Mexico City. PATIENTS AND METHODS Patients admitted at the lnstituto National de Cardiolog/a “lgnacio Chavez”
from June 1982 to June 1983 were selected when they had a prosthetic heart valve and culture evidence of the genus Salmonella. All patients in the series were seen in consultation during hospitalization by one or more of us. Salmonella was isoiated and identified by routine methods using serotyping (Salmonella test serum, Behringwerke AG). Antibiotic sensitivity was determined by the standard Kirby-Bauer technique [ 1 l] and, in most cases, by an antibiotic dilution method in broth. From the infectious Diseases and Medical MicrobiologySections, lnstitutoNational de Cardiologia“lgnacio Chavez,” Mexico City, Mexico. Manuscriptaccepted January19, 1984. Currentaddressandaddressfor reprintrequests: Division of Infectious Diseases, Veterans Administration Medical Center, Mountain Home, Tennessee37884. l
CASE REPORTS A summary of the five patients is presented in Table I. Patlent 1. A 29-year-old man with rheumatic heart disease and a mitral vahre prosthesis (Starr-Edwards)since 1989 was admitted with historyof chills and fever for two weeks. Findings on physical examination were normal except for a systolic murmur with normal prosthetic heart sounds. No peripheral stigmata of endocarditis were observed.
July 1984
The American Journal of Medlclne Volume 77
61
SALMONELLA BACTEREMIA IN PATIENTS WITH HEART PROSTHESES-ALVAREZ-ELCORO
TABLE I
ET AL
Summary of Clinical and Laboratory Features* Duration
Patlent Number
Blood Cullures
Age/Sex
Valve
1
29/M
Starr-Edwards
Salmonella
1/3+
2
23/F
Duramater
3
31/F
Duramater
Salmonella typhi Salmonella
BraunwaldCutter BjorkShilley
typhi Salmonella typhi Salmonella typhi
4
28/F
5
15/F
Therapy
of Therapy (weeks)
Cktal Activity
Minimal InhibitorY Csecentration
4
ND
ND
216
Ampicillin, chloramphenicol Ampicillin
4
1:16/1:126
9.4 CLg
616
Ampicillin
4
1:1/1:8
6.8 pg
616
Ampicillin, chloramphenicol Ampicillin
5
1:16/1:128
3.12 pg
4
1:2/1:64
3.12 pg
416
Echocardiographic results were negative in all patients, and all patients were cured. + Number of positive results per number of specimens cultured. l
The echocardiographic results were considered normal. One of the three blood cultures grew Salmonella. Administration of ampicillin was begun, but fever continued up to 39OC. New blood culture specimens were obtained and reportedly showed no growth. Chloramphenicol was administered, with excellent clinical response. He received a total of four weeks of chloramphenicol and remains well one year later. Patient 2. A 23-year-old woman with mitral stenosis and a cardiac prosthesis (Duramater) since 1978 was admitted with a one-week history of fever, shaking chills, night sweats, and joint pains. Findings on physical examination were normal except for hepatomegly. No stigmata of endocarditis were observed. Echocardiographic results were normal without evidence of vegetations. Two of the initial six blood cultures grew a gram-negative bacilli. Administration of gentamicin and cephalothin was begun, and when a Salmonella species was identified, ampicillin was given with excellent clinical improvement. Therapy was continued for four weeks. She was discharged and remains well 10 months later. Patlent 3. A 31-year-old woman with rheumatic heart disease with mitral stenosis and a valve prothesis (Duramater) since 1980 was admitted with fever and dysuria. She received oral ampicillin, with improvement of her urinary symptoms but remained febrile. Physical examination revealed normal prosthetic heart sounds and discrete hepatomegaly. Echocardiography revealed no vegetations. After blood culture specimens were obtained, she was given gentamicin and cephalothin. The six blood cultures grew Salmonella species. Ampicillin was given, and she remained febrile for four days and then became afebrile. New blood cultures showed no growth. Ampicillin was administered for a total of four weeks. She was discharged and remains asymptomatic nine months later. Patlent 4. A 28.year-old woman with rheumatic heart disease and mitral valve replacement (Braunwald-Cutter) in 1977, had history of probable infectious endocarditis in 1979 (with negative results of blood culture) treated with antibiotics alone for six weeks. She was admitted with history of nausea and vomiting,
82
July 19B4
The American Journal of Medicine
Volume 77
diarrhea, fever, and headache for one week. She was febrile (40°C), and the sclera were icteric. The prosthetic heart sounds were considered normal. Painful hepatomegaly 6 cm below the costal margin was palpated. No peripheral findings of endocarditis were observed. The white blood cell count was 3,100/mm3. The total bilirubin level was 10.5 mg/dl, with elevated serum glutamic oxaloacetic transaminase and alkaline phosphatase levels. Six blood cultures grew a gram-negative bacilli later identified as Salmonella typhi. Administration of ampicillin was begun, and she remained febrile with no growth on blood culture after six days of therapy. Chloramphenicol was given, with excellent clinical response and improvement of her general condition. She received a total of five weeks of chloramphenicol therapy and remains asymptomatic after three months. Patient 5. A 15year-old girl with rheumatic heart disease and mitral valve replacement (BjorkShilley) in February 1982 was admitted with a threeday history of fever and headache. Findings on admission physical examination were normal. She became afebrile without treatment, and blood cultures showed no growth. Two weeks later, sha had fever again, and four of the six blood culture specimens obtained grew Salmonella. Administration of ampicillin was begun, with excellent response. She received four weeks of treatment and remains asymptomatic two months later. COMMENTS
A diagnostic and therapeutic dilemma arises when bacteremia develops in a patient with an intracardiac prosthesis, especially in the early postoperative period. Sande and Johnson [l] suggested an approach for the resolution of this clinically important, difficult, and now quite common diagnostic challenge. They suggested, from their data, that the development of bacteremia shortly after implantation of a prosthetic valve in the heart should not always be interpreted as indicating infection in the prosthesis. Those patients with prosthetic valve infection had positive blood culture results
SALMONELLA BACTERl%IA IN PATtENTS WfTH HEART PROSTHESES-ALVAREZILCORO
ET AL
25 days or more after the operation, with gram-positive organisms, no obvious source for bacteremia, and new or changing mumurs. The group without proved valvular infection had earlier bacteremia, with gram-negative bacilli and obvious possible sources of bacteremia. Evidence of extracardiac sources of bacteremia such as sternal infection, the presence of intravenous catheters, pneumonia, or suppurative phlebitis makes involvement of the prosthetic valve quite unlikely. However, it should be clear that these criteria, singly or in any combination, will not always distinguish intracardiac from extracardiac infections. Even the detection of an infected area outside the heart does not always exclude intracardiac infection, because the peripheral lesion may be the source from which organisms may invade the circulation and colonize the prosthesis. The Salmonella are primarily intestinal pathogens. Cardiac complications of salmonellosis are uncommon, and endocarditis caused by Salmonella is a rare disease [6,9]. Most of the patients with documented Salmonella endocarditis were younger than 50 and had an underlying valvular disease. Antibiotic treatment has cured only four of the 32 previously described patients [6,9,12]. These poor results suggest that prompt diagnostic evaluation and an attempt at surgical excision of the lesion is worth consideration, despite the very limited experience to date with surgical therapy
in this disease, there is a predilection for previously diseased valves or endocardial surfaces, and several valves frequently are affected [9]. There was no evidence of valvular dysfunction in any of the patients in this group. The echocardiographic findings were also negative, and the favorable clinical response with sterile blood cultures after antibiotic therapy make this diagnosis highly unlikely. All of our patients received therapy for at least four weeks. We believe that when a person in a high-risk group has Salmonella bacteremia and negative results of diagnostic studies for valvular infection, prolonged parenteral antibiotic therapy is indicated because this could prevent or sterilize an early endothelial lesion. Chloramphenicol remains the drug of choice of typhoid fever. High-dose ampicillin, a bactericidal drug, was used as initial therapy in our patients, with negative findings on blood culture soon after treatment was begun. However, two patients remained febrile despite ampicillin therapy, and chloramphenicol was given with good clinical improvement. Antibiotics do prolong fecal excretion of Salmonella and do increase the frequency of resistant stool isolates [ 131. However, none of our patients had positive findings on stool culture during the acute illness or the post-therapy period.
[lOI.
We are very grateful to Dr. William R. McCabe for reviewing the article, and to Ms. Ana Mar/a Martinez for typing the manuscript.
None of our patients had clinical features of Salmonella endocarditis. When cardiac involvement occurs
ACKNOWLEDGMENT
REFERENCES 1.
2.
3. 4. 5. 6.
7.
Sande MA, Johnson WD: Sustained bacteremia in patients with prosthetic cardiac valves. N Engl J Med 1972; 286: 1067-1070. Weinstein L: Infected prosthetic valves. A diagnostic and therapeutic dilemma. N Engl J Med 1972; 286: 11081109. Wilson WB, Danielson GK, Giuliani ER, Geraci JE: Prosthetic valve endocardltis. Mayo Clin Proc 1982; 57: 155-161. Wilson WR, Jaumin PM: Prosthetic valve endocarditis. Ann Intern Med 1975; 82: 751-756. Dismukes WE, Karchmer AW: Prosthetic valve endocarditis, analysis of 38 cases. Circulation 1973; 48: 365-377. Cohen PS, O’Brien TF, Schoenbaum SC, Medeiros AA: The risk of endothellal infection In adults with Salmonella bacteremia. Brief reports. Ann Intern Med 1978; 89: 931-932. Meade RH, Moran JM: Salmonella arteritis. N Engl J Med 1969; 281: 310-312.
8. 9.
10.
11.
12.
13.
Weinstein L, Kaplan K: Salmonella aortitis in a patient with a Hufnagel valve. Circulation 1965; 31: 755-757. Scheider PJ, Nernoff J, Gold JA: Acute Salmonella endocarditis. Report of a case and review. Arch intern Med 1967; 120: 478-482. Yamamoto N, Magidson 0, Posner C, Mender AM, Zubiate P, Kay JH: Probable Salmonella endocarditis treated with prosthetic valve replacement. A case report. Surgery 1974; 76: 878-68 1. Bauer AW, Kirby WMM, Sherris JC, Turk M: Antlbiotlc susceptibility testing by a standard single disc method. Am J Clin Pathol 1966; 45: 492-496. Doraiswami S, Friedman SA, Kagan A: Salmonella endocarditis complicated by a myocardial abscess. Am J Cardiol 1970; 26: 104-105. Aserkoff B, Bennett JV: Effect of antibiotic therapy In acute salmonellosis on the fecal excretion of Salmonella. N Engl J Med 1969; 281: 636-640.
July 1984
The American Journal of Medicine
Volume 77
63