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Localization of endovascular infection by selective catheterization with serial cultures
Localization of endovascular infection by selective catheterization with serial cultures P.;eudomonas infection developed at the suture line of an aortic graft in a patient 13 years after the operation. The site of the infection was localized by quantitative blood cultures taken with the aid of selective arterial catheterization. This technique may be of great help in localizing the source of endovascular infection in difficult cases.
Michael C. Bach, M.D., F.R.C.P.(C), Edward B. Lewin, M.D.,* Edward T. Sheaff, M.Sc, Ph.D., Leonard Schwartz, M.D., F.R.C.P.(C), and Michael E. De Bakey, M.D., Toronto, Ontario, Canada, and Houston, Texas
Infection complicating vascular prostheses has been a difficult cardiovascular problem. One of the major difficulties that arises when a sustained bacteremia develops in a patient who has a vascular graft has been identification of the site of infection when clinical evidence of valvular dysfunction or radiologic evidence of infection in the graft is lacking. We were recently faced with this dilemma in a man who, 13 years previously, had had excision of a thoracic aneurysm and replacement by an aortic bypass graft. We were able to direct the surgeons to the specific site of infection by means of selective arterial catheterization and quantitative blood cultures of the specimens obtained. Case report A 60-year-old man, whose right kidney was removed in 1954 because of miliary tuberculosis, From the Departments of Medicine (Infectious Diseases and Cardiology) and Medical Microbiology, University of Toronto, the Medical Service, Toronto General Hospital, Toronto, Ontario, Canada, the Cora and Webb Mading Department of Surgery, Baylor College of Medicine, and the Division of Surgery, The Methodist Hospital, Houston, Texas. Received for publication Aug. 19, 1974. Address for reprints: Dr. Michael C. Bach, Room 102 University Wing, Toronto General Hospital, Toronto, Ontario, Canada M5G 1L7. •Present address: Division of Infectious Diseases, Department of Pediatrics, Strong Memorial Hospital, Rochester, N. Y.
had an aortic bypass graft inserted in Houston, Texas, in 1960. The graft, which extended from the thoracic to the lower abdominal aorta, was needed because of a large, symptomatic, saccular aneurysm of the thoracic aorta. He remained in perfect health until August, 1973, when he was admitted to the Mount Sinai Hospital in Toronto because of fever and dysuria of 3 days' duration. There was no history of genitourinary manipulation or dental extraction. His temperature was 40° C , and he had a soft Grade 2/6 basal ejection systolic murmur which had been documented 13 years previously in Houston. The white blood cell count was 12,500 per cubic millimeter and the hemoglobin was 13.8 Gm. per 100 ml. Retrograde pyelography showed nothing of importance. Twenty-four hours later he became hypotensive, and blood cultures taken on admission were reported to be growing Pseudomonas aeruginosa, although the urine culture was sterile. He was treated with intravenous injections of gentamicin (160 mg. daily) and carbenicillin (24 Gm. daily), colloid and crystalloid, with improvement of the hypotension. An intravenous pyelogram and nephrotomograms showed no evidence of abscess or pyelonephritis. Gentamicin blood levels were in the range of 3.5 to 4.5 meg. per milliliter titrated according to assay measurement because of an elevated serum creatinine. After 2 weeks the antibiotic therapy was discontinued, and within 24 hours he again had shaking chills and fevers up to 40° C. Blood cultures were again positive for Pseudomonas. Serum creatinine again rose, and examination of urine sediment revealed red and white blood cell casts compatible with a diagnosis of glomeruiitis.
377
The Journal of
378
Bach et al.
Thoracic and Cardiovascular Surgery
Fig. 1. Aortic angiogram shows the aorta and the upper (A) and lower (B) ends of the prosthetic bypass graft. Note the smooth lining with no evidence suggesting infection or mucosal irregularity.
Fig. 2. Diagrammatic sketch illustrates the sites of cultures taken from the aorta, graft, and left ventricle.
He also had clubbing of the nailbeds. A latex fixation titer was 1/640, and the sedimentation rate was 126 mm. per hour (Westergren). Intravenous administration of gentamicin was restarted in a dosage of 240 mg. daily and carbenicillin in a dosage of 30 Gm. daily. After another 4 weeks of treatment, a maculopapular cutaneous eruption
developed and necessitated discontinuation of the carbenicillin. One week later, while still taking gentamicin, he again developed shaking chills. It was believed that the infection was probably not under control. To determine whether the new fever was in fact due to a Pseudomonas infection, we discontinued the gentamicin. Within 48 hours, the blood cultures were again positive for Pseudomonas aeruginosa. Administration of gentamicin and carbenicillin was restarted, but almost immediately the same pruritic maculopapular rash developed. At this point the patient was transferred to the Methodist Hospital in Houston under the care of one of us (M. E. D.). Complete investigation including gastrointestinal roentgenography, bone and gallium scans, and aortography failed to disclose the source of the bacteremia. In particular, views of the graft showed a normal smooth lining with no defects to suggest an infected focus (Fig. 1). The patient was transferred to Toronto General Hospital for another full 6 weeks' course of gentamicin (180 mg. daily) and carbenicillin (36 Gm. daily). The carbenicillin rash was controlled by oral administration of antihistamines. The minimum inhibitory concentration of gentamicin and carbenicillin for the organism were 3.1 and 25 meg. per milliliter, respectively. Blood levels for gentamicin were in the range of 4 to 5 meg. per milliliter after the intravenous infusion, and serum cidal levels immediately after the carbenicillin infusions were 1:8 to 1:16. Good synergism, as documented by in vitro testing using the standard
Volume 69 Number 3
Localization of endovascular infection
379
March, 1975
Fig. 3. Culture plates after 24 hours' incubation taken simultaneously from the brachial artery catheter (upper row) and the femoral artery catheter (lower row) in series A.
Fig. 4. Culture plates after 24 hours' incubation in series B. Cultures from the brachial artery catheter (upper row) and femoral artery catheter (lower row). checkerboard square technique, was obtained with this antibiotic combination. The 24 hour urinary protein excretion rose to 1.3 Gm. from a base-line excretion rate of 30 mg., and the urinary sediment showed granular casts; this development was interpreted as a possible early sign of gentamicin nephrotoxicity. Throughout the course, he had no new cardiac murmurs and no other evidence pointing to a possible source of the Pseudomonas infection. While on antibiotic therapy, he was perfectly well and asymptomatic, enjoying a good appetite. Thirty-six hours after antibiotic therapy was discontinued, he again had rigors, and blood cultures were positive for Pseudomonas aeruginosa, with the same antibiotic sensitivity pattern as the previous isolates. Discussions with a number of infectious disease clinicians and cardiologists yielded no uniform opinion on whether the site of infection was the aortic valve or the 12-yearold, presumably well-endothelialized prosthetic graft. Quantitative blood cultures were done according to the following method: The right brachial artery was catheterized with a No. 8 Fr. Sones catheter and the right femoral artery with a No. 8 Fr. Cordis all-purpose cath-
eter. Concomitantly, 5 ml. blood samples were aspirated through both catheters from the sites, shown in Fig. 2. The first set of cultures was obtained by passing the brachial catheter into the aorta and down through the aortic valve (Table I, cultures 1 to 5, series A). During this sequence, the femoral artery catheter lay in the femoral artery without approaching the graft; thus it was possible to evaluate the aortic valve area before passing up the graft. The brachial catheter was then pulled back into the brachial artery and the Cordis catheter was advanced up the aorta and through the graft (Table I, cultures 6 to 11, series B); aliquots of blood (0.05, 0.1, and 0.2 ml.) were pipetted onto fresh trypticase soy agar plates as soon as the specimens were collected in the catheterization room. The blood was spread over the agar by means of curved sterile glass rods and then incubated at 37° C. for 24 hours. Two milliliter aliquots of blood were also inoculated into Becton-Dickinson vacutainer blood culture tubes. An aortic root angiogram revealed no evidence of aortic regurgitation or abnormality of the aortic valve leaflets. There was also no mitral regurgitation on left ventriculography. Table I shows the results of colony counts
The Journal of
380
Bach et al.
Thoracic and Cardiovascular Surgery
Table I. Results of selective catheterization of the brachial and femoral arteries with colony counts of blood specimens from different sites
Culture
site
Brachial artery culture (col./ml.)
Femoral artery culture (col./ml.)
A. Advancing brachial catheter 1. Brachial artery 2. Junction of brachiocephalic artery and aorta 3. Aortic root 4. Left ventricle 5. Ascending aorta
0 20
10 10
0 350 70
0 300 80
B. Advancing femoral catheter 6. Lower pouch 7. Lower graft 8. Midgraft 9. Upper graft 10. Upper blind pouch 11. Aortic root
0 0 0 120 500 500
20 0 0 300 500 500
obtained from the catheter specimens. The numbered sites correspond to the numbers in the diagram in Fig. 2 and show a heavy concentration of organisms at the upper blind pouch of the aorta and the upper part of the graft. The left ventricle culture, taken through the brachial artery catheter, and a concomitant femoral artery specimen were also positive. AH the specimens inoculated into the blood culture tubes, from all sites, yielded Pseudomonas after 24 hours of incubation. This indicates that he was having a constant but low-grade bacteremia. Fig. 3 illustrates the culture plates taken with the brachial artery catheter (series A). Fig. 4 highlights the culture plates taken from blood drawn from the femoral catheter as it was advanced up the graft (series B). When the infected sites were reached, cultures from both the brachial and the femoral catheters were positive, an observation suggesting that the catheter dislodged vegetations which then made a complete circuit through the circulation. Based on the results of this study, the patient was transferred back to Houston where, after bilateral axillofemoral bypass grafts were implanted, he underwent total resection of the original graft. Infected laminated thrombus was found around the original suture line at the two sites at the upper end of the graft, as documented by the culture data. He was treated with antibiotics for 3 more
weeks postoperatively, and this therapy was then discontinued successfully. He has remained afebrile and well for the past 8 months.
Discussion The catheterization data suggested that the major focus of infection was located at the upper end of the graft, and this was confirmed at operation. We attribute the positive culture at the aortic root in series B to the fact that a vegetation may have been picked up and carried along as the catheter passed through the infected upper graft. The positive culture from the left ventricle in series A was perplexing. We were concerned that the patient may have had an aortic valvular infection as well; fortunately, this did not prove to be the case, as shown by his clinical course. One might postulate that at the time we were sampling the aortic valve area, he experienced a spontaneous, sudden high-grade burst of bacteria; Bennett and Beeson1 report that this is often the case with endovascular lesions. On the other hand, he may in fact have had aortic valve infection which was cured by the subsequent 3 week course of therapy. Endovascular infection with Pseudomonas is relatively rare. Saroff and associates- reported a case in a heroin addict who was cured with polymyxin B, gentamicin, and a short course of carbenicillin. They noted only five reports of well-documented cases of cured Pseudomonas endocarditis. A study similar to ours was recently reported by Bazin and associates (Abstract 35, American College of Physicians, New York, 1974). Two patients with refractory endocarditis underwent quantitative blood cultures proximal and distal to the suspected sites of infection. Their technique successfully localized the infection, although in 1 of the patients there was only a small difference in colony counts between the two sites of the valve in question. In patients with prosthetic grafts in place, the identification of the source of a sustained bacteremia may prove to be a real problem when there is no good radiologic evidence of infection or when there are no signs of valvular dysfunction suggestive of a valvular
Volume 69 Number 3
Localization of endovascular infection
381
March, 1975
lesion. In these patients, careful colony counts of blood samples taken from selected suspected areas of the vascular tree may be of help in the localization of the infection. We would like to thank Dr. D. Kasler for referring the patient and A. deHaney, R. T., and the staff of the Microbiology Laboratory, Toronto General Hospital, for their help in this case.
REFERENCES 1 Bennett, I. L., Jr., and Beeson, P. B.: Bacteremia: A Consideration of Some Experimental and Clinical Aspects, Yale J. Biol. Med. 26: 241, 1954. 2 Saroff, A. L., Armstrong, D., and Johnson, W. D., Jr.: Pseudomonas Endocarditis, Am. J. Cardiol. 32: 234, 1973.
Michael C. Bach, M.D., F.R.C.P.(C), Edward B. Lewin, M.D.,* Edward T. Sheaff, M.Sc, Ph.D., Leonard Schwartz, M.D., F.R.C.P.(C), and Michael E. De Bakey, M.D., Toronto, Ontario, Canada, and Houston, Texas
Infection complicating vascular prostheses has been a difficult cardiovascular problem. One of the major difficulties that arises when a sustained bacteremia develops in a patient who has a vascular graft has been identification of the site of infection when clinical evidence of valvular dysfunction or radiologic evidence of infection in the graft is lacking. We were recently faced with this dilemma in a man who, 13 years previously, had had excision of a thoracic aneurysm and replacement by an aortic bypass graft. We were able to direct the surgeons to the specific site of infection by means of selective arterial catheterization and quantitative blood cultures of the specimens obtained. Case report A 60-year-old man, whose right kidney was removed in 1954 because of miliary tuberculosis, From the Departments of Medicine (Infectious Diseases and Cardiology) and Medical Microbiology, University of Toronto, the Medical Service, Toronto General Hospital, Toronto, Ontario, Canada, the Cora and Webb Mading Department of Surgery, Baylor College of Medicine, and the Division of Surgery, The Methodist Hospital, Houston, Texas. Received for publication Aug. 19, 1974. Address for reprints: Dr. Michael C. Bach, Room 102 University Wing, Toronto General Hospital, Toronto, Ontario, Canada M5G 1L7. •Present address: Division of Infectious Diseases, Department of Pediatrics, Strong Memorial Hospital, Rochester, N. Y.
had an aortic bypass graft inserted in Houston, Texas, in 1960. The graft, which extended from the thoracic to the lower abdominal aorta, was needed because of a large, symptomatic, saccular aneurysm of the thoracic aorta. He remained in perfect health until August, 1973, when he was admitted to the Mount Sinai Hospital in Toronto because of fever and dysuria of 3 days' duration. There was no history of genitourinary manipulation or dental extraction. His temperature was 40° C , and he had a soft Grade 2/6 basal ejection systolic murmur which had been documented 13 years previously in Houston. The white blood cell count was 12,500 per cubic millimeter and the hemoglobin was 13.8 Gm. per 100 ml. Retrograde pyelography showed nothing of importance. Twenty-four hours later he became hypotensive, and blood cultures taken on admission were reported to be growing Pseudomonas aeruginosa, although the urine culture was sterile. He was treated with intravenous injections of gentamicin (160 mg. daily) and carbenicillin (24 Gm. daily), colloid and crystalloid, with improvement of the hypotension. An intravenous pyelogram and nephrotomograms showed no evidence of abscess or pyelonephritis. Gentamicin blood levels were in the range of 3.5 to 4.5 meg. per milliliter titrated according to assay measurement because of an elevated serum creatinine. After 2 weeks the antibiotic therapy was discontinued, and within 24 hours he again had shaking chills and fevers up to 40° C. Blood cultures were again positive for Pseudomonas. Serum creatinine again rose, and examination of urine sediment revealed red and white blood cell casts compatible with a diagnosis of glomeruiitis.
377
The Journal of
378
Bach et al.
Thoracic and Cardiovascular Surgery
Fig. 1. Aortic angiogram shows the aorta and the upper (A) and lower (B) ends of the prosthetic bypass graft. Note the smooth lining with no evidence suggesting infection or mucosal irregularity.
Fig. 2. Diagrammatic sketch illustrates the sites of cultures taken from the aorta, graft, and left ventricle.
He also had clubbing of the nailbeds. A latex fixation titer was 1/640, and the sedimentation rate was 126 mm. per hour (Westergren). Intravenous administration of gentamicin was restarted in a dosage of 240 mg. daily and carbenicillin in a dosage of 30 Gm. daily. After another 4 weeks of treatment, a maculopapular cutaneous eruption
developed and necessitated discontinuation of the carbenicillin. One week later, while still taking gentamicin, he again developed shaking chills. It was believed that the infection was probably not under control. To determine whether the new fever was in fact due to a Pseudomonas infection, we discontinued the gentamicin. Within 48 hours, the blood cultures were again positive for Pseudomonas aeruginosa. Administration of gentamicin and carbenicillin was restarted, but almost immediately the same pruritic maculopapular rash developed. At this point the patient was transferred to the Methodist Hospital in Houston under the care of one of us (M. E. D.). Complete investigation including gastrointestinal roentgenography, bone and gallium scans, and aortography failed to disclose the source of the bacteremia. In particular, views of the graft showed a normal smooth lining with no defects to suggest an infected focus (Fig. 1). The patient was transferred to Toronto General Hospital for another full 6 weeks' course of gentamicin (180 mg. daily) and carbenicillin (36 Gm. daily). The carbenicillin rash was controlled by oral administration of antihistamines. The minimum inhibitory concentration of gentamicin and carbenicillin for the organism were 3.1 and 25 meg. per milliliter, respectively. Blood levels for gentamicin were in the range of 4 to 5 meg. per milliliter after the intravenous infusion, and serum cidal levels immediately after the carbenicillin infusions were 1:8 to 1:16. Good synergism, as documented by in vitro testing using the standard
Volume 69 Number 3
Localization of endovascular infection
379
March, 1975
Fig. 3. Culture plates after 24 hours' incubation taken simultaneously from the brachial artery catheter (upper row) and the femoral artery catheter (lower row) in series A.
Fig. 4. Culture plates after 24 hours' incubation in series B. Cultures from the brachial artery catheter (upper row) and femoral artery catheter (lower row). checkerboard square technique, was obtained with this antibiotic combination. The 24 hour urinary protein excretion rose to 1.3 Gm. from a base-line excretion rate of 30 mg., and the urinary sediment showed granular casts; this development was interpreted as a possible early sign of gentamicin nephrotoxicity. Throughout the course, he had no new cardiac murmurs and no other evidence pointing to a possible source of the Pseudomonas infection. While on antibiotic therapy, he was perfectly well and asymptomatic, enjoying a good appetite. Thirty-six hours after antibiotic therapy was discontinued, he again had rigors, and blood cultures were positive for Pseudomonas aeruginosa, with the same antibiotic sensitivity pattern as the previous isolates. Discussions with a number of infectious disease clinicians and cardiologists yielded no uniform opinion on whether the site of infection was the aortic valve or the 12-yearold, presumably well-endothelialized prosthetic graft. Quantitative blood cultures were done according to the following method: The right brachial artery was catheterized with a No. 8 Fr. Sones catheter and the right femoral artery with a No. 8 Fr. Cordis all-purpose cath-
eter. Concomitantly, 5 ml. blood samples were aspirated through both catheters from the sites, shown in Fig. 2. The first set of cultures was obtained by passing the brachial catheter into the aorta and down through the aortic valve (Table I, cultures 1 to 5, series A). During this sequence, the femoral artery catheter lay in the femoral artery without approaching the graft; thus it was possible to evaluate the aortic valve area before passing up the graft. The brachial catheter was then pulled back into the brachial artery and the Cordis catheter was advanced up the aorta and through the graft (Table I, cultures 6 to 11, series B); aliquots of blood (0.05, 0.1, and 0.2 ml.) were pipetted onto fresh trypticase soy agar plates as soon as the specimens were collected in the catheterization room. The blood was spread over the agar by means of curved sterile glass rods and then incubated at 37° C. for 24 hours. Two milliliter aliquots of blood were also inoculated into Becton-Dickinson vacutainer blood culture tubes. An aortic root angiogram revealed no evidence of aortic regurgitation or abnormality of the aortic valve leaflets. There was also no mitral regurgitation on left ventriculography. Table I shows the results of colony counts
The Journal of
380
Bach et al.
Thoracic and Cardiovascular Surgery
Table I. Results of selective catheterization of the brachial and femoral arteries with colony counts of blood specimens from different sites
Culture
site
Brachial artery culture (col./ml.)
Femoral artery culture (col./ml.)
A. Advancing brachial catheter 1. Brachial artery 2. Junction of brachiocephalic artery and aorta 3. Aortic root 4. Left ventricle 5. Ascending aorta
0 20
10 10
0 350 70
0 300 80
B. Advancing femoral catheter 6. Lower pouch 7. Lower graft 8. Midgraft 9. Upper graft 10. Upper blind pouch 11. Aortic root
0 0 0 120 500 500
20 0 0 300 500 500
obtained from the catheter specimens. The numbered sites correspond to the numbers in the diagram in Fig. 2 and show a heavy concentration of organisms at the upper blind pouch of the aorta and the upper part of the graft. The left ventricle culture, taken through the brachial artery catheter, and a concomitant femoral artery specimen were also positive. AH the specimens inoculated into the blood culture tubes, from all sites, yielded Pseudomonas after 24 hours of incubation. This indicates that he was having a constant but low-grade bacteremia. Fig. 3 illustrates the culture plates taken with the brachial artery catheter (series A). Fig. 4 highlights the culture plates taken from blood drawn from the femoral catheter as it was advanced up the graft (series B). When the infected sites were reached, cultures from both the brachial and the femoral catheters were positive, an observation suggesting that the catheter dislodged vegetations which then made a complete circuit through the circulation. Based on the results of this study, the patient was transferred back to Houston where, after bilateral axillofemoral bypass grafts were implanted, he underwent total resection of the original graft. Infected laminated thrombus was found around the original suture line at the two sites at the upper end of the graft, as documented by the culture data. He was treated with antibiotics for 3 more
weeks postoperatively, and this therapy was then discontinued successfully. He has remained afebrile and well for the past 8 months.
Discussion The catheterization data suggested that the major focus of infection was located at the upper end of the graft, and this was confirmed at operation. We attribute the positive culture at the aortic root in series B to the fact that a vegetation may have been picked up and carried along as the catheter passed through the infected upper graft. The positive culture from the left ventricle in series A was perplexing. We were concerned that the patient may have had an aortic valvular infection as well; fortunately, this did not prove to be the case, as shown by his clinical course. One might postulate that at the time we were sampling the aortic valve area, he experienced a spontaneous, sudden high-grade burst of bacteria; Bennett and Beeson1 report that this is often the case with endovascular lesions. On the other hand, he may in fact have had aortic valve infection which was cured by the subsequent 3 week course of therapy. Endovascular infection with Pseudomonas is relatively rare. Saroff and associates- reported a case in a heroin addict who was cured with polymyxin B, gentamicin, and a short course of carbenicillin. They noted only five reports of well-documented cases of cured Pseudomonas endocarditis. A study similar to ours was recently reported by Bazin and associates (Abstract 35, American College of Physicians, New York, 1974). Two patients with refractory endocarditis underwent quantitative blood cultures proximal and distal to the suspected sites of infection. Their technique successfully localized the infection, although in 1 of the patients there was only a small difference in colony counts between the two sites of the valve in question. In patients with prosthetic grafts in place, the identification of the source of a sustained bacteremia may prove to be a real problem when there is no good radiologic evidence of infection or when there are no signs of valvular dysfunction suggestive of a valvular
Volume 69 Number 3
Localization of endovascular infection
381
March, 1975
lesion. In these patients, careful colony counts of blood samples taken from selected suspected areas of the vascular tree may be of help in the localization of the infection. We would like to thank Dr. D. Kasler for referring the patient and A. deHaney, R. T., and the staff of the Microbiology Laboratory, Toronto General Hospital, for their help in this case.
REFERENCES 1 Bennett, I. L., Jr., and Beeson, P. B.: Bacteremia: A Consideration of Some Experimental and Clinical Aspects, Yale J. Biol. Med. 26: 241, 1954. 2 Saroff, A. L., Armstrong, D., and Johnson, W. D., Jr.: Pseudomonas Endocarditis, Am. J. Cardiol. 32: 234, 1973.