New Concepts in the Treatment of the Uncontrollable Infection Agustin Arbulu, M.D., Ali Kafi, M.D., Norman W. Thorns, M.D., and Robert F. Wilson, M.D. ABSTRACT Our experience with 25 patients with right-sided bacterial endocarditis is described; 23 were heroin addicts. The clinical manifestations of right-sided endocarditis are primarily related to septic pulmonary embolism. When the infection was due to gram-positive cocci, antibiotics always cured the patient. However, if the infection was due to Pseudomonas aeruginosa resistant to therapy, excision of the infected tricuspid or tricuspid and pulmonary valves without prosthetic replacement effected a cure. Nine out of 10 long-term survivors treated in this manner have had no significant hemodynamic difficulties. Antibiotic therapy must be limited to six weeks or less, because if the infection persists beyond this period it may also spread to the left side of the heart, where valve excision without replacement is impossible. S ince 1970 we have observed a marked increase in the incidence of right-sided bacterial endocarditis, especially among drugs addicts. The clinical manifestations of this type of endocarditis follow a consistent pattern: 1. Drug addiction to heroin, self-administered intravenously 2. No previous congenital or acquired heart disease 3. Chills and fever 4. Pleuritic type of chest pain 5. Shortness of breath 6. Minimal cardiac manifestations, such as transient soft cardiac murmurs 7. Pulmonary infiltrates on chest roentgenograms Successful treatment of these patients is extremely rare when the blood cultures are persistently positive for Pseudomonas aeruginosa in spite of intensive antibiotic therapy. Virtually all these patients will eventually die of their infection unless aggressive surgical treatment is carried out, namely, single or double valvulectomy without prosthetic replacement. The purpose From the Robert S. Marx Surgical Laboratories, Department of Surgery, Wayne State University School of Medicine, and Detroit General Hospital, Detroit, Mich. Supported by the Detroit General Hospital Research Corporation. Presented at the Ninth Annual Meeting of The Society of Thoracic Surgeons, Houston, Tex., Jan. 22-24, 1973. Address reprint requests to Dr. Arbulu, Gordon H. Scott Hall of Basic Medical Sciences, 540 E. Canfield Ave., Detroit, Mich. 48201. 136 THE ANNALS OF THORACIC SURGERY
of this paper is to review our experience with the management of patients affected by this disease. Clinical Material Since 1970 on the Surgical Service of Wayne State University School of Medicine, we have treated 25 patients with right-sided bacterial endocarditis. Twenty-one were men, and 4 were women; their ages ranged from 19 to 42 years. Twenty-three were drug addicts who for periods of three months to twenty-three years prior to their hospital admission had been using heroin self-administered intravenously. Two patients were not drug addicts; 1 of these (Patient 19) had developed pneumonia complicated by empyema due to P. aeruginosa. Several weeks later, while still under antibiotic therapy, he developed tricuspid Pseudomonas valvulitis that later required surgical treatment. The second nonaddict (Patient 9) was a 21-year-old man who had tetralogy of Fallot that had been treated with a Blalock shunt at 3 years of age. Five years prior to his current admission he had had total correction of his tetralogy. Since that time he had had intermittent bouts of bacterial endocarditis due to coagulase-positive Staphylococcus aureus. His infection was controlled by intensive antibiotic treatment. In this series of 25 patients with right-sided bacterial endocarditis, only 1 patient had a previous history of congenital heart disease (Patient 9). The other 24 patients had no history of congenital or acquired heart problems. The 25 patients can be divided into three groups according to their blood cultures. Group A. In 11 patients blood cultures were positive for gram-positive cocci. Ten had coagulase-positive S. aureus, and 1 had p-hemolytic streptococcus. Group B. In 4 patients gram-positive cocci grew on the initial blood cultures, but within a week of antibiotic treatment these cocci were replaced by P. aeruginosa in the blood cultures. Group C. In 10 patients P. aeruginosa grew on the initial blood cultures. Results Group A. Of 11 patients with infections of gram-positive cocci that were controlled by antibiotics, 10 were drug addicts and only 1 was a nonaddict (Patient 9, who had tetralogy of Fallot). Ten of these patients were cured with intravenous administration of the antibiotic to which the bacterium was most sensitive on in vitro tests. The eleventh patient signed himself out of the hospital while undergoing treatment. The only death in this group was that of a 42-year-old man who had been an addict for 23 years; he died of a hypertensive crisis two years after his right-sided bacterial endocarditis had been controlled.
ARBULU ET AL. Group B. All 4 of these patients were drug addicts. All remained infected, first with gram-positive cocci and then with P. aeruginosa, in spite of intensive antibiotic treatment given for periods of six weeks to eight months. Three of these patients were moribund when they were considered for surgical treatment. Two died following operation; they will be discussed later. Group C. All 10 of these patients had blood cultures positive for P. aeruginosa from the beginning. Groups B and C together consist of 14 patients who developed rightsided endocarditis due to P. aeruginosa that failed to respond to long-term intensive antibiotic therapy; all 14 of these patients were operated upon. The first 2 patients among the 14 had tricuspid valvulectomy with prosthetic replacement. In the first patient we used a Starr-Edwards prosthesis. Immediately following operation his blood cultures were negative for P. aeruginosa, and his general condition improved significantly. This patient was discharged from the hospital at the end of his second postoperative week. Six weeks later he was brought to the emergency room, and he died within a few hours. The postmortem examination showed that the Starr-Edwards prosthesis was covered with Pseudomonas vegetations. His aortic valve showed similar findings, and he had a brain abscess positive for the same bacterium. In the other patient we inspected all four cardiac valves before replacing the tricuspid valve with a Kay-Shiley prosthesis. Grossly, the tricuspid valve was the only one diseased. This patient died ten days later due to overwhelming Klebsiella pneumoniae sepsis. The family did not consent to a postmortem examination. In the remaining 12 patients our surgical treatment consisted of total valvulectomy without prosthetic replacement. In 1 1 patients only the tricuspid valve was removed, and in 1 the tricuspid and pulmonary valves were excised. Among these 12 patients, 2 died. One of them was a 36-year-old man who had been a heroin user for fifteen years. This man was on intensive antibiotic treatment for eight months because he consistently refused surgical treatment. He was operated upon after he became convinced that he was dying. Following the tricuspid valvulectomy without prosthetic replacement, he had a three-week period of clinical improvement in his condition and his blood cultures were intermittently positive for P. aeruginosa. He died fiftytwo days after operation from overwhelming Pseudomonas sepsis. A postmortem examination was denied. The other patient who died was a 35- year-old man who had been a heroin user for twelve years; he was operated upon after three months of intensive antibiotic treatment. Blood cultures obtained from the radial artery immediately following operation were positive for P. aeruginosa. During the first twenty-three days following operation his temperature was normal and venous blood cultures were intermittently positive for P. aeruginosa. After the twenty-third postoperative day his blood cultures were persistently positive for P. aeruginosa. Later 138 THE ANNALS OF THORACIC SURGERY
in his clinical course he developed symptoms of meningeal involvement and signs of cerebral emboli, and he finally died on the fifty-sixth postoperative day. The clinical picture strongly suggests that this man had a combined right- and left-sided P. aeruginosa infection; however, we could not confirm this because postmortem examination was not permitted. The remaining 10 patients among the 12 who had valvulectomy without prosthetic replacement are all alive and well three to twenty-nine months postoperatively. All these patients had antibiotic therapy for six to twelve weeks prior to operation. Only 1 patient (Patient 19), a nonaddict, required reoperation to insert a prosthesis in the tricuspid position six months following the initial operation. In this patient the liver was gradually enlarging, and he was becoming dyspneic while performing moderate physical activities. A year later he was in excellent clinical health. Comment Our experience with 25 patients with right-sided bacterial endocarditis indicates that the incidence of this disease has risen concomitantly with the increased prevalence of drug addiction by the intravenous self-administration of heroin. The clinical manifestations of right-sided bacterial endocarditis are commonly related to the respiratory system because there is pulmonary embolization of vegetations from the infected right-sided heart valves. Cardiac manifestations are generally minimal and transient, as was demonstrated in our patients; this clinicopathological observation of rightsided bacterial endocarditis has been noted by other investigators [2]. It is also noteworthy that 24 out of these 25 patients had no previous heart disease, either congenital or acquired. Our experience suggests that when right-sided bacterial endocarditis is due to a gram-positive coccus, intensive antibiotic treatment is uniformly successful. However, if the infection is due to P. aeruginosa and the bacteria persist in the blood cultures for more than six weeks in spite of intensive antibiotic therapy, the treatment of choice is excision of the infected valves with antibiotic coverage. The findings in our series of patients indicate that the surgical treatment of choice is single or double total valvulectomy without prosthetic replacement. The majority of our patients have done well and have suffered no significant hemodynamic difficulties [ 11. Nevertheless, these patients should be followed very closely, because if cardiac decompensation does develop, a valvular prosthesis should be inserted without delay. Unsuccessful antibiotic treatment should not be continued for more than six heeks because the delay may allow spread of the right-sided endocarditis to the left side of the heart, a development that precludes total excision of the infected valvular tissue. The failure of operative management VOL. 16, NO. 2, AUGUST, 1973 159
AKBULU ET AL. in the 2 patients who had three and eight months of antibiotic therapy, respectively, attests to this recommendation. References 1. Arbulu, A., Thoms, N. W., and Wilson, R. F. Valvulectomy without prosthetic replacement. J. Thorac. Cardiovasc. Surg. 64: 103, 1972. 2. Roberts, E. C., and Buchbinder, N. A. Right-sided valvular infective endocarditis: A clinicopathologic study of twelvi necropsy patients. Am. J. Med. 53:7, 1972. Discussion DR. ARTHUR C. BEALL, JR. (Houston, Tex.): Fortunately, our addicts here in Houston seem to use a little better sterile technique, and we have not seen the frequent gram-negative involvement of the tricuspid valve that has been reported to us this afternoon. However, in 2 patients seen at the Ben Taub General Hospital the results appear to agree with Dr. Arbulu s experience. I think this paper is important in two respects. First, as has been pointed out, it is an old surgical principle that a foreign body such as a prosthesis will keep an infection from clearing. But because of our experience in patients with acquired valvular heart disease with mitral insufficiency and long-standing pulmonary hypertension, we have been afraid not to replace the tricuspid valve when it was necessary to remove it for infection. What we failed to recognize is that the pulmonary lesions in these patients with bacterial endocarditis are infective in nature, that they will resolve very rapidly, and that the patients will do quite well without a tricuspid valve. On the other hand, we must remember that we cannot apply these same principles to other patients with acquired valvular heart disease. As Dr. Starr has shown very clearly with cardiac output studies, patients with acquired valvular disease have relatively fixed pulmonary hypertension that will remain for a period of time, and only with tricuspid replacement can many of these patients be brought through the postoperative period. The important thing here, then, is that we are dealing with apples and oranges and we should not mix them up. PRESIDENT BENSON B. ROE: I would like to ask you one question: what is the total base in terms of acute bacterial endocarditis that your tricuspid lesions represent? Most of us in this country have seen nearly ten times as many aortic valve lesions as tricuspid valve lesions, and I wonder what your ratio is. DR. ARBULU: Dr. Roe, at the present time I do not have the precise answer to your question. We are reviewing our experience. But as we complete this review, we are discovering that right-sided bacterial endocarditis represents about ZOO/, of our population of patients with bacterial endocarditis treated in the Detroit General Hospital. This figure will probably change when we complete this review. I would like to thank Dr. Beall very much for his comments, and I certainly agree with him 100~o that we are dealing here with patients different from the usual ones we operate upon because of cardiac disease. The patients that I reported today usually had normal hearts prior to the onset of their bacterial endocarditis. We are not dealing here with patients with previous congenital or acquired heart disease. In closing, I would like to stress that through this experience we have learned it is possible for a heart to live and perform quite well without the rightsided valves as long as the left side of the heart is perfectly normal or almost so and the pulmonary circulation is normal. 140 THE ANNALS OF THORACIC SURGERY