Ann Thorac Surg 1999;68:1410-1411
© 1999 The Society of Thoracic Surgeons
Case Reports
Early fungal endocarditis in homograft recipients
Paul A. Fedalen, MDa,c,
Carol A. Fisher, BAa,c,
Barbara A. Todd, MSNa,c,d,
Paul J. Mather, MDb,c,
V. Paul Addonizio, MDa,c,d
a Division of Cardiac and Thoracic Surgery, Philadelphia, Pennsylvania, USA
b Department of Cardiology, Philadelphia, Pennsylvania, USA
c Temple University Health Sciences Center, Philadelphia, Pennsylvania, USA
d Abington Memorial Hospital, Philadelphia, Pennsylvania, USA
Address reprint requests to Dr Addonizio, Division of Cardiac and Thoracic Surgery, Temple University Health Sciences Center, 300 Parkinson Pavilion, 3401 N Broad St, Philadelphia, PA 19140
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Abstract
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Retrospective analysis of 200 homograft valve recipients at our institution revealed two cases of fungal endocarditis. Pathogenesis appears to be related to either recipient seeding in one elderly immunocompromised patient or a previously contaminated donor valve implanted in an otherwise healthy recipient. Therefore, our experience underscores the need for both meticulous prevention of fungal infection preoperatively in the recipient and elimination of previously contaminated homograft valves from the donor pool.
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Introduction
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The cryopreserved homograft has become the replacement valve of choice for many clinical situations in cardiac valve operations [1]. An attractive feature is a low incidence of early valve endocarditis when compared to that identified for mechanical and xenograft valve substitutes [2]. However, our series of 200 homograft recipients identified 2 patients with early prosthetic valve endocarditis (PVE) for whom the cultured pathogen was a fungus.
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Case reports
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Patient 1
On June 1, 1995, a 78-year-old man with a history of Hodgkin’s lymphoma, prostate cancer, coronary artery disease, and congestive heart failure underwent aortic valve replacement for symptomatic aortic insufficiency (AI) using a 23-mm homograft.
Postoperatively, persistent paroxysmal atrial tachycardia developed in this patient, requiring the insertion of a dual-chamber pacemaker and anticoagulation with Coumadin. The patient was discharged on postoperative day 11. Approximately 2.5 months later, the patient presented to an outside hospital with a fever of 38.5°C, chills, and shortness of breath.
Work-up included three sets of blood cultures, which were all positive for Candida albicans, and a transthoracic echocardiograph that showed severe AI, an ejection fraction of 25%, and a paravalvular abscess that extended into the mediastinum. He was treated with intravenous amphotericin B (Bristol-Meyer-Squibb, Princeton, NJ) and transferred to our Cardiac and Thoracic service for explantation of the infected prosthesis, implantation of a 26-mm homograft with aortic root replacement, two-vessel coronary artery bypass, and drainage of a paravalvular abscess that extended beyond the confines of the heart into the mediastinum. The preoperative transesophageal echocardiogram confirmed the paravalvular abscess cavity that was seen on transthoracic echocardiography. Postoperatively, transesophageal echocardiogram showed no AI, an aortic valve area of 3.6 cm2, and an ejection fraction of 20% with no abscess.
Histopathology of the surrounding aorta and valve showed multiple vegetations that were consistent with Candida albicans. Gram stain from the abscess contents showed Gram-positive cocci and yeast; however, none of these species grew in culture for identification. Postoperatively, the patient’s course was uneventful with treatment including amphotericin B and vancomycin (Lilly, Indianapolis, IN). The original pacemaker was retained, and the patient was eventually discharged to a geriatric skilled care facility on postoperative day 16. He has been followed since his operation by office visits and telephone calls and has not shown any signs of infection or valvular dysfunction. He remains on daily fluconazole (Roerig, New York, NY).
Patient 2
On January 28, 1998, a 41-year-old man with a history of hypothyroidism, smoking, alcohol abuse, and aortic stenosis presented with symptoms of worsening dyspnea on exertion. Work-up included a cardiac catheterization and transthoracic echocardiography, which showed normal coronary arteries, left ventricular hypertrophy, severe aortic stenosis with an aortic valve area of 0.5 cm2, peak gradient of 110 mm Hg, and an ejection fraction of 50%. A 22-mm aortic homograft was inserted resulting in an uneventful postoperative course and discharge on postoperative day 5. Two weeks later, the patient returned with a fever of 39°C and chills.
His work-up included two sets of positive blood cultures for Candida albicans and a transthoracic echocardiogram that showed a valvular vegetation, no abscess, and mild AI. He was placed on intravenous amphotericin B for 5 days before undergoing removal of the infected homograft with insertion of a 23-mm homograft with aortic root replacement. The preoperative transesophageal echocardiogram confirmed the valvular vegetation that was seen on transthoracic echocardiography. Postoperative transesophageal echocardiogram showed no AI, an aortic valve area of 2.3 cm2, a peak gradient of 10 mm Hg, an ejection fraction of 55%, and no vegetation. Histopathologic examination of the homograft leaflets showed findings consistent with fungal infection, and culture of the vegetation grew Candida albicans. The patient remained on amphotericin B throughout his hospitalization and was later discharged after an uneventful postoperative course on day 8. He has been followed as an outpatient since this hospitalization without any signs of infection or valvular dysfunction and is taking fluconazole daily.
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Comment
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In our series of 200 homografts implanted from 1990 to 1998, two cases of PVE were identified; both were of fungal origin. Although these observations are made on a limited population of CryoLife (Kennesaw, GA) homograft valve recipients, they represent a study looking specifically at the relative susceptibility of the homograft to fungal PVE.
Several factors may have contributed to the development of fungal endocarditis. In patient 1, the recipient was elderly, had been hospitalized many times in the past, had previously received chemotherapy and radiation for cancer, and had had a pacemaker inserted after the valve grafting procedure. Insertion of central venous catheters, prolonged use of antibiotics, total parenteral nutrition, and immunosuppression of the valve recipient may have all contributed to the enhanced risk of contamination with an opportunistic organism such as Candida albicans. Similar factors have been associated with a dramatic increase in the documented number of nosocomial bloodstream infections due to Candida albicans (487% increase from 1980 to 1989) in large teaching hospitals [3, 4].
Causes for PVE in patient 2 were not as obvious. The recipient was young with no apparent predisposing factors for infection. Although fungal seeding from the recipient remains a possible cause for PVE, the clinical profile and very early onset suggests that the source of infection originated from the implanted donor valve. Interestingly, the Morbidity and Mortality Weekly Report recently cited a case of Candida albicans PVE associated with a contaminated donor aortic valve homograft. The Candida albicans cultured from the donor valve trimmings during processing and at the time of its removal from the recipient were genetically similar as revealed by DNA finger-printing [5]. This report led us to consider the possibility of factory-acquired infection.
CryoLife, with the largest series, reported more than 22,000 homografts implanted with 22 cases of fungal PVE. Information from CryoLife regarding processing of their homograft valves is proprietary. Nonetheless, the information they did provide indicates that all donor homograft valves are tested for sterility by culturing trimmed paravalvular tissue. These homografts, even if initially cultured positive for fungus, are sterilized in warm (37°C) solution for 24 hours with multiple antibiotics and antifungal agents to destroy common bacterial and fungal contaminants before cryopreservation. After cryopreservation and storage, these valves are recultured for organisms and then distributed for clinical use [5].
In summary, our experience emphasizes the need for meticulous prevention of fungal infection preoperatively in the recipient, but for maximum assurance of homograft sterility, such measures should include mandatory elimination of fungal-contaminated homografts from the donor pool. Once fungal PVE is diagnosed, removal and replacement of the infected valve along with systemic antifungal therapy is required [2]. Postoperative adjuvant medical management with 6 to 7 weeks of intravenous amphotericin B followed by oral fluconazole is recommended. However, the appropriate duration of treatment with fluconazole in the absence of symptoms remains uncertain (6 months versus lifelong) [6]. This disparity of treatment length is based on the chance of a second reoccurrence versus the risk of developing PVE with a fluconazole-resistant fungus. Moreover, the rarity of fungal PVE and the scarcity of literature on the subject fail to provide treatment guidelines.
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Acknowledgments
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Dr V. Paul Addonizio is a John A. Hartford Foundation Scholar, New York, New York.
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References
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O’Brien M.F., Stafford E.G., Gardner M.A., et al. Allograft valve replacement. Ann Thorac Surg 1995;60:S65-S70.
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Cowgill L.D., Addonizio V.P., Hopeman A.R., et al. A practical approach to prosthetic valve endocarditis. Ann Thorac Surg 1987;43:450-457.[Abstract]
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Melgar G.R., Nasser R.M., Gordon S.M., et al. Fungal prosthetic valve endocarditis in 16 patients. Medicine 1997;76:94-103.[Medline]
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Nasser R.M., Melgar G.R., Longworth D.L., et al. Incidence and risk of developing fungal prosthetic valve endocarditis after nosocomial candidemia. Am J Med 1997;103:25-32.[Medline]
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Clark E., Chia J., Waterman S., et al. Candida albicans endocarditis associated with a contaminated aortic valve allograft—California, 1996. MMWR 1997;46:261-263.[Medline]
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Muehrcke D.D., Lytle B.W., Cosgrove D.M., III Surgical and long-term antifungal therapy for fungal prosthetic valve endocarditis. Ann Thorac Surg 1995;60:538-543.[Abstract/Free Full Text]
Accepted for publication March 25, 1999.
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Abstract
Introduction
