An allograft heart valve is an implanted valve obtained from a person not related to the recipient. Fungal endocarditis secondary to extrinsic valve contamination is a rare but potentially fatal complication of allograft valve replacement; its incidence following surgery for heart valve replacement with allografts is approximately 0.3% (1,2). Treatment often is unsuccessful, and death is a frequent outcome (3). This report describes the investigation of a case of Candida albicans endocarditis associated with a contaminated aortic valve allograft. The findings indicated that antimicrobial processing of the initial aortic valve allograft did not eliminate C. albicans from the tissue.

In May 1996, a patient in California received an aortic valve allograft (Cryolife, Incorporated, Kennesaw, Georgia *) for aortic insufficiency. No postoperative complications occurred, and 5 days later, the patient was discharged. Eleven days after discharge, the patient was readmitted with fever of 104 F (40 C), nausea, diarrhea, and marked abdominal tenderness. His white blood cell count was 6800/mL3. Cultures of blood specimens drawn on admission were positive for Candida albicans, and the next day, amphotericin B and 5-fluorocytosine therapy was initiated. Fungal endocarditis was suspected, and a transesophageal echocardiogram revealed dehiscence of the aortic valve allograft. Intraoperative examination confirmed dehiscence of the aortic valve from the septum; in addition, an intramyocardial abscess and multiple vegetations were present in and around the suture line. The allograft was replaced with another allograft from the same supplier.

Photomicroscopic examination of smears of the valve surface from the first allograft prepared with potassium hydroxide revealed yeast elements, and culture of the valve yielded C. albicans. Following surgery to replace the allograft, the patient's fever resolved, and 7 days after the second surgery, he was discharged. He received a total of 57 days of therapy with amphotericin B, and as of March 1997, he remained symptom-free.

A review of the harvest and processing history of the allograft determined that, during processing, culture of tissue sampled from the allograft valve was positive for C. albicans. The harvested valve then was soaked in an antimicrobial solution containing fluconazole, amphotericin B, vancomycin, imipenem, and netilmicin (the temperature and duration of the disinfection process are considered proprietary information by the supplier). After disinfection, a sample trimming of the valve was recultured, and no fungal growth was evident.

The C. albicans isolates, obtained from valve trimmings during processing and when the valve was removed from the recipient, were highly similar by DNA fingerprinting using Southern blot hybridization with the DNA probe Ca3 (4,5). Antifungal susceptibility testing determined that the isolate obtained from the valve on removal from the recipient was more resistant to fluconazole and amphotericin B than the isolate obtained during processing (for fluconazole, minimum inhibitory concentration {MIC} was 0.5 ug/mL at harvest compared with 64 ug/mL at removal; for amphotericin B, MIC was 0.5 ug/mL at harvest compared with 2 ug/mL at removal).

Reported by: E Clark, MPH, J Chia, MD, Torrance Memorial Medical Center, Torrance; S Waterman, MD, State Epidemiologist, California Dept of Health Svcs. D Soll, PhD, Univ of Iowa, Iowa City. Hospital Infections Program, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: An allograft heart valve is harvested from a brain-dead or postmortem donor not related to the recipient; preparation for storage includes incubation in an antimicrobial disinfection solution and cryopreservation. Tissue samples for sterility testing are obtained by trimming the valve when harvested; the "trimmings" are cultured for bacteria, fungi, and acid-fast bacilli before and after antimicrobial disinfection and after cryopreservation (6). Microbial contamination is common at harvesting, but fungal contamination is unusual. Contaminants found before disinfection usually consist of gastrointestinal tract flora (e.g., coliforms and Streptococcus viridans) and skin flora (e.g., Staphylococcus aureus, S. epidermidis, and Bacillus sp.).

The use of mixtures of antimicrobials for disinfection of valve allografts was first described in 1968 (7). Cryopreservation techniques developed in the mid-1970s enabled valves to be stored for prolonged periods. Since then, antimicrobial disinfection protocols have been modified to improve efficacy and valve viability, thereby increasing the supply of usable allografts (1,8). Several different combinations of antifungal agents have been used to optimize viability and reduce contamination rates of allografts; these have been associated with contamination rates ranging from 1.7% to 28.0% (2). However, antifungal agents used for disinfection may damage allograft valve tissue and may be ineffective (1,2,6); some studies indicate an equal incidence of fungal contamination after disinfection with regimens containing antifungal agents when compared with those that do not include antifungal agents. Some tissue banks have removed antifungal agents from the disinfection protocol because of these concerns.

Six tissue banks supply most of the heart valve allografts in the United States. Five nonprofit allograft processing companies are accredited by the American Association of Tissue Banks (AATB), which requires that its accredited tissue banks "disinfect tissues via a time-specific antibiotic incubation" and facilities "establish, validate, and document antibiotic regimens and microbial surveillance methods" (9). These organizations employ a similar disinfection protocol, which includes use of a solution containing four antimicrobials (cefoxitin, lincomycin, polymyxin B, and vancomycin) in which valve tissues are incubated at 35.6 F-45.4 F (2 C-8 C) for approximately 24 hours. All five companies affiliated with AATB routinely discard valves with documented contamination from fungal or other pathogens specified on a compulsory discard list. The sixth tissue bank, Cryolife, is a commercial supplier not affiliated with AATB.

In the case described in this report, genetic analyses indicated that the C. albicans isolates obtained from allograft trimmings at harvest were identical with those obtained after the valve was removed from the patient. Processing in the antimicrobial solution may have resulted in the emergence of a more resistant strain, accounting for differences in drug-susceptibility results.

Food and Drug Administration (FDA) regulations do not require companies processing heart valve allografts to specify details of the disinfection process (e.g., type of antimicrobials used, temperature and duration, sterility testing, or culture findings that prompt processors to routinely discard a valve). Under a proposal published by FDA for regulation of cellular and tissue-based products (10), human heart valve allografts would be subject to donor screening and testing, processing, labeling, and registration requirements. Additional measures that could be considered by the tissue banking community include standardization and validation of disinfection methods and identification of culture results that indicate allografts must be discarded.

References

1. Wain WH, Pearce HM, Riddell RW, Ross DN. A re-evaluation of antibiotic sterilisation of heart valve allografts. Thorax 1977;32:740-2.

2. Gall K, Smith S, Willmette C, Wong M, O'Brien M. Allograft heart valve sterilization: a six-year in-depth analysis of a twenty-five-year experience with low dose antibiotics. J Thor Cardiovasc Surg 1995;110:680-7.

3. Wain WH. Antifungal treatment of allograft tissue for cardiac surgery. Sabouraudia 1981;19:199-204.

4. Anderson J, Srikantha T, Morrow B, et al. Characterization and partial nucleotide sequence of the DNA fingerprinting probe Ca3 of Candida albicans. J Clin Microbiol 1993;31:1472-80.

5. Schmid J, Voss E, Soll DR. Computer-assisted methods for assessing strain relatedness in Candida albicans by fingerprinting with the moderately repetitive sequence Ca3. J Clin Microbiol 1990;28:1236-43.

6. Wain W, Ahmed M, Thompson R, Yacoub M. The role of chemotherapy in the management of fungal endocarditis following homograft valve replacement. Postgrad Med J 1979;55:629-31.

7. Stinson EB, Angell WW, Iben AB, Shumway NE. Aortic valve replacement with the fresh valve homograft. Am J Surg 1968;116:204-9.

8. O'Brien MF, Stafford EG, Gardner MA, et al. Allograft aortic valve replacement: long-term follow-up. Ann Thorac Surg 1995;60(2 suppl):S65-S70.

9. American Association of Tissue Banks. Standards for cardiovascular tissue. In: Linden JV, ed. Standards for tissue banking. McLean, Virginia: American Association of Tissue Banks, 1996:97-108.

10. Food and Drug Administration. Proposed approach to regulation of cellular and tissue-based products: availability and public meeting. Federal Register 1997;62:9721.

* Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.

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