Propionibacterium acnes as the Cause of Endocarditis in a Liver Transplant Recipient

Isolation of Propionibacterium acnes in body fluids is generally interpreted as having no clinical significance since the organism is part of the flora of the skin. Here we present a case of endocarditis caused by P. acnes in an immunosuppressed patient following solid organ transplantation. This finding highlights the importance of a careful clinical-pathological interpretation, when diphteroid bacteria are isolated from human tissue. A 64-year-old man with a history of hypertension, non-insulin-dependent diabetes mellitus, alcoholism, and chronic hepatitis C virus infection underwent liver transplantation in 1996 because of cirrhosis. After transplantation, he received immunosuppressive therapy with tacrolimus (4 mg/d) and low doses of prednisone (5 mg/d). Two years later, the patient presented to the hospital with fever (temperature, 39.5°C), cough, anemia (requiring blood transfusion), peripheral edema, and a left-sided pleural effusion. He was diagnosed clinically and radiographically with pneumonia, although no causative organism was identified in routine microbiological investigations of blood, sputum, and a pleural aspirate. The patient was treated with iv ampicillin and trimethoprim/sulfamethoxazole, with clinical improvement. He was then discharged from the hospital to complete a course of antibiotic therapy at home. Two weeks later, the patient returned to the hospital with shortness of breath, orthopnea, intermittent fever, and bilateral pleural effusions. At this time, the patient had stopped antibiotic therapy. Echocardiography confirmed the diagnosis of congestive heart failure with severe aortic insufficiency and moderate mitral regurgitation. No cardiac valve vegetations were seen. Repeated blood cultures were negative. Treatment with gentamicin and vancomycin was initiated, and surgery was performed to replace the aortic and mitral valves. At surgery, vegetations typical of infective endocarditis were noted on both valves. Cultures of the excised cardiac valves revealed pure growth of P. acnes, which was initially interpreted as a contaminant. Examination of the valves showed similar pathological changes in each valve, consisting of mild sclerosis and the presence of a single friable vegetation on both the mitral and the aortic valves (which measured 0.7 and 0.6 cm, respectively). Microscopically, there was a myxoid change of the connective tissue with focal calcific deposits consistent with mild sclerosis. A fibrinous exudate with an associated neutrophilic infiltrate was attached to the surface of both valves. Granulation tissue was found in the underlying valve tissue (figure 1A). Gram and Warthin-Starry staining of a section of the mitral valve revealed clusters of gram-positive, pleomorphic, slender bacilli with blunted ends within the vegetation, which were morphologically consistent with P. acnes (figure 1B). There was no evidence of chronic valve disease such as rheumatic fever. A, Hematoxylin-eosin-stained section of the mitral valve of a liver transplant recipient with Propionibacterium acnes endocarditis that shows granulation tissue (black arrows) and vegetation of infective endocarditis (white arrows; original magnification, ×200). B, Warthin-Starry-stained section of the patient's mitral valve that shows slender, pleomorphic diphtheroid bacteria (black arrows) consistent with P. acnes within a vegetation (original magnification, ×1000). The infection was therefore documented by positive cultures of vegetations on the cardiac valves and detection of the organism in tissue sections. Treatment with broad-spectrum antibiotics was continued after surgery until the patient's discharge from the hospital. During a 3-year follow-up, there was no recurrent endocarditis. P. acnes is an anaerobic, non-spore-forming, gram-positive diphtheroid bacterium. The isolation of diphtheroids in cultures of blood and other body fluids is usually interpreted as contamination and considered to have no clinical significance, because these organisms are part of the normal flora of the skin and mucous membranes [1]. However, in circumstances where there is a structural abnormality or in the presence of a foreign body, P. acnes may cause serious infections. For example, this organism has been implicated as a causative agent of splenic abscesses in patients with sickle cell anemia [2], of endocarditis in patients with prosthetic valves [3–5], and in native cardiac valves previously damaged by rheumatic disease [3]. P. acnes endocarditis usually presents as subacute disease. Indeed, in retrospect, it seems likely that this patient had endocarditis at the time of his first admission when pneumonia was diagnosed. Exposure to antibiotics may have caused the failure to isolate this organism from the blood, since this organism is typically susceptible to a wide range of antibiotics, including ampicillin [6]. The only predisposition for the unusual infection in this case was immunosuppression. It is unclear, however, how this commensal organism gained access to the circulation. The patient gave no history of iv drug abuse, and considering the degree of inflammation and tissue destruction seen in the histological sections and the virulence of P. acnes, it is possible that this was a long-standing process. Infections are considered late complications of liver transplantation, accounting for morbidity and mortality up to 1 year after the transplant procedure [7, 8]. Despite the routine immunosuppressive therapy that follows transplantation of solid organs, endocarditis accounts for a small proportion of infectious complications. To our knowledge, this is the first report of endocarditis caused by an anaerobic bacterium after solid organ transplantation [9].