Failure of Caspofungin to Treat Brain Abscesses Secondary to Candida albicans Prosthetic Valve Endocarditis

Sir—Caspofungin has provided physicians with an effective, well-tolerated alternative to amphotericin B for the treatment of invasive candidiasis [1]; however, we have a serious reservation regarding its use against candidal endocarditis. Caspofungin is currently listed as an option for treating endocarditis in the latest Infectious Diseases Society of America guidelines [2]. We report the case of a 35-year-old man with prosthetic aortic valve endocarditis caused by Candida albicans that was complicated in early stages by embolic strokes and later by brain abscesses despite treatment with caspofungin and surgery. In October 2003, the patient underwent replacement of a bicuspid aortic valve. In November 2003, he returned to the hospital with fever, chills, and delirium. Blood cultures yielded C. albicans, and a transesophageal echocardiogram (TEE) revealed an aortic valve vegetation. A CT scan of the patient's head showed left occipital and temporal lobe infarcts. The isolate was susceptible in vitro to amphotericin B, fluconazole, voriconazole, and caspofungin (MIC, 0.03 µg/mL). He was treated with caspofungin and underwent a second aortic valve replacement. In January 2004, he presented with worsening neurological symptoms. A CT scan of his head revealed a new left thalamic infarct, and a TEE showed a paravalvular abscess. A cerebral angiogram did not demonstrate vasculitis or mycotic aneurysms. Therapy was briefly switched to amphotericin B lipid complex, which had to be discontinued because of renal insufficiency. Caspofungin therapy was resumed. On 18 February 2004, he underwent a third aortic valve replacement with a cryopreserved homograft. Results of perioperative blood cultures were negative, but histopathological staining of the excised valve revealed budding yeast. The patient continued caspofungin therapy until 26 March 2004, at which time his therapy was switched to voriconazole because of the development of brainstem abscesses with resulting hydrocephalus. On 27 April 2004, he developed worsening headaches and diplopia. On 29 April 2004, the patient was transferred to our institution for further management. A CT scan of his head revealed hydrocephalus due to enhancing masses in the left cerebral peduncle and left thalamus. Blood cultures were negative for pathogens, and a TEE revealed no vegetations. We concluded that the brain abscesses were likely caused by C. albicans infection because of the patient's history of embolic strokes. He was treated with liposomal amphotericin B (Ambisome; Fujisawa Healthcare) at a dosage of5 mg/kg iv once per day and fluconazole at a dosage of 400 mg orally twice per day. His headaches and diplopia improved with medical therapy. Candidal prosthetic valve endocarditis is typically managed with valve replacement and antifungal therapy with an amphotericin B preparation (with or without 5-flucytosine) or fluconazole [2]. There are few published data regarding treatment of candidal endocarditis or brain abscesses with caspofungin [3, 4]. Caspofungin has poor CNS penetration in animal studies [5, 6]. The progression to candidal brain abscesses during caspofungin therapy for endocarditis raises the concern that these animal model findings may be clinically relevant. Patients with systemic candidiasis may have unrecognized CNS involvement at the time of diagnosis [7–9]. Clinicians should use caution if caspofungin is considered for treatment of endocarditis because of the risk of possible unrecognized foci of infection, such as the brain, where caspofungin levels may be inadequate. Conflict of interest. R.M.P. and R.O.: No conflict.