Clinical aspects of invasive candidiasis: endocarditis and other localized infections

Candida endocarditis was previously considered a rare disease. However, its incidence is increasing, partly as a consequence of increased use of prosthetic intravascular devices. In patients with prosthetic valve endocarditis, Candida infection may occur via a two-step process; firstly, post-operative transitory candidaemia occurs during the intensive care unit stay, leading to colonization of the prosthetic valve and subsequent biofilm formation, with reduced susceptibility to antifungal agents. This theory lends support for pre-emptive antifungal therapy with agents that display activity against biofilm-associated Candida in patients with prosthetic heart valves at risk of candidaemia. Current guidelines recommend treatment with amphotericin B with or without 5-fluorocytosine, or an echinocandin, with valve replacement where possible. Recent data suggest that amphotericin B shows reduced activity against Candida biofilm, and poor penetration into vegetations and blood clots in experimental models of infectious endocarditis, whereas echinocandins, and in particular anidulafungin, display potent in vitro activity against sessile Candida cells within biofilms. The incidence of ocular candidiasis has been decreasing among inpatients with candidaemia, possibly because of earlier identification and treatment of candidaemia. The therapeutic approach includes prolonged treatment with fluconazole or voriconazole. The role of systemic echinocandins may be limited since they achieve undetectable vitreous concentrations. Vitrectomy with local instillation of amphotericin B, azoles or echinocandins may play a role in the treatment of chronic complications such as epiretinal membrane formation. The role of Candida in CNS infections is unclear. Diffuse encephalitis in candidaemia is misleading, since alterations of the mental status are generally attributed to candidaemia-associated sepsis syndrome, and neuroimaging studies and cerebrospinal fluid cultures are rarely performed as part of the diagnostic work-up. Osteomyelitis caused by Candida is considered infrequent. In contrast, Candida is frequently implicated in nosocomial non-postneurosurgery spondylodiscitis. Optimal management of such cases may require surgical debridement and, after initial intravenous antifungal therapy, prolonged administration of oral azoles. The role of Candida in endocarditis is fairly well established. With the increasing numbers of patients at risk of Candida endocarditis, there is a need for agents with potent efficacy against Candida biofilms. Echinocandins represent a potential therapeutic option in this setting. Antifungal agents may also be of use in the treatment of complications in patients with ocular candidiasis and in CNS infections.