Management of invasive candidiasis in critically ill patients.

Candida species have become predominant pathogens in critically ill patients. In this population, invasive candidiasis is associated with a poor prognosis but adequate management can limit the attributable mortality. Adequate management, however, is hampered by a problematic diagnosis as the clinical picture of invasive disease is non-specific and blood cultures have a low sensitivity. Moreover, it is often hard to differentiate colonisation from infection and many critically ill patients are heavily colonised with Candida species, especially when receiving broad-spectrum antibacterials. The question of which antifungal agent to choose has become more complex as the development of new drugs raises promising expectations. Until the 1980s therapy for invasive candidiasis was limited to amphotericin B, but with the advent of new antifungal agents, such as azoles and echinocandins, less toxic therapeutic options are possible and doors have opened towards prevention and optimised therapy in the case of documented candidiasis. Through the arrival of these new antifungal agents, a range of therapeutic strategies for the management of invasive candidiasis has been developed: antifungal prophylaxis, pre-emptive therapy, and empirical and definitive antifungal therapy. Each of these strategies has a specific target population, as defined by specific underlying conditions and/or individual risk factors. Antifungal prophylaxis, in order to prevent candidal infection, is based on the type of underlying diseases with a high risk for invasive candidiasis. Individual risk factors are not taken into account. Potential indications are bone marrow transplantation, liver transplantation, recurrent gastrointestinal perforations or leakages, and surgery for acute necrotising pancreatitis. Pre-emptive therapy is also a preventive strategy. It can be recommended on the basis of an individual risk profile including overt candidal colonisation. Empirical therapy is started in patients with a risk profile for invasive candidiasis. It is recommended in the presence of clinical signs of infection, deteriorating clinical parameters, or a clinical picture of infection not responding to antibacterials but in the absence of a clear causative pathogen. Definitive antifungal therapy is defined as therapy in patients with documented invasive infection. The main goal is to maintain a balance between optimal prevention and timely initiation of therapy on one hand, and to minimise selection pressure in order to avoid a shift towards less susceptible Candida species on the other hand.