Current pharmacological concepts for wise use of echinocandins in the treatment ofCandidainfections in septic critically ill patients

Abstract

Candida infections represent challenging causes of severe sepsis and/or of septic shock in the critically ill patients. Knowledge of current pharmacological concepts may promote a more wise use of echinocandins in the management of Candida infections in this setting. Echinocandins have some advantages over azoles, both pharmacodynamically (rapid fungicidal activity, anti-biofilm activity, unmodified activity against Candida isolates with decreased susceptibility to azoles and anti-cytokine/anti-chemokine activity) and pharmacokinetically (low interindividual variability, low potential for drug-drug interactions), that may influence the timing and the choice of therapy of Candida diseases in the critically ill patients. However, concerns exist in regards to the feasibility of fixed dosing regimens of echinocandins in all of the different patient populations and in regards to the effectiveness of echinocandin monotherapy in some clinical settings. In presence of deep-seated infections, voriconazole or liposomal amphotericin B may be valuable alternatives or add-on therapy.

How much European prescribing physicians know about invasive fungal infections management?

“…More surprisingly to us was to find that 12% and 9.2% of physicians would select L-AmB and voriconazole, respectively, instead of a candin to treat these fluconazole-resistant Candida infections. L-AmB should be restricted to selected cases of intra-abdominal candidiasis [ 35 , 36 ] or intolerance to other antifungal agents due to its potential toxicity and higher cost, and voriconazole should be limited to step-down oral therapy for selected cases of candidiasis due to C. krusei or voriconazole-susceptible C. glabrata [ 7 ]. Finally, we would like to stress that there are differences among published guidelines regarding some diagnostic and therapeutic aspects of candidiasis that need to be clarified for the sake of a more clear understanding by the prescribing physicians [ 37 ].…”

The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection

“…Although C. albicans is the most common yeast found with IAI, non-C. albicans species, including C. glabrata, C. parapsilosis, and C. tropicalis, are isolated with increasing frequency [375,[502][503][504]. Candida glabrata may be intrinsically resistant or demonstrate dose-dependent susceptibility to fluconazole; voriconazole has much better activity against this organism [505].…”

Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score–Adjusted Analysis

“…Furthermore, among septic patients, echinocandin exposure seems to be lower than in healthy volunteers [26–28], and patients with severe hypoalbuminemia have lower plasma trough levels of echinocandins [29]. Considering the rather frequent occurrence of malnutrition and severe hypoalbuminemia in the elderly [30], all these findings justify pharmacokinetic studies of the 3 echinocandins in this patient population. Finally, we recorded a high mortality rate among patients without septic shock receiving fluconazole (32.2%) vs those receiving echinocandins (14.2%; P = .002).…”