Supplement: Trends in invasive Candida infections and their treatment: focus on echinocandins

Abstract

Candida spp. are currently the fourth most common cause of bloodstream infections in US hospitals, and the third most common cause of bloodstream infections in the intensive care unit. Over the last 2 decades there has been a shift towards a greater involvement of non-Candida albicans spp. as the cause of candidemia. Several of these non-albicans spp. (e.g., C. glabrata and C. krusei ) exhibit resistance to traditional triazole antifungals like fluconazole, and cross-resistance with newer triazoles, focusing attention on the first-line use of antifungals such as the echinocandins, which possess improved activity against fluconazole-resistant strains. Recent treatment guidelines from the Infectious Diseases Society of America (IDSA) recommend an echinocandin as primary therapy for nonneutropenic or neutropenic patients with moderately severe to severe candidiasis and for patients at risk for infection with a triazole-resistant strain. However, further improvement in candidemia-associated mortality will only be attainable with the development and validation of new diagnostic tools that will allow earlier detection, discrimination, and treatment of invasive candidiasis. Clinicians should remain vigilant to wider emergence of Candida spp. with echinocandin resistance.

Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation

“…Our data are in line with the histological description of nonnecrotizing granulomas formed during bacterial infections, such as during M. tuberculosis infection (37, 39, 45). Moreover, the technical manipulation and isolation of these complex structures were similar to those implemented for mycobacterial in vitro granulomas.…”

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection

“…Furthermore, the amount of time that elapsed between the start of micafungin therapy after injury was shorter (mean times, 7.7 days in the previous study [16] compared to 16.2 days in the present study). Indeed, it may be that the hypermetabolic phase (beyond 48 h after the burn injury), which can affect the intensity of physiological changes over different days, contributed to the altered and highly variable PKs (11). This lower level of exposure to micafungin observed in our patients has also been reported for other antifungals in burn patients (17,29,30).…”

“…CL, clearance; V central , volume of distribution of the central compartment; k ct , rate constant for the drug distribution from the central to tissue fluid compartment; k tc , rate constant for the drug distribution from the tissue fluid to the central compartment; k cp , rate constant for the drug distribution from the central to the peripheral compartment; k pc , rate constant for the drug distribution from the peripheral to the central compartment. and the authors suggested the need to optimize the doses to reduce this variability (11). Unfortunately, patients treated with micafungin were not included in that study.…”

“…Critically ill patients with severe burn injuries may present with various pathophysiologies (burns with various sizes and depths, sepsis, hypoalbuminemia, altered capillary permeability, altered renal function, various degrees of hydration, and the need for renal replacement therapies) that can significantly alter antifungal pharmacokinetics (PKs) (10). A high interindividual variability in the PKs of fluconazole, anidulafungin, caspofungin, and micafungin has been observed in this population (11,12).…”

“…Micafungin exhibits a concentration-dependent fungicidal activity (13) and has very low MICs that are similar for most Candida spp., typically ranging from 0.06 to 0.12 mg/liter (14). It has been approved for use in Europe and the United States for the treatment of invasive candidiasis, includ-ing candidemia (15).…”