Antifungal activity and killing kinetics of anidulafungin, caspofungin and amphotericin B against Candida auris

Abstract

Background Candida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking. Objectives Our aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time–kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species. Methods The susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose–response and time–kill patterns were determined. Results Echinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively). Conclusions Amphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.

Prevalence and Antifungal Susceptibility Pattern of Candida Isolates from Women with Recurrent Vulvovaginal Candidiasis in Ghana - A Review of Laboratory Reports.

“…This pattern of Candida resistance to amphotericin B is unexpected because the drug is usually reserved for treating serious systemic fungal infections. Amphotericin B resistance has also been observed in 10-15% of C. krusei fungaemia (Dudiuk et al, 2019). Reports of emergence of resistance in some of the strains of Candida could be worrisome especially in resource limited settings like Africa.…”

In vitro and in vivo Effect of Exogenous Farnesol Exposure Against Candida auris

“…Over 90% of clinical isolates are resistant to fluconazole whereas resistance to newer triazoles is variable (Dudiuk et al, 2019;Romera et al, 2019). The ratio of strains resistant to amphotericin B ranges from 8 to 50%, while echinocandin resistance remains infrequent (2 to 8%) (Dudiuk et al, 2019).…”

“…Over 90% of clinical isolates are resistant to fluconazole whereas resistance to newer triazoles is variable (Dudiuk et al, 2019;Romera et al, 2019). The ratio of strains resistant to amphotericin B ranges from 8 to 50%, while echinocandin resistance remains infrequent (2 to 8%) (Dudiuk et al, 2019). Alarmingly, isolates of C. auris with resistance to all three major antifungal classes have been reported in multiple countries including the United States (Ostrowsky et al, 2020).…”

Echinocandins as Biotechnological Tools for Treating Candida auris Infections

“…Recent reports indicate that 2% of C. auris could be resistant to echinocandins [2,27]. C. auris tolerance to echinocandins was also in vitro reported, revealing that some isolates showed high tolerance to anidulafungin, micafungin and caspofungin [35,39].…”

“…Alarming data from Indian hospitals indicate a 37% rate of resistance to caspofungin, based on the analysis of 102 C. auris isolates [42]. Even so, experiments using animal models indicate these drugs as the most effective against C. auris infections, leading to the need for more tests [1,5,39].…”