The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality

Abstract

In patients with acute leukaemia, a shift in candidaemia epidemiology was noted with a 99% predominance of non-albicans species. Non-susceptibility of Candida strains to caspofungin or multidrug resistance were independent markers of poor outcome in this patient population.

Pharmacological Blockade of the Chemokine Receptor CCR1 Protects Mice from Systemic Candidiasis of Hematogenous Origin

“…Our preliminary data suggest that adjunct pharmacological blockade of CCR1 along with antifungal therapy may represent a potential therapeutic intervention in selected patients with systemic candidiasis, particularly those with renal involvement and papillary necrosis (8). Further animal studies are required to examine the role of adjunct CCR1 in the treatment of emerging multidrug-resistant Candida species such as Candida auris or azole-and echinocandin-resistant Candida glabrata, for which the antifungal treatment options available in the clinic are limited (15)(16)(17).…”

Virulência de isolados clínicos de Candida tropicalis

“…As infecções por C. tropicalis são comumente associadas a malignidade, com alguns estudos relatando sua alta incidência entre pacientes com doenças hematológicas, como por exemplo, leucemia mieloide aguda 8,9,10,11 , sendo causa comum de infecção em unidades de terapia intensiva, é um problema particular em pacientes neutropênicos 12,13, 14 . A mortalidade associada à candidemia por C. tropicalis nessas populações varia de 30 a 70%, com as maiores taxas observadas entre os idosos 8,9,15,11, 16 . Os principais fatores de virulência de Candida associados às infecções sanguíneas incluem produção de hemolisina, produção de proteinases e formação de biofilmes 17,18,19 .…”

Dose escalation studies with caspofungin against Candida glabrata

“…to echinocandins is low worldwide (Perlin, 2014), secondary resistance to caspofungin at some medical centres is more substantial (Alexander et al, 2013;Beyda et al, 2014;Pappas et al, 2007;Perlin, 2014;Pfaller et al, 2012;Shields et al, 2013). In a tertiary-care cancer centre in the USA, caspofungin resistance rates of C. glabrata among patients suffering from cancer (Farmakiotis et al, 2014) and acute leukaemia (Wang et al, 2015) were 10.3% (15 out of 146 isolates) and 58.3% (7 out of 12 isolates), respectively. Both studies reported a strong correlation between caspofungin resistance and increased 28-day all-cause mortality rates, suggesting that caspofungin-resistant isolates are more virulent than susceptible ones (Farmakiotis et al, 2014;Wang et al, 2015).…”

“…In a tertiary-care cancer centre in the USA, caspofungin resistance rates of C. glabrata among patients suffering from cancer (Farmakiotis et al, 2014) and acute leukaemia (Wang et al, 2015) were 10.3% (15 out of 146 isolates) and 58.3% (7 out of 12 isolates), respectively. Both studies reported a strong correlation between caspofungin resistance and increased 28-day all-cause mortality rates, suggesting that caspofungin-resistant isolates are more virulent than susceptible ones (Farmakiotis et al, 2014;Wang et al, 2015). These alarming clinical observations were confirmed by Borghi et al (2014) in their animal model using sequential C. glabrata clinical isolates with and without the S663P mutation.…”

“…As C. glabrata rapidly develops resistance to echinocandins, even during short treatment periods (Alexander et al, 2013;Beyda et al, 2014;Lepak et al, 2012;Perlin, 2014;Shields et al, 2013), rapid detection of the most common FKS mutations would best be achieved by FKS sequencing in C. glabrata isolates, as published for C. albicans (Dudiuk et al, 2015). As mutations in the FKS genes are not equal in terms of the level of resistance provided (Beyda et al, 2014;Fernández-Silva et al, 2014;Lepak et al, 2012), and non-FKS-related mechanisms may also emerge over time (Perlin, 2014), MIC testing in RPMI 1640 with or without 50% serum is still useful to detect isolates with decreased susceptibility (Farmakiotis et al, 2014;Perlin, 2014;Wang et al, 2015). Finally, the fitness and virulence of echinocandin-susceptible and -resistant isogenic isolates should be compared in future studies to obtain relevant data on the relationship between echinocandin resistance and virulence.…”