Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: a potential benefit from infectious disease consultation

Abstract

In patients with malignancies, Candida glabrata is one of the most frequent non-albicans Candida clinical isolates. As antifungal resistance in C. glabrata is common, we investigated the relationship between early appropriate antifungal treatment, infectious disease (ID) consultation and mortality in a contemporary cohort of cancer patients with C. glabrata fungaemia. We included patients with at least one C. glabrata-positive blood culture and symptoms or signs of infection seen at the MD Anderson Cancer Center between March 2005 and September 2013. In vitro susceptibility to antifungals was defined according to the 2010 CLSI clinical breakpoints. One-hundred and forty-six episodes of candidaemia were studied. Thirty isolates (20.5%) had fluconazole MIC ≥ 64 mg/L and 15 (10.3%) were caspofungin-resistant. Early (within 48 h after blood culture collection) initiation of appropriate antifungal treatment (hazard ratio 0.374, p 0.003) and early ID consultation (hazard ratio 0.421, p 0.004) were associated with decreased mortality, after adjustment for significant confounders. Thirty-two of 58 patients (55.2%) followed by ID were on appropriate antifungals within 48 h, compared with 16/88 patients (18.2%) who were not followed by ID an ID specialist (p <0.001). The median time-to-reporting of blood culture positivity for yeast was 71 h. Delayed time-to-reporting was associated with increased 28-day all-cause mortality (log-rank p 0.023). The benefits from early initiation of appropriate antifungal treatment and ID consultation were more prominent in patients with non-catheter-related candidaemia. In conclusion, in cancer patients with C. glabrata fungaemia, early ID consultation may lead to timely initiation of appropriate treatment and improved clinical outcomes.

Clinical and microbiological characteristics, and impact of therapeutic strategies on the outcomes of children with candidemia

“…However, few researchers have investigated the reasons of treatment failure for children with candidemia 12–14 . The benefit of modifiable therapeutic strategies for candidemia is mainly derived from data and studies conducted in the adult settings 17–20 . Studies of pediatric candidemia were often limited by small sample sizes 4, 14 , lack of antifungal susceptibility testing 4, 13, 16 , or did not analyze the impact of different treatment strategies on outcome 4, 15, 16 .…”

Utility of in-house fluconazole disk diffusion susceptibility testing in the treatment of candidemia

“…Echinocandin resistance rates >10% (Alexander et al, 2013; Beyda et al, 2014; Farmakiotis et al, 2014, 2015; Shields et al, 2012) and multidrug resistance (MDR) (Farmakiotis et al, 2014) have been reported from different tertiary centers. The optimal treatment for MDR Candida isolates has not been defined, and many clinicians would consider using polyene-based regimens, which have been associated with nephrotoxicity and increased mortality rates (Alexander et al, 2013).…”

“…Despite advances in the diagnosis and treatment of invasive candidiasis (IC), mortality rates close to 50% are still reported (Farmakiotis et al, 2015; Gudlaugsson et al, 2003). There are many therapeutic options for treatment of IC.…”

Dose escalation studies with caspofungin against Candida glabrata

“…The mortality rate due to C. glabrata is high in intensive care units where 50-69% mortality rates have been reported (Farmakiotis et al, 2014Lortholary et al, 2014). This unacceptably high mortality rate is especially alarming because echinocandin usage, as first-line therapeutic agents, has doubled or tripled in intensive care units (Colombo et al, 2014;Farmakiotis et al, 2014Farmakiotis et al, , 2015Lortholary et al, 2014).…”

“…As C. glabrata clinical isolates often show resistance to fluconazole, echinocandins are recommended as the primary treatment for invasive C. glabrata infections (Alexander et al, 2013;Betts et al, 2009;Colombo et al, 2014;Farmakiotis et al, 2014Farmakiotis et al, , 2015Li et al, 2015;Lortholary et al, 2014;Pappas et al, 2007Pappas et al, , 2009Pfaller et al, 2012). The mortality rate due to C. glabrata is high in intensive care units where 50-69% mortality rates have been reported (Farmakiotis et al, 2014Lortholary et al, 2014).…”