Breakthrough candidemia after the introduction of broad spectrum antifungal agents: A 5-year retrospective study

Abstract

Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis. Sequential Candida isolates from BrC were identified by internal transcribed spacer sequencing, genotyped with amplified fragment length polymorphism fingerprinting (AFLP), and tested for antifungal susceptibility. From 148 candidemia episodes, 27 breakthrough episodes (18%) were identified, with neutropenia and mucositis being independent risk factors for BrC. Candida non-albicans was more frequent in the BrC group (P < .001). AFLP showed high correlation with conventional methods of identification among breakthrough isolates and a high genetic similarity among isolates from the same patient was observed. C. albicans was the most susceptible species with low MIC values for all antifungal agents tested. In contrast, we found isolates of C. glabrata, C. parapsilosis and C. tropicalis resistant to triazoles and echinocandins. In conclusion, BrC occurred mainly in severely immunosuppressed patients, with neutropenia and mucositis. Mortality did not differ between the groups. Candida non-albicans species were more recovered from BrC, with C. albicans being the most susceptible to antifungals.

Breakthrough invasive fungal infections: Who is at risk?

“…Single-nucleotide polymorphisms (SNPs) within genes encoding for proteins involved in innate and adaptive immune responses (dectin-1 and DC-SIGN, TLR4 and others) convey an increased risk for mould infections despite prophylaxis. [26][27][28][29][30] Although comorbidities such as diabetes mellitus, chronic pulmonary disease, chronic kidney disease, chronic liver disease and hemodialysis are risk factors for invasive fungal infections, there is little evidence that these comorbidities 21,[31][32][33][34] or comorbidity risk scores such as the Charlson score 21,35 increase the risk for bIFI compared to non-breakthrough IFIs.…”

“…18 Neutropenia has been described as risk factor for bIFI caused by yeasts and mou lds. 19,20,22,35,91,[99][100][101][102] Results are summarised in Table 2.…”

“…Mucositis 35,36,81,102 fungal translocation 109,110,146 Impaired mucosal barrier with translocation of pathogens, primarily Candida, to the blood 107,109,110,146 Central venous catheters 34,81,102 Port of entry and nidus of infection for fungal pathogens, primarily Candida 122…”

“…Broad-spectrum antibiotic use 20,22,35,81,101 Alters gut flora and increases colonisation from Candida spp., increasing risk for IC; selective pressures and increase in Candida spp. resistance; alterations in host immune response to Candida spp.…”

Breakthrough invasive candidiasis in pediatric patient with Ewing’s sarcoma: dinical case report and literature review

“…Инвазивный кандидоз у детей с онкологическими заболеваниями сопряжен с высокой летальностьюдо 54 % [9,12,14,21,24,27,44]. Ряд исследователей отмечают увеличение риска летального исхода в случае ИК, вызванных штаммами C. albicans, по сравнению с видами не-albicans [9,21,29,45].…”