Breakthrough candidaemia in the era of broad-spectrum antifungal therapies

Abstract

We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.

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

“…However, whether prompt catheter removal contributes significantly to outcome remains a debatable issue because there are no randomized controlled trials, either in the adult or pediatric settings, to document the benefit when the source of candidemia is not the catheter. The conflicting conclusions of previous studies most likely resulted from different study designs and failure of controlling the bias of illness severity 11, 22, 29–33 , especially as there might also be selection bias in their hospital. Nonetheless, based on our findings and the expert guidelines 34, 35 , we believe that CVC removal should be attempted in children with candidemia when feasible.…”

“…The impact of CVC management on the outcome of candidemic patients have been extensively investigated 22, 30–33 . While recent multicenter studies did not find significant impact of early CVC removal on outcome in either neonates or children 4, 11, 28 , we documented delayed CVC removal not only exerted a significant effect on the odds of clinical failure but also was associated with prolonged candidemia and final in-hospital mortality.…”

“…The issue of breakthrough candidemia was rarely mentioned in the pediatric studies, and previous reports concluded breakthrough candidemia mainly occurred in acutely ill patients, those with serious comorbid conditions, frequently neutropenic or previously treated with corticosteroids or other immunosuppressive drugs 22, 44–46 . In our cohort, breakthrough candidemia were mainly caused by non- albicans Candida species (73.3%), and in patients with neutropenia (44.4%), underlying hematological/oncological malignancy (24.4%) and under immunosuppressants (28.9%).…”

“…Episodes were considered to be separate if they occurred ≥1 month apart 21, 22 . Catheter-related Candida BSI was diagnosed when the catheter tip culture was positive for the same Candida species as those obtained from the peripheral vein and no evidence of infection at other site 18 .…”

Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings

“…Candida spp. infection during antifungal treatment has been reported to occur more frequently with Candida non- albicans species, and these are often resistant to fluconazole [48–50]. Mold infection breakthrough has been reported in patients receiving echinocandins [51], voriconazole [52], and posaconazole [53].…”