Antifungal Resistance and Breakthrough Candidemia Among Pediatric Cancer Patients: An Emerging Threat

Abstract Background Cancer patients are at risk for candidemia. Resistance and breakthrough Candida represent an emerging threat. The study aims to analyze the clinical features, resistance patterns and breakthrough candidemia among pediatric cancer patients. Methods The retrospective study was conducted from 2014 - 2020 in children admitted to Children Cancer Hospital, Egypt. Clinical, microbiological, and outcomes were analyzed. Mortality was estimated within 30 days from Candida spp. Isolation from blood. Results Three hundred fifty (350) pediatric cancer patients were diagnosed with candidemia. The median age was four years (4 months- 18 years). Most of the patients had hematological malignancies (54%) while solid tumors represent (46%). Clinical features of the patients included neutropenia (80%), the presence of central venous line (57%), ICU admission (44%), and steroid use (43%). Non-Albicans candida was predominant (71%) compared to Candida Albicans (29%). The isolated species were: C. Albicans (29%), C.Tropicalis (29%), C. parapsilosis (21%), C. krusei (7%), C.glabrata(3%), C. guilliermondii (1.5%)and C. famata (2%). Chronic disseminated candidiasis was reported in 30 (9%) patients, with the liver being the most affected organ. Breakthrough candidemia on top of echinocandin prophylaxis was reported among 62(18%) patients with C. parapsilosis is the most common 31(50%) isolated pathogen. From 96 patients with breakthrough candidemia, all-cause mortality was reported in 32 patient (33%) while candida attributable cause of death in elven (11%) patients. Antifungal resistance was reported in 74(21%) patients: fluconazole (15%), liposomal ampho-B (6%), echinocandin (5%) and voriconazole (3%). Among 74 patients with resistant candidemia, death was reported in 24%. Echinocandin Resistant candida was a direct cause of mortality in 3(17%) patients. The overall day- 30 mortality rate was 24% (85/350 patients), while candida attributable of mortality was (10%). Patients with septic shock, ICU admission, and resistant candida had a higher mortality risk. Conclusion Echinocandin-resistant and breakthrough Candida are significant threat with a high mortality rate among pediatric cancer patients. Antifungal stewardship may be helpful. Figure 1. Resistance Pattern of Candidemia among Pediatric Cancer Patients