Prognosis of Amphotericin B in the Treatment of Breakthrough Candidemia in Patients with Hematologic Malignancies

Background Candidemia is greatly affects patient mortality, especially in patients with malignant hematologic diseases, despite improvements in diagnosis, prophylaxis, and management, but also with a crude mortality rate of 25-50% . The choice of the antifungal therapy for candidemia must take into account several factors such as type of patient, presence of devices, severity of illness, recent exposure to antifungals, local epidemiology, organs involvement, and Candida species. Echinocandin is a broad-spectrum antifungal agent that is effective against most Candida species,and also choice for neutropenic patients, but their resistance limits their clinical application, especially for immunodeficient patients we often need stronger antifungal drugs, Amphotericin B and liposomal amphotericin B are still widely used, and the effectiveness and safety of both are subject to further clinical analysis.

Objective Analyze the clinical characteristics of patients with hematologic malignancies complicated by candidemia. compared the prognosis of patients with candidemia treated with amphotericin B and amphotericin B liposomes, and compared the differences in overall survival rate of breakthrough candidemia between patients who received or did not receive allogeneic hematopoietic stem cell transplantation.

Method We collected clinical and microbiological data from a single centre of patients with hematological malignancies and breakthrough candidemia, recording results at 7, 30 and 100 days of follow-up, comparing the prognosis of patients with hematological malignancies complicated by breakthrough candidemia with amphotericin B. Kaplan-Meier survival estimates were used to generate survival curves.

Result Of 30 enrolled patients, 10 were diagnosed with acute lymphoblastic leukaemia, 10 with acute myeloid leukaemia, 2 with chronic myeloid leukaemia, 4 with lymphoma, 3 with myelodysplastic syndrome and 1 with aplastic anemia. All patients had agranulocytosis during the course of the disease, with a median duration of 19.5 days of agranulocytosis, and 28 of these patients had sepsis at the time of agranulocytosis. Of the 30 pathogenic breakthrough Candida strains, one was Candida albicans, one was Candida guilliermondi, three were Candida subsmoothis and 25 were Candida tropicalis. 14 of these patients received hematopoietic stem cell transplants. Attributable mortality was 5/14 (35.71%) and 4/12 (33.33%) in the transplant and non-transplant groups respectively (P=0.694).At day 7, 30 and 100, overall survival rates were 100%, 82.6% and 39.1% for patients in the amphotericin B group and 85.6%, 28.6% and 28.6% for patients in the non-amphotericin B group respectively, with significant differences in 30-day survival rates between the two groups(P=0.00051). We found that among patients in the transplant group, the overall survival rates at 30 and 100 days were 91.0% and 36.3% for patients using amphotericin B, respectively, and 0% and 0% for patients without amphotericin B at 30 and 100 days, and that there was a significant difference between them (P=0.0025, P=0.0023). In the transplant group, the overall survival rates at 30 and 100 days were higher in patients with post-transplant candidemia than in those with peri-transplant candidemia, but none of the differences were statistically significant (P=0.40, P=0.38).

Conclusion Early candidemia in transplant patients severely affects patient prognosis, increasing non-recurrent post-transplant mortality and reducing overall survival. Amphotericin B has shown good efficacy in the treatment of breakthrough candidemia in both transplant and non-transplant patients, and although the guideline recommendation for candidemia is caspofungin or micafungin, amphotericin and amphotericin liposomes as an alternative, the choice of antifungal agent for breakthrough candidemia in immunodeficient patients may need to be patient-specific.

No relevant conflicts of interest to declare.