A Study for Relationship between Fever in Neutropenic Patients and Bacteria-Derived Microvesicles

Background Fever is a common problem when neutrophils are reduced by chemotherapy. Clinically proven infections are seen in 20∼30% and bacteremia in 10∼25%. Various bacteria are known to secrete microvesicles. it is presumed that excessive inflow of the bacteria-derived microvesicles into the body through the injured mucosa in neutropenic patients may cause fever or septicemia itself. The study was designed to assess the role of bacteria-derived microvesicles in fever of neutropenic patients. Methods Patients who were expected to have neutropenia due to conditioning chemotherapy for allogeneic or autologous hematopoietic stem cell transplantation were enrolled. Blood and urine specimens collected at the time of admission and if there was a fever of over 38°C. Additional blood and urine samples should be collected three days after fever and then collected at weekly intervals. Storage samples were subjected to the metagenomic test for bacteria-derived microvesicles. Results A total of 22 patients were enrolled between May 2017 and December 2017. Blood and urine samples were collected from a total of 509 and 346, respectively. Alpha diversity analysis showed that in both blood and urine sample groups, the control group had higher richness than the leukopenia group. (Figure 1) At the genus level, both urine and blood sample groups showed distinct clustering and separation of microbial taxa between control and leukopenia groups. At the phylum level, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes occupied over 85% of both control and leukopenia urine sample group relative abundance. However, there were significant difference among Proteobacteria (34.6% vs. 40.6%) and Firmicutes (35.4% vs. 27.0%) relative abundance between the control and leukopenia groups, respectively (P Conclusions This study showed the usefulness of bacteria-derived microvesicles as a diagnosis of neutropenic-causing bacteria. For the proper treatment of neutropenic patients, analyses of changes in bacterial microvesicles needs to be analyzed.