P1528: diagnostic and therapeutic evaluation of carbapenem-resistant organisms bloodstream infection from gut colonization in hsct patients underwent carbapenemase genes guided therapy

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Recently, the worldwide spread of carbapenem-resistant organisms (CRO) arose as a rigorous medical and public health problem. Carbapenemase-producing(CP) is the most problematic and accounts for approximately 85% of CRO worldwide. Previous studies have shown that CRO bloodstream infection (BSI) originate from gut colonized pathogens. However, not all gut colonized pathogens will eventually develop into BSI. The explicit evidence of CRO translocation from the gut to the circulatory system is still lacking. The Xpert Carba-R assay was mainly used for detection of carbapenemase genes from rectal swabs which can represent gut colonization status. Whether it can reflect infected strain in blood in CRO colonized patients remains elusive. Identifying the consistency of strains and carbapenemase between blood and gut would help determine if CRO BSI originated from gut and evaluate the feasibility of early precise CRO-targeted interventions guided by CRO colonization in CRO BSI patients. Aims: We compared bacterial strains between the gut and bloodstream in hematopoietic stem cell transplantation (HSCT) patients aiming to elucidate the strains translocation from the gut to the blood and then evaluate the performance of gut carbapenemase gene colonization surveillance for guiding the early diagnosis and therapy of CRO BSI patients undergoing HSCT. Methods: We conducted a retrospective of 10 hematologic malignancies (HM) patients with CRO BSI who had previous CRO gut colonization and 2 strains obtained from rectal swabs (RS) samples and blood samples were simultaneously collected from the same patients. Intrapatient evolutionary relationship of CROs between gut and blood was identified by whole-genome sequencing (WGS) and Xpert Carba-R assay.Then, a prospective study was conducted in HSCT patients. Two rectal swabs per patient were simultaneously collected for CRO traditional culture (RS-culture) and Xpert Carba-R assay (immediate RS-Carba-R). If a patient developed febrile neutropenia (FN) for the first time after HSCT, antibiotic therapy was guided by the carbapenemase gene result.We compared the anti-infection effectivity including duration of fever resolution, total duration of hospitalization, the effective rate of antibiotic therapy and mortality between study group which was guided by RS-Carba-R and/or RS-culture colonization surveillance and historic group which was guided by RS-culture colonization surveillance. Results: Phylogenetic analysis showed that the gut and BSI strains from the same patient are more closely related than strains from different patients and the carbapenemase genes results detected by WGS and Carba-R were identical. The overall CRO colonized rate was 22.3% and the sensitivity, specificity, positive predictive value, and negative predictive value of HSCT patients for immediate RS-Carba-R were 96.6%, 72.8%, 90.6% and 88.9%, respectively. CRO targeted therapy guided by combined culture/Carba-R method shortened the duration of fever resolution and total duration of hospitalization in all HSCT patients and CROs-colonized patients, in the meantime the effective rate of CROs-targeted therapy increased and the mortality decreased. Active surveillance significantly decreased the colonization rate from 23.5% to 5.8 % in HSCT patients Summary/Conclusion: Our data demonstrated that CRO strains from blood and gut had highly homology and CRO colonization diagnosed by combined culture/Carba-R method can guide CROs-targeted therapy of subsequent infection which can effectively overcome the drug resistance and break the chains of transmission.Keywords: Sepsis, Fever, Allogeneic hematopoietic stem cell transplant, Febrile neutropenia