Time-Dependent Shifts in Intestinal Bacteriome, <i>Klebsiella</i> Colonization and Incidence of Antibiotic-Resistance Genes after Allogeneic Hematopoietic Stem Cell Transplantation
Oleg V. Goloshchapov,
Alexey B. Chukhlovin,
Dmitrii E. Polev,
Yury A. Eismont,
Dmitry S. Bug,
Alexey V. Kusakin,
Oleg V. Kosarev,
Ruslana V. Klementeva,
Vladimir V. Gostev,
Vladimir A. Ageevets,
Nikita P. Volkov,
Anastasia S. Ipatova,
Ivan S. Moiseev,
Anna A. Spiridonova,
Sergey V. Sidorenko,
Alexander D. Kulagin
Affiliations
Oleg V. Goloshchapov
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Alexey B. Chukhlovin
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Dmitrii E. Polev
Pasteur Institute of Epidemiology and Microbiology, Mira St, 14, 197101 St. Petersburg, Russia
Yury A. Eismont
Pediatric Research and Clinical Center for Infectious Diseases, Prof. Popov St, 9, 197022 St. Petersburg, Russia
Dmitry S. Bug
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Alexey V. Kusakin
Pediatric Research and Clinical Center for Infectious Diseases, Prof. Popov St, 9, 197022 St. Petersburg, Russia
Oleg V. Kosarev
Department of Informatics and Computer Technologies, St. Petersburg Mining University, 199106 St. Petersburg, Russia
Ruslana V. Klementeva
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Vladimir V. Gostev
Pediatric Research and Clinical Center for Infectious Diseases, Prof. Popov St, 9, 197022 St. Petersburg, Russia
Vladimir A. Ageevets
Pediatric Research and Clinical Center for Infectious Diseases, Prof. Popov St, 9, 197022 St. Petersburg, Russia
Nikita P. Volkov
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Anastasia S. Ipatova
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Ivan S. Moiseev
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Anna A. Spiridonova
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Sergey V. Sidorenko
Pediatric Research and Clinical Center for Infectious Diseases, Prof. Popov St, 9, 197022 St. Petersburg, Russia
Alexander D. Kulagin
R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia
Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p p K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.
