Authors
Russkih A. A.
Postgraduate student, Chair for Epidemiology, Microbiology and Virology1
Luk'janenko N. V.
Doctor of Medicine, Professor, Chair for Epidemiology, Microbiology and Virology1
Rudenko A. V.
Head, Educational laboratory, Lecturer1
Kolomiets A. A.
Vice-Rector for Regional Healthcare Development1
Petrova A. A.
Head, Epidemiological Department2
Mikhailova Y. V.
PhD (Biology), Head, Laboratory of Molecular Mechanisms of Antibiotic Resistance3
1 - Altai State Medical University, Barnaul, Russian Federation
2 - Regional Clinical Hospital, Barnaul, Russian Federation
3 - Central Research Institute of Epidemiology, Moscow, Russian Federation
Corresponding Author
Russkih Artjom Aleksandrovich; e-mail: Likvidator20110@mail.ru
Conflict of interest
None declared.
Funding
The study had no sponsorship.
Abstract
Introduction. Klebsiella pneumoniae, one of the leading causative agents of nosocomial infections, is included in the group of so-called «ESKAPE» pathogens – microorganisms associated with increased antibiotic resistance, representing a serious problem for public health. K. pneumoniae is widespread and has a pronounced ability to acquire resistance to antimicrobial drugs. Inadequate antibacterial therapy in patients with nosocomial infections worsens the prognosis of the disease and increases hospital mortality, therefore, the prescribing of medications should be based on knowledge of the current profile of antibiotic resistance of the pathogen in a particular hospital. The study of the genetic diversity of K. pneumoniae will reveal the main mechanisms of resistance of this pathogen and formulate recommendations for rational antibiotic therapy. Objective. Genome-wide analysis of resistant K. pneumoniae isolates in the context of epidemiological surveillance of healthcare associated infections (HAI) in a multidisciplinary hospital. Materials and methods of research. 41 isolates of bacteria of the genus Klebsiella isolated in a multidisciplinary hospital in Barnaul from clinical samples were studied. Genome-wide sequencing was performed using NextSeq 2000 (Illumina). Research results and their discussion. A comparative analysis of the microbiological background in a multidisciplinary hospital and hospitals in Russia demonstrated the predominance of K. pneumonia in the overall structure: 39.2% and 27.86%. In the course of genome-wide analysis of resistant strains of K. pneumoniae, combinations of beta-lactamase genes and genes encoding mechanisms of resistance to disinfectants were identified. Genes associated with the resistance of Klebsiella pneumoniae to hydrogen peroxide were found, genes of carbapenemases of the OXA-48 group, genes of extended-spectrum beta-lactamases of the CTX-M group, as well as metallo-b-lactamases of the NDM group were identified among the studied cultures. Conclusion. The use of genome-wide sequencing of isolates of HAI pathogens in clinical practice (using the example of Klebsiella pneumoniae) determines the choice of antibacterial therapy, the use of disinfectants and antiseptics in the organization of preventive and antiepidemic measures.
Key words
Klebsiella pneumoniae, antibiotic resistance, genome-wide sequencing
DOI
References
1. Chebotar' I.V., Bocharova Yu.A., Podoprigora I.V., Shagin D.A. Pochemu Klebsiella pneumoniae stanovitsya lidiruyushchim opportunisticheskim patogenom. [Why Klebsiella pneumoniae becomes the leading opurtonistic pathogen.] Klinicheskaya mikrobiologiya i antimikrobnaya himioterapiya [Clinical microbiology and antimicrobial chemotherapy] 2020; 22(1): 4-19. (In Russ.)
2. Yakovlev S.V., Suvorova M.P., Beloborodov V.B., Basin E.E., Eliseeva E.V., Kovelenov S.V., Portnyagina U.S., Rog A.A., Rudnov V.A., Barkanova O.N. Rasprostranennost' i klinicheskoe znachenie nozokomial'nyh infekcij v lechebnyh uchrezhdeniyah Rossii: issledovanie ERGINI. [Prevalence and clinical significance of nosocomial infections in medical institutions of Russia: ERGINI study] Antibiotiki i himioterapiya [Antibiotics and chemotherapy] 2016; 61(5-6): 32-42. (In Russ.)
3. Rodríguez-Baño J., Cisneros J.M., Cobos-Trigueros N., Fresco G., Navarro-San Francisco C., Gudiol C., Horcajada J.P., López-Cerero L., Martínez J.A., Molina J., Montero M., Paño-Pardo J.R., Pascual A., Peña C., Pintado V., Retamar P., Tomás M., Borges-Sa M., Garnacho-Montero J., Bou G. Study Group of Nosocomial Infections (GEIH) of the Spanish Society of Infectious Diseases, Infectious Diseases (SEIMC). Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin. 2015; 33(5): 337.e1-337.e21, doi: 10.1016/j.eimc.2014.11.009
4. Paczosa M.K., Mecsas J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol. Mol. Biol. Rev. 2016; 80(3): 629-661, doi: 10.1128/MMBR.00078-15
5. Hou X.H., Song X.Y., Ma X.B., Zhang S.Y., Zhang J.Q. Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates. Braz J Microbiol. 2015; 46(3): 759-768, doi: 10.1590/S1517-838246320140138
6. Navon-Venezia S., Kondratyeva K., Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol. Rev. 2017; 41(7): 252-275, doi: 10.1093/femsre/fux013
7. Ramirez M.S., Traglia G.M., Lin D.L., Tran T., Tolmasky M.E. Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-Negatives: the Klebsiella pneumoniae Paradigm. Microbiol Spectr. 2014; 2(5), doi: 10.1128/microbiolspec.PLAS-0016-2013
8. Kaushik M., Kumar S., Kapoor R.K., Virdi J.S., Gulati P. Integrons in Enterobacteriaceae: diversity, distribution and epidemiology. Int. J. Antimicrob. Agents 2018; 51(2): 167-176, doi: 10.1016/j.ijantimicag.2017.10.004
9. Ageevec V.A., Partina I.V., Lisicyna E.S., Batyrshin I.M., Popenko L.N., Shlyapnikov S.A., Il'ina E.N., Sidorenko S.V. Chuvstvitel'nost' gramotricatel'nyh bakterij, producentov karbapenemaz, k antibiotikam razlichnyh grupp. [Sensitivity of gram-negative bacteria, producers of carbapenemases, to antibiotics of various groups.] Antibiotiki i himioterapiya [Antibiotics and chemotherapy] 2013; 58(3-4): 10-13. (In Russ.)
10. Bush K., Jacoby G.A. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010; 54: 969-976.
11. Sukhorukova M.V., Edelstein M.V., Skleenova E.Ju., et al. Antibiotikorezistentnost' nozokomial'nyh shtammov Enterobacteriaceae v stacionarah Rossii: rezul'taty mnogocentrovogo epidemiologicheskogo issledovaniya MARAFON v 2011-2012 gg. [Antibiotic resistance of nosocomial strains of Enterobacteriaceae in Russian hospitals: results of the MARATHON multi-centre epidemiological survey in 2011-2012.] Klinicheskaja mikrobiologija i antimikrobnaja himioterapija [Clinical microbiology and antimicrobial chemotherapy] 2014; 16(4): 254-265. (In Russ.)
12. Munoz-Price L.S., Poirel L., Bonomo R.A., et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013; 13: 785-796.
13. Bialek-Davenet S., Criscuolo A., Ailloud F., et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis. 2014; 20: 1812-1820.
14. Monaco M., Giani T., Raffone M., Arena F., Garcia-Fernandez A., Pollini S.; Network EuSCAPE-Italy; Grundmann H., Pantosti A., Rossolini G.M. et al. Colistin resistance superimposed to endemic carbapenemresistand Klebsiella pneumoniae: a rapidly evolving problem in Italy November 2013 to April 2014. Euro Surveill. 2014; 19(42): 14-18.
15. Ageevets V.A., Partina I.V., Lisitsyna E.S., Ilina E.N., Lobzin Y.V., Shlyapnikov S.A., Sidorenko S.V. Emergence of carbapenemase-producing gram-negative bacteria in Saint Petersburg, Russia. Int J Antimicrob Agents 2014; 44: 152-155.
16. Kazama H., Hamashima H., Sasatsu M., Arai T. Distribution of the antiseptic-resistance genes qacE and qacEA1 in Gram-negative bacteria. FEMS Microbiol. Lett. 1998; 159(2): 173-178.
17. Kucken D., Heinz-Hubert F., Kaukfers P.M. Association of qacE and qacEA1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria. FEMS Microbiol. Lett. 2000; 183(1): 95-98.
18. Paulsen I.T., Littlejohn T.G., Radstrom P., et al. The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants. Antimicrob. Agents Chemother. 1993; 37(4): 761-768.
19. Paulsen I.T., Brown M.H., Skurray R.A. Proton-dependent multidrug efflux systems. Microbiol. Rev. 1996; 60(4): 575-608.