Study of Cases of Bacteremia with Gram-Negative Pathogens with Multiple and Extreme Antibiotic Resistance in Real Clinical Practice

Aim: To study cases of bacteremia caused by multidrug-resistant (MDR) and extremely-resistant (XDR) gram-negative bacteria in the departments of a multidisciplinary hospital.

Material and Methods. Since 2017, a retrospective epidemiological study has been conducted to investigate cases of infections with bacteremia caused using gram-negative bacteria with multiple or extreme antibiotic resistance. The pathogens were identified using the MALDI-TOF MS method, the sensitivity to antibacterial drugs was determined using the automatic Phoenix system, the beta-lactamase genes were detected using real-time PCR on a GeneXpert analyzer.

Results. In 2017, bacteremia caused by MDR and XDR pathogens was detected in 42 and 76 patients, in 2018 — in 57 and 81 patients, in 2019 — in 65 and 111 patients, respectively. During three years of observation, the most frequent XDR microorganisms were, in descending order, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa. In 2019, among 11 K.pneumoniae strains, class D carbapenemase (OXA-48) was detected in 5 cases (45.5%), 3 strains produced NDM metallo-carbapenemase, and 3 strains had a combination of NDM and OXA-48 enzymes. Infections caused by MDR and XDR pathogens were characterized by high mortality. Thus, the relative risk of death in patients with XDR infection was 1.33 times higher than in patients from the MDR group (95% CI 1.04-1.69, P<0.05) in 2019. The duration of hospital stay also increased: in the XDR group — up to 29.5 days, in the MDR group – up to 16.4 days, with an average length of hospitalization of 6.0 bed-days in 2019.

Conclusions. K.pneumoniae and A.baumannii with extreme antibiotic resistance are the main causative agents of severe late nosocomial infections in immunosuppressed patients. Nosocomial infections with bacteremia caused by gram-negative bacteria with the XDR phenotype and resistant to carbapenems are characterized by a high mortality rate (from 72 to 80%), and increase the duration of hospitalization by more than 4 times.

1. Kozlov R.S. Selektsiya rezistentnykh mikroorganizmov pri ispol'zovanii antimikrobnykh prepratov: kontseptsiya «parallel'nogo ushcherba». Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2010, 12 (4): 284–294. (in Russian).

2. Magiorakos A.P., Srinivasan A., Carey R.B. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18: 268–281.

3. Internet sajt VOZ: https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed

4. Ejdel'shtejn M.V., Sukhorukova M.V., Skleenova E.Jyu., Ivanchik N.V., Mikotina A.V., Shek E.A., i issledovatel'skaya gruppa «MARAFON». Antibiotikorezistentnost' nozokomial'nykh shtammov Enterobacteriaceae v statsionarakh Rossii: rezul'taty mnogotsentrovogo epidemiologicheskogo issledovaniya «MARAFON» 2013–2014. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2017; 19 (1): 49–56. (in Russian).

5. Shajdullina E.R., Ejdel'shtejn M.V., Skleenova E.Jyu., Sukhorukova M.V., Kozlov R.S. Antibiotikorezistentnost' nozokomial'nykh karbapenemazoprodutsirujyushchikh shtammov Enterobacteriaceae v Rossii: rezul'taty epidemiologicheskogo issledovaniya 2014–2016 gg. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2018; 20 (4): 362–369. (in Russian).

6. Ejdel'shtejn M.V., Sukhorukova M.V., Skleenova E.Jyu., Ivanchik N.V., Mikotina A.V., Shek E.A., i issledovatel'skaya gruppa «MARAFON». Antibiotikorezistentnost' nozokomial'nykh shtammov Pseudomonas aeruginosa v statsionarakh Rossii: rezul'taty mnogotsentrovogo epidemiologicheskogo issledovaniya «MARAFON» 2013–2014. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2017; 19 (1): 37–41. (in Russian).

7. Ejdel'shtejn M.V., Sukhorukova M.V., Skleenova E.Jyu., Ivanchik N.V., Mikotina A.V., Shek E.A., i issledovatel'skaya gruppa «MARAFON». Antibiotikorezistentnost' nozokomial'nykh shtammov Acinetobacter spp. v statsionarakh Rossii: rezul'taty mnogotsentrovogo epidemiologicheskogo issledovaniya «MARAFON» 2013–2014. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2017; 19 (1): 42–48. (in Russian).

8. Yakovlev S.V., Suvorova M.P., Beloborodov V.B., Basin E.E., Eliseeva E.V., Kovelenov S.V., i chleny issledovatel'skoj gruppy ERGINI. Rasprostranennost' i klinicheskoe znachenie nozokomial'nykh infektsij v lechebnykh uchrezhdeniyakh Rossii: issledovanie ERGINI. Antibiotiki i Khimioter. 2016, 61 (5– 6): 32–42. (in Russian).

9. Kuz'menkov A.Jyu., Trushin I.V., Avramenko A.A., Ejdel'shtejn M.V., Dekhnich A.V., Kozlov R.S. AMRmap: internet-platforma monitoringa antibiotikorezistentnosti. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2017; 19 (2): 84–90. (in Russian).

10. Vinogradova A.G., Kuz'menkov A.Jyu. Prakticheskoe primenenie AMRmap: elementy podkhoda «ot obshchego k chastnomu» na primere Klebsiella pneumoniae. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2019; 21 (2): 181–186. DOI: 10.36488/cmac.2019.2.181-186. (in Russian).

11. GOST R ISO 20776-1-2010 Klinicheskie laboratornye issledovaniya i diagnosticheskie test-sistemy in vitro. Issledovanie chuvstvitel'nosti infektsionnykh agentov i otsenka funktsional'nykh kharakteristik izdelij dlya issledovaniya chuvstvitel'nosti k antimikrobnym sredstvam. Chast' 1. Referentnyj metod laboratornogo issledovaniya aktivnosti antimikrobnykh agentov protiv bystrorastushchikh aerobnykh bakterij, vyzyvajyushchikh infektsionnye bolezni. (in Russian).

12. Programma SKAT (Strategiya Kontrolya Antimikrobnoj Terapii) pri okazanii statsionarnoj meditsinskoj pomoshchi. Rossijskie klinicheskie rekomendatsii. Pod red. S.V.Yakovleva, N.I.Briko, S.V.Sidorenko, D.N.Protsenko. M.: Izdatel'stvo «Pero», 2018; 156. (in Russian).

13. Kozlov R.S., Stetsjyuk O.U., Andreeva I.V. Tseftazidim-avibaktam: novye «pravila igry» protiv polirezistentnykh gramotritsatel'nykh bakterij. Klinicheskaya Mikrobiologiya i Antimikrobnaya Khimioterapiya. 2018; 20 (1): 24–34. (in Russian).

14. Magiorakos A.P., Srinivasan A., Carey R.B. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18 (3): 268–281.

15. Bassetti M., Righi E., Vena A., Graziano E., Russo A., Peghin M. Risk stratification and treatment of ICU-acquired pneumonia caused by multidrug-resistant/extensively drug-resistant/pandrug-resistant bacteria. Curr Opin Crit Care. 2018; 24 (5): 385–393.