Аннотация
Цель — анализ антибиотикорезистентности, определение типов карбапенемаз устойчивых к карбапенемам штаммов K.
pneumoniae, выделенных из клинического материала при вторичных инфекциях от пациентов фтизиатрических клиник г. Москвы.
Материал и методы. В период с октября 2022 по февраль 2023 гг. в исследование включены клинические штаммы K.
pneumoniae, продуцирующие карбапенемазы. Обследованы 215 пациентов, из различных локусов которых выделено 80 клинических изолятов K. pneumoniae. Проведён мониторинг профиля антибиотикорезистентности клинических изолятов к широкому спектру АМП. Фенотипическое определение чувствительности выделенных штаммов микроорганизмов к АМП проведено на бактериологическом анализаторе Walk-Away 90-Plus (Beckman Coulter, USA). Для детекции генов приобретённых
карбапенемаз использован иммунохроматографический экспресс-тест (ИХ) NG-test Carba 5.
Результаты. К меропенему устойчивы 58 (72,5%) клинических штаммов, к имипенему 55 (68,7%). 22 (27,5%) клинических
штамма K. pneumoniae проявляли чувствительность к меропенему в 100% случаев. Клинические изоляты K. pneumoniae,
устойчивые к меропенему проявляли высокий уровень устойчивости к большинству β-лактамных АМП и к другим группам АМП. Выделено 22 клинических штамма K. pneumoniae, чувствительных к меропенему. Иммунохроматографический
экспресс-тест показал, что 27,5% клинических изолятов обладают одновременно двумя генами blaOXA+blaNDM — (класса D
и металло-β-лактамаза класс B), 27,5% blaКРС — (класса А). Продуцентов OXA — 12 штаммов (20,6%), гена blaNDM — 7 изолятов (12,0%), 7 штаммов (12,0%) продуцируют сочетанные карбапенемазы KPC+NDM-типа (класса А и B). Все изоляты
K. pneumoniae демонстрируют высокий уровень устойчивости к карбапенемам (МПК>8,0 мкг/мл), к β-лактамам, ципрофлоксацину, аминогликозидам, триметоприм/сульфаметоксазолу, но проявляют в 50,0% чувсвительность к тигециклинцу.
Обсуждение. Спектр карбапенемаз K. pneumoniae, выделенных в туберкулёзном стационаре, типичен для России и г. Москвы, но имеет ряд особенностей: большой удельный вес приходится на продукцию двойных карбапенемаз OXA+NDM-типа,
и карбапенемаз КРС-типа. Хотя карбапенемазы группы KPC не характерны для РФ в целом и для г. Москвы. Клинические
изоляты, несущие разные гены карбапенемаз характеризуются MDR-фенотипом.
Заключение. Грамотрицательные бактерии, продуцирующие карбапенемазы, являются одной из глобальных угроз, часто
являются причиной внутрибольничных инфекций, приводящих к неэффективности антибактериальной терапии у пациентов с тяжёлыми инфекциями
Annotation
Purpose. Analysis of antibiotic resistance, determination of carbapenemase types of carbapenemase-resistant strains of K. pneumoniae
isolated from clinical material in secondary infections from patients of TB clinics in Moscow.
Material and methods. Between October 2022 and February 2023, clinical carbapenemase-producing strains of K. pneumoniae were
included in the study. A total of 215 patients were examined, from various loci of which 80 clinical isolates of K. pneumoniae were
isolated. The antibiotic resistance profile of clinical isolates to a wide range of antibiotics was monitored. Phenotypic determination of
the sensitivity of isolated strains of microorganisms to AMP was carried out on an automatic Walk-Away 90-Plus canalizer (Beckman
Coulter, USA). To detect the genes of acquired carbapenemases, the NG-test Carba 5 rapid immunochromatographic test (IC) was used.
Outcomes. 58 (72.5%) clinical strains are resistant to meropenem, and 55 (68.7%) are resistant to imipenem. 22 (27.5%) clinical strains
of K. pneumoniae were susceptible to meropenem in 100% of cases. Meropenem-resistant clinical isolates of K. pneumoniae showed
a high level of resistance to most β-lactam AMPs and to other groups of AMPs. 22 clinical strains of K. pneumoniae susceptible to
meropenem have been isolated. Rapid immunochromatographic test showed that 27.5% of clinical isolates simultaneously possess two
genes blaOXA+blaNDM (class D and metallo-β-lactamase class B), 27.5% blaKPC (class A). 12 strains (20.6%) of OXA producers,
7 isolates (12.0%) of the blaNDM gene, and 7 strains (12.0%) produce combined KPC+NDM-type carbapenemases (class A and B).
All isolates of K. pneumoniae demonstrate a high level of resistance to carbapenems (BMD>8.0 μg/ml), β-lactams, ciprofloxacin,
aminoglycosides, co-trimoxazole, but show 50.0% sensitivity to tigecycline.
Discussion. The spectrum of K. pneumoniae carbapenemases isolated in a tuberculosis hospital is typical for Russia and Moscow, but
has a number of features: a large specific gravity falls on the production of OXA+NDM-type double carbapenemases, and bovinetype carbapenemases. Although the carbapenemases of the KPC group are not typical for the Russian Federation as a whole and for
Moscow. Clinical isolates carrying different carbapenemase genes are characterized by the MDR phenotype.
Conclusion. Gram-negative carbapenemase-producing bacteria are one of the global threats, often causing hospital-acquired
infections leading to the failure of antibiotic therapy in patients with severe infections.
Key words: K. pneumonia; producer; carbapenemase genes; antibiotic resistance; tuberculosis
Список литературы
1. Brazhenko N.A., Brazhenko O.N., Katicheva A.V. Impact of chronic
obstructive pulmonary disease on the life quality in tuberculosis
patients Tuberkulyoz i bolezni lyogkikh. 2018; 96(7): 66-7. DOI:
10.21292/2075-1230-2018-96-7-66-67. (in Russian)
2. Gizatullina E. D. The characteristic of nonspecific microflora at
patients with tuberculosis Prakticheskaya meditsina. 2010; 1(40):
78-81. (in Russian)
3. Gavrilyev S.S., Nikolaev V.P., Vinokurova M.K., Petukhova N.Yu.,
Gavrilova L.P., Malogulova I. S. Improving the technology of
chemotherapy for pulmonary tuberculosis, burdened with concomitant
diseases. Problemy tuberkulyoza. 2001; 2: 8-11. (in Russian)
4. Egorova S.A., Kaftyreva L.A., Lipskaya L.V., Konovalenko I.B.,
Pyasetskaya M.F., Kurchikova T.S. Enterobakteriaceae, producing
ESBL and metallo-β-laktamase NDM-1, isolated in hospitals of
Baltic region countries. Infektsiya i immunitet. 2013; 3(1): 29-36.
(in Russian)
5. Ibragimova M.R., Bagisheva N.V., Ibragimova A.R. Cardiopulmonary
comorbidity: effects of cardiovascular diseases on the course
of chronic obstructive pulmonary disease and newly diagnosed
tuberculosis. Sibirskiy meditsinskiy zhurnal 2017; 32(1): 70-3. DOI:
10.29001/2073-8552-2017-32-1-70-73. (in Russian)
6. Alekseeva L.P., Bukatina A.A., Vaneeva T.V., Eremenko T.A., Galkina K.Yu., Dorozhkova I.R. et al. In: Laboratory studies in tuberculosis. V. I. Litvinov, A. M. Moroz, eds. Moscow: Moskovskiy nauchnoprakticheskiy tsentr bor’by s tuberkulyozom; 2013. (in Russian)
7. Kryzhanovskaya O.A., Lazareva A.V., Alyabyaeva N.M., Tapaev
R.F., Karaseva O.V., Chebotar I.V. et al. Antibiotic resistance and
its molecular mechanisms in carbapenem-nonsusceptible Klebsiella
pneumoniae isolated in pediatric ICUs in Moscow. Antibiotiki i khimioterapiya. 2016; 61: 7-8. (in Russian)
8. Lushnikova A.V., Velikaya O.V. Pulmonary tuberculosis and COPD.
Sovremennye problemy nauki i obrazovaniya. 2013; 6: 624. (in Russian)
9. Mishin V.Yu., Zavrazhnov S.P. The effectiveness of chemotherapy in patients with pulmonary tuberculosis with concomitant nonspecific bronchopulmonary infection. Pul`monologiya. 2005; 6: 208. (in Russian)
10. Rudenko S.A., Mordyk A.V., Bagisheva N.V., Emel’yanova Yu.A.
Comparative aspects of bacteriological detection, clinical course and
treatment outcomes of newly diagnosed tuberculosis, both isolated
and combined with chronic obstructive pulmonary disease. Chelovek
i ego zdorov’e. 2017; 3: 49-54. DOI: 10.21626/vestnik/2017-2/08.
(in Russian)
11. Rachina S.A., Ivanchik N.V., Kozlov R.S. Microbiology diagnostic of community acquired pneumonia in adultis. Prakticheskaya
pul’monologiya. 2016; 4: 40-6. (in Russian)
12. Skala L.Z., Sidorenko S.V., Nekhorosheva A.G. Practical aspects of
modern clinical microbiology Tver’: Triada; 2004. (in Russian)
13. Spiridonova L.G., Ten M.B., Labutin I.V., Mezhebovskiy V.R. Features
of detection of nonspecific microflora and its drug resistentans wihth
respiratory tuberculosis. Effektivnaya farmakoterapiya. 2019; 15(7):
8-11. DOI: 10.33978/2307-3586-2019-15-7-8-11. (in Russian)
14. Sukhorukova M.V., Eidelstein M.V., Sklyanova E.Yu., Ivanchik
N.V., Timokhova A.V., Shek E.A. et al. Antimicrobial resistance
of nosocomial Enterobacteriaceae isolates in Russia: results of
national multicenter surveillance study «MARATHON» 2011–2012.
Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya.
2014; 16(4): 254-65. (in Russian)
15. Timofeeva O.G., Polikarpova S.V. Local microbiological monitoring
of carbapenemases-producing Enterobacterales. Laboratornaya sluzhba.
2019; 8(3): 14-9. DOI: 10.17116/labs2019803114. (in Russian)
16. Khanin A.L., Kravets S.L. Chronic obstructive pulmonary disease
and tuberculosis: the latest problem in real clinical practice. Vestnik
sovremennoy klinicheskoy meditsiny. 2017; 10(6): 60-70. (in Russian)
17. Anganova E.V., Vetokhina A.V., Raspopina L.A., Kichigina E.L., Savilova E.D. State of antibiotics resistance of Klebsiellae pneumoniae.
Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2017; (5): 70-
7. DOI: 10.36233/0372-9311-2017-5-70-77. (in Russian)
18. Ambler R. P. The structure of beta-lactamases. Philos. Trans. R Soc.
Lond B Biol. Sci. 1980; 289(1036): 321-31.
19. Bozhkova S.A., Kasimova A.R., Tikhilov R.M., Polyakova E.M.,
Rukina A.N. et.al. Adversa trends in the aetiology of orthopaedic infection: results of 6-year monitoring of the structure and resistance of
leading pathogens. Travmatologiya i ortopediya Rossii. 2018; 24(4):
20-31. DOI: 10.21823/2311-2905-2018-24-4-20-31. (in Russian)
20. Boucher H.W., Talbot G.H., Benjamin Jr D.K, Bradley J., Guidos
R.J. Jones R.N. et al. 10×20 Progress-Development of new drugs
active against gram-negative bacilli: An update from the infectious
diseases society of America. Clin. Infect. Dis. 2013, 56 (12): 1685-
94. DOI: 10.1093/cid/cit152.
21. ForcinaA., BaldanR., Marasco V., Cichero P. BondanzaA., Noviello
M. et al. Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation. Bone Marrow Transplant. 2017; 52(1): 114-9. DOI: 10.1038/
bmt.2016.234.
22. Magiorakos A.P., Srinivasan A., Carey R.B., Carmeli Y, Falagas M.E.
Giske C.G. 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): 268-81. DOI: 10.1111/j.1469-0691.2011.03570.x.
23. Meletis G. Carbapenem resistance: overview of the problem and future perspectives. Ther. Adv. Infect. Dis. 2016; 3(1): 15-21. DOI:
10.1177/2049936115621709.
24. Morrill H.J., Pogue J.M., Kaye K.S., LaPlante K.L. Treatment options
for carbapenem-resistant Enterobacteriaceae infections. Open Forum
Infect. Dis. 2015; 2(2): ofv 050. DOI: 10.1093/ofid/ofv050.
25. Munoz-Price L.S., Poirel L., Bonomo R.A., Schwaber M.J., Daikos
G.L., Cormican M. et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect. Dis.
2013; 13(9): 785-96. DOI: 10.1016/S1473-3099(13)70190-7.
26. Pitout J.D., Nordmann P., Poirel L. Carbapenemase-producing
Klebsiella pneumoniae, a key pathogen set for global nosocomial
dominance. Antimicrob. agents Chemother. 2015 Oct; 59(10): 5873-
84. DOI: 10.1128/AAC.01019-15.
27. Sanchez G.V., Master R.N., Clark R.B., Fyyaz M., Duvvuri P., Ekta
G. et al. Klebsiella pneumoniae antimicrobial drug resistance,
United States, 1998-2010. Emerg. Infect. Dis. 2013; 19 (1): 133-6.
DOI:10.3201/eid1901.120310.
28. Shabanova V.V., Krasnova M.V., Bozhkova S.A., Ageevets V.A.,
Lazareva I.V., Rukina A.N. et al. The first case of isolation of
Klebsiella pneumoniae ST147, producing NDM-1 carbapenemase, in
trauma and orthopedic hospital in Russia. Travmatologiya i ortopediya
Rossii. 2015; (2): 90-8. (in Russian)
29. Sien G.E., Babinchak T. Tigecycline:an update. Diagn.
Microbiol. Infect. Dis. 2013; 75 (4): 331-6. DOI: 10.1016/j.
diagmicrobio.2012.12.004.
30. WHO publishes list of bacteria for which new antibiotics are urgently
needed. WHO, 2017. Saudi Medical Journal 2017; 38(4):444-445.