The Prevalence of Metallo-β-Lactamases and Efflux-Mediated Mechanisms in Carbapenem Nonsusceptible Nosocomial Pseudomonas aeruginosa Isolated in Moscow in 2012–2015

Cover Page

Abstract


Background. Pseudomonas aeruginosa, the major nosocomial opportunistic pathogen, is an important cause of infectious morbidity and mortality among immunocompromised patients.

Objective. To establish the role of metallo-β-lactamases (MBL) and efflux-mediated mechanisms in conferring carbapenem resistance in nosocomial isolates of P. aeruginosa.

Methods. We analyzed carbapenem nonsusceptible nosocomial P. aeruginosa isolates obtained from pediatric and adult patients at three hospitals in Moscow in 2012–2015. Carbapenem susceptibility was assessed using the E-test. In addition, minimal inhibitory concentrations (MICs) of meropenem were tested by the broth microdilution method. The presence of MBL was determined using the EDTA-mediated suppression test. Efflux-dependent resistance was measured using an assay based on MIC modification by an ionophore carbonyl cyanide 3-chlorophenyl hydrazine (CCCP).

Results. A total of 54 carbapenem nonsusceptible P. aeruginosa isolates was examined. The presence of an MBL was detected in 37 (69%) isolates, 29 (54%) isolates had efflux-mediated resistance. In 10 (19%) isolates neither MBL nor efflux activity was found. Five out of 6 isolates (83%) with highly active efflux were MBL-positive. Among isolates with low efflux activity, 74% (17/23) possessed MBL, whereas in isolates with no efflux the rate of MBL-positivity was 60% (15/25).

Conclusion. The prevalence of MBL- and efflux-mediated carbapenem resistance in nosocomial P. aeruginosa is high. Moreover, our results reveal that several resistance mechanisms may combine at the isolate level. These data may contribute to the development of novel strategies in combating carbapenem resistance.


About the authors

Anna Valer'evna Lazareva

Scientific Centre of Children Health

Author for correspondence.
Email: annalaz71@mail.ru

Russian Federation MD, PhD, Professor

Ol'ga Andreevna Kryzhanovskaya

Scientific Centre of Children Health

Email: o-kryzhanovskaya@yandex.ru

Russian Federation MD

Yuliya Aleksandrovna Bocharova

Scientific Centre of Children Health

Email: ivrin7@mail.ru

Russian Federation assistant

Igor' Viktorovich Chebotar'

Scientific Centre of Children Health

Email: nizarnn@yandex.ru

Russian Federation MD, PhD

Nikolay Andreevich Mayanskiy

Scientific Centre of Children Health

Email: mayansky@nczd.ru

Russian Federation MD, PhD, Professor

References

  1. Руднов ВА, Бельский ДВ, Дехнич АВ. Инфекции в ОРИТ России: результаты национального многоцентрового исследования. Клиническая микробиология и антимикробная химиотерапия. 2011;13(4):294–304.
  2. Custovic A, Smajlovic J, Hadzic S, Ahmetagic S, Tihic N, Hadzagic H. Epidemiological surveillance of bacterial nosocomial infections in the surgical intensive care unit. Materia socio-medica. 2014;26 (1):7–11. doi: 10.5455/msm.2014.26.7–11
  3. Сухорукова МВ, Эйдельштейн МВ, Склеенова ЕЮ, Иванчик НВ, Тимохова АВ, Шек ЕА, Дехнич АВ, Козлов РС. Антибиотикорезистентность нозокомиальных штаммов Pseudomonas aeruginosa в стационарах России. Результаты многоцентрового эпидемиологического исследования МАРАФОН в 2011–2012 гг. Клиническая микробиология и антимикробная химиотерапия. 2014;16(4):273–279.
  4. Страчунский ЛС, Белоусов ЮБ, Козлов СН. Практическое руководство по антиинфекционной химиотерапии. Смоленск: НИИАХ СГМА. 2002. 586 с.
  5. Fritsche TR, Sader HS, Toleman MA, Walsh TR, Jones RN. Emerging metallo-β-lactamase mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program. Clin Infect Dis. 2005;41(Suppl.4):276–278.
  6. Cornaglia G, Akova M, Amicosante G, Cantón R, Cauda R, Docquier JD, Edelstein M, Frère JM, Fuzi M, Galleni M, Giamarellou H, Gniadkowski M, Koncan R, Libisch B, Luzzaro F, Miriagou V, Navarro F, Nordmann P, Pagani L, Peixe L, Poirel L, Souli M, Tacconelli E, Vatopoulos A, Rossolini GM. Metallo-beta-lactamases as emerging resistance determinants in Gram negative pathogens: open issues. Int J Antimicrob Agents. 2007;29(4):380–888. doi: 10.1016/j.ijantimicag.2006.10.008
  7. Hrabák J, Cervená D, Izdebski R, Duljasz W, Gniadkowski M, Fridrichová M, Urbásková P, Zemlicková H. Regional spread of Pseudomonas aeruginosa ST357 producing IMP-7 metallo-β-lactamase in Central Europe. J Clin Microbiol. 2011;49(1):474–475. doi: 10.1128/JCM.00684-10
  8. Hong DJ, Bae IK, Jang IH, Jeong SH, Kang HK, Lee K. Epidemiology and characteristics of metallo-β-lactamase producing Pseudomonas aeruginosa. Infect Сhemother. 2015;47(2):81–97. doi: 10.3947/ic.2015.47.2.81
  9. Определение чувствительности микроорганизмов к антимикробным препаратам. Государственное санитарно-эпидемиологическое нормирование Российской Федерации. Клинические рекомендации. М. 2014.
  10. EUCAST Clinical breakpoints bacteria. URL: http://www.eucast.org. (Available: 14.11.2015).
  11. Шевченко ОВ, Эйдельштейн МВ, Степанова МН. Металло-β-лактамазы: значение и методы выявления у грамотрицательных неферментирующих бактерий. Клиническая микробиология и антимикробная химиотерапия. 2007;1:211–218.
  12. ГОСТ Р ИСО 20776-1-2010. Клинические лабораторные исследования и диагностические тест-системы in vitro. Исследование чувствительности инфекционных агентов и оценка функциональных характеристик изделий для исследования чувствительности к антимикробным средствам. Часть 1. Референтный метод лабораторного исследования активности антимикробных агентов против быстрорастущих аэробных бактерий, вызывающих инфекционные болезни. 2010.
  13. Ardebili A, Lari AR, Talebi M. Correlation of ciprofloxacin resistance with the AdeABC efflux system in Acinetobacter baumannii clinical isolates. Ann Lab Med. 2014;34(6):433–438. doi: 10.3343/alm.2014.34.6.433
  14. Edelstein MV, Skleenova EN, Shevchenko OV, D’souza JW, Tapalski DV, et al. Spread of extensively resistant VIM-2 positive ST235 Pseudomonas aeruginosa in Belarus, Kazakhstan, and Russia: a longitudinal epidemiological and clinical study. Lancet Infect. Dis. 2013;13(10):867–876.
  15. Zhao WH, Hu Z, Chen G, Ito R, Hu ZQ. Contributions of IMP-10 metallo-β-lactamase, the outer membrane barrier and the MexAB-OprM efflux system to high level carbapenem resistance in Pseudomonas aeruginosa. Chemotherapy. 2009;55(3):168–174. doi: 10.1159/000217745
  16. Al-Kabsi AM, Yusof MYBM, Mansor M, Siok Yan GO, Manikam R, Sekaran SD. Multidrug efflux pumps over expression and its association with porin down regulation and β-lactamase production among nosocomial P. aeruginosa isolates from University of Malaya Medical Center, Malaysia. IJCEBS. 2015;3(2):125–135.
  17. Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med. 2006;119(6):3–10. doi: 10.1016/j.amjmed.2006.03.011
  18. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXYOprM efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000;44(12):3322–3327. doi: 10.1128/AAC.44.12.3322-3327.2000
  19. Nikaido H. Antibiotic resistance caused by gram negative multidrug efflux pumps. Clin Infect Dis. 1998;27(Suppl.1):32–41.
  20. Xavier DE, Picao RC, Girardello R, Fehlberg LCC, Gales AC. Efflux pumps expression and its association with porin down regulation and β-lactamase production among Pseudomonas aeruginosa causing bloodstream infections in Brazil. BMC Microbiol. 2010;10:217. doi: 10.1186/1471-2180-10-217
  21. Sacha P, Michalska A, Ojdana D, Wieczorek P, Hauschild T, Majewski P, Tryniszewska E. Identification of plasmid OXA and other β-lactamase genes among carbapenem resistant isolates of Pseudomonas aeruginosa from the Clinical University Hospital in northeastern Poland. New Microbiol. 2015;38(2):271–275.
  22. Li H, Luo YF, Williams BW, Blackwell TS, Xie CM. Structure and function of OprD protein in Pseudomonas aeruginosa: from antibiotic resistance to novel therapies. Int J Med Microbiol. 2012;302(2):63–68. doi: 10.1016/j.ijmm.2011.10.001

Statistics

Views

Abstract - 260

PDF (Russian) - 122

Cited-By


PlumX

Dimensions



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies