Carbapenemase production in hospital isolates of multidrug-resistant Klebsiella pneumoniae and Escherichia coli in Serbia

  • Anika Djordje Trudić Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
  • Zora Jelesić University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
  • Mira Mihajlović-Ukropina University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
  • Deana Medić University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
  • Branka Zivlak University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
  • Vera Gusman University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
  • Milan Djilas Institute for Public Health of Vojvodina, Novi Sad, Serbia
Keywords: enterobacteriaceae, drug resistance, bacterial, carbapenems, cross infection, genome, serbia, beta lactamases,

Abstract


Abstract

Background/Aim. Carbapenem resistance has escalated in medically important enterobacteria such as Klebsiella pneumoniae and Escherichia coli worldwide. Multidrug-resistant strains represent an important source of concern as effective therapeutic options of infections they cause are limited or none. There were no comprehensive studies considering the presence of carbapenemase production in enterobacteria in Serbia so far. The aim of the study was to determine carbapenemase production in hospital isolates of multidrug-resistant K. pneumoniae and E. coli in Serbia. Methods. Strains of K. pneumoniae and E. coli resistant to at least one carbapenem (imipenem, meropenem, ertapenem) were collected from November 2013 to May 2014. Isolates were obtained from clinical samples of patients treated in 14 hospitals in Serbia. Carbapenem resistance was confirmed using phenotypic tests and polymerase chain reaction (PCR) in National Reference Laboratory for Registration and Surveillance of Antimicrobial Resistance of Bacterial Strains in Novi Sad. Results. Of 129 collected strains, 121 (93.8%) were K. pneumoniae and 8 (6.2%) were E. coli. Seventy (54.3%) strains were obtained from urine, 26 (20.2%) from blood, 19 (14.7%) from wound secretions and 14 (10.9%) from lower respiratory tract secretions. Carbapenemase genes were detected in 58 (45%) isolates. The gene bla New Delhi-metallo-beta-lactamases (blaNDM) was found in 33 (27.3%) K. pneumoniae, bla oxacillinases-48 (blaOXA-48) in 10 (8.3%), bla K. pneumonia carbapenemase (blaKPC) in 1 (0.8%), and 7 (5.4%) strains harbored both blaOXA-48 and blaNDM. Seven E. coli harbored blaNDM gene. Conclusion. In Serbia, the most common type of carbapenemase in both multidrug-resistant K. pneumoniae and E. coli is NDM. Co-production of OXA-48 and NDM was found in K. pneumoniae. To our knowledge, KPC production was detected for the first time in Serbia.

Author Biographies

Anika Djordje Trudić, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
Center for Microbiology, Virology and Immunology, asist. dr
Zora Jelesić, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
Center for Microbiology, prof. dr
Mira Mihajlović-Ukropina, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
Center for Microbiology, prof. dr
Deana Medić, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
Center for microbiology, doc. dr
Branka Zivlak, University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Institute for Public Health of Vojvodina, Novi Sad, Serbia
Center for microbiology, asist. dr

References

Hawkey PM. Multidrug-resistant Gram-negative bacteria: A product of globalization. J Hosp Infect 2015; 89(4): 241−7.

Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert pro-posal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18(3): 268−81.

Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Car-bapenems: Past, present, and future. Antimicrob Agents Che-mother 2011; 55(11): 4943−60.

Nordmann P, Naas T, Poirel L. Global spread of Carbapene-mase-producing Enterobacteriaceae. Emerging Infect Dis 2011; 17(10): 1791−8.

Nordmann P, Poirel L, Dortet L. Rapid detection of carbapene-mase-producing Enterobacteriaceae. Emerg Infect Dis 2012; 18(9): 1503−7.

Glasner C, Albiger B, Buist G, Tambić-Andrašević A, Canton R, Carmeli Y, et al. Carbapenemase-producing Enterobacteriaceae in Europe: A survey among national experts from 39 coun-tries. Euro Surveill 2013; 18(28): pii: 20525.

Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Ente-robacteriaceae: Here is the storm. Trends Mol Med 2012; 18(5): 263−72.

Nordmann P, Poirel L. Strategies for identification of carbape-nemase-producing Enterobacteriaceae. J Antimicrob Che-mother 2013; 68(3): 487−9.

Miriagou V, Cornaglia G, Edelstein M, Galani I, Giske CG, Gniad-kowski M, et al. Acquired carbapenemases in Gram-negative bacterial pathogens: Detection and surveillance issues. Clin Microbiol Infect 2010; 16(2): 112−22.

Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-third informa-tional supplement M100-S23. Wayne, PA, USA: CLSI; 2013.

Manchanda V, Rai S, Gupta S, Rautela RS, Chopra R, Rawat DS, et al. Development of TaqMan real-time polymerase chain reaction for the detection of the newly emerging form of car-bapenem resistance gene in clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Indian J Med Microbiol 2011; 29(3): 249−53.

Marchaim D, Navon-Venezia S, Schwaber MJ, Carmeli Y. Isolation of imipenem-resistant Enterobacter species: Emergence of KPC-2 carbapenemase, molecular characterization, epidemiol-ogy, and outcomes. Antimicrob Agents Chemother 2008; 52(4): 1413−8.

Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: The phantom menace. J. Antimicrob Chemother 2012; 67(7): 1597−606.

Ellington MJ, Kistler J, Livermore DM, Woodford N. Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. J Antimicrob Chemother 2007; 59(2): 321−2.

Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: Clinical perspectives on detection, treatment and infection control. J Intern Med 2015; 277(5): 501−12.

Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25(4): 682−707.

Grundmann H, Livermore DM, Giske CG, Canton R, Rossolini GM, Campos J, et al. Carbapenem-non-susceptible Enterobacteria-ceae in Europe: Conclusions from a meeting of national ex-perts. Euro Surveill 2010; 15(46): pii: 19711.

Cohen SJ, Leverstein-Van Hall MA. Guideline for phenotypic screening and confirmation of carbapenemases in Enterobac-teriaceae. Int J Antimicrob Agents 2010; 36(3): 205−10.

Giske CG, Gezelius L, Samuelsen Ø, Warner M, Sundsfjord A, Woodford N. A sensitive and specific phenotypic assay for de-tection of metallo-β-lactamases and KPC in Klebsiella pneu-moniae with the use of meropenem disks supplemented with aminophenylboronic acid, dipicolinic acid and cloxacillin. Clin Microbiol Infect 2011; 17(4): 552−6.

Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae se-quence type 14 from India. Antimicrob. Agents Chemother 2009; 53(12): 5046−54.

Jovcic B, Lepsanovic Z, Suljagic V, Rackov G, Begovic J, Topisirovic L, et al. Emergence of NDM-1 metallo-β-lactamase in Pseudo-monas aeruginosa clinical isolates from Serbia. Antimicrob Agents Chemother 2011; 55(8): 3929−31.

Mirovic V, Tomanovic B, Lepsanovic Z, Jovcic B, Kojic M. Isolation of Klebsiella pneumoniae producing NDM-1 metallo-β-lactamase from the urine of an outpatient baby boy receiving antibiotic prophylaxis. Antimicrob Agents Chemother 2012; 56(11): 6062−3.

Poirel L, Savov E, Nazli A, Trifonova A, Todorova I, Gergova I, et al. Outbreak caused by NDM-1- and RmtB-producing Esche-richia coli in Bulgaria. Antimicrob. Agents Chemother 2014; 58(4): 2472−4.

Markovska R, Schneider I, Stoeva T, Bojkova K, Boyanova L, Bauern-feind A, et al. First identification of KPC-2 and VIM-1 produc-ing Klebsiella pneumoniae in Bulgaria. Diagn. Microbiol Infect Dis 2013; 77(3): 252−3.

Zujić Atalić V, Bedenić B, Kocsis E, Mazzariol A, Sardelić S, Barišić M, et al. Diversity of carbapenemases in clinical isolates of En-terobacteriaceae in Croatia: The results of a multicentre study. Clin Microbiol Infect 2014; 20(11): 894−903.

Giakkoupi P, Papagiannitsis CC, Miriagou V, Pappa O, Polemis M, Tryfinopoulou K, et al. An update of the evolving epidemic of blaKPC-2-carrying Klebsiella pneumoniae in Greece (2009-10). J Antimicrob Chemother 2011; 66(7): 1510−3.

Bogaerts P, Bouchahrouf W, Castro RR, Deplano A, Berhin C, Piérard D, et al. Emergence of NDM-1-producing Enterobacteriaceae in Belgium. Antimicrob Agents Chemother 2011; 55(6): 3036−8.

Székely E, Damjanova I, Jánvári L, Vas KE, Molnár S, Bilca DV, et al. First description of bla(NDM-1), bla(OXA-48), bla(OXA-181) producing Enterobacteriaceae strains in Romania. Int J Med Microbiol 2013; 303(8): 697−700.

Mirović V, Carević B, Stepanović S, Lepšanović Z. An outbreak of infection due to metallo-beta-lactamase-producing Proteus mi-rabilis in the surgical intensive care unit. Scr Med 2011; 42(2): 75−9.

Carrër A, Poirel L, Eraksoy H, Cagatay AA, Badur S, Nordmann P. Spread of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in Istanbul, Turkey. Antimicrob Agents Chemother 2008; 52: 950−4.

Pirš M, Andlovic A, Cerar T, Žohar-Čretnik T, Kobola L, Kolman J, et al. A case of OXA-48 carbapenemase-producing Klebsiella pneumoniae in a patient transferred to Slovenia from Libya, November 2011. Euro Surveill 2011; 16(50): 20042.

Jánvári L, Damjanova I, Lázár A, Rácz K, Kocsis B, Urbán E, et al. Emergence of OXA-162-producing Klebsiella pneumoniae in Hungary. Scand J Infect Dis 2014; 46(4): 320−4.

Ben Nasr A, Decré D, Compain F, Genel N, Barguellil F, Arlet G. Emergence of NDM-1 in association with OXA-48 in Kleb-siella pneumoniae from Tunisia. Antimicrob. Agents Che-mother 2013; 57(8): 4089−90.

Barguigua A, El Otmani F, Lakbakbi EI Yaagoubi F, Talmi M, Ze-rouali K, et al. First report of a Klebsiella pneumoniae strain coproducing NDM-1, VIM-1 and OXA-48 carbapenemases isolated in Morocco. APMIS 2013; 121(7): 675−7.

Kilic A, Baysallar M. The First Klebsiella pneumoniae Isolate Co-Producing OXA-48 and NDM-1 in Turkey. Ann Lab Med 2015; 35(3): 382−3.

Seiffert SN, Marschall J, Perreten V, Carattoli A, Furrer H, Endi-miani A. Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland. Int J Antimicrob Agents 2014; 44(3): 260−2.

Tóth A, Damjanova I, Puskás E, Jánvári L, Farkas M, Dobák A, et al. Emergence of a colistin-resistant KPC-2-producing Kleb-siella pneumoniae ST258 clone in Hungary. Clin Microbiol In-fect 2014; 20(1): 27−9.

Published
2017/09/19
Section
Original Paper