head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2019, vol. 25, issue2
Subject Area: Medicine
-
DOI: 10.5272/jimab.2019252.2457
Published online: 01 April 2019

Original article

J of IMAB. 2019 Apr-Jun;25(2):2457-2464
MOLECULAR EPIDEMIOLOGY OF MULTIDRUG RESISTANT ENTEROBACTER CLOACAE BLOOD ISOLATES FROM A UNIVERSITY HOSPITAL
Dobromira Dimitrova1ORCID logo, Temenuga Stoeva1ORCID logo Corresponding Autoremail, Rumyana Markovska2ORCID logo, Petya Stankova2ORCID logo, Kalina Mihova3ORCID logo, Radka Kaneva3ORCID logo, Ivan Mitov2ORCID logo,
1) Department of Microbiology and Virology, University Hospital Saint Marina, Medical University, Varna, Bulgaria
2) Department of Medical Microbiology, Medical University, Sofia, Bulgaria
3) Molecular Medicine Center, Medical University, Sofia, Bulgaria.

ABSTRACT:
Purpose: to evaluate the epidemiological relationship between 3rd generation cephalosporin resistant Enterobacter cloacae blood isolates collected from patients in the University Hospital in Varna city during the period March 2014 and January 2017 and to characterize the ESBLs production in these isolates.
Materials and methods: a total of 47 consecutive (nonduplicate) 3rd generation cephalosporin resistant isolates of Enterobacter cloacae, obtained from blood samples of patients admitted in different wards in Varna University Hospital, were investigated. Antimicrobial susceptibility to set of antimicrobial agents was tested by disc diffusion method and Phoenix (BD), and the results were interpreted according to EUCAST guidelines 2017. Identification of ESBL encoding genes was    performed by PCR and sequencing. Isolates were genotyped by ERIC PCR.
Results: The antimicrobial susceptibility in the whole collection of isolates, shown in decreasing order, is as follows: amikacin, 97.8% < levofloxacin, 76.6% < trimethoprime/ sulphometoxazole, 40.4% < ciprofloxacin, 19% < gentamicin, 8.4% < cefepime, 4.2% < piperacillin/ tazobactam, tobramycin, 2.1%. Multidrug resistance was detected in 70.2% of the isolates. The most widespread enzyme was CTX-M-15, found in 95.5% (n=43). Nine different ERIC types were detected. The dendrogram of similarity revealed three main clones of E. cloacae: Clone I, comprising two closely related subclones (ERIC type A and Aa) (similarity coefficient 0.92), was predominant, detected in Haematology (n=9), Haemodialysis (n=8), ICU (n=6), Cardio surgery (n=3), Pulmonology (n=4) and Gastroenterology (n=1); Clones II (ERIC type C) and III were presented by 5, and 3 isolates with identical profiles, obtained from patients, hospitalized in different wards. The ERIC profiles K, L, M and P, were found in single isolates only and were interpreted as sporadic.
Conclusions: multi-drug resistance in E. cloacae was associated with successful intrahospital dissemination of three CTX-M-15 producing E. cloacae clones. Clone I was predominant, demonstrating high cross-transmission, epidemic and invasive potential. BlaCTX-M-15 was identified as a major mechanism of resistance to 3rd generation cephalosporins in E. cloacae.

Keywords: Enterobacter cloacae, ESBL genes, epidemiology, epidemic clones,

pdf - Download FULL TEXT /PDF 604 KB/
Please cite this article as: Dimitrova D, Stoeva T, Markovska R, Stankova P, Mihova K, Kaneva R, Mitov I. Molecular Epidemiology of Multidrug Resistant Enterobacter cloacae blood isolates from a University Hospital. J of IMAB. 2019 Apr-Jun;25(2):2457-2464. DOI: 10.5272/jimab.2019252.2457

Corresponding AutorCorrespondence to: Prof. Temenuga Stoeva, MD, PhD, Department of Microbiology and Virology, Medical University, Varna; 55, Marin Drinov Str., Varna, Bulgaria; E-mail: temenuga.stoeva@abv.bg

REFERENCES:
1.  Sanders WE Jr, Sanders CC. Enterobacter spp.: pathogens poised to flourish at the turn of the century. Clin Microbiol Rev. 1997 Apr;10(2):220-41. [PubMed]
2. Lee CC, Lee NY, Yan JJ, Lee HC, Chen PL, Chang CM, et al. Bacteremia due to extended-spectrum-beta-lactamase-producing Enterobacter cloacae: role of carbapenem therapy. Antimicrob Agents Chemother. 2010 Sep;54(9):3551-6. [PubMed] [Crossref]
3. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. WHO. 27 February 2017. [Internet]
4. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.1, valid from 2017-03-10. [Internet]
5. Markovska R, Schneider I, Keuleyan E, Sredkova M, Ivanova D, Markova B, et al. Extended-spectrum beta-lactamase-producing Enterobacteriaceae in Bulgarian hospitals. Microb Drug Resist. 2008 Jun;14(2):119–128.
6. Davin-Regli A, Pages J. Enterobacter aerogenes and Enterobacter cloacae: versatile bacterial pathogens confronting antibiotic treatment. Front Microbiol. 2015 May;6:392. [PubMed] [Crossref]
7. Guanghui L, Demei Z, Fu W, Zhidong H, Quan L, Ziyong S, et al. The distribution and antibiotic resistance of clinical isolates from blood culture in 2012 CHINET surveillance program in China. Chin J Infect Chemother. 2014;6:474 - 81.
8. Chen C, Huang C. Risk factor analysis for extended-spectrum beta-lactamase-producing Enterobacter cloacae bloodstream infections in central Taiwan. BMC Infect Dis. 2013 Sep;13:417. [PubMed] [Crossref]
9. Wang S, Xiao S-Z, Gu F-F, Tang J, Guo XK, Ni Y-X, et al. Antimicrobial susceptibility and molecular epidemiology of clinical Enterobacter cloacae bloodstream isolates in Shanghai, China. PLoS ONE. 2017 Dec;12 (12): e0189713. [PubMed] [Crossref]
10. Coque TM, Novais A, Carattoli A, Poirel L, Pitout J, Peixe L, et al. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum betalactamase CTX-M-15. Emerg Infect Dis. 2008 Feb;14(2):195–200.
11. Guiral E, Pons M, Vubil D, Marí-Almirall M, Sigaúque B, Soto S, et al. Epidemiology and molecular characterization of multidrug-resistant Escherichia coli isolates harboring blaCTX-M group 1 extended-spectrum β-lactamases causing bacteremia and urinary tract infection in Manhiça, Mozambique. Infect Drug Resistance. 2018 Jul;11:927-936. [PubMed] [CrossRef]
12. Oteo J, Cercenado E, Vindel A, Bautista V, Fernandez-Romero S, Sae´z D, et al. Outbreak of multidrug-resistant CTX-M-15- producing Enterobacter cloacae in a neonatal intensive care unit. J Med Microbiol. 2013;62: 571-575.
13. Manzur A, Tubau F, Pujol M, Calatayud L, Dominguez M, Pena C, et al. Nosocomial Outbreak Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacter cloacae in a Cardiothoracic Intensive Care Unit. J Clin Microbiol. 2007 Aug;45 (8): 2365-2369.
14. Markovska R, Stoeva T, Bojkova K, Mitov I. Epidemiology and molecular characterization of Extended Spectrum Beta-Lactamases producing Enterobacter spp., Pantoea agglomerans and Serratia marcescens isolates from a Bulgarian Hospital. Microbial Drug Resistance. 2014 Apr;20(2): 131-137.
15. Guérin F. Infections caused by Enterobacter cloacae complex: Antibiotic resistance and treatment. Jornel des Anti-infectieux. 2015 Apr;17(3):79-89.
16.Souna D, Amir A, Bekhoucha S, Berrazeg M, Drissi M. Molecular typing and characterization of TEM, SHV, CTX-M, and CMY-2 β-lactamases in Enterobacter cloacae strains isolated in patients and their hospital environment in the west of Algeria. Med Mal Infect. 2014 Apr;44(4):146-52. [PubMed
17. Livermore D, Canton R, Gniadkowski M, Nordmann P, Rossolini G, Arlet G. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007 Feb;59(2):165-74. [PubMed]
18. Izdebski R, Baraniak A, Herda M, Fiett J, Bonten M, Carmeli Y, et al. MLST reveals potentially high-risk international clones of Enterobacter cloacae. J Antimicrob Chemother. 2015 Jan;70(1):48-56. [PubMed] [Crossref]
19. Ho P, Shek R, Chow K, Duan R, Mak G, Lai L, et al. Detection and characterization of extended-spectrum beta-lactamases among bloodstream isolates of Enterobacter spp. in Hong Kong, 2000-2002. J Antimicrob Chemother. 2005 Mar;55(3): 326-32. [PubMed] [Crossref]
20. Seki L, Pereira P, de Souza Conceicao M, Souza M, Marques E, Carballido JM, et al. Molecular epidemiology of CTX-M producing Enterobacteriaceae isolated from bloodstream infections in Rio de Janeiro, Brazil: emergence of CTX-M-15. The Braz J Infect  Dis. 2013 Nov-Dec;17(6):640–6.
21. Mshana M, Gerwing L, Minde M, Hain T, Domann E, Lyamuya E et al. Outbreak of a novel Enterobacter spp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania. Int J Antimicrob Agents. 2011 Sept;38(3):265-9. [PubMed].
22. Qureshi Z, Paterson D, Pakstis D, Adams-Haduch J, Sandkovsky G, Sordillo E, et al. Risk factors and outcome of extended-spectrum beta-lactamase-producing Enterobacter cloacae bloodstream infections. Inter J Antimicrob Agents. 2011  Jan;37(1):26–32.
23. Goossens H, Grabein B. Prevalence and antimicrobial susceptibility data for extended-spectrum beta-lactamase- and AmpC-producing Enterobacteriaceae from the MYSTIC Program in Europe and the United States (1997–2004). Diagnostic Мicrobiol Infect Dis. 2005 Dec;53(4):257-64.
24. Pai H, Hong J, Byeon J, Kim Y, Lee H. High prevalence of extended-spectrum beta-lactamase-producing strains among blood isolates of Enterobacter spp. collected in a tertiary hospital during an 8-year period and their antimicrobial susceptibility patterns. Antimicrob Agents Chemother. 2004 Aug;48(8):3159-3161.
25. Rawat D, Nair D. Extended-spectrum beta-lactamases in Gram Negative Bacteria. J Glob Infect Dis. 2010 Sep;2(3): 263-74.  
26. Strahilevitz J, Jacoby G, Hooper D, Robicsek A. Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat. Clin Microbiol Rev. 2009 Oct;22(4):664-89.
27. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2016. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2017. [Internet]
28. Chow J, Fine M, Shlaes D, Quinn J, Hooper D, Johnson M, et al. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991 Oct;115(8):585-590.
29. Ye Y, Li J, Ye D, Jiang Z. Enterobacter bacteremia: clinical features, risk factors for multiresistance and mortality in a Chinese University Hospital. Infection. 2006 Oct;34(5):252-257.
30. Yu W, Cheng K, Chi C, Chen H, Chuang Y, Wu L. Characterisation and molecular epidemiology of extended-spectrum beta-lactamase-producing Enterobacter cloacae isolated from a district teaching hospital in Taiwan. Clin Microbiol Infect. 2006 Jun;12(6):579-582.
31. Yu W, Chuang Y, Walther-Rasmussen J. Extended-spectrum beta-lactamases in Taiwan: epidemiology, detection, treatment and infection control. J Microbiol Immunol Infect. 2006 Aug;39(4):264-277.
32. Goncalves C, Vaz T, Leite D, Pisani B, Simoes M, Prandi M, et al. Molecular epidemiology of a nosocomial outbreak due to Enterobacter cloacae and Enterobacter agglomerans in campinas Sao Paulo, Brazil. Rev Inst Med Trop S Paulo. 2000 Feb;42(1):1-7.
33. Maki D, Rhame F, Mackel D, Bennett J. Nationwide epidemic of septicemia caused by contaminated intravenous products: Epidemiologic and clinical features. American J Med. 1976 Apr;60(4):471-485.
34. Beyrouthy R, Barets M, Marion E, Dananche C, Dauwalder O, Robin F, et al. Novel Enterobacter Lineage as Leading Cause of Nosocomial Outbreak Involving Carbapenemase-Producing Strains. Emerg Infect Dis. 2018 Aug;24(8):1505-1515. [PubMed] [Crossref]
35. Fernández J, Montero I, Martínez O, Fleites A, Poirel L, Nordmann P, et al. Dissemination of multiresistant Enterobacter cloacaeisolates producing OXA-48 and CTX-M-15 in a Spanish hospital. Int J Antimicrob Agents. 2015 Oct;46(4):469-74. [PubMed] [Crossref]
36. Glupczynski Y, Noel A, Michaux I, Dupont S, Lessire S, Dincq A, et al. A large common point source nosocomial outbreak caused by ESBL-producing Enterobacter cloacae at one Belgian university hospital. ECCMID Vienna. 23-04-2017. OSO316. [Internet]
37. Girlich D, Poirel L, Nordmann P. Clonal distribution of multidrug-resistant Enterobacter cloacae. Diagn Microbiol Infect Dis. 2015 Apr;81(4):264-8. [PubMed] [Crossref]..

Received: 30 October 2018
Published online: 01 April 2019

back to Online Journal