COMPARISON OF ANTIBIOTIC SUSCEPTIBILITIES OF CARBAPENEM RESISTANT AND CARBAPENEMSUSCEPTIBLE PSEUDOMONAS AERUGINOSA STRAINS AND INVESTIGATING SOME CARBAPENEMASE GENES IN CARBAPENEM RESISTANT STRAINS

​

Vecihe Azizoglu, Burçin Ozer, Aycan Gundogdu

 

ABSTRACT: Aim: It was aimed to compare the antimicrobial susceptibility of carbapenem resistant (CRPA) andsusceptible P. aeruginosa (CSPA) strains and to determine the presence of carbapenemasegenes in CRPA strains. Methods: Fifty CRPA and 251 CSPA were included into the study. Antibiotic susceptibilities were determined using the automated system. The presence of carbapenemasegenes (blaIMP, blaSPM, blaAIM, blaNDM, blaOXA-48, blaKPC) in CRPA strains were investigated by multiplex polymerase chain reaction method. Results: CRPA isolates were found to be more resistant to amikacin, aztreonam, gentamicin, netilmicin, tobramycin, ciprofloxacin, levofloxacin, cefepime, ceftazidime, piperacillin, piperacillin / tazobactamthan CSPA. Amikacin, aztreonam, ceftazidime, ciprofloxacin, colistin, cefepime, gentamicin, levofloxacin, netilmycin, piperacillin, tobramycin, piperacillin/tazobactam MIC values of CRPA strains were found to be higher than MIC values of CSPA strains. The multidrug resistance (MDR) rate was 14,6% and higher in the CRPA group. Inthe CRPA strains, among blaIMP, blaVIM, blaSPM, blaNDM, blaKPC, blaAIM and blaOXAgenes, blaIMP was found in one strain and blaVIM gene in three strains. Conclusions: The carbapenem resistance and MDR rate in ours tudy, were found to be lesser than the rates in our country. It was found that CRPA were also more resistant to other antibiotics than CSPA. IMP and VIM type enzymes were found in our study. Together with other studies conducted in our hospital, this study showed that carbapenemases were not common in P. Aeruginosa strains isolated in our hospital. Identifying these enzymes epidemiologically is important in preventing the spread of resistance.

 

KEY WORDS: P. aeruginosa, antibiotic, resistance, carbapenem, carbapenemase

​

REFERENCES:

1. Barbier F, Andremont A, Wolff MveBouadma L. Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med 2013; 19, 3 :216–228.

2. Ruhnke M, Arnold RveGastmeier P. Infection control issues in patients with haematological malignancies in the era of multidrug-resistant bacteria. Lancet Oncol 2014; 15, 13: 606–619.

3. Borgatta B, Lagunes L, Imbiscuso AT, Larrosa MN, Lujan M,Rello J. Infections in intensive care unit adult patients harboring multidrug-resistant Pseudomonas aeruginosa: implications for prevention and therapy. Eur J ClinMicrobiol Infect Dis2017; 36, 7:1097-1104.

4. Brooks GF, Carroll KC, Butel JS, Morse SA veMietzner TA.Bacteriology.In: Medical Microbiology. Jawetz, Melnick and Adelbergs, 26th Ed, McGraw-Hill Companies, New York, 2013, s.149-405.

5. Suárez C, Peña C, Gavaldà L, Tubau F, Manzur A, Dominguez M.A, Pujol M,Gudiol F,Ariza J Influence of carbapenem resistance on mortality and the dynamics of mortality in Pseudomonas aeruginosabloodstream infection. Int J Infect Dis 2010; 14: e73-78.

6. Buehrle DJ, Shields RK, Clarke LG, Potoski BA, Clancy CJ and Nguyen MH.Carbapenem-resistant bacteremia: Risk factors for mortality and microbiologic treatment failure. Antimicrob Agents Chemother 2016; 61,1: e01243-16.

7. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Nicola Magrini C, WHO Pathogens Priority List Working Group Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis.Lancet Infect Dis 2018; 18, 3:318–327.

8. Centres for Disease Control and Prevention (US)..Centres for Disease Control and Prevention, US Department of Health and Human Services.

9. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, Edwards JR, Sievert DM. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control HospEpidemiol 2016; 37, 11:1288 –1301.

10. Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, Westblade LF. Carbapenemase-Producing Organisms: A Global Scourge.Clin Infect Dis 2018; 66, 8 :1290-1297.

11. Walther-Rasmussen J. and Hoiby N. OXA-type carbapenemases.J.Antimicrob Chemother 2006; 57(3):373-83.

12. Nordmann P, Cuzon G. and Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9, 4:228-236.

13. EUCAST. European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters Version 10.0, 2020: 22-27.

14. Hassuna NA, Ibrahim Mohamed AH, Abo- Eleuoon SM andHawa R. High prevalence of multidrug resistant Pseudomonas aeruginosa recovered from infected burn wounds in children. Archives of ClinMicrobiol 2015; 6,4: 1-7.

15. [15] Poirel L, Naas T, Nicolas D, Collet L, Bellais S,Cavallo JD,Nordmann P. Characterization of VIM-2, a carbapenem-hydrolyzing metallo-beta-lactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob Agents Chemother 2000;44, 4 :891-897.

16. [16] Ozer B, Inci M, Duran N, Kurtgoz S, Alagoz G, Pasa O, Kilic C. Comparison of antibiotic resistance of Acinetobacter and Pseudomonas aeruginosa strains isolated from intensive care units with other clinics. Acta Medica Mediterranea 2016; 32:117-122.

17. Pasa O, Ozer B, Duran N, Inci M, Yula E. Beta lactamase enzymes in clinical Pseudomonas aeruginosa strains. West Indian Med J2015;16 ;65, 1:40-45.

18. Neidig A,Yeung AT, Rosay T, Tettmann B, Strempel N, Rueger M, Lesouhaitier O, Overhage J. TypA is involved in virulence, antimicrobial resistance and biofilm formation in Pseudomonas aeruginosa. BMC Microbiol2013;13, 1:77.

19. Bassetti M,Vena A, Croxatto A, Righi E and Guery B. How to manage Pseudomonas aeruginosa infections. Drugs in Context;2018;7.

20. Antimicrobial resistance surveillance in Europe 2012 [http://ecdc.europa.eu /en/publications-data/antimicrobial-resistance-surveillance-europe-2012].

21. Antimicrobial resistance surveillance in Europe 2016 [http://ecdc.europa.eu/en /publications-data/antimicrobial-resistance-surveillance-europe-2016].

22. Ozer B, Duran N, Onlen YandSavas L. Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit. 2012;, 1:9-13.

23. Rizek C, Fu L, dos Santos LC, Leite G, Ramos J, Rossi F, Guimaraes T, Levin AS, Costa SF.Characterization of carbapenem-resistant Pseudomonas aeruginosa clinical isolates, carrying multiple genes coding for this antibiotic resistance. Ann ClinMicrobiol Antimicrob2014;13, 1:1-5.

24. Farrell DJ, Flamm RK, Sader HS and Jones RN. Antimicrobial activity of ceftolozane-tazobactam tested against Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in US hospitals (2011-2012). 2013;, 12:6305-6310.

25. Telling K,Laht M, Brauer A, Remm M, Kisand V, Maimets M, Tenson T, Lutsar I.Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals.BMC Infect Dis2018;18, 1:513.

26. European Centre for Disease Prevention and Control; Surveillance Atlas of Infectious Diseases [online tool]. Stockholm, 2019 (https://ecdc. europa.eu/en/antimicrobial-  resistance/surveillance-anddisease-data/data-ecdc, accessed 28 October 2019).

27. Hong DJ,Bae IK, Jang IH, Jeong SH, Kang HK, Lee K. Epidemiology and characteristics of metallo-beta-lactamase-producing Pseudomonas aeruginosa. 2015;, 2:81-97.

28. World Health Organization. Central Asian and European Surveillance of Antimicrobial Resistance, Annual Report 2019.

29. Canton R, Akova M, Carmeli Y, Giske CG, Glupczynski Y, Gniadkowski M, Livermore DM, Miriagou V, Naas T, Rossolini GM, Samuelsen Ø, Seifert H, Woodford N, Nordmann P, European Network on Carbapenemases. Rapid evolution andspread of carbapenemases among Enterobacteriaceae in Europe. ClinMicrobiol Infect 2012; 18, 5,:413-431.

30. Gulay Z. Molecular Epidemiology of Carbapenemases in Enterobacteriaceae. Bulletin of AntimicrobChemother

31. Ozgumus OB, Caylan R, TosunI, Sandalli C, Aydin K, Koksal I. Molecular epidemiology of clinical Pseudomonas aeruginosa isolates carrying IMP-1 metallo-beta-lactamase gene in a university hospital in Turkey. Microbial Drug Resist 2007;13, 3:191-198.

32. Castanheira M, Deshpande LM, Costello A, Davies TA and Jones RN. Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries. J AntimicrobChemother 2014; 69:1804-1814.

33. Walsh TR. The emergence and implications of metallo-beta-lactamases in Gram-negative bacteria.Clin Microbiol Infect 2005;11:2–9.

34. Iraz M,Duzgun AO, Cicek AC, Bonnin RA, Ceylan Aet al. Characterization of novel VIM carbapenemase, VIM-38, and first detection of GES-5 carbapenem-hydrolyzing beta-lactamases in Pseudomonas aeruginosa in Turkey. DiagnMicrobiol Infect Dis 2014; 78, 3 :292-294.

35. Ocak M,Özer B, İnci M, Duran N. Antibiotic Resistance and Investigation of IMP-1, IMP-2, VIM-1 and VIM-2 Metallo-β-Lactamases in Acinetobacter Strains Isolated From Clinical Samples. KLIMIK Journal2015;28, 1:23-27.

36. Sekirov I, Croxen MA, Ng C, Azana R, Chang Y, Mataseje L, Boyd D, Mangat C, Mack B, Tadros M, Brodkin E, Kibsey P, Stefanovic A, Champagne S,Mulvey MR,Hoang LMN.Epidemiologic and genotypic review of carbapenemase-producing organisms in British Columbia, Canada, between 2008 and 2014. J ClinMicrobiol 2016;54, 2:317-327.

37. Ghamgosha M, Shahrekizahedani S, Kafilzadeh F, Bameri Z, Taheri RA, Farnoosh G. Metallo-beta-lactamase VIM-1, SPM-1, and IMP-1 Genes Among Clinical Pseudomonas aeruginosa Species Isolated in Zahedan, Iran. Jundishapur J Microbiol 2015;8, 4: e17489.

38. Rodríguez-Martínez J, Poirel L, Nordmann P. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa. Antimicrob Agents and Chemother 2009; 53, 11:4783–4788.

39. Kateete DP,Nakanjako R, Namugenyi J, Erume J, Joloba ML Najjuka CF. Carbapenem resistant Pseudomonas aeruginosa and Acinetobacterbaumannii at Mulago Hospital in Kampala, Uganda (2007–2009). Springerplus 2016;5, 1:1308.

40. Lagatolla C,Tonin EA, Monti-Bragadin C, Dolzani L, Gombac F, Bearzi C, Edalucci E, Gionechetti F, Rossolini GM. Endemic carbapenem resistant Pseudomonas aeruginosa with acquired metallo-β-lactamase determinants in European hospital. Emerg Infect Dis 2004;10, 3:535-538.