The role of the blaKPC gene in antimicrobial resistance of Klebsiella pneumoniae
,
Abstract
Background and Objectives: Klebsiella pneumoniae isolates that produce K. pneumoniae carbapenemase (KPC) have become a grave concern for the treatment of infections. KPC-producing strains are not only able to hydrolyze carbapenems but are also resistant to a variety of β-lactam and non-β-lactam antibiotics. The present study evaluated the prevalence of blaKPC in K. pneumoniae infections and determined the antimicrobial susceptibility of the isolates.
Materials and Methods: The K. pneumoniae isolates were identified by biochemical tests and confirmed by genotyping. The modified Hodge test (MHT) was performed to detect carbapenemases, and antimicrobial susceptibility was determined for all isolates by the disc diffusion method. Also, for MHT-positive isolates, supposed to carbapenemases isolates, broth microdilution method was used to measure the minimum inhibitory concentrations (MICs) of meropenem and colistin.
Results: The blaKPC genotypic evaluation revealed that only 5 of 96 isolates carried blaKPC genes. Antimicrobial pattern showed that isolates carrying blaKPC were resistant to cefepime, ticarcillin/tazobactam, and aztreonam discs. Also, results of broth microdilution method showed that KPC-producing K. pneumoniae was resistant to meropenem and colistin, according to the CLSI and EUCAST.
Conclusion: In this study nearly half the isolates showed carbapenemase activity as shown by MHT results, but only few of them were carrying blaKPC. Thus blaKPC gene is not the main cause of resistance spread to carbapenems in Isfahan, Iran.
1. Diaz A, Ortiz DC, Trujillo M, Garces C, Jaimes FRestrepo AV. Clinical characteristics of carbapenem-resistant Klebsiella pneumoniae infections in Ill and colonized children in Colombia. Pediatr Infect Dis J 2016; 35: 237-241.
2. Ferreira RL, da Silva BCM, Rezende GS, Nakamura-Silva R, Pitondo-Silva A, Campanini EB, et al. High prevalence of multidrug-resistant Klebsiella pneumoniae harboring several virulence and beta-lactamase encoding genes in a Brazilian intensive care unit. Front Microbiol 2019; 9: 3198.
3. Pereira PS, de Araujo CF, Seki LM, Zahner V, Carvalho-Assef AP, Asensi MD. Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob Chemother 2013; 68: 312-316.
4. Wasfi R, Elkhatib WFAshour HM. Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep 2016; 6: 38929.
5. Bellich B, Ravenscroft N, Rizzo R, Lagatolla C, D'Andrea MM, Rossolini GM, et al. Structure of the capsular polysaccharide of the KPC-2-producing Klebsiella pneumoniae strain KK207-2 and assignment of the glycosyltransferases functions. Int J Biol Macromol 2019; 130: 536-544.
6. Essayagh T, Karimou AElhamzaoui S. Carbapenemases among Klebsiella pneumoniae: sensitivity, E-test and Hodge test. Ann Biol Clin (Paris) 2012; 70: 299-304.
7. Nordmann P, Cuzon GNaas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9: 228-236.
8. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8: 321-331.
9. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20: 440-458.
10. Cuzon G, Naas T, Nordmann P.. Functional characterization of Tn4401, a Tn3-based transposon involved in blaKPC gene mobilization. Antimicrob Agents Chemother 2011; 55: 5370-5373.
11. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45: 1151-1161.
12. Scavuzzi AML, Maciel MAV, de Melo HRL, Alves LC, Brayner FA, Lopes ACS. Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2. J Med Microbiol 2017; 66: 477-484.
13. Rojas LJ, Weinstock GM, De La Cadena E, Diaz L, Rios R, Hanson BM, et al. An Analysis of the epidemic of KPC-producing Klebsiella pneumoniae: Convergence of two evolutionary mechanisms creates the "Perfect Storm". J Infect Dis 2017;217:82-92.
14. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 2014; 22: 686-696.
15. Wolter DJ, Kurpiel PM, Woodford N, Palepou MF, Goering RV, Hanson ND. Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4. Antimicrob Agents Chemother 2009; 53: 557-562.
16. Cai JC, Zhou HW, Zhang R, Chen GX. Emergence of serratia marcescens, Klebsiella pneumoniae, and Escherichia coli isolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital. Antimicrob Agents Chemother 2008; 52: 2014-2018.
17. Doi Y, Paterson DL. Carbapenemase-producing Enterobacteriaceae. Semin Respir Crit Care Med 2015; 36: 74-84.
18. Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: Report from the China CRE Network. Antimicrob Agents Chemother 2018; 62(2): e01882-17.
19. Cornaglia G, Rossolini GM. The emerging threat of acquired carbapenemases in Gram-negative bacteria. Clin Microbiol Infect 2010; 16: 99-101.
20. Ghasemnejad A, Doudi MA, Mirmozafari N. Evaluation of modified hodge test as a non-molecular assay for accurate detection of KPC-producing Klebsiella pneumoniae. Pol J Microbiol 2018; 67: 291-295.
21. Liu Y, Liu C, Zheng W, Zhang X, Yu J, Gao Q, et al. PCR detection of Klebsiella pneumoniae in infant formula based on 16S-23S internal transcribed spacer. Int J Food Microbiol 2008; 125: 230-235.
22. CLSI CaLSI, Performance standards for antimicrobial susceptibility testing; Twenty-sixth informational supplement, M100-S25 2016, Wayne, PA.
23. EUCAST Ecoast, Breakpoint tables for interpretation for MICs and zone diameters. 2016, Basel, Switzerland.
24. CLSI CaLSI, Methods for dilution Antimicrobial susceptibility test for bacteria that grow aerobically, M07-A9. 2012, Wayne, PA.
25. Papadimitriou-Olivgeris M, Fligou F, Bartzavali C, Zotou A, Spyropoulou A, Koutsileou K, et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients: risk factors and predictors of mortality. Eur J Clin Microbiol Infect Dis 2017; 36: 1125-1131.
26. Castanheira M, Farrell SE, Krause KM, Jones RN, Sader HS. Contemporary diversity of beta-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent beta-lactamase groups. Antimicrob Agents Chemother 2014; 58: 833-838.
27. Ageevets VA, Partina IV, Lisitsyna ES, Ilina EN, Lobzin YV, Shlyapnikov SA, et al. Emergence of carbapenemase-producing Gram-negative bacteria in Saint Petersburg, Russia. Int J Antimicrob Agents 2014; 44: 152-155.
28. Campos AC, Albiero J, Ecker AB, Kuroda CM, Meirelles LE, Polato A, et al. Outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: A systematic review. Am J Infect Control 2016; 44: 1374-1380.
29. Battikh H, Harchay C, Dekhili A, Khazar K, Kechrid F, Zribi M, et al. Clonal Spread of colistin-resistant Klebsiella pneumoniae coproducing KPC and VIM Carbapenemases in Neonates at a Tunisian University Hospital. Microb Drug Resist 2017; 23: 468-472.
30. Woodford N, Zhang J, Warner M, Kaufmann ME, Matos J, Macdonald A, et al. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J Antimicrob Chemother 2008; 62: 1261-1264.
31. Jelic M, Butic I, Plecko V, Cipris I, Jajic I, Bejuk D, et al. KPC-producing Klebsiella pneumoniae isolates in Croatia: A nationwide survey. Microb Drug Resist 2016; 22: 662-667.
32. Perilli M, Bottoni C, Grimaldi A, Segatore B, Celenza G, Mariani M, et al. Carbapenem-resistant Klebsiella pneumoniae harbouring blaKPC-3 and blaVIM-2 from central Italy. Diagn Microbiol Infect Dis 2013; 75: 218-221.
2. Ferreira RL, da Silva BCM, Rezende GS, Nakamura-Silva R, Pitondo-Silva A, Campanini EB, et al. High prevalence of multidrug-resistant Klebsiella pneumoniae harboring several virulence and beta-lactamase encoding genes in a Brazilian intensive care unit. Front Microbiol 2019; 9: 3198.
3. Pereira PS, de Araujo CF, Seki LM, Zahner V, Carvalho-Assef AP, Asensi MD. Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob Chemother 2013; 68: 312-316.
4. Wasfi R, Elkhatib WFAshour HM. Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep 2016; 6: 38929.
5. Bellich B, Ravenscroft N, Rizzo R, Lagatolla C, D'Andrea MM, Rossolini GM, et al. Structure of the capsular polysaccharide of the KPC-2-producing Klebsiella pneumoniae strain KK207-2 and assignment of the glycosyltransferases functions. Int J Biol Macromol 2019; 130: 536-544.
6. Essayagh T, Karimou AElhamzaoui S. Carbapenemases among Klebsiella pneumoniae: sensitivity, E-test and Hodge test. Ann Biol Clin (Paris) 2012; 70: 299-304.
7. Nordmann P, Cuzon GNaas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9: 228-236.
8. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8: 321-331.
9. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20: 440-458.
10. Cuzon G, Naas T, Nordmann P.. Functional characterization of Tn4401, a Tn3-based transposon involved in blaKPC gene mobilization. Antimicrob Agents Chemother 2011; 55: 5370-5373.
11. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45: 1151-1161.
12. Scavuzzi AML, Maciel MAV, de Melo HRL, Alves LC, Brayner FA, Lopes ACS. Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2. J Med Microbiol 2017; 66: 477-484.
13. Rojas LJ, Weinstock GM, De La Cadena E, Diaz L, Rios R, Hanson BM, et al. An Analysis of the epidemic of KPC-producing Klebsiella pneumoniae: Convergence of two evolutionary mechanisms creates the "Perfect Storm". J Infect Dis 2017;217:82-92.
14. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 2014; 22: 686-696.
15. Wolter DJ, Kurpiel PM, Woodford N, Palepou MF, Goering RV, Hanson ND. Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4. Antimicrob Agents Chemother 2009; 53: 557-562.
16. Cai JC, Zhou HW, Zhang R, Chen GX. Emergence of serratia marcescens, Klebsiella pneumoniae, and Escherichia coli isolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital. Antimicrob Agents Chemother 2008; 52: 2014-2018.
17. Doi Y, Paterson DL. Carbapenemase-producing Enterobacteriaceae. Semin Respir Crit Care Med 2015; 36: 74-84.
18. Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: Report from the China CRE Network. Antimicrob Agents Chemother 2018; 62(2): e01882-17.
19. Cornaglia G, Rossolini GM. The emerging threat of acquired carbapenemases in Gram-negative bacteria. Clin Microbiol Infect 2010; 16: 99-101.
20. Ghasemnejad A, Doudi MA, Mirmozafari N. Evaluation of modified hodge test as a non-molecular assay for accurate detection of KPC-producing Klebsiella pneumoniae. Pol J Microbiol 2018; 67: 291-295.
21. Liu Y, Liu C, Zheng W, Zhang X, Yu J, Gao Q, et al. PCR detection of Klebsiella pneumoniae in infant formula based on 16S-23S internal transcribed spacer. Int J Food Microbiol 2008; 125: 230-235.
22. CLSI CaLSI, Performance standards for antimicrobial susceptibility testing; Twenty-sixth informational supplement, M100-S25 2016, Wayne, PA.
23. EUCAST Ecoast, Breakpoint tables for interpretation for MICs and zone diameters. 2016, Basel, Switzerland.
24. CLSI CaLSI, Methods for dilution Antimicrobial susceptibility test for bacteria that grow aerobically, M07-A9. 2012, Wayne, PA.
25. Papadimitriou-Olivgeris M, Fligou F, Bartzavali C, Zotou A, Spyropoulou A, Koutsileou K, et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients: risk factors and predictors of mortality. Eur J Clin Microbiol Infect Dis 2017; 36: 1125-1131.
26. Castanheira M, Farrell SE, Krause KM, Jones RN, Sader HS. Contemporary diversity of beta-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent beta-lactamase groups. Antimicrob Agents Chemother 2014; 58: 833-838.
27. Ageevets VA, Partina IV, Lisitsyna ES, Ilina EN, Lobzin YV, Shlyapnikov SA, et al. Emergence of carbapenemase-producing Gram-negative bacteria in Saint Petersburg, Russia. Int J Antimicrob Agents 2014; 44: 152-155.
28. Campos AC, Albiero J, Ecker AB, Kuroda CM, Meirelles LE, Polato A, et al. Outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: A systematic review. Am J Infect Control 2016; 44: 1374-1380.
29. Battikh H, Harchay C, Dekhili A, Khazar K, Kechrid F, Zribi M, et al. Clonal Spread of colistin-resistant Klebsiella pneumoniae coproducing KPC and VIM Carbapenemases in Neonates at a Tunisian University Hospital. Microb Drug Resist 2017; 23: 468-472.
30. Woodford N, Zhang J, Warner M, Kaufmann ME, Matos J, Macdonald A, et al. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J Antimicrob Chemother 2008; 62: 1261-1264.
31. Jelic M, Butic I, Plecko V, Cipris I, Jajic I, Bejuk D, et al. KPC-producing Klebsiella pneumoniae isolates in Croatia: A nationwide survey. Microb Drug Resist 2016; 22: 662-667.
32. Perilli M, Bottoni C, Grimaldi A, Segatore B, Celenza G, Mariani M, et al. Carbapenem-resistant Klebsiella pneumoniae harbouring blaKPC-3 and blaVIM-2 from central Italy. Diagn Microbiol Infect Dis 2013; 75: 218-221.
| Files | ||
| Issue | Vol 11 No 4 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v11i4.1465 | |
| Keywords | ||
| bla Klebsiella pneumoniae Infectious disease Carbapenemase Colistin | ||
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How to Cite
1.
Ghasemnejad A, Doudi M, Amirmozafari N. The role of the blaKPC gene in antimicrobial resistance of Klebsiella pneumoniae. Iran J Microbiol. 2019;11(4):288-293.
