Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Greece

Future Microbiology

Volumn 11, Issue 6, 2016, Pages 809-823

  Karampatakis, Theodoros ^a   Antachopoulos, Charalampos ^a   Iosifidis, Elias ^a   Tsakris, Athanassios ^b   Roilides, Emmanuel ^a  

^a ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^b UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Gram negative bacteria; Klebsiella pneumoniae; multidrug resistance; nosocomial infections

Indexed keywords

ANTIBIOTIC AGENT; BACTERIAL PROTEIN; BETA LACTAMASE; CARBAPENEM DERIVATIVE; CARBAPENEMASE; PENICILLIN BINDING PROTEIN; PORIN; PROTEIN OMPK35; PROTEIN OMPK36; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT;

ACINETOBACTER BAUMANNII; BACTERIAL STRAIN; BACTERIUM ISOLATE; CARBAPENEM RESISTANT ENTEROBACTERIACEAE; CARBAPENEM RESISTANT KLEBSIELLA PNEUMONIAE; GRAM NEGATIVE BACTERIUM; GREECE; HOSPITAL INFECTION; INFECTION CONTROL; KLEBSIELLA PNEUMONIAE; MOLECULAR EPIDEMIOLOGY; NONHUMAN; PHYLOGENETIC TREE; PREVALENCE; PRIORITY JOURNAL; PROTEIN MODIFICATION; PSEUDOMONAS AERUGINOSA; REVIEW; VERTICAL TRANSMISSION; CLASSIFICATION; DRUG EFFECTS; GENETICS; HUMAN; ISOLATION AND PURIFICATION; KLEBSIELLA INFECTIONS; MICROBIOLOGY;

ANTI-BACTERIAL AGENTS; CARBAPENEMS; GREECE; HUMANS; KLEBSIELLA INFECTIONS; KLEBSIELLA PNEUMONIAE; MOLECULAR EPIDEMIOLOGY;

EID: 84971509010     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb-2016-0042     Document Type: Review

References (94)

1. Tanwar J, Das S, Fatima Z, Hameed S. Multidrug resistance: an emerging crisis. Interdiscip. Perspect. Infect. Dis. 2014, 541340 (2014).
2. WHO. Prevention of Hospital-Acquired Infections. A Practical Guide (2nd Edition). Ducel G, Fabry J, Nicolle L (Eds). WHO, Malta, 4-5 (2002).
3. Magiorakos AP, Srinivasan A, Carey RB et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard defnitions for acquired resistance. Clin. Microbiol. Infect. 18(3), 268-281 (2012).
4. Mischnik A, Kaase M, Lubbert C, Seifert H, Kern WV. Carbapenem-resistance in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. Dtsch Med. Wochenschr. 140(3), 172-176 (2015).
5. HCDCP. Action plan for the management of infections by multidrug-resistant Gram negative pathogens in health care facilities. Procrustes 2-3 (2010).
6. Hall BG, Barlow M. Revised Ambler classifcation of (beta)-lactamases. J. Antimicrob. Chemother. 55(6), 1050-1051 (2005).
7. Zeng ZR, Wang WP, Huang M, Shi LN, Wang Y, Shao HF. Mechanisms of carbapenem resistance in cephalosporin-susceptible Pseudomonas aeruginosa in China. Diagn. Microbiol. Infect. Dis. 78(3), 268-270 (2014).
8. Li XZ, Plesiat P, Nikaido H. The challenge of effux-mediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28(2), 337-418 (2015).
9. Moya B, Beceiro A, Cabot G et al. Pan-beta-lactam resistance development in Pseudomonas aeruginosa clinical strains: molecular mechanisms, penicillin-binding protein profles, and binding affnities. Antimicrob. Agents Chemother. 56(9), 4771-4778 (2012).
10. Bush K, Jacoby GA, Medeiros AA. A functional classifcation scheme for beta-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39(6), 1211-1233 (1995).
11. Akinci E, Vahaboglu H. Minor extended-spectrum beta-lactamases. Expert Rev. Anti. Infect. Ther. 8(11), 1251-1258 (2010).
12. El Salabi A, Borra PS, Toleman MA, Samuelsen O, Walsh TR. Genetic and biochemical characterization of a novel metallo-beta-lactamase, TMB-1, from an Achromobacter xylosoxidans strain isolated in Tripoli, Libya. Antimicrob. Agents Chemother. 56(5), 2241-2245 (2012).
13. Marsik FJ, Nambiar S. Review of carbapenemases and AmpC-beta lactamases. Pediatr. Infect. Dis. J. 30(12), 1094-1095 (2011).
14. Antunes NT, Lamoureaux TL, Toth M, Stewart NK, Frase H, Vakulenko SB. Class D beta-lactamases: are they all carbapenemases? Antimicrob. Agents Chemother. 58 (4), 2119-2125 (2014).
15. VIM-1 amplifcation causing high-level carbapenem resistance. J. Antimicrob. Chemother. 70(11), 3000-3003 (2015).
16. Giakkoupi P, Xanthaki A, Kanelopoulou M et al. VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae strains in Greek hospitals. J. Clin. Microbiol. 41(8), 3893-3896 (2003).
17. IMP) in gram-negative rods resistant to broad-spectrum beta-lactams. J. Clin. Microbiol. 34(12), 2909-2913 (1996).
18. Osano E, Arakawa Y, Wacharotayankun R et al. Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob. Agents Chemother. 38(1), 71-78 (1994).
19. Koh TH, Sng LH, Babini GS, Woodford N, Livermore DM, Hall LM. Carbapenem-resistant Klebsiella pnuemoniae in Singapore producing IMP-1 beta-lactamase and lacking an outer membrane protein. Antimicrob. Agents Chemother. 45 (6), 1939-1940 (2001).
20. (IMP- 8) in a University Medical Center in Taiwan. J. Clin. Microbiol. 39(12), 4433-4439 (2001).
21. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg. Infect. Dis. 17(10), 1791-1798 (2011).
22. Limbago BM, Rasheed JK, Anderson KF et al. IMP-producing carbapenem-resistant Klebsiella pneumoniae in the United States. J. Clin. Microbiol. 49(12), 4239-4245 (2011).
23. Li B, Xu XH, Zhao ZC, Wang MH, Cao YP High prevalence of metallo-beta-l actamase among carbapenem-resistant Klebsiella pneumoniae in a teaching hospital in China. Can. J. Microbiol. 60(10), 691-695 (2014).
24. Jian Z, Li Y, Liu W et al. Detection of the novel IMP-38 among carbapenemase-producing Enterobacteriaceae in a University Hospital, China. J. Infect. Dev. Ctries 8(8), 1044-1048 (2014).
25. Poirel L, Naas T, Nicolas D et al. 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. 44(4), 891-897 (2000).
26. Lauretti L, Riccio ML, Mazzariol A et al. Cloning and characterization of bla, a new VIM integron-borne metallo-beta-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob. Agents Chemother. 43(7), 1584-1590 (1999).
27. Miriagou V, Tzelepi E, Gianneli D, Tzouvelekis LS. Escherichia coli with a self-transferable, multiresistant plasmid coding for metallo-beta-lactamase VIM-1. Antimicrob. Agents Chemother. 47(1), 395-397 (2003).
28. Ikonomidis A, Tokatlidou D, Kristo I et al. Outbreaks in distinct regions due to a single Klebsiella pneumoniae clone carrying a bla VIM-1 metallo-(beta)-lactamase gene. J. Clin. Microbiol. 43(10), 5344-5347 (2005).
29. Zagorianou A, Sianou E, Iosifdis E et al. Microbiological and molecular characteristics of carbapenemase-producing Klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010. Euro. Surveill. 17(7), pii: 20088 (2012).
30. Pournaras S, Ikonomidis A, Tzouvelekis LS et al. VIM-12, a novel plasmid-mediated metallo-beta-lactamase from Klebsiella pneumoniae that resembles a VIM-1/VIM-2 hybrid. Antimicrob. Agents Chemother. 49(12), 5153-5156 (2005).
31. Sneath PHA, Sokal RR. Numerical Taxonomy. Freeman, CA, USA (1973).
32. Nei M, Kumar S. Molecular Evolution and Phylogenetics. Oxford University Press, N Y, USA (2000).
33. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol. Biol. Evol. 30, 2725-2729 (2013).
34. SHV-5 in a French University Hospital. J. Antimicrob. Chemother. 57(1), 142-145 (2006).
35. VIM-1-positive Klebsiella pneumoniae in Athens, Greece: a prospective survey. J. Antimicrob. Chemother. 61(1), 59-63 (2008).
36. VIM in Greece at the peak of the epidemic of 2005-2006: clonal expansion of Klebsiella pneumoniae clonal complex 147. Clin. Microbiol. Infect. 20(1), 34-37 (2013).
37. Papagiannitsis CC, Giakkoupi P, Kotsakis SD et al. OmpK35 and OmpK36 porin variants associated with specifc sequence types of Klebsiella pneumoniae. J. Chemother. 25(4), 250-254 (2013).
38. VIM-12 in a University Hospital. J. Clin. Microbiol. 46(3), 1005-1008 (2008).
39. Samuelsen O, Toleman MA, Hasseltvedt V et al. Molecular characterization of VIM-producing Klebsiella pneumoniae from Scandinavia reveals genetic relatedness with international clonal complexes encoding transferable multidrug resistance. Clin. Microbiol. Infect. 17(12), 1811-1816 (2011).
40. Pournaras S, Poulou A, Voulgari E, Vrioni G, Kristo I, Tsakris A. Detection of the new metallo-beta-lactamase VIM-19 along with KPC-2, CMY-2 and CTX-M-15 in Klebsiella pneumoniae. J. Antimicrob. Chemother. 65(8), 1604-1607 (2010).
41. Papagiannitsis CC, Giakkoupi P, Vatopoulos AC, Tryfnopoulou K, Miriagou V, Tzouvelekis LS. Emergence of Klebsiella pneumoniae of a novel sequence type (ST383) producing VIM-4, KPC-2 and CMY-4 beta-lactamases. Int. J. Antimicrob. Agents 36(6), 573-574 (2010).
42. Papagiannitsis CC, Miriagou V, Giakkoupi P, Tzouvelekis LS, Vatopoulos AC. Characterization of pKP1780, a novel IncR plasmid from the emerging Klebsiella pneumoniae ST147, encoding the VIM-1 metallo-beta-lactamase. J. Antimicrob. Chemother. 68(10), 2259-2262 (2013).
43. Papagiannitsis CC, Kotsakis SD, Petinaki E et al. Characterization of metallo-beta-lactamase VIM-27, an A57S mutant of VIM-1 associated with Klebsiella pneumoniae ST147 Antimicrob. Agents Chemother. 55(7), 3570-3572 (2011).
44. Papagiannitsis CC, Izdebski R, Baraniak A et al. Survey of metallo-beta-lactamase-producing Enterobacteriaceae colonizing patients in European ICUs and rehabilitation units, 2008-11. J. Antimicrob. Chemother. 70(7), 1981-1988 (2015).
45. (ND, and a novel (M-1) erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 53(12), 5046-5054 (2009).
46. Moellering RC Jr. NDM-1-a cause for worldwide concern. N. Engl. J. Med. 363(25), 2377-2379 (2010).
47. Voulgari E, Gartzonika C, Vrioni G et al. The Balkan region: N DM-1-producing Klebsiella pneumoniae ST11 clonal strain causing outbreaks in Greece. J. Antimicrob. Chemother. 69(8), 2091-2097 (2014).
48. Spyropoulou A, Bartzavali C, Vamvakopoulou S et al. The frst NDM metallo-beta-lactamase producing Klebsiella pneumoniae isolate in a University Hospital of southwestern Greece. J. Chemother. doi:10. 1179/1973947815Y.0000000003 (2015) (Epub ahead of print).
49. Giakkoupi P, Tryfnopoulou K, Kontopidou F et al. Emergence of NDM-producing Klebsiella pneumoniae in Greece. Diagn. Microbiol. Infect. Dis. 77(4), 382-384 (2013).
50. Landman D, Bratu S, Kochar S et al. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY J. Antimicrob. Chemother. 60(1), 78-82 (2007).
51. Kitchel B, Rasheed JK, Patel JB et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob. Agents Chemother. 53(8), 3365-3370 (2009).
52. Maltezou HC, Giakkoupi P, Maragos A et al. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J. Infect. 58(3), 213-219 (2009).
53. Tsakris A, Kristo I, Poulou A, Markou F, Ikonomidis A, Pournaras S. First occurrence of KPC-2-possessing Klebsiella pneumoniae in a Greek hospital and recommendation for detection with boronic acid disc tests. J. Antimicrob. Chemother. 62(6), 1257-1260 (2008).
54. Navon-Venezia S, Leavitt A, Schwaber MJ et al. First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States. Antimicrob. Agents Chemother. 53(2), 818-820 (2009).
55. Pournaras S, Protonotariou E, Voulgari E et al. Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece. J. Antimicrob. Chemother. 64(2), 348-352 (2009).
56. Giakoupi P, Maltezou H, Polemis M, Pappa O, Saroglou G, Vatopoulos A. KPC-2-producing Klebsiella pneumoniae infections in Greek hospitals are mainly due to a hyperepidemic clone. Euro. Surveill. 14(21) pii:19218 (2009).
57. Kontopoulou K, Protonotariou E, Vasilakos K et al. Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin. J. Hosp. Infect 76(1), 70-73 (2010).
58. KPC 2-carrying Klebsiella pneumoniae in Greece (2009-10). J. Antimicrob. Chemother. 66(7), 1510-1513 (2011).
59. Papagiannitsis CC, Miriagou V, Giakkoupi P, Tzouvelekis LS, Vatopoulos AC. Characterization of pKP1433, a novel KPC-2-encoding plasmid from Klebsiella pneumoniae sequence type 340. Antimicrob. Agents Chemother. 57(7), 3427-3429 (2013).
60. Tzouvelekis LS, Miriagou V, Kotsakis SD et al. KPC-producing, multidrug-resistant Klebsiella pneumoniae sequence type 258 as a typical opportunistic pathogen. Antimicrob. Agents Chemother. 57(10), 5144-5146 (2013).
61. Papadimitriou-Olivgeris M, Marangos M, Fligou F et al. KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the signifcance of risk factors for its development and its impact on mortality. Diagn. Microbiol. Infect. Dis. 77(2), 169-173 (2013).
62. Daikos GL, Tsaousi S, Tzouvelekis LS et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob. Agents Chemother. 58(4), 2322-2328 (2014).
63. KPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected? Clin. Microbiol. Infect. 19(5), 451-456 (2013).
64. Borer A, Saidel-Odes L, Eskira S et al. Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae. Am J. Infect. Control 40(5), 421-425 (2012).
65. Papadimitriou-Olivgeris M, Spiliopoulou A, Fligou F et al. Association of KPC-producing Klebsiella pneumoniae colonization or infection with Candida isolation and selection of non-albicans species. Diagn. Microbiol. Infect. Dis. 80(3), 227-232 (2014).
66. Papadimitriou-Olivgeris M, Christofdou M, Fligou F et al. The role of colonization pressure in the dissemination of colistin or tigecycline resistant KPC-producing Klebsiella pneumoniae in critically ill patients. Infection 42(5), 883-890 (2014).
67. Poirel L, Jayol A, Bontron S et al. The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae. J. Antimicrob. Chemother. 70(1), 75-80 (2014).
68. Cannatelli A, Giani T, D'andrea MM et al. MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. Antimicrob. Agents Chemother. 58 (10), 5696-5703 (2014).
69. KPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: emergence of multiple non-ST258 clones. PLoS ONE 10 (7), e0132936 (2014).
70. Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48(1), 15-22 (2004).
71. Cuzon G, Naas T, Bogaerts P, Glupczynski Y, Huang TD, Nordmann P. Plasmid-encoded carbapenem-hydrolyzing beta-lactamase OXA-48 in an imipenem-susceptible Klebsiella pneumoniae strain from Belgium. Antimicrob. Agents Chemother. 52(9), 3463-3464 (2008).
72. Voulgari E, Zarkotou O, Ranellou K et al. Outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae in Greece involving an ST11 clone. J. Antimicrob. Chemother. 68(1), 84-88 (2013).
73. Villa J, Viedma E, Branas P, Mingorance J, Chaves F. Draft whole-genome sequence of OXA-48-producing multidrug-resistant Klebsiella pneumoniae K P- S T11-OX A-48. Genome Announc 2 (4), e 00737-14 (2014).
74. Tsakris A, Poulou A, Bogaerts P, Dimitroulia E, Pournaras S, Glupczynski Y. Evaluation of a new phenotypic OXA-48 disk test for differentiation of OXA-48 carbapenemase-producing Enterobacteriaceae clinical isolates. J. Clin. Microbiol. 53(4), 1245-1251 (2015).
75. Pereira PS, Borghi M, De Araujo CF et al. Clonal dissemination of OXA-370-producing Klebsiella pneumoniae in Rio de Janeiro, Brazil. Antimicrob. Agents Chemother. 59(8), 4453-4456 (2015).
76. Shi W, Li K, Ji Y et al. Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated with porin OmpK36 loss and DHA-1 beta-lactamase production. Braz. J. Microbiol. 44(2), 435-442 (2013).
77. Llobet E, March C, Gimenez P, Bengoechea JA. Klebsiella pneumoniae OmpA confers resistance to antimicrobial peptides. Antimicrob. Agents Chemother. 53(1), 298-302 (2009).
78. Hernandez-Alles S, Conejo M, Pascual A, Tomas JM, Benedi VJ, Martinez-Martinez L. Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae. J. Antimicrob. Chemother. 46(2), 273-277 (2000).
79. Domenech-Sanchez A, Martinez-Martinez L, Hernandez-Alles S et al. Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob. Agents Chemother. 47(10), 3332-3335 (2003).
80. KPC carbapenemase genes in Australia. Int. J. Antimicrob. Agents 45(2), 130-136 (2015).
81. Tang HJ, Ku YH, Lee MF, Chuang YC, Yu WL. In vitro activity of imipenem and colistin against a carbapenem-resistant Klebsiella pneumoniae isolate coproducing SHV-31, CMY-2, and DHA-1. Biomed. Res. Int. 2015, 568079 (2015).
82. VIM-1. J. Antimicrob. Chemother. 58(3), 669-672 (2006).
83. Poulou A, Voulgari E, Vrioni G et al. Outbreak caused by an ertapenem-resistant, CTX-M-15-producing Klebsiella pneumoniae sequence type 101 clone carrying an OmpK36 porin variant. J. Clin. Microbiol. 51(10), 3176-3182 (2013).
84. Domenech-Sanchez A, Hernandez-Alles S, Martinez-Martinez L, Benedi VJ, Alberti S. Identifcation and characterization of a new porin gene of Klebsiella pneumoniae: its role in beta-lactam antibiotic resistance. J. Bacteriol. 181(9), 2726-2732 (1999).
85. Kaczmarek FM, Dib-Hajj F, Shang W, Gootz TD. High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is due to the combination of bla(ACT-1) beta-lactamase production, porin OmpK35/36 insertional inactivation, and down-regulation of the phosphate transport porin phoe. Antimicrob. Agents Chemother. 50 (10), 3396-3406 (2006).
86. Ogawa W, Li DW, Yu P et al. Multidrug resistance in Klebsiella pneumoniae MGH78578 and cloning of genes responsible for the resistance. Biol. Pharm. Bull. 28(8), 1505-1508 (2005).
87. Abuzaid A, Hamouda A, Amyes SG. Klebsiella pneumoniae susceptibility to biocides and its association with cepA, qacDeltaE and qacE effux pump genes and antibiotic resistance. J. Hosp. Infect. 81(2), 87-91 (2012).
88. Pages JM, Lavigne JP, Lefon-Guibout V et al. Effux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS ONE 4(3), e4817 (2009).
89. Ogawa W, Onishi M, Ni R, Tsuchiya T, Kuroda T. Functional study of the novel multidrug effux pump KexD from Klebsiella pneumoniae. Gene 498(2), 177-182 (2012).
90. Srinivasan VB, Singh BB, Priyadarshi N, Chauhan NK, Rajamohan G. Role of novel multidrug effux pump involved in drug resistance in Klebsiella pneumoniae. PLoS ONE 9(5), e96288 (2014).
91. Kayama S, Koba Y, Shigemoto N et al. Imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae producing OXA-181 in Japan. Antimicrob. Agents Chemother. 59(2), 1379-1380 (2015).
92. Jeong SH, Lee KM, Lee J et al. Clonal and horizontal spread of the blaOXA-232 gene among Enterobacteriaceae in a Korean hospital. Diagn. Microbiol. Infect. Dis. 82(1), 70-72 (2015).
93. Novais A, Rodrigues C, Branquinho R et al. Spread of an OmpK36-modifed ST15 Klebsiella pneumoniae variant during an outbreak involving multiple carbapenem-resistant Enterobacteriaceae species and clones. Eur. J. Clin. Microbiol. Infect. Dis 31(11), 3057-3063 (2012).
94. Tsai YK, Liou CH, Fung CP, Lin JC, Siu LK. Single or in combination antimicrobial resistance mechanisms of Klebsiella pneumoniae contribute to varied susceptibility to different carbapenems. PLoS ONE 8(11), e79640 (2013).