Carbapenemase-producing Klebsiella pneumoniae: (When) might we still consider treating with carbapenems?

Clinical Microbiology and Infection

Volumn 17, Issue 8, 2011, Pages 1135-1141

  Daikos, G L ^a   Markogiannakis, A ^b  

^a UNIVERSITY OF ATHENS   (Greece)

^b LAIKO GENERAL HOSPITAL   (Greece)

Author keywords

Carbapenemases; Carbapenems; Klebsiella pneumoniae; KPC and VIM lactamases; Therapeutic efficacy

Indexed keywords

AZTREONAM; CARBAPENEM; CARBAPENEMASE; COLISTIN; DORIPENEM; ERTAPENEM; GENTAMICIN; IMIPENEM; MEROPENEM; TIGECYCLINE;

ANTIBIOTIC SENSITIVITY; ANTIBIOTIC THERAPY; BACTERICIDAL ACTIVITY; BACTERIOSTASIS; BACTERIUM ISOLATE; CARBAPENEMASE PRODUCING KLEBSIELLA PNEUMONIAE; CARBAPENEMASE PRODUCING KLEBSIELLA PNEUMONIAE INFECTION; DRUG EFFICACY; DRUG EXPOSURE; DRUG MEGADOSE; HUMAN; IN VITRO STUDY; KLEBSIELLA PNEUMONIAE; KLEBSIELLA PNEUMONIAE INFECTION; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME;

ANIMALIA; KLEBSIELLA PNEUMONIAE;

EID: 79960697003     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1111/j.1469-0691.2011.03553.x     Document Type: Review

References (59)

1. Coque TM, Baquero F, Canton R. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro Surveil 2008; 13: pii: 19044. Available at: (last accessed 12 May 2011).
2. Bush K. Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol 2010; 13: 558-564.
3. Quenan EM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20: 440-458.
4. Vatopoulos A. High rates of metallo-betalactamase-producing Klebsiella pneumoniae in Greece-a review of the current evidence. Euro Surveil 2008; 13: pii: 8023. Available at: (last accessed 12 May 2011).
5. Schwaber MJ, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: a potential threat. JAMA 2008; 300: 2911-2913.
6. Nordmann P, Cuzon G, Nas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9: 228-236.
7. Gundmann H, Livermore DM, Giske GG et al. Carbapenem non-susceptible Enterobacteriaceae in Europe: conclusions from a meeting of national experts. Euro Surveil 2010; 15: pii: 19711. Available at: (last accessed 12 May 2011).
8. Cuzon G, Naas T, Truong H et al. Worldwide diversity of Klebsiella pneumoniae that produces β-lactamase blaKPC-2 gene. Emerg Infect Dis 2010; 16: 1349-1356.
9. Qi Y, Wei Z, Li S et al. ST1, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J Antimicrob Chemother 2010; 66: 307-312.
10. Bratu S, Landman D, Haag R et al. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York city: a new threat to our antibiotic armamentarium. Arch Intern Med 2005; 165: 1430-1435.
11. Yan J-J, Ko W-C, Tsai S-H. Outbreak of infection with multidrug-resistant Klebsiella pneumoniae carrying blaIMP-8 in a university medical center in Taiwan. J Clin Microbiol 2001; 39: 4433-4439.
12. Kurnarasamy KK, Toleman MA, Walsh TR et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: a molecular, biological and epidemiological study. Lancet Infect Dis 2010; 10: 597-602.
13. Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem Klebsiella pneumoniae. Antimicrob Agents Chemother 2004; 48: 15-22.
14. Mathers AJ, Cox HL, Bonatti H et al. Fatal cross infection by carbapenem-resistant Klebsiella in two liver transplant recipients. Transpl Infect Dis 2009; 11: 257-265.
15. Mouloudi E, Protonariou E, Zagorianou A et al. Bloodstream infections caused by metallo-β-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patient in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect Control Hosp Epidemiol 2010; 31: 1250-1256.
16. Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J Antimicrob Chemother 2010; 65: 1119-1126.
17. Daly MW, Riddle DJ, Ledeboer NA et al. Tigecycline for treatment of pneumonia and empyema caused by carbapenemase-producing Klebsiella pneumoniae. Pharmacotherapy 2007; 27: 1052-1057.
18. Souli M, Kontopidou FV, Papadomichelakis E et al. Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-β-lactamase in a Greek university hospital. Clin Infect Dis 2008; 46: 847-854.
19. Antoniadou A, Kontopidou F, Poulakou F et al. Colistin-resistant Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multinational cluster. J Antimicrob Chemother 2007; 59: 786-790.
20. Elemam A, Rahimian J, Mandell W. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clin Infect Dis 2009; 49: 271-274.
21. Kontopoulou K, Protonariou E, Vasilakos K et al. Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 β-lactamase resistant to colistin. J Hosp Infect 2010; 76: 70-73.
22. Lomaestro BM, Tobin EH, Shang W, Gootz T. The spread of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae to upstate New York. Clin Infect Dis 2006; 43: e26-e28.
23. Weisenberg SA, Morgan DJ, Espinal-Witter R, Larone DH. Clinical outcomes of patients with KPC-producing Klebsiella pneumoniae following treatment with imipenem or meropenem. Diagn Microbiol Infect Dis 2009; 64: 233-235.
24. Daikos GL, Karabinis A, Paramithiotou E et al. VIM-1 producing Klebsiella pneumoniae bloodstream infections: analysis of 28 cases. Int J Antimicrob Agents 2007; 29: 471-483.
25. Daikos GL, Petrikkos P, Psichogiou M et al. Prospective observational study of the impact of VIM-1 metallo-β-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2009; 53: 1868-1873.
26. Psichogiou M, Tassios PT, Avlamis A et al. Ongoing epidemic of blaVIM-1 positive Klebsiella pneumoniae in Athens, Greece: a prospective survey. J Antimicrob Chemother 2008; 61: 59-63.
27. Endimiani A, Hujer AM, Perez F. Characterization of bla-KPC containing Klebsiella pneumoniae isolates detected in different institutions in eastern United States. J Antimicrob Chemother 2009; 63: 427-437.
28. EUCAST. EUCAST Clinical Breakpoint Table v. 1.1 1010-4-27, Enterobacteriaceae, 2010.Available at: (last accessed 10 October 2010).
29. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing M02-A10 and M07-A8. M100-S21-U. Volume 31 No. 1. January 2010. Wayne, PA: CLSI, 2010.
30. Clinical and Laboratory Standards Institute. M100-S20-U. Performance standards for antimicrobial susceptibility testing: 20th informational supplement (June 2010 Update). Wayne, PA: CLSI, 2010.
31. Endimiani A, Perez F, Bajaksouzian S et al. Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility. J Clin Microbiol 2010; 48: 4417-4425.
32. Bodey GP, Middleman E, Umsawadi T, Rodriguez V. Infections in cancer patients. Results with gentamicin sulfate therapy. Cancer 1972; 29: 1697-1701.
33. Daikos GL, Panagiotakopoulou A, Tzelepi E et al. Activity of imipenem against VIM-1 metallo-β-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model. Clin Microbiol Infect 2007; 13: 196-215.
34. Souli M, Konstantinidou E, Tzelepi E et al. Efficacy of carbapenems against a metallo-β-lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model. J Antimicrob Chemother 2010; 66: 611-617.
35. Bulik CC, Nicolau DP. In vivo efficacy of simulated human dosing regiments of prolonged-infusion doripenem against carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2010; 54: 4112-4115.
36. Kuti JL, Dandekar P, Nightgale CH, Nicolau DP. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol 2003; 43: 1116-1123.
37. Bulik CC, Christensen H, Li P et al. Comparison of activity of a human simulated, high-dose, prolonged infusion of meropenem against Klebsiella pneumoniae producing the KPC carbapenemase versus that against Pseudomonas aeruginosa in a in vitro pharmacodynamic model. Antimicrob Agents Chemother 2010; 54: 804-810.
38. Bulik CC, Nicolau DP. Double carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother, in press. doi:.
39. Lee N-Y, Lee H-C, Liu K-H. Clinical experiences of bacteremia caused by metallo-β-lactamase-producing gram-negative organisms. J Microbiol Immunol Infect 2004; 37: 343-349.
40. Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S et al. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008; 52: 1028-1033.
41. Endimiani A, Carias LL, Hujer AM et al. Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae isolates possessing blaKPC in the United States. Antimicrob Agents Chemother 2008; 52: 2680-2682.
42. Villegas MV, Lolans K, Corre A et al. First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob Agents Chemother 2006; 50: 2880-2882.
43. Wei Z-Q, Du X-X, Yu Y-S et al. Plasmid-mediated KPC-2 in a Klebsiella pneumoniae isolate form China. Antimicrob Agents Chemother 2007; 51: 763-765.
44. Dandekar PK, Maglio D, Sutherland CA et al. Pharmacokinetics of meropenem 0.5g and 2g every 8h administered as 3h infusion. Pharmacotherapy 2003; 23: 988-991.
45. Li C, Kuti JL, Nightgale CH, Nicolau DP. Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients. J Clin Pharmacol 2006; 46: 1171-1178.
46. Jaruratanasirikul S, Sriwiriyajan S. Comparison of the pharmacodynamics of meropenem in healthy volunteers following administration by intermittent infusion or bolus injection. J Antimicrob Chemother 2003; 52: 518-521.
47. Jaruratanasirikul S, Sriwiriyajan S, Punyo J. Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection. Antimicrob Agents Chemother 2006; 49: 1337-1339.
48. Perrott J, Mabasa VH, Ensom MH. Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic principles: a qualitative systematic review. Ann Pharmacother 2010; 44: 557-564.
49. Ariano RE, Nyhlen A, Donelly JP et al. Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia. Ann Pharmacother 2005; 39: 32-38.
50. Rodloff AC, Goldstein EJC, Torres A. Two decades of imipenem therapy. J Antimicrob Chemother 2006; 58: 916-929.
51. Keel RA, Sutherland CA, Crandon JL, Nicolau DP. Stability of doripenem, imipenem and meropenem at elevated room temperatures. Int J Antimicrob Ag 2011; 37: 174-185.
52. Mendes RE, Bell JM, Yang Q et al. Carbapenem-resistant isolates of Klebsiella pneumoniae in China and detection of a conjugative plasmid (blaKPC-2 plus qnrB4) and blaIMP-4 gene. Antimicrob Agents Chemother 2008; 52: 798-799.
53. Marschall J, Tibbets RJ, Dunne WM et al. Presence of KPC carbapenemase gene in Enterobacteriaceae causing bacteremia and its correlation with in vitro carbapenem susceptibility. J Clin Microbiol 2009; 47: 239-241.
54. Benenson S, Navon-Venezia S, Carmeli Y. Carbapenem-resistant Klebsiella pneumoniae endocarditis in a young adult: successful treatment with gentamicin and colistin. Int J Infect Dis 2009; 13: e295-e298.
55. Bradford PA, Bratu S, Urban C et al. Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor resistant TEM-30 β-lactamases in New York City. Clin Infect Dis 2004; 39: 55-60.
56. Maltezou HC, Giakkoupi P, Maragos A et al. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital of Crete (Greece). J Infect 2009; 58: 213-219.
57. Endimiani A, DePasquale JM, Forero S et al. Emergence of blaKPC-containing Klebsiella pneumoniae in a long-term acute care hospital: a new challenge to our healthcare system. J Antimicrob Chemother 2009; 64: 1102-1110.
58. Nadkarni AS, Schliep T, Khan L et al. Cluster of bloodstream infections caused by KPC-2 carbapenemase-producing Klebsiella pneumoniae in Manhattan. Am J Infect Control 2009; 37: 121-126.
59. Souli M, Galani I, Antoniadou A et al. An outbreak of infection due to β-lactamase Klebsiella pneumoniae carbapenemase-2-producing K. pneumoniae in a Greek university hospital: molecular characterization, epidemiology and outcomes. Clin Infect Dis 2010; 50: 364-373.