Emergence of Klebsiella pneumoniae Carbapenemase-Producing Bacteria

Authors: Ryan S. Arnold, MD, Kerri A. Thom, MD, MS, Saarika Sharma, MD, MA, Michael Phillips, MD, J. Kristie Johnson, PhD, Daniel J. Morgan, MD


Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality. Once confined to outbreaks in the northeastern United States (US), they have spread throughout the US and most of the world. KPCs are an important mechanism of resistance for an increasingly wide range of Gram-negative bacteria and are no longer limited to K pneumoniae. KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing and incorrectly reported as sensitive to carbapenems; however, resistance to the carbapenem antibiotic ertapenem is common and a better indicator of the presence of KPCs. Carbapenem antibiotics are generally not effective against KPC-producing organisms. The best therapeutic approach to KPC-producing organisms has yet to be defined; however, common treatments based on in vitro susceptibility testing are the polymyxins, tigecycline, and less frequently, aminoglycoside antibiotics. The purpose of this review is to identify the various challenges that KPC-producing bacteria present to clinicians. These include the need for special techniques for microbiological detection, the potential for nosocomial transmission, and therapeutic challenges related to limited, relatively unproven antimicrobial treatment options.

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005;18:657–686.
2. Rhomberg PR, Jones RN. Summary trends for the Meropenem Yearly Susceptibility Test Information Collection Program: a 10-year experience in the United States (1999–2008). Diagn Microbiol Infect Dis2009;65:414–426.
3. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniaeAntimicrob Agents Chemother 2001;45:1151–1161.
4. Lee J, Patel G, Huprikar S, et al. Decreased susceptibility to polymyxin B during treatment of carbapenem-resistant Klebsiella pneumoniae infection. J Clin Microbiol 2009;47:1611–1612.
5. 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 2009;53:3365–3370.
6. Centers for Disease Control and Prevention (CDC). Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR Morb Mortal Wkly Rep 2009;58:256–260.
7. 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.
8. Bratu S, Tolaney P, Karumudi U, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother 2005;56:128–132.
9. Phillips M, Sharma S. Clinical Outcomes of Infections Caused by KPC-Producing Organisms. Bethesda, NIH Workshop on ESKAPE Pathogens, 2009.
10. Naas T, Nordmann P, Vedel G, et al. Plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC in a Klebsiella pneumoniae isolate in France. Antimicrob Agents Chemother 2005;49:4423–4424.
11. Leavitt A, Navon-Venezia S, Chmelnitsky I, et al. Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital. Antimicrob Agents Chemother 2007;51:3026–3029.
12. Osterblad M, Kirveskari J, Koskela S, et al. First isolations of KPC-2-carrying ST258 Klebsiella pneumoniae strains in Finland, June and August 2009. Euro Surveill 2009;14:pii:19349.
13. Endimiani A, Hujer AM, Perez F, et al. Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA. J Antimicrob Chemother 2009;63:427–437.
14. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9:228–236.
15. Marchaim D, Navon-Venezia S, Schwaber MJ, et al. Isolation of imipenem-resistant Enterobacterspecies: emergence of KPC-2 carbapenemase, molecular characterization, epidemiology, and outcomes. Antimicrob Agents Chemother 2008;52:1413–1418.
16. Weisenberg SA, Morgan DJ, Espinal-Witter R, et al. Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem. Diagn Microbiol Infect Dis 2009;64:233–235.
17. Anderson KF, Lonsway DR, Rasheed JK, et al. Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in EnterobacteriaceaeJ Clin Microbiol 2007;45:2723–2725.
18. Samra Z, Bahar J, Madar-Shapiro L, et al. Evaluation of CHROMagar KPC for rapid detection of carbapenem-resistant EnterobacteriaceaeJ Clin Microbiol 2008;46:3110–3111.
19. 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.
20. Gasink LB, Edelstein PH, Lautenbach E, et al. Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniaeInfect Control Hosp Epidemiol 2009;30:1180–1185.
21. Patel G, Huprikar S, Factor SH, et al. Outcomes of carbapenem-resistant Klebsiella pneumoniaeinfection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29:1099–1106.
22. 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 2009;58:213–219.
23. Borer A, Saidel-Odes L, Riesenberg K, et al. Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia. Infect Control Hosp Epidemiol 2009;30:972–976.
24. 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.
25. Hidron AI, Edwards JR, Patel J, et al; National Healthcare Safety Network Team; Participating National Healthcare Safety Network Facilities. NSHN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 2008;29:996–1011.
26. Kochar S, Sheard T, Sharma R, et al. Success of an infection control program to reduce the spread of carbapenem-resistant Klebsiella pneumoniaeInfect Control Hosp Epidemiol 2009;30:447–452.
27. Endiminai A, Depasquale JM, Forero S, et al. Emergence of blaKPC-containing Klebsiella pneumoniae in a long-term acute care hospital: a new challenger to our healthcare system. J Antimicrob Chemother 2009;4:1102–1110.
28. Munoz-Price LS, Hayden MK, Lolans K, et al. Successful control of an outbreak of Klebsiella pneumoniae at a long-term acute care hospital. Infect Control Hosp Epidemiol 2010;31:341–347.
29. Sakka SG, Glauner AK, Bulitta JB, et al. Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion of imipenem-cilastin in critically ill patients in a randomized, controlled trial. Antimicrob Agents Chemother 2007;51:3304–3310.
30. Giamarellou H, Poulakou G. Multidrug-resistant gram-negative infections: what are the treatment options? Drugs 2009;69:1879–1901.
31. Petrosillo N, Ioannidou E, Falagas ME. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal, and clinical studies. Clin Microbiol Infect 2008;14:816–827.
32. Castanheira M, Sader HS, Deshpande LM, et al. Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-beta-lactamase-producing Enterobacteriaceae: report from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 2008;52:570–573.
33. Livermore DM, Hope R, Brick G, et al. Non-susceptibility trends among Enterobacteriaceae from bacteraemias in the UK and Ireland, 2001–06. J Antimicrob Chemother 2008;62(suppl 2):ii41–ii54.
34. Kelesidis T, Karageorgopoulos DE, Kelesidis I, et al. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother 2008;62:895–904.
35. Anthony KB, Fishman NO, Linkin DR, et al. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis 2008;46:567–570.
36. Daly MW, Riddle DJ, Ledeboer NA, et al. Tigecycline for treatmnet of pneumonia and empyema caused by carbapenemase-producing Klebsiella pneumoniaePharmacotherapy 2007;27:1052–1057.
37. Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother 2009;64(suppl 1):i29–i36.
38. Endimiani A, Hujer KM, Hujer A, et al. ACHN-490, a neoglycoside with potent in vitro activity against multidrug-resistant Klebsiella pneumoniae isolates. Antimicrob Agents Chemother 2009;53:4504–4507.
39. Eleman 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.
40. Endimiani A, Patel G, Hujer KM, et al. In vitro activity of fosfomycin against blaKPC-containingKlebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/or colistin. Antimicrob Agents Chemother 2010;54:526–529.
41. Stachyra T, Levasseur P, Péchereau M, et al. In vitro activity of the {beta}-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother 2009;64:326–329.
42. Livermore D, Mushtaq S, Warner M, et al. NXL104 combinations versus Enterocbacteriaceae with CTX-M extended-spectrum beta-lactamases and carbapenemases. J Antimicrob Chemother2008;62:1053–1056.
43. Vaara M, Fox J, Loidl G, et al. Novel polymyxin derivatives carrying only three positive charges are effective antibacterial agents. Antimicrob Agents Chemother 2008;52:3229–3232.