Klebsiella pneumoniae Carbapenemase: Extended-Spectrum beta-Lactamase Continues to Go Global

Luke F. Chen, MBBS, FRACP


February 12, 2009

In This Article

Introduction to Klebsiella pneumoniae Carbapenemases

Carbapenems, such as imipenem and meropenem, are often used to treat infections caused by extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria. A new class of bacterial enzymes capable of inactivating carbapenems, known as Klebsiella pneumoniae carbapenemases (KPCs), has rapidly spread in the United States and continues to be extensively reported elsewhere in the world. KPCs are class A carbapenemases[1] that reside on transferable plasmids and can hydrolyze all penicillins, cephalosporins, and carbapenems.

The options for treating infections caused by KPCs are limited, and often require the use of polymyxins, which fell into disuse in the 1980s due to high rates of nephrotoxicity. The epidemiology of KPC-producing organisms remains largely unknown, and is being intensively studied by researchers. The following aims to review our current understanding of KPCs and to summarize important results presented at a special session on KPCs at the 2008 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and Infectious Diseases Society of America (IDSA) joint annual meeting in Washington, DC.

First Isolate of KPC-producing Bacteria

In 1996, the first isolate of KPC-producing bacteria was discovered in a clinical specimen of K pneumoniae from a hospital in North Carolina involved in the Intensive Care Antimicrobial Resistance Epidemiology (ICARE) surveillance program.[2] KPCs were infrequently isolated until 2001, when KPC-producing Enterobacteriaceae were reported in several extended outbreaks in metropolitan hospitals of New York and New Jersey.[3,4,5] KPC-producing organisms have continued to spread over time and have now been reported in 27 states in the United States,[6] and in many countries around the world, including China,[7] Colombia,[8] Brazil,[9] France,[10] and Israel.[11]

The epidemiology of KPC-producing organisms continues to evolve. Although most KPCs are detected in isolates of Klebsiella and Escherichia coli, KPCs have been extensively reported in other genera of the Enterobacteriaceae family, such as Proteus,[12]Serratia,[13]Salmonella,[14] and Citrobacter.[15] Worse still, KPC resistance has been reported in inherently resistant organisms such as Pseudomonas.[16] Akpaka and colleagues,[17] from Trinidad, studied an isolate of multidrug-resistant Pseudomonas aeruginosa that harbored a novel KPC-6 gene, and presented their findings at the recent ICAAC/IDSA meeting. Of interest, the isolate was obtained from a patient who had no history of recent travel, suggesting that the specific isolate of KPC-producing Pseudomonas emerged locally, and probably continued to circulate in that region of the world.


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