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Klebsiella Pneumoniae Carbapenemase (KPC)
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KPC (Klebsiella pneumoniae carbapenamases)

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KPC (Klebsiella pneumoniae Carbapenemases) producing bacteria has become a global threat, mainly due to the limited treatment options.

This video gives a basic outline of the KPC enzyme and KPC-producing bacteria.

You can view a video of this presentation here: https://youtu.be/vp7oyKyAq1s

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KPC (Klebsiella pneumoniae carbapenamases)

  1. 1. K p C KPC Klebsiella pneumoniae Carbapenemases
  2. 2. Image credit: National Institute of Allergy and Infectious Diseases (NIAID) human neutrophil Carbapenem-resistant Klebsiella pneumoniae
  3. 3. Cephalosporin Penicillin Aztreonam β-Lactam Ring β-Lactam Antibiotics
  4. 4. e.g. Imipenem, Meropenem Highly resistant to most β-Lactams including ESBLs Broad-spectrum antibiotics Last resort against ESBL–producing Enterobacteriaceae & MDR Gram-negative bacilli
  5. 5. Active Carbapenemases Hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. β-Lactamases Inactive Image Source: Trends in Molecular Medicine
  6. 6. β- 1—4 Based on the substrate profile Molecular Classification Bush-Jacoby-Medeiros Classification (BJM) A—D Based on the enzyme structure Functional Classification Ambler's Classification Classification of beta-lactamases
  7. 7. BJM system Major subgroups Ambler System Main attributes Group 1 cephalosporinases – C (cephalosporinases) Usually chromosomal; Resistance to all β- lactams except carbapenems; Not inhibited by clavulanate Group 2 penicillinases 2a A (serine β-lactamases) Staphylococcal penicillinases (clavulanicacidsusceptible) 2b A Broad-spectrum – TEM-1, TEM-2, SHV-1 2be A Extended-spectrum – TEM-3–160, SHV-2–101 2br A Inhibitor resistant TEM (IRT) 2c A Carbenicillin-hydrolyzing 2e A Cephalosporinases inhibited by clavulanate 2f A Carbapenemases inhibited by clavulanate 2d D(oxacillin-hydrolyzing) Cloxacillin-hydrolyzing (OXA) Group 3 metallo-β-lactamase 3a B (metalloenzymes) Zinc-dependent carbapenemases 3b B 3c B Group 4 Not classified Misc enzymes, most not yet sequenced Perez, Federico, et al. "The continuing challenge of ESBLs." Curr opin pharm 7.5 (2007): 459-469. KPC Classification of beta-lactamases
  8. 8. KPC Ambler Class A Serine β-lactamase, BMJ group 2f First discovered in a Klebsiella pneumonia—North Carolina, US (1996) – KPC1 Klebsiella pneumoniae Carbapenemases Later found in other genera of the Enterobacteriaceae family Klebsiella oxytoca Citrobacter freundii Enterobacter aerogenes & E. Cloacae Also in Pseudomonas aeruginosa & Acinetobacter baumannii Escherichia coli Serratia marcescens
  9. 9. KPC 16 variants (KPC-2 to KPC-17)—Most frequent KPC-2 and KPC-3 The most clinically significant enzymes of the class A carbapenemases Klebsiella pneumoniae Carbapenemases Clinical detection—often challenging Hydrolyze β-lactams of all classes Penicillins All cephalosporins Monobactams Carbapenems and β-lactamase inhibitors Multidrug resistant—High mortality rates Greatest potential for spread—Located on plasmids
  10. 10. KPC Queenan, Anne Marie, and Karen Bush. "Carbapenemases: the versatile β-lactamases." Clinical microbiology reviews 20.3 (2007): 440-458. Emergence of class A carbapenemases
  11. 11. KPC-1 Munoz-Price, L. Silvia, et al. "Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases." The Lancet infectious diseases 13.9 (2013): 785-796. KPC
  12. 12. Antibiotic sensitivity tests—inconsistent results Carbapenemases alone doesn’t produce compete resistance. Some KPC-producers are susceptible to carbapenems. Variable levels of carbapenem resistance Insufficient cell numbers  Imipenem or Meropenem is not sensitive enough.  Ertapenem —best so far But ertapenem resistance by itself is not a marker for KPC expression. Confirmatory tests are necessary. Modified Hodge Test Molecular tools should become the gold standard. Sensitivity varies with the substrate KPC
  13. 13. E.coli ATCC 25922 suspension in broth/saline Diluted 1:10 Spread on a MHA plate Place 10 μg antibiotic disk in the center Streak test organism(s) Incubation overnight at 35⁰C ± 2⁰ C Susceptible to carbapenems KPC E.coli ATCC 25922
  14. 14. Bora, Arijit, et al. "Incidence of metallo-beta-lactamase producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in central Nepal." BMC research notes 7.1 (2014): 557. Test organism secretes KPC and inactivates the antibiotic. E. Coli grows along the edges. clover leaf-type indentation No E.coli growthTest organism doesn’t secrete KPC. Antibiotic remains active. E. Coli growth inhibited. KPC
  15. 15. • Perez, Federico, et al. "The continuing challenge of ESBLs." Current opinion in pharmacology 7.5 (2007): 459-469. • Queenan, Anne Marie, and Karen Bush. "Carbapenemases: the versatile β-lactamases." Clinical microbiology reviews 20.3 (2007): 440-458. • Robledo, Iraida E., Edna E. Aquino, and Guillermo J. Vázquez. "Detection of the KPC gene in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii during a PCR-based nosocomial surveillance study in Puerto Rico." Antimicrobial agents and chemotherapy55.6 (2011): 2968-2970. • Sacha, Paweł, et al. "The KPC type beta-lactamases: new enzymes that confer resistance to carbapenems in Gram-negative bacilli." Folia Histochemica et Cytobiologica 47.4 (2009): 537-543. • Wang, Dongguo, et al. "Phenotypic and Enzymatic Comparative Analysis of the KPC Variants, KPC-2 and Its Recently Discovered Variant KPC-15." (2014): e111491. • Walther-Rasmussen, Jan, and Niels Høiby. "Class A carbapenemases."Journal of antimicrobial chemotherapy 60.3 (2007): 470-482. • Yigit, Hesna, et al. "Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae." Antimicrobial agents and chemotherapy 45.4 (2001): 1151-1161. • Yigit, Hesna, et al. "Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae." Antimicrobial agents and chemotherapy 52.2 (2008): 809.
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KPC (Klebsiella pneumoniae Carbapenemases) producing bacteria has become a global threat, mainly due to the limited treatment options. This video gives a basic outline of the KPC enzyme and KPC-producing bacteria. You can view a video of this presentation here: https://youtu.be/vp7oyKyAq1s

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