This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yigit, H.
Right arrow Articles by Tenover, F. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yigit, H.
Right arrow Articles by Tenover, F. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2003, p. 3881-3889, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3881-3889.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Carbapenem-Resistant Strain of Klebsiella oxytoca Harboring Carbapenem-Hydrolyzing ß-Lactamase KPC-2

Hesna Yigit,1 Anne Marie Queenan,2 J. Kamile Rasheed,3 James W. Biddle,3 Antonio Domenech-Sanchez,4 Sebastian Alberti,5 Karen Bush,2 and Fred C. Tenover3*

Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492,1 The R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869,2 Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,3 Unidad de Investigacion, Hospital Son Dureta, Andrea Doria, Palma de Mallorca 07014,4 Area de Microbiologia, Universidad de las Islas Baleares, Crtra.Valldemosa, Palma de Mallorca 07071, Spain5

Received 6 May 2003/ Returned for modification 14 July 2003/ Accepted 31 August 2003

We investigated a Klebsiella oxytoca isolate demonstrating resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The MICs of both imipenem and meropenem were 32 µg/ml. The ß-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. Isoelectric focusing studies demonstrated five ß-lactamases with pIs of 8.2 (SHV-46), 6.7 (KPC-2), 6.5 (unknown), 6.4 (probable OXY-2), and 5.4 (TEM-1). The presence of the blaSHV and blaTEM genes was confirmed by specific PCR assays and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the ß-lactamase with a pI of 6.7, Klebsiella pneumoniae carbapenemase-2 (KPC-2), was encoded on an approximately 70-kb conjugative plasmid that also carried SHV-46, TEM-1, and the ß-lactamase with a pI of 6.5. The blaKPC-2 determinant was cloned in E. coli and conferred resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of KPC-2 showed a single amino acid difference, S174G, when compared with KPC-1, another carbapenem-hydrolyzing ß-lactamase from K. pneumoniae 1534. Hydrolysis studies showed that purified KPC-2 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and aztreonam. KPC-2 had the highest affinity for meropenem. The kinetic studies revealed that KPC-2 was inhibited by clavulanic acid and tazobactam. An examination of the outer membrane proteins of the parent K. oxytoca strain demonstrated that it expressed detectable levels of OmpK36 (the homolog of OmpC) and a higher-molecular-weight OmpK35 (the homolog of OmpF). Thus, carbapenem resistance in K. oxytoca 3127 is due to production of the Bush group 2f, class A, carbapenem-hydrolyzing ß-lactamase KPC-2. This ß-lactamase is likely located on a transposon that is part of a conjugative plasmid and thus has a very high potential for dissemination.

* Corresponding author. Mailing address: Division of Healthcare Quality Promotion (G08), Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-3375. Fax: (404) 639-1381. E-mail: fnt1{at}cdc.gov.

Antimicrobial Agents and Chemotherapy, December 2003, p. 3881-3889, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3881-3889.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baraniak, A., Izdebski, R., Herda, M., Fiett, J., Hryniewicz, W., Gniadkowski, M., Kern-Zdanowicz, I., Filczak, K., Lopaciuk, U. (2009). Emergence of Klebsiella pneumoniae ST258 with KPC-2 in Poland. Antimicrob. Agents Chemother. 53: 4565-4567 [Full Text]  
  • Shen, P., Wei, Z., Jiang, Y., Du, X., Ji, S., Yu, Y., Li, L. (2009). Novel Genetic Environment of the Carbapenem-Hydrolyzing {beta}-Lactamase KPC-2 among Enterobacteriaceae in China. Antimicrob. Agents Chemother. 53: 4333-4338 [Abstract] [Full Text]  
  • Kitchel, B., Rasheed, J. K., Patel, J. B., Srinivasan, A., Navon-Venezia, S., Carmeli, Y., Brolund, A., Giske, C. G. (2009). Molecular Epidemiology of KPC-Producing Klebsiella pneumoniae Isolates in the United States: Clonal Expansion of Multilocus Sequence Type 258. Antimicrob. Agents Chemother. 53: 3365-3370 [Abstract] [Full Text]  
  • Gootz, T. D., Lescoe, M. K., Dib-Hajj, F., Dougherty, B. A., He, W., Della-Latta, P., Huard, R. C. (2009). Genetic Organization of Transposase Regions Surrounding blaKPC Carbapenemase Genes on Plasmids from Klebsiella Strains Isolated in a New York City Hospital. Antimicrob. Agents Chemother. 53: 1998-2004 [Abstract] [Full Text]  
  • Fenosa, A., Fuste, E., Ruiz, L., Veiga-Crespo, P., Vinuesa, T., Guallar, V., Villa, T. G., Vinas, M. (2009). Role of TolC in Klebsiella oxytoca resistance to antibiotics. J Antimicrob Chemother 63: 668-674 [Abstract] [Full Text]  
  • Endimiani, A., Hujer, A. M., Perez, F., Bethel, C. R., Hujer, K. M., Kroeger, J., Oethinger, M., Paterson, D. L., Adams, M. D., Jacobs, M. R., Diekema, D. J., Hall, G. S., Jenkins, S. G., Rice, L. B., Tenover, F. C., Bonomo, R. A. (2009). Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA. J Antimicrob Chemother 63: 427-437 [Abstract] [Full Text]  
  • Wolter, D. J., Kurpiel, P. M., Woodford, N., Palepou, M.-F. I., Goering, R. V., Hanson, N. D. (2009). Phenotypic and Enzymatic Comparative Analysis of the Novel KPC Variant KPC-5 and Its Evolutionary Variants, KPC-2 and KPC-4. Antimicrob. Agents Chemother. 53: 557-562 [Abstract] [Full Text]  
  • Cole, J. M., Schuetz, A. N., Hill, C. E., Nolte, F. S. (2009). Development and Evaluation of a Real-Time PCR Assay for Detection of Klebsiella pneumoniae Carbapenemase Genes. J. Clin. Microbiol. 47: 322-326 [Abstract] [Full Text]  
  • Petrella, S., Ziental-Gelus, N., Mayer, C., Renard, M., Jarlier, V., Sougakoff, W. (2008). Genetic and Structural Insights into the Dissemination Potential of the Extremely Broad-Spectrum Class A {beta}-Lactamase KPC-2 Identified in an Escherichia coli Strain and an Enterobacter cloacae Strain Isolated from the Same Patient in France. Antimicrob. Agents Chemother. 52: 3725-3736 [Abstract] [Full Text]  
  • Hindiyeh, M., Smollen, G., Grossman, Z., Ram, D., Davidson, Y., Mileguir, F., Vax, M., Ben David, D., Tal, I., Rahav, G., Shamiss, A., Mendelson, E., Keller, N. (2008). Rapid Detection of blaKPC Carbapenemase Genes by Real-Time PCR. J. Clin. Microbiol. 46: 2879-2883 [Abstract] [Full Text]  
  • Cai, J. C., Zhou, H. W., Zhang, R., Chen, G.-X. (2008). Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli Isolates Possessing the Plasmid-Mediated Carbapenem-Hydrolyzing {beta}-Lactamase KPC-2 in Intensive Care Units of a Chinese Hospital. Antimicrob. Agents Chemother. 52: 2014-2018 [Abstract] [Full Text]  
  • Rasheed, J. K., Biddle, J. W., Anderson, K. F., Washer, L., Chenoweth, C., Perrin, J., Newton, D. W., Patel, J. B. (2008). Detection of the Klebsiella pneumoniae Carbapenemase Type 2 Carbapenem-Hydrolyzing Enzyme in Clinical Isolates of Citrobacter freundii and K. oxytoca Carrying a Common Plasmid. J. Clin. Microbiol. 46: 2066-2069 [Abstract] [Full Text]  
  • Naas, T., Cuzon, G., Villegas, M.-V., Lartigue, M.-F., Quinn, J. P., Nordmann, P. (2008). Genetic Structures at the Origin of Acquisition of the {beta}-Lactamase blaKPC Gene. Antimicrob. Agents Chemother. 52: 1257-1263 [Abstract] [Full Text]  
  • Schwaber, M. J., Klarfeld-Lidji, S., Navon-Venezia, S., Schwartz, D., Leavitt, A., Carmeli, Y. (2008). Predictors of Carbapenem-Resistant Klebsiella pneumoniae Acquisition among Hospitalized Adults and Effect of Acquisition on Mortality. Antimicrob. Agents Chemother. 52: 1028-1033 [Abstract] [Full Text]  
  • Zhang, R., Yang, L., Cai, J. C., Zhou, H. W., Chen, G.-X. (2008). High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression. J Med Microbiol 57: 332-337 [Abstract] [Full Text]  
  • Walther-Rasmussen, J., Hoiby, N. (2007). Class A carbapenemases. J Antimicrob Chemother 60: 470-482 [Abstract] [Full Text]  
  • Queenan, A. M., Shang, W., Kania, M., Page, M. G. P., Bush, K. (2007). Interactions of Ceftobiprole with {beta}-Lactamases from Molecular Classes A to D. Antimicrob. Agents Chemother. 51: 3089-3095 [Abstract] [Full Text]  
  • Anderson, K. F., Lonsway, D. R., Rasheed, J. K., Biddle, J., Jensen, B., McDougal, L. K., Carey, R. B., Thompson, A., Stocker, S., Limbago, B., Patel, J. B. (2007). Evaluation of Methods To Identify the Klebsiella pneumoniae Carbapenemase in Enterobacteriaceae. J. Clin. Microbiol. 45: 2723-2725 [Abstract] [Full Text]  
  • Queenan, A. M., Bush, K. (2007). Carbapenemases: the Versatile {beta}-Lactamases. Clin. Microbiol. Rev. 20: 440-458 [Abstract] [Full Text]  
  • Villegas, M. V., Lolans, K., Correa, A., Kattan, J. N., Lopez, J. A., Quinn, J. P., and the Colombian Nosocomial Resistance Study Grou, (2007). First Identification of Pseudomonas aeruginosa Isolates Producing a KPC-Type Carbapenem-Hydrolyzing {beta}-Lactamase. Antimicrob. Agents Chemother. 51: 1553-1555 [Abstract] [Full Text]  
  • Zhang, R., Zhou, H. W., Cai, J. C., Chen, G.-X. (2007). Plasmid-mediated carbapenem-hydrolysing {beta}-lactamase KPC-2 in carbapenem-resistant Serratia marcescens isolates from Hangzhou, China. J Antimicrob Chemother 59: 574-576 [Full Text]  
  • Wei, Z.-Q., Du, X.-X., Yu, Y.-S., Shen, P., Chen, Y.-G., Li, L.-J. (2007). Plasmid-Mediated KPC-2 in a Klebsiella pneumoniae Isolate from China. Antimicrob. Agents Chemother. 51: 763-765 [Abstract] [Full Text]  
  • Kaczmarek, F. M., Dib-Hajj, F., Shang, W., Gootz, T. D. (2006). High-Level Carbapenem Resistance in a Klebsiella pneumoniae Clinical Isolate Is Due to the Combination of blaACT-1 {beta}-Lactamase Production, Porin OmpK35/36 Insertional Inactivation, and Down-Regulation of the Phosphate Transport Porin PhoE.. Antimicrob. Agents Chemother. 50: 3396-3406 [Abstract] [Full Text]  
  • Virginia Villegas, M., Lolans, K., Correa, A., Jose Suarez, C., Lopez, J. A., Vallejo, M., Quinn, J. P., the Colombian Nosocomial Resistance Study Group, (2006). First Detection of the Plasmid-Mediated Class A Carbapenemase KPC-2 in Clinical Isolates of Klebsiella pneumoniae from South America.. Antimicrob. Agents Chemother. 50: 2880-2882 [Abstract] [Full Text]  
  • Alba, J., Ishii, Y., Thomson, K., Moland, E. S., Yamaguchi, K. (2005). Kinetics Study of KPC-3, a Plasmid-Encoded Class A Carbapenem-Hydrolyzing {beta}-Lactamase. Antimicrob. Agents Chemother. 49: 4760-4762 [Abstract] [Full Text]  
  • Landman, D., Salvani, J. K., Bratu, S., Quale, J. (2005). Evaluation of Techniques for Detection of Carbapenem-Resistant Klebsiella pneumoniae in Stool Surveillance Cultures. J. Clin. Microbiol. 43: 5639-5641 [Abstract] [Full Text]  
  • Paterson, D. L., Bonomo, R. A. (2005). Extended-Spectrum {beta}-Lactamases: a Clinical Update. Clin. Microbiol. Rev. 18: 657-686 [Abstract] [Full Text]  
  • Naas, T., Nordmann, P., Vedel, G., Poyart, C. (2005). Plasmid-Mediated Carbapenem-Hydrolyzing {beta}-Lactamase KPC in a Klebsiella pneumoniae Isolate from France. Antimicrob. Agents Chemother. 49: 4423-4424 [Full Text]  
  • Bratu, S., Mooty, M., Nichani, S., Landman, D., Gullans, C., Pettinato, B., Karumudi, U., Tolaney, P., Quale, J. (2005). Emergence of KPC-Possessing Klebsiella pneumoniae in Brooklyn, New York: Epidemiology and Recommendations for Detection. Antimicrob. Agents Chemother. 49: 3018-3020 [Abstract] [Full Text]  
  • Bratu, S., Landman, D., Alam, M., Tolentino, E., Quale, J. (2005). Detection of KPC Carbapenem-Hydrolyzing Enzymes in Enterobacter spp. from Brooklyn, New York. Antimicrob. Agents Chemother. 49: 776-778 [Abstract] [Full Text]  
  • Woodford, N., Tierno, P. M. Jr., Young, K., Tysall, L., Palepou, M.-F. I., Ward, E., Painter, R. E., Suber, D. F., Shungu, D., Silver, L. L., Inglima, K., Kornblum, J., Livermore, D. M. (2004). Outbreak of Klebsiella pneumoniae Producing a New Carbapenem- Hydrolyzing Class A {beta}-Lactamase, KPC-3, in a New York Medical Center. Antimicrob. Agents Chemother. 48: 4793-4799 [Abstract] [Full Text]  
  • Hossain, A., Ferraro, M. J., Pino, R. M., Dew, R. B. III, Moland, E. S., Lockhart, T. J., Thomson, K. S., Goering, R. V., Hanson, N. D. (2004). Plasmid-Mediated Carbapenem-Hydrolyzing Enzyme KPC-2 in an Enterobacter sp.. Antimicrob. Agents Chemother. 48: 4438-4440 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»