Issue
The prevalence of CMY-2, OXA-48 and KPC-2 genes in clinical isolates of Klebsiella spp.
Corresponding Author(s) : Ali Mojtahedi
Cellular and Molecular Biology,
Vol. 64 No. 3: Issue 3
Abstract
Klebsiella pneumoniae is a Gram-negative bacterium which causes several human infections. Treatment of infections related to K. pneumoniae has become problematic, because of increasing trend of extended spectrum β-lactamases producing (ESBLs) strains. The present study was aimed to detect the prevalence of ESBL-producing Klebsiella spp. and KPC-2, CMY-2 and OXA-48 β-lactamase encoding genes in clinical isolates of Klebsiella spp. isolated from hospitalized patients. In this cross-sectional study carried out from February to August 2014, 144 isolates of Klebsiella spp. were collected from different clinical specimens in hospitals in the North of Iran. Klebsiella isolates were identified using standard microbiological procedure. Antimicrobial susceptibility patterns were determined using disk diffusion method in accordance with CLSI recommendation. The presence of antibiotic resistance genes were investigated by PCR method. Among 144 Klebsiella spp., 118 isolates were identified as K. pneumoniae and 26 isolates as Klebsiella oxytoca. Antibiotic susceptibility test showed the most resistance rates were against amoxicillin (96.5%) and ampicillin (95.8%). On the other hand, the most effective antibiotic was revealed to be imipenem with resistance rate of 4.9% (Table 2). Among 144 isolated Klebsiella strains, 57 cases (39.6%) were ESBL producers. The OXA-48 and KPC-2 genes were not detected among Klebsiella spp. during the present study, but 21.1% of isolates contained CMY-2 gene. This is the first report of CMY-2 gene detection in Klebsiella spp. in Iran. The homology between CMY-2 genes identified in isolates from Northern Iran and in other countries showed the wide dispersion of this gene around the world.
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- Nejabat M, Khashei R, Bazargani A, Sedigh Ebrahim-Saraie H, Motamedifar M. Evaluation of High-Level of Mupirocin Resistance among Clinical Isolates of Methicillin-Resistant Staphylococcus aureus from Shiraz, Iran (2008-2009). Pharm Sci. 2015;21:225-8.
- Kunz AN, Brook I. Emerging resistant Gram-negative aerobic bacilli in hospital-acquired infections. Chemotherapy. 2010;56:492-500.
- Ko WC, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A, Mohapatra S, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis. 2002;8:160-6.
- Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med. 2004;140:26-32.
- Yum JH, Kim S, Lee H, Yong D, Lee K, Cho SN, et al. Emergence and wide dissemination of CTX-M-type ESBLs, and CMY-2- and DHA-1-type AmpC beta-lactamases in Korean respiratory isolates of Klebsiella pneumoniae. J Korean Med Sci. 2005;20:961-5.
- Shaikh S, Fatima J, Shakil S, Rizvi SM, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi J Biol Sci. 2015;22:90-101.
- Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54:969-76.
- Philippon A, Arlet G, Jacoby GA. Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother. 2002;46:1-11.
- Bauernfeind A, Stemplinger I, Jungwirth R, Giamarellou H. Characterization of the plasmidic beta-lactamase CMY-2, which is responsible for cephamycin resistance. Antimicrob Agents Chemother. 1996;40:221-4.
- Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9:228-36.
- Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20:440-58, table of contents.
- Cagnacci S, Gualco L, Roveta S, Mannelli S, Borgianni L, Docquier JD, et al. Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian outbreak. J Antimicrob Chemother. 2008;61:296-300.
- Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2004;48:15-22.
- Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother. 2010;54:24-38.
- Thomson KS, Sanders CC. Detection of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae: comparison of the double-disk and three-dimensional tests. Antimicrob Agents Chemother. 1992;36:1877-82.
- Wayne P. Performance Standards for Antimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute (CLSI) 2015;25th Informational Supplement.
- Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30:2725-9.
- Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539.
- Sundin DR. Hidden Beta-Lactamases in the Enterobacteriaceae – Dropping the Extra Disks for Detection, Part II. Clin Microbiol Newsletter. 2009;31:47-52.
- Martínez P, Espinal P, Máttar S. Epidemiología molecular de Pseudomonas aeruginosa resistente a β - lactámicos de amplio espectro en el Hospital San Jerónimo de Montería. Infectio. 2007;11:6-15.
- Demirdag K, Hosoglu S. Epidemiology and risk factors for ESBL-producing Klebsiella pneumoniae: a case control study. J Infect Dev Ctries. 2010;4:717-22.
- Villegas MV, Blanco MG, Sifuentes-Osornio J, Rossi F. Increasing prevalence of extended-spectrum-beta-lactamase among Gram-negative bacilli in Latin America--2008 update from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Braz J Infect Dis. 2011;15:34-9.
- Schito GC, Naber KG, Botto H, Palou J, Mazzei T, Gualco L, et al. The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections. Int J Antimicrob Agents. 2009;34:407-13.
- Ghafourian S, Sekawi Z, Neela V, Khosravi A, Rahbar M, Sadeghifard N. Incidence of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in patients with urinary tract infection. Sao Paulo Med J. 2012;130:37-43.
- Amirmozafari N, Tehrani HF, Tavaf Langeroodi Z, Abdullahi A. Survey of drug resistance due to extended spectrum β-lactamases in Klebsiella pneumoniae strains isolated from hospitalized patients. Res Med. 2007;31:241-5.
- Mansury D, Motamedifar M, Sarvari J, Shirazi B, Khaledi A. Antibiotic susceptibility pattern and identification of extended spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae from Shiraz, Iran. Iran J Microbiol. 2016;8:55-61.
- Woodford N, Reddy S, Fagan EJ, Hill RL, Hopkins KL, Kaufmann ME, et al. Wide geographic spread of diverse acquired AmpC beta-lactamases among Escherichia coli and Klebsiella spp. in the UK and Ireland. J Antimicrob Chemother. 2007;59:102-5.
- Hanson ND, Moland ES, Hong SG, Propst K, Novak DJ, Cavalieri SJ. Surveillance of community-based reservoirs reveals the presence of CTX-M, imported AmpC, and OXA-30 beta-lactamases in urine isolates of Klebsiella pneumoniae and Escherichia coli in a U.S. community. Antimicrob Agents Chemother. 2008;52:3814-6.
- Tenover FC, Emery SL, Spiegel CA, Bradford PA, Eells S, Endimiani A, et al. Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol. 2009;47:294-9.
- Tan TY, Ng SY, Teo L, Koh Y, Teok CH. Detection of plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. J Clin Pathol. 2008;61:642-4.
- Mata C, Miro E, Alvarado A, Garcillan-Barcia MP, Toleman M, Walsh TR, et al. Plasmid typing and genetic context of AmpC beta-lactamases in Enterobacteriaceae lacking inducible chromosomal ampC genes: findings from a Spanish hospital 1999-2007. J Antimicrob Chemother. 2012;67:115-22.
References
Nejabat M, Khashei R, Bazargani A, Sedigh Ebrahim-Saraie H, Motamedifar M. Evaluation of High-Level of Mupirocin Resistance among Clinical Isolates of Methicillin-Resistant Staphylococcus aureus from Shiraz, Iran (2008-2009). Pharm Sci. 2015;21:225-8.
Kunz AN, Brook I. Emerging resistant Gram-negative aerobic bacilli in hospital-acquired infections. Chemotherapy. 2010;56:492-500.
Ko WC, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A, Mohapatra S, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis. 2002;8:160-6.
Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med. 2004;140:26-32.
Yum JH, Kim S, Lee H, Yong D, Lee K, Cho SN, et al. Emergence and wide dissemination of CTX-M-type ESBLs, and CMY-2- and DHA-1-type AmpC beta-lactamases in Korean respiratory isolates of Klebsiella pneumoniae. J Korean Med Sci. 2005;20:961-5.
Shaikh S, Fatima J, Shakil S, Rizvi SM, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi J Biol Sci. 2015;22:90-101.
Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54:969-76.
Philippon A, Arlet G, Jacoby GA. Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother. 2002;46:1-11.
Bauernfeind A, Stemplinger I, Jungwirth R, Giamarellou H. Characterization of the plasmidic beta-lactamase CMY-2, which is responsible for cephamycin resistance. Antimicrob Agents Chemother. 1996;40:221-4.
Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9:228-36.
Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20:440-58, table of contents.
Cagnacci S, Gualco L, Roveta S, Mannelli S, Borgianni L, Docquier JD, et al. Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian outbreak. J Antimicrob Chemother. 2008;61:296-300.
Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2004;48:15-22.
Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother. 2010;54:24-38.
Thomson KS, Sanders CC. Detection of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae: comparison of the double-disk and three-dimensional tests. Antimicrob Agents Chemother. 1992;36:1877-82.
Wayne P. Performance Standards for Antimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute (CLSI) 2015;25th Informational Supplement.
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30:2725-9.
Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539.
Sundin DR. Hidden Beta-Lactamases in the Enterobacteriaceae – Dropping the Extra Disks for Detection, Part II. Clin Microbiol Newsletter. 2009;31:47-52.
Martínez P, Espinal P, Máttar S. Epidemiología molecular de Pseudomonas aeruginosa resistente a β - lactámicos de amplio espectro en el Hospital San Jerónimo de Montería. Infectio. 2007;11:6-15.
Demirdag K, Hosoglu S. Epidemiology and risk factors for ESBL-producing Klebsiella pneumoniae: a case control study. J Infect Dev Ctries. 2010;4:717-22.
Villegas MV, Blanco MG, Sifuentes-Osornio J, Rossi F. Increasing prevalence of extended-spectrum-beta-lactamase among Gram-negative bacilli in Latin America--2008 update from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Braz J Infect Dis. 2011;15:34-9.
Schito GC, Naber KG, Botto H, Palou J, Mazzei T, Gualco L, et al. The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections. Int J Antimicrob Agents. 2009;34:407-13.
Ghafourian S, Sekawi Z, Neela V, Khosravi A, Rahbar M, Sadeghifard N. Incidence of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in patients with urinary tract infection. Sao Paulo Med J. 2012;130:37-43.
Amirmozafari N, Tehrani HF, Tavaf Langeroodi Z, Abdullahi A. Survey of drug resistance due to extended spectrum β-lactamases in Klebsiella pneumoniae strains isolated from hospitalized patients. Res Med. 2007;31:241-5.
Mansury D, Motamedifar M, Sarvari J, Shirazi B, Khaledi A. Antibiotic susceptibility pattern and identification of extended spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae from Shiraz, Iran. Iran J Microbiol. 2016;8:55-61.
Woodford N, Reddy S, Fagan EJ, Hill RL, Hopkins KL, Kaufmann ME, et al. Wide geographic spread of diverse acquired AmpC beta-lactamases among Escherichia coli and Klebsiella spp. in the UK and Ireland. J Antimicrob Chemother. 2007;59:102-5.
Hanson ND, Moland ES, Hong SG, Propst K, Novak DJ, Cavalieri SJ. Surveillance of community-based reservoirs reveals the presence of CTX-M, imported AmpC, and OXA-30 beta-lactamases in urine isolates of Klebsiella pneumoniae and Escherichia coli in a U.S. community. Antimicrob Agents Chemother. 2008;52:3814-6.
Tenover FC, Emery SL, Spiegel CA, Bradford PA, Eells S, Endimiani A, et al. Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol. 2009;47:294-9.
Tan TY, Ng SY, Teo L, Koh Y, Teok CH. Detection of plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. J Clin Pathol. 2008;61:642-4.
Mata C, Miro E, Alvarado A, Garcillan-Barcia MP, Toleman M, Walsh TR, et al. Plasmid typing and genetic context of AmpC beta-lactamases in Enterobacteriaceae lacking inducible chromosomal ampC genes: findings from a Spanish hospital 1999-2007. J Antimicrob Chemother. 2012;67:115-22.