Archives of Clinical Infectious Diseases

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Colistin-Resistant Klebsiella pneumoniae: Prevalence of Integrons and Synergistic Out Turn for Colistin-Meropenem

Prasanth Manohar 1 , Thamaraiselvan Shanthini 1 , Pandey Ekta 1 , Mahesan J B 1 , Kodiveri Muthukaliannan Gothandam 1 , Bulent Bozdogan 2 and Nachimuthu Ramesh 1 , *
Authors Information
1 Antibiotic Resistance and Phage Therapy Laboratory, Department of Biomedical Sciences, School of Bioscience and Technology, VIT University, Vellore, Tamil Nadu, India
2 Medical Microbiology Department, Adnan Menderes University, Aydin, Turkey
Article information
  • Archives of Clinical Infectious Diseases: January 2018, 13 (1); e55099
  • Published Online: January 28, 2018
  • Article Type: Research Article
  • Received: August 9, 2017
  • Revised: June 17, 2017
  • Accepted: September 20, 2017
  • DOI: 10.5812/archcid.55099

To Cite: Manohar P, Shanthini T, Ekta P, J B M, Muthukaliannan Gothandam K, et al. Colistin-Resistant Klebsiella pneumoniae: Prevalence of Integrons and Synergistic Out Turn for Colistin-Meropenem, Arch Clin Infect Dis. 2018 ; 13(1):e55099. doi: 10.5812/archcid.55099.

Copyright © 2018, Archives of Clinical Infectious Diseases. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Methods
3. Results
4. Discussion
  • 1. European Centre for Disease Prevention and Control . Surveillance of antimicrobial consumption in Europe 2012. Stockholm: ECDC; 2014.
  • 2. Courvalin P. Predictable and unpredictable evolution of antibiotic resistance. J Intern Med. 2008;264(1):4-16. doi: 10.1111/j.1365-2796.2008.01940.x. [PubMed: 18397243].
  • 3. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 2008;197(8):1079-81. doi: 10.1086/533452. [PubMed: 18419525].
  • 4. Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969-76. doi: 10.1128/AAC.01009-09. [PubMed: 19995920].
  • 5. Winn WC. Koneman's color atlas and textbook of diagnostic microbiology. Koneman EW, editor. Lippincott williams & wilkins; 2006.
  • 6. Agodi A, Mura I. The Italian Network SPIN-UTI: Protocol design and validation for active surveillance of ICU-acquired infections. Int J Comp Res. 2011;18(3/4):373-83.
  • 7. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006;6(9):589-601. doi: 10.1016/S1473-3099(06)70580-1. [PubMed: 16931410].
  • 8. Leverstein-van Hall MA, M. Blok HE , T. Donders AR , Paauw A, Fluit AC, Verhoef J. Multidrug resistance among Enterobacteriaceae is strongly associated with the presence of integrons and is independent of species or isolate origin. J Infect Dis. 2003;187(2):251-9. doi: 10.1086/345880. [PubMed: 12552449].
  • 9. Schmitz FJ, Hafner D, Geisel R, Follmann P, Kirschke C, Verhoef J, et al. Increased prevalence of class I integrons in Escherichia coli, Klebsiella species, and Enterobacter species isolates over a 7-year period in a German university hospital. J Clin Microbiol. 2001;39(10):3724-6. doi: 10.1128/JCM.39.10.3724-3726.2001. [PubMed: 11574602].
  • 10. Salem MM, Muharram M, Alhosiny IM. Distribution of classes 1 and 2 integrons among multi drug resistant E. coli isolated from hospitalized patients with urinary tract infection in Cairo, Egypt. Aust J Basic Appl Sci. 2010;4(3):398-407.
  • 11. Leverstein-Van Hall MA, Paauw A, Box AT, Blok HE, Verhoef J, Fluit AC. Presence of integron-associated resistance in the community is widespread and contributes to multidrug resistance in the hospital. J Clin Microbiol. 2002;40(8):3038-40. doi: 10.1128/JCM.40.8.3038-3040.2002. [PubMed: 12149373].
  • 12. Nordmann P, Poirel L. Plasmid-mediated colistin resistance: an additional antibiotic resistance menace. Clin Microbiol Infect. 2016;22(5):398-400. doi: 10.1016/j.cmi.2016.03.009. [PubMed: 27021419].
  • 13. Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents. 2011;37(5):415-9. doi: 10.1016/j.ijantimicag.2011.01.012. [PubMed: 21429716].
  • 14. Tascini C, Tagliaferri E, Giani T, Leonildi A, Flammini S, Casini B, et al. Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2013;57(8):3990-3. doi: 10.1128/AAC.00179-13. [PubMed: 23752510].
  • 15. Ramesh N. Colistin susceptibility of gram-negative clinical isolates from Tamil Nadu, India. Asian Biomed. 2016;10(1):35. doi: 10.5372/1905-7415.1001.462.
  • 16. Yu HS, Lee JC, Kang HY, Ro DW, Chung JY, Jeong YS, et al. Changes in gene cassettes of class 1 integrons among Escherichia coli isolates from urine specimens collected in Korea during the last two decades. J Clin Microbiol. 2003;41(12):5429-33. doi: 10.1128/JCM.41.12.5429-5433.2003. [PubMed: 14662921].
  • 17. Kargar M, Mohammadalipour Z, Doosti A, Lorzadeh S, Japoni-Nejad A. High Prevalence of Class 1 to 3 Integrons Among Multidrug-Resistant Diarrheagenic Escherichia coli in Southwest of Iran. Osong Public Health Res Perspect. 2014;5(4):193-8. doi: 10.1016/j.phrp.2014.06.003. [PubMed: 25379369].
  • 18. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, et al. Identification of a novel plasmid-mediated colistin-resistance gene,mcr-2, inEscherichia coli, Belgium, June 2016. Eurosurveillance. 2016;21(27). doi: 10.2807/
  • 19. Goel G, Hmar L, Sarkar De M, Bhattacharya S, Chandy M. Colistin-resistant Klebsiella pneumoniae: report of a cluster of 24 cases from a new oncology center in eastern India. Infect Control Hosp Epidemiol. 2014;35(8):1076-7. doi: 10.1086/677170. [PubMed: 25026633].
  • 20. Poudyal A, Howden BP, Bell JM, Gao W, Owen RJ, Turnidge JD, et al. In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2008;62(6):1311-8. doi: 10.1093/jac/dkn425. [PubMed: 18922815].
  • 21. Olaitan AO, Diene SM, Kempf M, Berrazeg M, Bakour S, Gupta SK, et al. Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria and France owing to inactivation of the PhoP/PhoQ regulator mgrB: an epidemiological and molecular study. Int J Antimicrob Agents. 2014;44(6):500-7. doi: 10.1016/j.ijantimicag.2014.07.020. [PubMed: 25264127].
  • 22. Ahangarzadeh Rezaee M, Langarizadeh N, Aghazadeh M. First report of class 1 and class 2 integrons in multidrug-resistant Klebsiella pneumoniae isolates from northwest Iran. Jpn J Infect Dis. 2012;65(3):256-9. doi: 10.7883/yoken.65.256. [PubMed: 22627310].
  • 23. Rao AN, Barlow M, Clark LA, Boring J3, Tenover FC, McGowan JJ. Class 1 integrons in resistant Escherichia coli and Klebsiella spp., US hospitals. Emerg Infect Dis. 2006;12(6):1011-4. [PubMed: 16707065].
  • 24. Lima AM, de Melo ME, Alves LC, Brayner FA, Lopes AC. Investigation of class 1 integrons in Klebsiella pneumoniae clinical and microbiota isolates belonging to different phylogenetic groups in Recife, State of Pernambuco. Rev Soc Bras Med Trop. 2014;47(2):165-9. doi: 10.1590/0037-8682-0021-2014. [PubMed: 24861289].
  • 25. Pankuch GA, Lin G, Seifert H, Appelbaum PC. Activity of meropenem with and without ciprofloxacin and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob Agents Chemother. 2008;52(1):333-6. doi: 10.1128/AAC.00689-07. [PubMed: 17967915].
  • 26. Sopirala MM, Mangino JE, Gebreyes WA, Biller B, Bannerman T, Balada-Llasat JM, et al. Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2010;54(11):4678-83. doi: 10.1128/AAC.00497-10. [PubMed: 20713678].
  • 27. Ceccarelli G, Falcone M, Giordano A, Mezzatesta ML, Caio C, Stefani S, et al. Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2013;57(6):2900-1. doi: 10.1128/AAC.00188-13. [PubMed: 23571536].
  • 28. Dickstein Y, Leibovici L, Yahav D, Eliakim-Raz N, Daikos GL, Skiada A, et al. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol. BMJ Open. 2016;6(4). e009956. doi: 10.1136/bmjopen-2015-009956. [PubMed: 27098822].
  • 29. Petersen PJ, Labthavikul P, Jones CH, Bradford PA. In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis. J Antimicrob Chemother. 2006;57(3):573-6. doi: 10.1093/jac/dki477. [PubMed: 16431863].
  • 30. Tangden T. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria. Ups J Med Sci. 2014;119(2):149-53. doi: 10.3109/03009734.2014.899279. [PubMed: 24666223].
  • 31. Zavascki AP, Bulitta JB, Landersdorfer CB. Combination therapy for carbapenem-resistant Gram-negative bacteria. Expert Rev Anti Infect Ther. 2013;11(12):1333-53. doi: 10.1586/14787210.2013.845523. [PubMed: 24191943].
  • 32. Zusman O, Avni T, Leibovici L, Adler A, Friberg L, Stergiopoulou T, et al. Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems. Antimicrob Agents Chemother. 2013;57(10):5104-11. doi: 10.1128/AAC.01230-13. [PubMed: 23917322].
  • 33. Mohamed AF, Kristoffersson AN, Karvanen M, Nielsen EI, Cars O, Friberg LE. Dynamic interaction of colistin and meropenem on a WT and a resistant strain of Pseudomonas aeruginosa as quantified in a PK/PD model. J Antimicrob Chemother. 2016;71(5):1279-90. doi: 10.1093/jac/dkv488. [PubMed: 26850719].
  • 34. Mezzatesta ML, Caio C, Gona F, Zingali T, Salerno I, Stefani S. Colistin Increases the Cidal Activity of Antibiotic Combinations Against Multidrug-Resistant Klebsiella pneumoniae: An In Vitro Model Comparing Multiple Combination Bactericidal Testing at One Peak Serum Concentration and Time-Kill Method. Microb Drug Resist. 2016;22(5):360-3. doi: 10.1089/mdr.2015.0160. [PubMed: 26909754].

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