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Abstract

Recently, plasmid-mediated and, therefore, transferable bacterial polymyxin resistance was discovered in strains from both humans and animals. Such a trait may widely spread geographically, while simultaneously crossing microbial species barriers. This may ultimately render the “last resort” polymyxin antibiotics therapeutically useless. Colistin is currently used to treat infections caused by Gram-negative carbapenemase producers and colistin resistance may lead to practical pan-antibiotic resistance. We here analyzed the medical and diagnostic consequences of (emerging) colistin resistance and propose pathways toward adequate diagnostics for timely detection of both asymptomatic carriage and infection. Culture-based testing using chromogenic and selective media for screening clinical (and veterinary) specimens may constitute key tools for that purpose. Relevant molecular tests are also discussed.

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References

  1. Rawson TM, Moore LS, Hatcher JC, Donaldson H, Holmes AH (2016) Plasmid-mediated colistin resistance mechanisms: is it time to revise our approach to selective digestive decontamination? Lancet Infect Dis 16:149–150

    Article  PubMed  Google Scholar 

  2. Castanheira M, Griffin MA, Deshpande LM, Mendes RE, Jones RN, Flamm RK (2016) Detection of mcr-1 among Escherichia coli clinical isolates collected worldwide as part of the SENTRY Antimicrobial Surveillance Program in 2014 and 2015. Antimicrob Agents Chemother 60:5623–5624

    Article  PubMed  Google Scholar 

  3. Agersø Y, Torpdahl M, Zachariasen C, Seyfarth A, Hammerum AM, Nielsen EM (2012) Tentative colistin epidemiological cut-off value for Salmonella spp. Foodborne Pathog Dis 9:367–369

    Article  PubMed  Google Scholar 

  4. Irrgang A, Roschanski N, Tenhagen BA, Grobbel M, Skladnikiewicz-Ziemer T, Thomas K, Roesler U, Käsbohrer A (2016) Prevalence of mcr-1 in E. coli from livestock and food in Germany, 2010–2015. PLoS One 11, e0159863

    Article  PubMed  PubMed Central  Google Scholar 

  5. Beceiro A, Moreno A, Fernández N, Vallejo JA, Aranda J, Adler B, Harper M, Boyce JD, Bou G (2014) Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob Agents Chemother 58:518–526

    Article  PubMed  PubMed Central  Google Scholar 

  6. Olaitan AO, Morand S, Rolain JM (2014) Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol 5:643

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jansen G, Mahrt N, Tueffers L, Barbosa C, Harjes M, Adolph G, Friedrichs A, Krenz-Weinreich A, Rosenstiel P, Schulenburg H (2016) Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung. Evol Med Public Health 2016:182–194

    Article  PubMed  PubMed Central  Google Scholar 

  8. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168

    Article  PubMed  Google Scholar 

  9. Du H, Chen L, Tang YW, Kreiswirth BN (2016) Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae. Lancet Infect Dis 16:287–288

    Article  CAS  PubMed  Google Scholar 

  10. Jain A, Hopkins KL, Turton J, Doumith M, Hill R, Loy R, Meunier D, Pike R, Livermore DM, Woodford N (2014) NDM carbapenemases in the United Kingdom: an analysis of the first 250 cases. J Antimicrob Chemother 69:1777–1784

    Article  CAS  PubMed  Google Scholar 

  11. Giani T, Arena F, Vaggelli G, Conte V, Chiarelli A, Henrici De Angelis L, Fornaini R, Grazzini M, Niccolini F, Pecile P, Rossolini GM (2015) Large nosocomial outbreak of colistin-resistant, carbapenemase-producing Klebsiella pneumoniae traced to clonal expansion of an mgrB deletion mutant. J Clin Microbiol 53:3341–3344

    Article  PubMed  PubMed Central  Google Scholar 

  12. Webb HE, Granier SA, Marault M, Millemann Y, den Bakker HC, Nightingale KK, Bugarel M, Ison SA, Scott HM, Loneragan GH (2016) Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 16:144–145

    Article  PubMed  Google Scholar 

  13. Haenni M, Poirel L, Kieffer N, Châtre P, Saras E, Métayer V, Dumoulin R, Nordmann P, Madec JY (2016) Co-occurrence of extended spectrum β lactamase and MCR-1 encoding genes on plasmids. Lancet Infect Dis 16:281–282

    Article  CAS  PubMed  Google Scholar 

  14. Figueiredo R, Henriques A, Sereno R, Mendonça N, da Silva GJ (2015) Antimicrobial resistance and extended-spectrum β-lactamases of Salmonella enterica serotypes isolated from livestock and processed food in Portugal: an update. Foodborne Pathog Dis 12:110–117

    Article  CAS  PubMed  Google Scholar 

  15. Olaitan AO, Thongmalayvong B, Akkhavong K, Somphavong S, Paboriboune P, Khounsy S, Morand S, Rolain JM (2015) Clonal transmission of a colistin-resistant Escherichia coli from a domesticated pig to a human in Laos. J Antimicrob Chemother 70:3402–3404

    CAS  PubMed  Google Scholar 

  16. Olaitan AO, Chabou S, Okdah L, Morand S, Rolain JM (2016) Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 16:147

    Article  PubMed  Google Scholar 

  17. Olaitan AO, Morand S, Rolain JM (2016) Emergence of colistin-resistant bacteria in humans without colistin usage: a new worry and cause for vigilance. Int J Antimicrob Agents 47:1–3

    Article  CAS  PubMed  Google Scholar 

  18. Falgenhauer L, Waezsada SE, Yao Y, Imirzalioglu C, Käsbohrer A, Roesler U, Michael GB, Schwarz S, Werner G, Kreienbrock L, Chakraborty T, RESET consortium (2016) Colistin resistance gene mcr-1 in extended-spectrum β-lactamase-producing and carbapenemase-producing Gram-negative bacteria in Germany. Lancet Infect Dis 16:282–283

    Article  CAS  PubMed  Google Scholar 

  19. Poirel L, Kieffer N, Liassine N, Thanh D, Nordmann P (2016) Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli. Lancet Infect Dis 16:281

    Article  CAS  Google Scholar 

  20. Poirel L, Hombrouck-Alet C, Freneaux C, Bernabeu S, Nordmann P (2010) Global spread of New Delhi metallo-β-lactamase 1. Lancet Infect Dis 10:832

    Article  PubMed  Google Scholar 

  21. Malhotra-Kumar S, Xavier BB, Das AJ, Lammens C, Hoang HT, Pham NT, Goossens H (2016) Colistin-resistant Escherichia coli harbouring mcr-1 isolated from food animals in Hanoi, Vietnam. Lancet Infect Dis 16:286–287

    Article  CAS  PubMed  Google Scholar 

  22. Kusumoto M, Ogura Y, Gotoh Y, Iwata T, Hayashi T, Akiba M (2016) Colistin-resistant mcr-1-positive pathogenic Escherichia coli in swine, Japan, 2007–2014. Emerg Infect Dis 22:1315–1317

    Article  PubMed  PubMed Central  Google Scholar 

  23. Arcilla MS, van Hattem JM, Matamoros S, Melles DC, Penders J, de Jong MD, Schultsz C; COMBAT consortium (2016) Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 16:147–149

    Article  PubMed  Google Scholar 

  24. Prim N, Rivera A, Rodríguez-Navarro J, Español M, Turbau M, Coll P, Mirelis B (2016) Detection of mcr-1 colistin resistance gene in polyclonal Escherichia coli isolates in Barcelona, Spain, 2012 to 2015. Euro Surveill 21(13)

  25. Hasman H, Hammerum AM, Hansen F, Hendriksen RS, Olesen B, Agersø Y, Zankari E, Leekitcharoenphon P, Stegger M, Kaas RS, Cavaco LM, Hansen DS, Aarestrup FM, Skov RL (2015) Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveill 20(49)

  26. Kluytmans-van den Bergh MF, Huizinga P, Bonten MJ, Bos M, De Bruyne K, Friedrich AW, Rossen JW, Savelkoul PH, Kluytmans JA (2016) Presence of mcr-1-positive Enterobacteriaceae in retail chicken meat but not in humans in the Netherlands since 2009. Euro Surveill 21(9)

  27. Mediavilla JR, Patrawalla A, Chen L, Chavda KD, Mathema B, Vinnard C, Dever LL, Kreiswirth BN (2016) Colistin- and carbapenem-resistant Escherichia coli harboring mcr-1 and bla NDM-5, causing a complicated urinary tract infection in a patient from the United States. MBio 7, e01191-16

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yao X, Doi Y, Zeng L, Lv L, Liu JH (2016) Carbapenem-resistant and colistin-resistant Escherichia coli co-producing NDM-9 and MCR-1. Lancet Infect Dis 16:288–289

    Article  CAS  PubMed  Google Scholar 

  29. Liassine N, Assouvie L, Descombes MC, Tendon VD, Kieffer N, Poirel L, Nordmann P (2016) Very low prevalence of MCR-1/MCR-2 plasmid-mediated colistin resistance in urinary tract Enterobacteriaceae in Switzerland. Int J Infect Dis 51:4–5

    Article  CAS  PubMed  Google Scholar 

  30. Nordmann P, Assouvie L, Prod’Hom G, Poirel L, Greub G (2016) Screening of plasmid-mediated MCR-1 colistin-resistance from bacteremia. Eur J Clin Microbiol Infect Dis 35(11):1891–1892

    Article  CAS  PubMed  Google Scholar 

  31. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, Malhotra-Kumar S (2016) Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Surveill 21(27)

  32. Di Pilato V, Arena F, Tascini C, Cannatelli A, Henrici De Angelis L, Fortunato S, Giani T, Menichetti F, Rossolini GM (2016) mcr-1.2, a new mcr variant carried on a transferable plasmid from a colistin-resistant KPC carbapenemase-producing Klebsiella pneumoniae strain of sequence type 512. Antimicrob Agents Chemother 60:5612–5615

    Article  PubMed  Google Scholar 

  33. Nordmann P, Poirel L (2016) Plasmid-mediated colistin resistance: an additional antibiotic resistance menace. Clin Microbiol Infect 22:398–400

    Article  CAS  PubMed  Google Scholar 

  34. van Duin D, Doi Y (2015) Outbreak of colistin-resistant, carbapenemase-producing Klebsiella pneumoniae: are we at the end of the road? J Clin Microbiol 53:3116–3117

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gray JW, Mahida N (2016) How do you solve a problem like multidrug-resistant Gram-negative bacteria? J Hosp Infect 92:1–2

    Article  CAS  PubMed  Google Scholar 

  36. Skov RL, Monnet DL (2016) Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds. Euro Surveill 21(9)

  37. McGann P, Snesrud E, Maybank R, Corey B, Ong AC, Clifford R, Hinkle M, Whitman T, Lesho E, Schaecher KE (2016) Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother 60:4420–4421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yu H, Qu F, Shan B, Huang B, Jia W, Chen C, Li A, Miao M, Zhang X, Bao C, Xu Y, Chavda KD, Tang YW, Kreiswirth BN, Du H, Chen L (2016) Detection of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae from different hospitals in China. Antimicrob Agents Chemother 60:5033–5035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nordmann P, Jayol A, Poirel L (2016) Rapid detection of polymyxin resistance in Enterobacteriaceae. Emerg Infect Dis 22:1038–1043

    Article  PubMed  PubMed Central  Google Scholar 

  40. Nordmann P, Jayol A, Poirel L (2016) A universal culture medium for screening polymyxin-resistant Gram-negative isolates. J Clin Microbiol 54:1395–1399

    Article  PubMed  PubMed Central  Google Scholar 

  41. Jayol A, Dubois V, Poirel L, Nordmann P (2016) Rapid detection of polymyxin-resistant Enterobacteriaceae from blood cultures. J Clin Microbiol 54:2273–2277

    Article  CAS  PubMed  Google Scholar 

  42. Bontron S, Poirel L, Nordmann P (2016) Real-time PCR for detection of plasmid-mediated polymyxin resistance (mcr-1) from cultured bacteria and stools. J Antimicrob Chemother 71:2318–2320

    Article  CAS  PubMed  Google Scholar 

  43. Nijhuis RH, Veldman KT, Schelfaut J, Van Essen-Zandbergen A, Wessels E, Claas EC, Gooskens J (2016) Detection of the plasmid-mediated colistin-resistance gene mcr-1 in clinical isolates and stool specimens obtained from hospitalized patients using a newly developed real-time PCR assay. J Antimicrob Chemother 71:2344–2346

    Article  CAS  PubMed  Google Scholar 

  44. Schwarz S, Johnson AP (2016) Transferable resistance to colistin: a new but old threat. J Antimicrob Chemother 71:2066–2070

    Article  PubMed  Google Scholar 

  45. Jayol A, Poirel L, Dortet L, Nordmann P (2016) National survey of colistin resistance among carbapenemase-producing Enterobacteriaceae and outbreak caused by colistin-resistant OXA-48-producing Klebsiella pneumoniae, France, 2014. Euro Surveill 21:(37)

  46. Wand ME, Bock LJ, Bonney LC, Sutton JM (2016) Mechanisms of increased resistance to chlorhexidine and cross-resistance to colistin following exposure of Klebsiella pneumoniae clinical isolates to chlorhexidine. Antimicrob Agents Chemother (in press)

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Correspondence to M. F. Gros.

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Caniaux, I., van Belkum, A., Zambardi, G. et al. MCR: modern colistin resistance. Eur J Clin Microbiol Infect Dis 36, 415–420 (2017). https://doi.org/10.1007/s10096-016-2846-y

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  • DOI: https://doi.org/10.1007/s10096-016-2846-y

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