title: How should we respond to the emergence of plasmid-mediated colistin resistance in humans and animals?
abstract: OBJECTIVE
  The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review.
  
  
  METHODS
  The literature on colistin resistance was reviewed.
  
  
  RESULTS
  Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2, has been isolated from porcine and bovine Escherichia coli.
  
  
  CONCLUSIONS
  The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans.
authors.affiliation: Johns Hopkins Aramco Healthcare, PO Box 76, Room A-428-2, Building 61, Dhahran Health Center, Dhahran 31311, Kingdom of Saudi Arabia; Indiana University School of Medicine, Indianapolis, Indiana, USA. Electronic address: jaffar.tawfiq@aramco.com.
authors.forename: Jaffar A
authors.initials: JA
authors.lastname: Al-Tawfiq
authors.affiliation: Center for Disease Dynamics, Economics, and Policy, Washington, DC, USA; Princeton University, Princeton, New Jersey, USA.
authors.forename: Ramanan
authors.initials: R
authors.lastname: Laxminarayan
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Marc
authors.initials: M
authors.lastname: Mendelson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000662:veterinary*; D006801:Humans; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Colistin resistance; Multi-drug resistant bacteria; Plasmid-mediated colistin