title: Ceftriaxone-resistant Salmonella enterica serotype typhimurium sequence type 313 from Kenyan patients is associated with the blaCTX-M-15 gene on a novel IncHI2 plasmid.
abstract: Multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidal Salmonella (NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to β-lactams, including to ceftriaxone, was associated with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade within S. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.
authors.affiliation: Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom samkariuki2@gmail.com.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kariuki
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Chinyere
authors.initials: C
authors.lastname: Okoro
authors.affiliation: Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Kiiru
authors.affiliation: Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Samuel
authors.identifier: http://orcid.org/0000-0001-6965-3681
authors.initials: S
authors.lastname: Njoroge
authors.affiliation: Aga Khan University Hospital, Nairobi, Kenya.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Omuse
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Gemma
authors.initials: G
authors.lastname: Langridge
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Aga Khan University Hospital, Nairobi, Kenya.
authors.forename: Gunturu
authors.initials: G
authors.lastname: Revathi
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002443:Ceftriaxone; D002444:Cefuroxime / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D007630:Kenya; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D065288:Serogroup
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002701:Chloramphenicol; D002443:Ceftriaxone; D000667:Ampicillin; D002444:Cefuroxime