title: In vitro activity of rifaximin against clinical isolates of Escherichia coli and other enteropathogenic bacteria isolated from travellers returning to the UK.
abstract: Rifaximin is licensed in the EU and USA for treating travellers' diarrhoea caused by non-invasive bacteria. Selection for resistance mechanisms of public health significance might occur if these are linked to rifamycin resistance. Rifaximin MICs were determined by agar dilution for 90 isolates each of Escherichia coli, Shigella spp., nontyphoidal Salmonella enterica, typhoidal S. enterica and Campylobacter spp., an additional 60 E. coli with CTX-M ESBLs isolated from patients with travellers' diarrhoea, and 30 non-diarrhoeal carbapenemase-producing E. coli. Comparators were rifampicin, ciprofloxacin, azithromycin, trimethoprim/sulfamethoxazole and doxycycline. Isolates with rifaximin MICs>32 mg/L were screened for arr genes, and critical rpoB regions were sequenced. Rifaximin was active at ≤32 mg/L against 436/450 (96.9%) diverse Enterobacteriaceae, whereas 81/90 (90%) Campylobacter spp. were resistant to rifaximin at ≥128 mg/L. Rifaximin MICs were ≥128 mg/L for two Shigella and five MDR E. coli producing NDM (n = 3), OXA-48 (n = 1) or CTX-M-15 (n = 1). Two of the five MDR E. coli had plasmids harbouring arr-2 together with bla(NDM), and two (one each with bla(NDM) and bla(CTX-M-15)) had His526Asn substitutions in RpoB. The rifamycin resistance mechanism remained undefined in one MDR E. coli isolate (with bla(OXA-48)) and the two Shigella isolates. Rifaximin showed good in vitro activity against diverse Enterobacteriaceae but was largely inactive against Campylobacter spp. Rifaximin has potential to co-select MDR E. coli in the gut flora, but much stronger associations were seen between ESBL and/or carbapenemase production and resistance to alternative treatments for travellers' diarrhoea, notably ciprofloxacin and azithromycin.
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK. Electronic address: katie.hopkins@phe.gov.uk.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Hopkins
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Shazad
authors.initials: S
authors.lastname: Mushtaq
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Judith F
authors.initials: JF
authors.lastname: Richardson
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Michel
authors.initials: M
authors.lastname: Doumith
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: de Pinna
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Cheasty
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK; Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK; Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D003967:Diarrhea / Q000382:microbiology*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology*; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000032:analysis; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin; D017422:Sequence Analysis, DNA; D014195:Travel; D006113:United Kingdom; D001618:beta-Lactamases / Q000235:genetics
chemical_list: C119094:ARR-2 protein, Bacteria; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D001618:beta-Lactamases; D000078262:Rifaximin
keywords: ADP-ribosyltransferases; CTX-M β-lactamases; Rifamycin resistance; Travellers’ diarrhoea; bla(NDM); rpoB