title: Within-population distribution of trimethoprim resistance in Escherichia coli before and after a community-wide intervention on trimethoprim use.
abstract: A 2-year prospective intervention on the prescription of trimethoprim reduced the use by 85% in a health care region with 178,000 inhabitants. Here, we performed before-and-after analyses of the within-population distribution of trimethoprim resistance in Escherichia coli. Phylogenetic and population genetic methods were applied to multilocus sequence typing data of 548 consecutively collected E. coli isolates from clinical urinary specimens. Results were analyzed in relation to antibiotic susceptibility and the presence and genomic location of different trimethoprim resistance gene classes. A total of 163 E. coli sequence types (STs) were identified, of which 68 were previously undescribed. The isolates fell into one of three distinct genetic clusters designated BAPS 1 (E. coli phylogroup B2), BAPS 2 (phylogroup A and B1), and BAPS 3 (phylogroup D), each with a similar frequency before and after the intervention. BAPS 2 and BAPS 3 were positively and BAPS 1 was negatively associated with trimethoprim resistance (odds ratios of 1.97, 3.17, and 0.26, respectively). In before-and-after analyses, trimethoprim resistance frequency increased in BAPS 1 and decreased in BAPS 2. Resistance to antibiotics other than trimethoprim increased in BAPS 2. Analysis of the genomic location of different trimethoprim resistance genes in isolates of ST69, ST58, and ST73 identified multiple independent acquisition events in isolates of the same ST. The results show that despite a stable overall resistance frequency in E. coli before and after the intervention, marked within-population changes occurred. A decrease of resistance in one major genetic cluster was masked by a reciprocal increase in another major cluster.
authors.affiliation: Department of Clinical Microbiology, Central Hospital, Växjö, Sweden Department of Medical Sciences, Division of Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Sundqvist
authors.affiliation: The Laboratory for Molecular Infection Medicine Sweden, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Granholm
authors.affiliation: Reference Centre for Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
authors.forename: Umaer
authors.initials: U
authors.lastname: Naseer
authors.affiliation: Department of Mathematics and Mathematical Statistics, Umeå University, Umeå, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydén
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alma
authors.initials: A
authors.lastname: Brolund
authors.affiliation: Reference Centre for Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
authors.forename: Arnfinn
authors.initials: A
authors.lastname: Sundsfjord
authors.affiliation: Department of Clinical Microbiology, Central Hospital, Växjö, Sweden Department of Medical Sciences, Division of Clinical Bacteriology, Uppsala University, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kahlmeter
authors.affiliation: The Laboratory for Molecular Infection Medicine Sweden, Department of Clinical Microbiology, Umeå University, Umeå, Sweden anders.johansson@climi.umu.se.
authors.forename: Anders
authors.identifier: http://orcid.org/0000-0003-0548-5943
authors.initials: A
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001437:Bacteriuria / Q000188:drug therapy / Q000382:microbiology; D002648:Child; D002874:Chromosome Mapping; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D057970:Inappropriate Prescribing / Q000517:prevention & control*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D058885:Multilocus Sequence Typing; D013548:Sweden; D014295:Trimethoprim / Q000627:therapeutic use*; D014296:Trimethoprim Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D014295:Trimethoprim