title: The antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL-producing Escherichia coli in Norway 2010-2011.
abstract: BACKGROUND
  The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10-15 years as part of a global pandemic. ESBL producers frequently express co-resistance to other important antimicrobial drug classes, limiting therapeutic options. This has led to regained interest in older antimicrobial agents. The aim of this study was to evaluate the antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin, as well as to perform a comparative analysis of resistance patterns in a nationwide collection of ESBL-producing E. coli.
  
  
  METHODS
  A nationwide collection of all 105 clinical isolates of ESBL-producing E. coli from the Norwegian Organisation for Surveillance of Antimicrobial Resistance (NORM) during 2010-2011 was analyzed. Detection and identification of ESBL-encoding genes were performed by PCR and sequencing for confirmation of ESBL variants of blaTEM and blaSHV (2010) or microarray (2011). Minimum inhibitory concentrations (MICs) or MIC correlates were determined using MIC gradient tests or VITEK 2, respectively. Comparative analysis of resistance patterns was performed.
  
  
  RESULTS
  All isolates were susceptible to fosfomycin, temocillin (urinary tract breakpoint) and meropenem. For mecillinam and nitrofurantoin, 6% and 9% of the isolates, respectively, were non-susceptible. A high level of susceptibility was also observed for amikacin (95%). In contrast, the non-susceptibility proportions to ampicillin (100%), cefotaxime (97%), ceftazidime (77%), aztreonam (87%), gentamicin (42%), tobramycin (52%), ciprofloxacin (76%) and trimethoprim-sulfamethoxazole (71%) were higher.
  
  
  CONCLUSIONS
  Overall, the in vitro susceptibility to nitrofurantoin, fosfomycin, mecillinam and temocillin was high, indicating that these drugs are good options for treating uncomplicated urinary tract infections caused by ESBL-producing E. coli.
authors.affiliation: a Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control , University Hospital of North Norway , Tromsø , Norway.|b Research Group for Host-Microbe Interactions, Department of Medical Microbiology, Faculty of Health Sciences , University of Tromsø - Arctic University of Norway , Tromsø , Norway.
authors.forename: Ilya Nikolaevich
authors.initials: IN
authors.lastname: Zykov
authors.affiliation: a Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control , University Hospital of North Norway , Tromsø , Norway.|b Research Group for Host-Microbe Interactions, Department of Medical Microbiology, Faculty of Health Sciences , University of Tromsø - Arctic University of Norway , Tromsø , Norway.
authors.forename: Arnfinn
authors.initials: A
authors.lastname: Sundsfjord
authors.affiliation: c Department of Pharmacy, Faculty of Health Sciences , University of Tromsø - Arctic University of Norway , Tromsø , Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Småbrekke
authors.affiliation: a Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control , University Hospital of North Norway , Tromsø , Norway.|c Department of Pharmacy, Faculty of Health Sciences , University of Tromsø - Arctic University of Norway , Tromsø , Norway.
authors.forename: Ørjan
authors.initials: Ø
authors.lastname: Samuelsen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology*; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009582:Nitrofurantoin / Q000494:pharmacology*; D009664:Norway; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D047090:beta-Lactams; D005578:Fosfomycin; D009582:Nitrofurantoin; D001618:beta-Lactamases
keywords: ESBL; fosfomycin; older antibiotics; temocillin