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 bla_TEM and bla_SHV (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.

Keywords:

• ESBL
• older antibiotics
• fosfomycin
• temocillin

Acknowledgements

This work was supported by a research grant from the Northern Norway Regional Health Authority (SFP1051-12). We acknowledge the excellent technical assistance from Bjørg Haldorsen and Bettina Aasnæs. We also acknowledge all participating laboratories in the Norwegian Organisation for Surveillance of Antimicrobial Resistance for excellent collaboration.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.