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Objectives Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam. Methods We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method. Results For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement ≥ 90%; bias ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used. Conclusions Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.
Objectives Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam. Methods We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method. Results For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement ≥ 90%; bias ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used. Conclusions Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.
Background : Mecillinam, an amidinopenicillin antibiotic, has been used to treat urinary tract infections and bacterial enteritis in many countries. In this study, we evaluated in vitro activity of mecillinam against Enterobacteriaceae isolates from urine, and Salmonella and Shigella isolates from patients with bacterial gastroenteritis. Results : In E. coli, rate of susceptibility to ampicillin was 30%, but 99-100% to amikacin and cefotaxime. Most (96%) of E. coli isolates, including extended-spectrum β-lactamase (ESBL) producers, were susceptible to mecillinam. All ESBL producers, except for one isolate, were inhibited by ≤4 µg/mL of mecillinam. MIC90 of mecillinam for K. pneumoniae and Enterobacter spp. was 8 µg/mL and 1 µg/mL, respectively, and the susceptibility rate was 92% and 97%, respectively. However, MIC90 of mecillinam for S. marcescens isolates was >128 µg/mL and most of them were resistant to mecillinam. All Salmonella isolates and 27 of 30 Shigella isolates were susceptible to mecillinam. Conclusion : Mecillinam was active in vitro against most Enterobacteriaceae, Salmonella, and Shigella isolates except for S. marcescens. Therefore, mecillinam can be a good alternative agent for treating urinary tract infection and bacterial gastroenteritis.
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