Fosfomycin Resistance in Escherichia coli Isolates from South Korea and in vitro Activity of Fosfomycin Alone and in Combination with Other Antibiotics

Abstract

We investigated fosfomycin susceptibility in Escherichia coli clinical isolates from South Korea, including community-onset, hospital-onset, and long-term care facility (LTCF)-onset isolates. The resistance mechanisms and genotypes of fosfomycin-resistant isolates were also identified. Finally, the in vitro efficacy of combinations of fosfomycin with other antibiotics were examined in susceptible or extended spectrum β-lactamase (ESBL)-producing E. coli isolates. The fosfomycin resistance rate was 6.7% and was significantly higher in LTCF-onset isolates than community-onset and hospital-onset isolates. Twenty-one sequence types (STs) were identified among 19 fosfomycin-resistant E. coli isolates, showing diverse genotypes. fosA3 was found in only two isolates, and diverse genetic variations were identified in three genes associated with fosfomycin resistance, namely, GlpT, UhpT, and MurA. Some fosfomycin-resistant E. coli isolates carried no mutations. In vitro time-kill assays showed that fosfomycin alone did not exhibit an excellent killing activity, compared with ciprofloxacin in susceptible isolates and with ertapenem in ESBL producers. However, combining fosfomycin with cefixime or piperacillin-tazobactam eradicated susceptible or ESBL-producing isolates, respectively, even with 0.5× minimum inhibitory concentrations. Overall, we found a relatively high fosfomycin resistance rate in E. coli isolates from South Korea. Based on their genotypes and resistance mechanisms, most of the fosfomycin-resistant E. coli isolates might occur independently. Antibiotic combinations with fosfomycin could be a suitable therapeutic option for infections caused by E. coli isolates.

Identification of metallo-β-lactamases and AmpC production among Escherichia coli strains isolated from hemodialysis patients with urinary tract infection

“…This phenomenon may arise from the high prevalence of different carbapenemase genes that can develop resistance to carbapenem antibiotics [ 28 ]. Although FOS was the most effective antibiotic, its resistance rate (12.8%) was higher than the rate reported in South Korea (6.7%) [ 29 ].…”

Novel Chromosomal Mutations Responsible for Fosfomycin Resistance in Escherichia coli

“…Unexpectedly, we found here novel mutations in uhpB and uhpC in mutants, which are not often detected in fosfomycinresistant clinical isolates. Indeed, fosfomycin resistance in E. coli clinical isolates is usually due to chromosomal mutations in uhpT, uhpA, glpT, murA, cyaA, and ptsI genes (Nilsson et al, 2003;Oteo et al, 2009;Takahata et al, 2010;Li et al, 2015b;Tseng et al, 2015;Ohkoshi et al, 2017;Lucas et al, 2018;Seok et al, 2020), and little is known about the involvement of mutations in other genes, especially those in uhpB and uhpC that have been exceptionally reported (Castaneda-Garcia et al, 2013).…”

High-Frequency Detection of fosA3 and blaCTX–M–55 Genes in Escherichia coli From Longitudinal Monitoring in Broiler Chicken Farms

“… Derington et al (2020) tested fosfomycin as a therapeutic option for treating complicated urinary tract infections, leading to the resolution of the evaluated conditions. Based on these results, they, and other authors report that fosfomycin is an essential human therapeutic option ( Wachino et al, 2010 ; Neuner et al, 2012 ; Jean et al, 2016 ; Cao et al, 2017 ; Abbott et al, 2020 ; Loras et al, 2020 ; Seok et al, 2020 ), against urinary infections for example, the second most important bacterial infection affecting humans ( Moeinizadeh and Shaheli, 2021 ).…”