BACKGROUND: FosA10-producing Enterobacterales have an extremely low incidence in Europe. PATIENTS AND METHODS: In March 2024, an 83-year-old woman, hospitalized in the Modena Province, developed an infection with fosfomycin-resistant Escherichia coli. The patient was treated with piperacillin/tazobactam and, after 10 days, the clinical picture was resolved. Fosfomycin MIC was evaluated with the reference agar dilution method and the production of FosA enzymes by phenotypic testing. Genomic characterization was assessed using long-read sequencing technology on the Sequel I platform. RESULTS: An E. coli isolate (FO_2) was collected from both blood and urine samples and showed high-level resistance to fosfomycin (MIC > 128 mg/L). The resistance to fosfomycin was ascribed to the production of FosA-like enzymes by phenotypic testing. The genomic analysis pointed to a FosA10-producing E. coli ST69. The fosA10 gene was carried by a highly conjugative IncB/O/K/Z plasmid that showed relevant similarities with other globally circulating plasmids. CONCLUSIONS: The acquisition of rare fosA-like genes in clinically relevant clones is concerning and the dissemination of FosA-producing E. coli should be continuously monitored.

• Publication type
• Journal Article MeSH

Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.

• Keywords
• Citrobacter freundii, carbapenemases, fosA3 gene, fosfomycin, fosfomycin resistance,
• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Bacterial Proteins * genetics   metabolism   MeSH
• beta-Lactamases * genetics   metabolism   MeSH
• Citrobacter freundii * genetics   enzymology   drug effects   MeSH
• Enterobacteriaceae Infections * microbiology   MeSH
• Fosfomycin * pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Drug Resistance, Multiple, Bacterial genetics   MeSH
• Plasmids genetics   MeSH
• Whole Genome Sequencing MeSH
• DNA Transposable Elements MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Italy epidemiology   MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Bacterial Proteins * MeSH
• beta-Lactamases * MeSH
• carbapenemase MeSH Browser
• Fosfomycin * MeSH
• DNA Transposable Elements MeSH

Fosfomycin-resistant FosA8-producing Enterobacterales are uncommon strains with extremely low incidence in Europe, based on only three reports in the literature. We detected FosA8-producing Escherichia coli ST131 in clinical isolates from two patients admitted in February 2023 to a rehabilitation unit in Italy. The occurrence of rare fosA-like genes in the high-risk clone ST131 is of clinical relevance. The dissemination of FosA-producing E. coli, although still at low levels, should be continuously monitored.

• Keywords
• E. coli ST131, FosA8, Fosfomycin, Fosfomycin resistance,,
• MeSH
• Anti-Bacterial Agents * pharmacology   therapeutic use   MeSH
• Drug Resistance, Bacterial MeSH
• beta-Lactamases genetics   metabolism   MeSH
• Escherichia coli * isolation & purification   genetics   drug effects   MeSH
• Fosfomycin pharmacology   therapeutic use   MeSH
• Escherichia coli Infections * microbiology   epidemiology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Multilocus Sequence Typing MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Geographicals
• Italy epidemiology   MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• beta-Lactamases MeSH
• Fosfomycin MeSH