Update on fosfomycin-modified genes in Enterobacteriaceae.

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Fosfomycin, a long-used antibiotic, is being re-evaluated for treating infections caused by extended-spectrum β-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE).
• Fosfomycin exhibits a strong bactericidal effect against these multidrug-resistant pathogens.
• However, the emergence of fosfomycin resistance due to fos genes, particularly in East Asia, poses a significant challenge.

Purpose of the Study:

• To review the prevalence and characteristics of fosfomycin-modified (fos) genes in Enterobacteriaceae.
• To assess the efficacy of fosfomycin in treating infections caused by multidrug-resistant Enterobacteriaceae.
• To highlight the role of mobile genetic elements in the dissemination of fos genes.

Main Methods:

• Literature review of studies reporting fos genes in Enterobacteriaceae.
• Analysis of the types and locations of identified fos genes (e.g., fosA, fosC2).
• Examination of the association between fos genes, mobile elements (plasmids, transposons, integrons), and antibiotic resistance.

Main Results:

• Over 10 types of fos genes have been identified in the last decade, with fosA and fosC2 being common in Enterobacteriaceae.
• Most fosA subtypes are located on mobile genetic elements, facilitating their spread.
• The fosA3 gene, prevalent in East Asia, has spread globally via IS26 elements, often through animal reservoirs.

Conclusions:

• Fosfomycin remains a valuable agent against ESBL- and CRE-producing Enterobacteriaceae.
• The increasing prevalence of fos genes necessitates careful monitoring and understanding of resistance mechanisms.
• Combined therapeutic strategies, such as fosfomycin with carbapenems, require further in vivo validation, including pharmacokinetic studies.