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Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
Screening and molecular characterization of plasmid-mediated fosfomycin resistance in Enterobacterales
1Department of Medical Microbiology, Konya Kulu State Hospital, Kulu, Konya, Turkey. atozluyurt92@gmail.com.
Background:
Fosfomycin, recently approved for intravenous use in several European countries for the treatment of soft-tissue, bloodstream, and urinary-tract infections, is increasingly threatened by resistance among Enterobacterales. This is particularly concerning for Escherichia coli, as fosfomycin often represents a last-resort option for urinary tract infections. To investigate the occurrence and genetic basis of resistance, 397 non-duplicate isolates (348 community-acquired and 49 hospital-acquired) were analyzed in a newly established hospital where there has been no use of fosfomycin. The isolates included Escherichia coli (n = 264), Klebsiella pneumoniae (n = 112), Enterobacter cloacae complex (n = 14), Klebsiella oxytoca (n = 6), Klebsiella aerogenes (n = 1).
Methods And Results:
Antimicrobial susceptibility testing and PCR screening for fosfomycin resistance genes revealed that only four E. coli isolates carried plasmid-mediated determinants, identified as fosA3 and fosA4, and confirmed by the sodium phosphonoformate (PPF) test. Mating-out and transformation assays showed no additional transferable fosfomycin resistance, suggesting that resistance in most Enterobacterales. was chromosomally encoded.
Conclusions:
In newly established hospital settings, such screening approaches may enable early detection of carriers and help prevent the dissemination of plasmid-mediated fosfomycin resistance via IncF-type plasmids. Routine surveillance for fosfomycin resistance may therefore support infection control efforts and help preserve the clinical effectiveness of fosfomycin.
Insights
Fosfomycin resistance in Enterobacterales is a growing concern. This study found limited plasmid-mediated resistance in a new hospital, suggesting chromosomal genes are the primary cause, highlighting the need for surveillance.
Area of Science:
- * Clinical microbiology and infectious diseases.
- * Antimicrobial resistance mechanisms and surveillance.
Background:
- * Fosfomycin is an important antibiotic for treating various infections, including urinary tract infections (UTIs).
- * Increasing resistance among Enterobacterales, particularly Escherichia coli, threatens fosfomycin's clinical utility.
- * A study was conducted in a new hospital with no prior fosfomycin use to assess resistance in Enterobacterales isolates.
Purpose of the Study:
- * To investigate the prevalence and genetic basis of fosfomycin resistance in Enterobacterales.
- * To identify potential mechanisms of resistance, including plasmid-mediated and chromosomal genes.
- * To inform infection control strategies in healthcare settings.
Main Methods:
- * Analysis of 397 non-duplicate Enterobacterales isolates (E. coli, K. pneumoniae, etc.).
- * Antimicrobial susceptibility testing and PCR screening for fosfomycin resistance genes (fosA3, fosA4).
- * Sodium phosphonoformate (PPF) test, mating-out, and transformation assays to assess resistance transferability.
Main Results:
- * Only four E. coli isolates exhibited plasmid-mediated fosfomycin resistance determinants (fosA3 and fosA4).
- * Transferability assays indicated that most fosfomycin resistance in Enterobacterales was chromosomally encoded.
- * No additional transferable fosfomycin resistance was detected.
Conclusions:
- * Early detection of fosfomycin resistance carriers is crucial in new hospital settings.
- * Screening can prevent the spread of plasmid-mediated resistance, particularly via IncF-type plasmids.
- * Routine surveillance of fosfomycin resistance supports infection control and preserves antibiotic effectiveness.
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