The increasing emergence of multidrug-resistant (MDR) bacteria has led to a growing need for new strategies to treat MDR bacterial infections. Fosfomycin is an older antibiotic that belongs to the group of phosphonic antibiotics. Due to its low molecular weight and low binding to plasma proteins in the body, it achieves good distribution and high tissue diffusibility. It reaches peak serum concentrations after 2-2.5 hours. Intravenously administered fosfomycin is excreted in the kidneys unchanged by glomerular filtration at a rate of 90%. Fosfomycin enters the bacterial cytoplasm through the hexose phosphate and glycerol-3-phosphate transport systems and functions as an analogue of phosphoenolpyruvate inhibiting the enzyme-catalysed first-stage reaction of peptidoglycan synthesis. It has a wide spectrum of activity as it is effective against several MDR Gram-negative and Gram-positive bacteria. It is an overall safe antibiotic indicated for treating uncomplicated urinary tract infection both in Europe and in the USA and may also be used in Europe for treating other urinary tract infections, sepsis and soft tissue infections. The most relevant resistance mechanism is enzyme inactivation. The reference method for determining the susceptibility of bacteria to fosfomycin according to EUCAST is the agar dilution method, which was performed to determine the distribution of minimum inhibitory concentrations (MIC) of selected Enterobacteriaceae isolates (N 506) and Acinetobacter baumannii (N 55). There are significant differences in MIC50, MIC90, and in tentative epidemiological cut-off values between individual Enterobacteriaceae species with the lowest values determined for Escherichia coli and Citrobacter spp., whereas the others were significantly higher. The susceptibility of E. coli isolates to oral fosfomycin was high and amounted to 93.4%. 95.5% of E. coli isolates, 66.2% of Klebsiella pneumoniae isolates, 92.2% of K. oxytoca isolates, 50.0% of Enterobacter cloacae complex isolates, and 97.1% of Citrobacter spp. isolates were susceptible to intravenous fosfomycin. A significant difference in susceptibility between non-MDR and MDR isolates was observed only for K. pneumoniae (79.8% and 39.6%). Considering the enterobacterial cut-off values, 1.8% of A. baumannii isolates would be susceptible to intravenous fosfomycin. Simpler commercial gradient diffusion tests are often used to determine MICs. EUCAST advises against them for fosfomycin susceptibility testing due to unreliable results. During our study, we analyzed categorical agreement and observed a major error rate of 0.8% and a very major error rate of 0.8% for oral fosfomycin, and a major error rate of 2.4% for intravenous fosfomycin which is no longer acceptable for a diagnostic test.
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