Assessment of the Susceptibility of Clinical Gram-Negative and Gram-Positive Bacterial Strains to Fosfomycin and Significance of This Antibiotic in Infection Treatment

Abstract

Multidrug resistance of bacteria has prompted intensive development work on new medicines, but also the search for effective options among the oldest antibiotics. Although intravenous fosfomycin (IVFOS) seems to be an interesting proposal, the recommended agar dilution method for susceptibility determination poses a major problem in routine diagnostic testing. As a consequence, there is a lack of comprehensive data on the frequency of isolation of susceptible or resistant strains. This fact triggered the disposition of EUCAST concerning the revision of IVFOS breakpoints (BPs), including withdrawal of BPs for Enterobacterales (excluding E. coli) and coagulase-negative staphylococci. Therefore, the aim of this study was to assess the activity of fosfomycin against numerous clinical strains using recommended methods. Materials and methods: A total of 997 bacterial strains were tested from the following genera: Enterobacterales, Pseudomonas spp., Staphylococcus spp., Acinetobacter spp., and Enterococcus spp., for which there are currently no BPs. The strains were isolated from various clinical materials from patients hospitalized in five hospitals. During the investigation, the recommended agar dilution method was used. Susceptibility to other antibiotics and resistance mechanisms were determined using an automatic method (Phoenix) the disk diffusion method, and E-tests. MIC values of fosfomycin were estimated for all strains and for susceptible and multidrug-resistant (MDR) strains individually. Results: Except for Acinetobacter and Enterococcus, 83% of the strains were susceptible to IVFOS, including the largest percentage of S. aureus and E. coli. Klebsiella spp. turned out to be the least susceptible strains (66%). The highest proportion of susceptibility to fosfomycin was found among strains that were sensitive to other antibiotics (80.9%), and the lowest was found among Gram-negative carbapenemase-producing bacteria (55.6%) and ESBL+ bacteria (61.6%). The MIC evaluation revealed the lowest MIC50 and MIC90 values for S. aureus (0.5 mg/L and 1 mg/L, respectively) and E. coli (4 mg/L and 32 mg/L, respectively). The highest values of MIC50 were found for Acinetobacter spp. (256 mg/L), while the highest values of MIC90 were found for Acinetobacter spp. and Klebsiella spp. (256 mg/L and 512 mg/L, respectively). Conclusions: IVFOS appears to be suitable for the treatment of many infections, including the empirical treatment of polymicrobial infections and those caused by MDR strains, since the sensitivity of the studied strains to this antibiotic in different groups ranged from 66% to as much as 99%. Sensitivity to fosfomycin was also demonstrated by 60% of carbapenem-resistant strains; therefore, IVFOS is one of the few therapeutic options that can be effective against the most resistant Gram-negative rods. In light of the general consultation posted by EUCAST, obtaining data such as IVFOS MIC value distributions may be vital for the decision of implementing fosfomycin into breakpoint tables.

Self-Charging, Breathable, and Antibacterial Poly(lactic acid) Nanofibrous Air Filters by Surface Engineering of Ultrasmall Electroactive Nanohybrids

“…As a result, the average diameter of ZIF-8 obtained on surface-functionalized BTO was notably reduced by 52%. We proposed the growth mechanisms of BTO@ZIF-8 to interpret the decreased diameter, and the surface functionalization of BTO accelerated its combination process with ZIF-8, which contributed to the growth termination of ZIF-8 . It is anticipated that BTO@ZIF-8 was embedded into PLA fibers to improve the PM capture capability and enhance the slip effect, lowering the air resistance of PLA/BZ NFMs and also contributing to the promotion of filtration efficiency …”

“…We proposed the growth mechanisms of BTO@ZIF-8 to interpret the decreased diameter, and the surface functionalization of BTO accelerated its combination process with ZIF-8, which contributed to the growth termination of ZIF-8. 32 It is anticipated that BTO@ZIF-8 was embedded into PLA fibers to improve the PM capture capability and enhance the slip effect, 33 lowering the air resistance of PLA/BZ NFMs and also contributing to the promotion of filtration efficiency. 25 The energy-dispersive spectrometry (EDS) mapping images showed that both Ba and Ti elements belonging to BTO, along with both Zn and N elements attributed to ZIF-8, were simultaneously determined in BTO@ZIF-8 (Figure 2d,e).…”

Reliability of E-Tests and the Phoenix Automated Method in Assessing Susceptibility to IV Fosfomycin—Comparative Studies Relative to the Reference Method

“…It is mentioned in combination therapy in infections with ESBL-producing strains as an alternative treatment regimen to carbapenems against carbapenemase-producing Gram-negative bacilli, colistin-resistant Gram-negative bacilli, difficult-to-treat P. aeruginosa , or infections with methicillin-resistant staphylococci [ 25 , 26 , 27 , 28 , 29 , 30 ]. High sensitivity to fosfomycin has been demonstrated in many studies, including our own published in 2022 [ 31 ]. At that time, nearly 78% of susceptible strains were found among Enterobacterales and nearly 91% in Pseudomonas spp.…”

“…At that time, nearly 78% of susceptible strains were found among Enterobacterales and nearly 91% in Pseudomonas spp. and Staphylococcus strains [ 31 ]. In addition, multi-resistant strains, such as MBL-producing Pseudomonas spp.…”

Use of Newer and Repurposed Antibiotics against Gram-Negative Bacteria in Neonates

“…Fosfomycin’s unique mechanism of action permits synergy with other antibiotics (carbapenems and aminoglycosides), as has been demonstrated in vitro. Resistance to fosfomycin can develop rapidly when it is used in monotherapy and can be either chromosomal or plasmid-mediated [ 126 ].…”