Background: fosfomycin (FOS) is a broad-spectrum antibiotic that inhibits cell wall synthesis. It has bactericidal activity against both gram-positive and gram-negative bacteria. FOS also promotes phagocytosis, has immunomodulatory effects, and protects against the toxicity caused by other drugs. On the contrary, deoxynivalenol (DON) causes cytotoxicity on tissues of rapid growth and fast turnover. Objectives: The aim of this study was to determine the percentage of nuclear changes indicative of DONinduced apoptosis on intestinal cell cultures (Caco-2) and to evaluate the protective effect of FOS on mycotoxin-exposed cells. Materials and Methods: Cell cultures were treated as follows: (1) DON: 2. 8 µ g/mL, (2) calcium FOS: 580 µ g/mL, (3) DON 2. 8 µ g/mL + calcium FOS 580 µ g/mL, and (4) negative control. Nuclear morphology was evaluated in fixed cells stained with 4′ , 6-diamino-2-phenylindol and then visualized under an immunofluorescence microscope. Results: Percentages of cells with nuclear changes were significantly higher in cells treated with DON (31. 53% ± 4. 17%) compared to those incubated with the antibiotic in conjunction with the mycotoxin (5. 63% ± 4. 23%). On the contrary, there were no significant differences between cells incubated with DON + FOS and cells incubated only with the antibiotic (1. 10% ± 1. 55%) when compared to the negative control (3. 50% ± 0. 09%). Conclusion: The results from this study showed that DON induces nuclear changes suggestive of apoptosis in intestinal cells and that FOS can protect cells from DNA damage. Further studies are needed to determine whether DON induces apoptosis only on cells of epithelial origin and to understand the implications of FOS protective effect under in vivo conditions.

Aims: Pseudomonas aeruginosa is considered as an important opportunistic bacterial pathogen associated with nosocomial infections. Therefore, it is important to identify this bacterium in clinical samples and report the results to health authorities. The aim of this study was the molecular identification of some virulence factors and fosfomycin resistance genes in P. aeruginosa strains. Materials & Methods: A total of 100 P. aeruginosa strains were isolated from clinical samples of patients with eye infections in three distinct laboratories in Tehran hospitals (Pars, Milad, and Motahari). The antibiogram of all isolates against eight antibiotics was determined by standard Kirby-Bauer disk diffusion method. Then DNA was extracted from the isolates, and the frequency of exoY, exoT, exoU, exoS, fosC, fosB, and fosA genes was evaluated by multiplex PCR (polymerase chain reaction). Findings: The highest resistance was observed to cotrimoxazole (85%), ceftazidime (83%), cefotaxime (79%), and cefepime (72%), and the highest sensitivity was observed to ciprofloxacin (55%), gentamicin (52%), and piperacillin (41%), respectively. Out of 60 investigated isolates, 58 isolates were positive for exoY, exoT, and exoU, while only four isolates were exoS positive. In addition, one strain (1.66%) had the fosC gene, two strains (3.33%) had the fosB gene, and 12 strains (20.02%) had the fosA gene. Conclusion: The results showed that the frequency of fosfomycin resistance genes, whose protein product modifies the epoxide group of fosfomycin and reduces the effectiveness of this antibiotic, was significantly low in the investigated strains.

Background & Aims: Escherichia coli, a gram-negative bacillus, is one of the most common pathogens causing urinary tract infections. Several studies have demonstrated that the antibiotic fosfomycin has a significant inhibitory effect on Gram-negative pathogens, including Escherichia coli, by inhibiting peptidoglycan production. This study aimed to better understand the effect of fosfomycin against multidrug-resistant Escherichia coli causing urinary tract infections. Materials and Methods: In this epidemiologic-descriptive study, 90 Escherichia coli isolates were collected between October 1401 and October 1402 from urine samples of teaching hospitals in Qazvin city. ESBL-and AmpC-producing strains were identified using the phenotypic method. Data were evaluated and analyzed using SPSS software version 2022 with a significance level of less than 0. 05. Results: Among the 90 isolates of Escherichia coli, the highest antibiotic resistance was observed for ampicillin (96. 6%), cefotaxime (90%), and ceftazidime (84. 4%), while the highest susceptibility was related to the antibiotics fosfomycin (98. 9%), meropenem (98. 8%), gentamicin (88. 8%), and nitrofurantoin (84. 4%). Conclusion: With the increase in antibiotic resistance and the spread of strains producing beta-lactamase enzymes, the treatment of infections caused by these strains has become a serious problem. In this study, the susceptibility of Escherichia coli isolates that produce broad-spectrum beta-lactamases and are resistant to multiple drugs to fosfomycin was investigated. It was found that 89 (98. 9%) isolates were sensitive to fosfomycin, indicating that fosfomycin is an effective antibiotic against ESBL isolates in Iran.

Background and Objectives: Urinary tract infection is one of the most common bacterial infections causing high morbidity and mortality. The alarming rise of multidrug-resistant uropathogens worldwide forced the clinician to re-think the old drugs like fosfomycin for its therapeutic management. Our objective was to compare agar dilution, disc diffusion and E-test method for antimicrobial susceptibility testing of fosfomycin against different drug-resistant uropathogens. Materials and Methods: Consecutive 181 uropathogens were tested for fosfomycin susceptibility using agar dilution, disc diffusion and E-test. Results were interpreted using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Whole genome sequencing analysis was done on the 4 XDR/PDR fosfomycin resistant Klebsiella pneumoniae isolates. Results: Escherichia coli was found as the most common (62. 4%) uropathogen followed by Klebsiella pneumoniae (21%). Considering agar dilution as the gold standard, 6. 1% of isolates were resistant to fosfomycin. Following CLSI breakpoints, the susceptibility of Escherichia coli, Klebsiella pneumoniae, other Enterobacterales and Pseudomonas aeruginosa were 92. 9%, 92. 1%, 100%, 100%,whereas using EUCAST breakpoints the susceptibility rates were 85. 7%, 86. 9%, 92. 9%, and 100%, respectively. The essential agreement, categorical agreement, major error, and very major error for E-test/ disc diffu-sion for all the organisms were 91. 2%/Not Applicable, 95%/93. 9%, 1. 8%/4. 7%, 9. 1%/9. 1%, respectively. Whole-genome sequencing showed mutation UhpT gene as well as the presence of plasmid-mediated fosA5 or fosA6 genes conferring Fos-fomycin resistance. Conclusion: This result supports very low resistance of Enterobacterales against fosfomycin,hence should be considered a valuable option to treat multidrug-resistant uropathogens. Disc diffusion was observed to be a convenient method for Fosfo-mycin susceptibility testing compared to agar dilution.

Background and Objectives: Biofilm formation is an important virulence factor for methicillin-resistant Staphylococcus aureus (MRSA). fosfomycin is a borad-spectrum antibiotic with inhibitory effects on biofilm production and β-Chloro-L-alanine (β-CLA) is an amino acid analog. The aim of this study was to determine effect of the combination of fosfomycin and β-CLA on biofilm production by MRSA isolates. Also, the clonal relatedness of the isolates was evaluated. Materials and Methods: To determine the ability of biofilm production by 42 MRSA isolates, microtiter plate method was used. Antibacterial activities of fosfomycin and β-CLA were investigated by determining MICs and MBCs. Antibiofilm activities were measured in the presence of sub-MIC concentrations of fosfomycin, β-CLA or a combination of both. RAPDPCR was used for investigating the clonal relationship between isolates by the two specific primers. Results: 21. 4% of isolates were strong and 5% were moderate biofilm producers. The effect of fosfomycin plus β-CLA treatment on biofilm production was significantly different from non-treated, fosfomycin and β-CLA groups (p=0. 00, 0. 004 and 0. 000 respectively). RAPD-PCR analysis revealed that the RAPD1 primer had more discriminatory power. The Sizes of RAPD-PCR bands ranged from 150 bp to 1500 bp and the number of bands varied from 1 to 13. Conclusion: Clonal relatedness of isolates showed that the majority of biofilm producing isolates had identical pattern and only three isolates showed more than 80% similarity. The combination of fosfomycin and β-CLA could be introduced as an excellent mixture for eradication of MRSA biofilms in vitro.