Phenotypic and Molecular Analysis of Fosfomycin Resistance Among P. aeruginosa Isolates from Cystic Fibrosis Patients.

Introduction: This study evaluated the prevalence of P. aeruginosa in cystic fibrosis(CF) patients, assessed its resistance patterns to commonly used antibiotics with an emphasis on fosfomycin, and examined the presence of resistance genes (glpT, fosA3, blaCTX-M) in these isolates. Material and Methods: A cross-sectional study was conducted at Shahid Beheshti University of Medical Sciences, Tehran, from January to June 2022. Sixty sputum samples from CF-confirmed patients were collected and cultured. Antibiotic susceptibility testing (AST) was performed using the Kirby-Bauer disk diffusion method according to CLSI guidelines. Minimum inhibitory concentrations (MICs) of fosfomycin were determined using E-test strips. PCR was employed to detect the presence of glpT, fosA3, and blaCTX-M resistance genes. Data were analyzed using SPSS version 21. Results: P. aeruginosa was isolated from 71.6% (43/60) of samples. Based on AST, significant antibiotic resistance was observed, particularly against fosfomycin (77.2%), imipenem, and amikacin (53.5%). Using the combined disk diffusion test (CDDT), 46% of isolates were identified as ESBL producers. PCR analysis revealed the presence of glpT gene in all isolates, fosA3 gene in 39.5%, and blaCTX-M gene in 30.2%. Discussion: The fosA3 gene showed a strong correlation with fosfomycin resistance, while blaCTX-M was associated with beta-lactam resistance. Molecular diagnostics targeting resistance genes such as glpT, fosA3, and blaCTX-M are essential for guiding antibiotic therapy. The resistance patterns observed, particularly against fosfomycin, highlight the need for innovative therapeutic approaches. Conclusion: This study reveals a high rate of multidrug resistance in P. aeruginosa isolates from CF patients, particularly to fosfomycin, imipenem, and amikacin. The presence of resistance genes suggests a genetic basis for these patterns, emphasizing the importance of developing new strategies to manage P. aeruginosa infections effectively. Future studies should focus on targeted inhibitors for these genes to overcome resistance and improve clinical outcomes.