Differential expression of blaCTX-M-33 with vancomycin/trimethoprim combination in Escherichia coli-producing extended-spectrum β-lactamase isolated from intensive care unit-acquired urinary tract infection

Aim: The aim of this study was to develop combination approach for the treatment of Escherichia coli-producing extended-spectrum β-lactamases (ESBLs) isolated from intensive care unit (ICU)-acquired urinary tract infections (UTIs). Materials and Methods: The observational study was conducted between January 5, 2018- June 5, 2019 to isolate and detect E. coli from UTI patients admitted to ICUs in Shahid Rajaee hospital, Gachsaran, Iran. Morphological, biochemical and molecular methods were conducted to identify E. coli isolates. Phenotypic confirmation of E. coli producing ESBL was performed using ESBL disc diffusion test according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The combination index assay set-up was based on CLSI guidelines to investigate antibacterial susceptibilities to vancomycin alone and in combination with trimethoprim and interpreted with the fractional inhibitory concentration (FIC) index. Eventually, the expression levels of blaCTX-M-33 gene were determined by real-time quantitative reverse transcription–polymerase chain reaction. Results: A total of 90 ICU-acquired UTIs occurred among 255 patients. The combination index assay results showed that vancomycin/trimethoprim combination would be reduced its minimal inhibitory concentration90 value. The vancomycin/trimethoprim combination revealed partial synergistic and indifferent effects (FIC = 0.52–1.50) in the isolates of E. coli-producing ESBL. The results of gene expression analysis indicated that vancomycin/trimethoprim combination caused downregulation of blaCTX-M-33 gene at negligible levels by 55.56–58.82-fold and stopped drug resistant. Conclusion: Vancomycin/trimethoprim combination may diminish resistance in the E. coli-producing ESBL isolated from ICU-acquired UTI patients.