UTI is one of the most common infections requiring antibiotic treatment and hospitalization. The rising trend in multidrug resistance to commonly used antibiotics has reduced the therapeutic options for treating these infections. Reexploring older antibiotics like nitrofurantoin and fosfomycin provide treatment options and help combat resistance. This prospective study was conducted in the Department of Microbiology, SRM Medical College Hospital and Research Center, from July 2021 to February 2022. The study included only clean catch midstream urine isolates of Escherichia coli and Klebsiella pneumonia from hospitalized patients and outpatients. Standard microbiological procedures were used to process the urine samples. Direct gram stain and conventional biochemical reactions were performed to identify the isolates. The antimicrobial susceptibility testing was carried out by the Kirby Bauer disk diffusion method and Minimum Inhibitory Concentration by E- test gradient method for fosfomycin. MIC for nitrofurantoin was determined by Micro Broth Well Dilution according to CLSI guidelines 2021. Among 150 urine samples, Escherichia coli 107 (71.3%) was higher than Klebsiella pneumonia 43 (29%). Carbapenemase production was seen in 58 (63.04%) isolates by the Kirby Bauer disc diffusion method. Among the 58 positive carbapenemase producers, E. coli was found to be 33 (56.8%), and Klebsiella pneumonia was 25 (43.1%). Fosfomycin susceptibility rates by E test were reported to be high in Escherichia coli, ranging from 0.5-1mg/L. Klebsiella pneumonia was less susceptible to fosfomycin ranging from 16-32mg/L. Only 7(21%) isolates of Escherichia coli showed MIC of 1-4µg/ml to nitrofurantoin by broth microdilution. 21 (63.63%) isolates of Escherichia coli and 11(44%) isolates of Klebsiella pneumonia were reported to have an intermediate category with MIC of 8-32µg/mL. A higher MIC of 64- > 256µg/ml was shown by 5 (15.15%) isolates of Escherichia coli and 14 (56%) isolates of Klebsiella pneumonia. Older medications may resurface as useful therapeutic choices as resistance to current treatment options grow.