Diabetic foot infections (DFI) are a major complication of diabetes mellitus. It contributes to the development of gangrene and non-traumatic lower extremity amputations with the life time risk up to 25 %. Since bacteria responsible for chronic wound infections are commonly within polysaccharide matrices known as biofilms, which to a large extent are refractory to antibiotics even when the bacteria are genetically susceptible to their action. In the first part of the study, we identified the neuropathy, ulcer grade, microbial profile, phenotypic and genotypic resistance prevalence of methicillin and ESBL genes in bacterial isolates of DFI patients registered at PIMS, Pakistan. Our results indicated that 46 (92 %) out of 50 patients, had sensory neuropathy. The most prevelant isolate was Staphylococcus aureus (25 %), followed by Pseudomonas aeruginosa (18.18%), E. coli (16.16%), Streptococcus spp (15.15%), Enterococcus spp (9%), Proteus spp (15.15%) and Klebsiella pneumonia (3%). The prevalence of MecA gene was found to be 88 % and 84% phenotypically and genotypically respectively. K. pneumonia had highest percentage of ESBL producers with 66.6 % prevalence by double disc synergy test and 100 % for CTX+CL/CAZ+CL by combination disc test. Pseudomonas aeruginosa had highest (100 %) number of metalo β-lactamase producers by EDTA synergy disk test. Overall prevalence of bla-CTX-M, bla-CTX-M15, bla-TEM, bla-OXA and bla-SHV genes was found to be 76.92, 76.92, 75.0, 57.69 and 84.6 % respectively in gram negative isolates from DFI. Molecular epidemiology of MecA and ESBL genes were found alarmingly high in DFI, posing one of the major cause of antibiotic treatment failure. In the second part of our study we determined whether combinations of antibiotics and bacteriophage were more effective for the treating biofilm populations of Abstract xvii Pseudomonas aeruginosa [the laboratory strain PA14, and the clinical strain, CFBR2)] on plastic surfaces and layers of human epithelial cells. Two newly isolated bacteriophage NP1 and NP3 at a titer of ~1E8 pfu/ml were added individually or as pairs and/or in combination with 1X MIC, 4XMIC and 8X MIC of ceftazidime, colistin, gentamicin or trobramycin to 48 hours PA biofilms in 6 well polystyrene plates. Parallel experiments were performed with 8-hour biofilm populations of epithelial Naso pharyngeal Detroit 562 (ATCC® CCl-138TM). Treatment with phage reduces the viable density of biofilm populations of P. aeruginosa. biofilms by three orders of magnitude as compared to untreated control. In combination with antibiotics phages are more effective than alone and increase efficacy of the antibiotics for treating bacteria in biofilms. In the third part of study we explored co-evolutionary dynamics of resistance between Pseudomonas aeruginosa 14 and its phages NP1 and NP3. Evolutionary dynamics experiments of single and two phages revealed that PA14 can easily evolve resistance against NP1 phage. NP3 phage maintained for 30 serial transfers and we observed host range in evolved bacteria. In cocktail, both phage support each for their long term maintenance in serial transfer experiments. Also, cocktail delayed the evolution of resistance and sustained high phage infectivity, suggesting phage cocktail is promising strategy to control or slow down evolution of resistance in bacteria against bacteriophages.