Objective:The purpose of this study is to analyze the antibiotic sensitivity pattern of microorganisms, to study the antibiotic usage pattern, and to conduct a cost-effectiveness analysis (CEA) for the antibiotics prescribed in a tertiary care teaching hospital in south India.Methods:This prospective study was carried out in the General Medicine and Pulmonology departments of the hospital for a period of 6 months. The study was carried out in three phases: A prospective analysis to check the sensitivity pattern of microorganisms to various antibiotics, data extraction and determining the cost of antibiotics and finally evaluation of the sensitivity pattern of microorganisms and the antibiotic usage. A total of 796 documented records were analyzed.Findings:It was found that Escherichia coli was the major organism identified in 36.4% of the isolated specimens, followed by Klebsiella sp. (18.9%), Streptococcus pneumoniae (15.8%), Staphylococcus aureus (12.4%), and Pseudomonas (9.3%). The sensitivity pattern data of the prospective study revealed that E. coli was highly sensitive to Amikacin (99.3%), Klebsiella to Amikacin (93.8%), Pseudomonas to Meropenem (97.6%), and S. pneumoniae to Ofloxacin (93.8%). In the prescribing pattern study, it was found that the most common disease (21.2%) was found to be lower respiratory tract infection in 51 patients. Cephalosporins (73%), in particular Ceftriaxone (63.5%) was highly prescribed, followed by fluoroquinolones (53.9%). In the CEA, it was revealed that Ceftriaxone was the cost-effective antibiotic with a cost-effectiveness ratio (CER) of 78.27 compared to Levofloxacin, which had a CER of 95.13.Conclusion:Continuous surveillance of susceptibility testing is necessary for cost-effective customization of empiric antibiotic therapy. Furthermore, reliable statistics on antibiotic resistance and policies should be made available.