Background: Microbiology of odontogenic infections was inconsistent. It was difficult to compare various bacteriological investigations because of different methods and materials used. Streptococci which can be seen in the composition of microbial dental plaque may cause inflammatory periodontal disease and dental caries. Microbiological isolation helped in identifying the organisms and advocating antibiotics. Case report: We present a case of buccal space infection in a 51–year–old patient presented with a swelling in the upper left cheek region. He was on antibiotics as prescribed by a dentist for toothache for a week. It was diagnosed as a buccal space infection due to periodontal origin. Intra orally there was chronic generalized periodontitis with 9mm probing pocket depth, clinical attachment loss of 6 mm, mobility & exudation in upper left first and second molar. Pus sample was collected and sent for Culture & antibiotic sensitivity. The culture revealed E. coli & streptococcus species. The testing revealed resistance to Ampicllin//trimethoprim/ciprofloxacin/nalidixic acid. PCR analysis was done for Streptococus pyogenes & P. gingivalis. PCR analysis revealed the presence of Streptococcus pyogenes. Conclusion: It is always appropriate to always begin with the empiric antibiotic regimen with correlation to clinical presentation thinking of the most likely suspected microorganisms involved in the infections, which are usually the normal flora of the region, without forgetting the importance of early surgical intervention to reduce morbidity and complications.