Introduction: Cystic fibrosis is a life-shortening disease of young children but it has been present in adults in recent days. Studies on epidemiology and microbiota of cystic fibrosis from the southern part of India are very few. So we tried to project the data of bacteria responsible for pulmonary exacerbations in cystic fibrosis patients and their antibiotic sensitivity. Materials and Methods: A total of 75 samples were collected from confirmed cystic fibrosis patients attending outpatient clinical departments and were processed for culture and sensitivity according to CLSI protocols. ESBL and MBL production among non fermenters were detected using antibiotic discs using modified Kirby bauer method. Results: Out of all isolated pathogens Pseudomonas aeruginosa isolates were 29 (40.8%), 15 (21.1%) isolates were Klebsiella pneumoniae, 12 (16.9%) Staphylococcus aureus, 7 (9.8%) Candida albicans, 4 (5.6%) Enterobacter cloacae, 2 (2.8%) Burkholderia cepacia, and 2 (2.8%) Burkholderia species. Out of 29 Pseudomonas aeruginosa isolates 68.9% showed ESBL production and 17.2% showed MBL production. All the Burkholderia cepacia tested were ESBL and MBL producers. 100% and 50% of Burkholderia species expressed ESBL and MBL enzymes respectively. Conclusion: Co-existence of S.aureus and P.aeruginosa in cystic fibrosis patients is still a matter of debate. Many hypotheses including the present study concluded that microorganisms are antagonistic invitro after a prolonged co-existence.