Background. Infections are the common cause of death in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods.A prospective cohort study was conducted on 100 patients with AECOPD in a tertiary care hospital in Hyderabad city in South India. Sputum culture of 100 patients was evaluated for the presence of Gram-positive and Gram-negative micro-organisms. Sensitivity and resistance patterns of the micro-organisms against commonly used antibiotics were also investigated. Results.During the period October 2015 to April 2016, 67% of the patients had sputum culture positive for the presence of pathogenic micro-organisms. Pathogens, most commonly, isolated were Gram-negative organisms like Klebsiella oxytoca (13%), followed by Klebsiella species (11%) and Klebsiella pneumoniae (10%). Amikacin was found to be the most effective antibiotic against all micro-organisms. A significantly higher proportion of organisms were pathogenic compared to non-pathogenic organisms (p=0.0014). Among pathogenic organisms, a significantly higher proportion of Gram-positive organisms were found compared to Gram-negative organisms (p=0.0180). Pathogenic microorganisms showed a high resistance rate to commonly used antibiotics. Except few strains of Klebsiella, Pseudomonas and Streptococcus, overall 62.9% strains were sensitive to doxycycline. Conclusions.Our observations suggest that doxycycline can be used as an empirical antibiotic in the treatment of AECOPD.