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The knowledge about pathogens and their antibiotic susceptibility patterns is essential to select an appropriate antibiotic.We investigated the microbiological profile in pancreatic and extrapancreatic infections, and antibiotic sensitivity pattern in patients with acute pancreatitis.Of 556 patients with acute pancreatitis, only 189 developed bacterial infection; however, bacteremia was present in 42 patients (7.6%). Culture-proven infected pancreatic necrotic collection was present in 161 patients (29%). Escherichia coli and Klebsiella pneumoniae were the most common organisms. Among the bacterial infection cohort, 164 patients developed multidrug-resistant bacterial infection. Infection with multidrug-resistant bacteria, especially at multiple sites, increased mortality. Nearly 50% of patients (n = 94) acquired extremely drug-resistant bacterial infection at some time and emerged as key reason for prolonged hospital and intensive care unit stay. Colistin resistance and tigecycline resistance were documented in 2.1% and 17.2% of the specimens at admission and in 4.6% and 21% of specimens during the hospital stay. Of 556 patients, 102 patients developed fungal infection and 28 patients had only fungal infection without bacterial infection.Colistin and tigecycline are best reserved as last-resort antibiotics. Fungal infection was found to be associated with increased mortality, median hospital stay, and intensive care unit stay.