Assessment of pathogens diversity and evolving drug-resistant pattern is quite essential in the systematic management of infections. To regulate the pyogenic infection, 1350 (783 males and 567 females) pus samples collected from individuals attending a tertiary care hospital in Northern Kerala. Pathogens isolated from the collected pus samples were identified based on the colony morphology, microscopic examination, and biochemical characteristics. About 84.44% of samples showed significant bacteria. The causative organisms were Staphylococcus aureus (28%), Escherichia coli (13%), Pseudomonas aeruginosa (12%), Klebsiella pneumonia (10%), coagulase negative Staphylococcus sp. (8%), Proteus mirabilis (6%), Streptococcus sp. (2%), Enterococcus faecalis (2%), Acenitobactor baumanii (1%), Citrobactor koseri (2%), Enterococcus faecium (2%), Enterococcus sp. (2%), Morganella morganii (1%), Proteus vulgaris (2%), and other less prominent bacteria (3%). The drug-resistant pattern of pathogens analyses against 29 contemporary antibiotics. Pathogenic Gram-negative bacteria (GNB) were sensitive to amikacin > imipenem > meropenem > tazobactum > gentamycin > chloramphenicol> ciprofloxacin > levofloxacin and resistant to clindamycin, erythromycin, linezolid, oxacillin, penicillin, and vancomycin. Gram-Positive Bacteria (GPB) were susceptible to linezolid > vancomycin > tetracycline > clindamycin > chloramphenicol > gentamycin > ciprofloxacin, and resistant to amikacin, imipenem, meropenem, and tazobactum. Overall, the study concludes that MDR S. aureus was the predominant cause of pyogenic infections, drug resistance pattern of the pathogens in the selected region and raises concerns for the need to analyze signaling mechanism that transforms a susceptible strain into a resistant to develop a suitable treatment strategy.