BACKGROUND This study was aimed to ascertain the response of microorganisms to third generation Cephalosporins. METHODOLOGY Blood, Urine, Pus, Sputum, Throat swabs, Broncho alveolar lavage (BAL), Endotracheal secretions (ET) and Vaginal swabs were collected and organisms were isolated from various Patients Sample with different pathological conditions and subjected to susceptibility tests for Cefoperazone/Sulbactam and Ceftazidime/Sulbactam. RESULTS 100% of Enterobacter, 50% of Acinetobacter, 42% of Klebsiella, 34 % of Salmonella and 30% of E. coli, were resistant to Cefoperazone/Sulbactam, whereas 100% of Enterobacter, 75% of Acinetobacter, 33 % of Salmonella, 20 % of Klebsiella, and 15% of E. coli, were resistant to Ceftazidime/Sulbactam. CONCLUSION The combination of third generations Cephalosporins (Cefoperazone/Sulbactam and Ceftazidime/Sulbactam) was not effective drug to treat the patients.