Objective · To analyze the bacterial origin and characteristics, and their influence on the process and prognosis in moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) patients with pancreatic/peri-pancreatic infections due to multiple drug resistant (MDR) Gram-negative bacteria (GNB). Methods · Patients of pancreatitis hospitalized in the Departments of Emergency, Pancreatic Surgery and Critical Care Medicine were enrolled in this study. The patients with pancreatic/peri-pancreatic GNB infections were screened and divided into MDR-GNB group and non-MDRGNB group. The basic clinical features, the source of resistant bacteria, the progress of the disease and the prognosis were analyzed and compared within two groups. Results · 92(46.70%) out of 197 MSAP and SAP patients were confirmed as GNB infected, 61 cases (66.30%) with MDR strains and 31 cases (33.70%) with non-MDR strains. 117 GNB were isolated. The main MDR strains were Klebsiella pneumoniae (KP) (39/69) and Acinetobacter Baumannii (AB) (22/69). The incidence of percutaneous catheter drainage (PCD) associated MDR bacterial infections in MDR-GNB group was significantly higher than that of non-MDR-GNB group (36.07% vs 12.90%, P0.020). The MDR-GNB infections could lead to prolonged mechanical ventilation[ (17.65±11.74) d vs (9.67±9.34) d, P0.001], increased of carbapenems and special antibiotics (P0.000), earlier intervention of first laparotomy [(21.92±11.45) d vs (29.36±21.48) d, P0.032], increased incidence of multiple operations (45.90% vs 22.58%, P0.029), prolonged total hospitalization [(54.44±42.38) d vs (32.51±27.62) d, P0.011] and higher mortality (34.43% vs 12.90%, P0.028). The incidence of MDR-KP infections in death patients was significantly higher than that in the surviving patients (85.71% vs 52.50%, P0.000), while the other MDR bacteria did not present statistical difference in the two groups. Conclusion · MDRKP and MDR-AB are the main resistant GNB in MSAP and SAP patients with pancreatic/peri-pancreatic infections. The PCD associated infection is the main source of nosocomial MDR bacterial infections. Infections due to MDR-GNB could lead to prolonged therapy course, increased of antibiotics, augmented operation, and poor outcome. The infection of MDR-KP is directly related to poor outcome.