Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis - A single-center randomized study

Pancreatic infection is the main indication for surgery and the principal d eterminant of prognosis in acute necrotizing pancreatitis. Previous studies on the effects of antibiotics have not, however, uniformly demonstrated an y reduction in the need for surgery or any decrease in mortality among thes e patients, although the incidence of pancreatic infections was significant ly reduced. This single-center randomized study was designed to compare ear ly vs. delayed imipenem treatment for acute necrotizing pancreatitis. Ninet y patients with acute necrotizing pancreatitis (C-reactive protein >150 mg/ L, necrosis on CT) were randomized within 48 hours either to a group receiv ing imipenem (1.0 g plus cilastatin intravenously 3 times a day) or a contr ol group. Not included were those who had been started on antibiotics at th e referring clinic, those who were taken directly to the intensive care uni t for multiorgan failure, and those who refused antibiotics or might have h ad adverse reactions. Thirty-two patients u ere excluded because they were over 70 years of age (not potentionally operable) or for any study violatio n. There were 25 patients in the imipenem group and 33 patients in the cont rol group. The main end point was the indication for necrosectomy due to in fection (i.e., after the initial increase and decrease, there was a second continuous increase in temperature, white blood cell count [>30%] and C-rea ctive protein [>30%], with other infections ruled out, or bacteria Mere fou nd on Gram stain of the pancreatic fine-needle aspirate). In the control gr oup, imipenem was started when the operative indication was fulfilled. Cons ervative treatment was continued for at least 5 days before necrosectomy, T he study groups did not differ from each other with regard to sex distribut ion, patient age, etiology; C-reactive protein concentration, and extent of pancreatic necrosis on CT. Two (8%) of 25 patients in the imipenem group c ompared to 14 (42 %) of 33 in the control group fulfilled the operative ind ications (P = 0.003). Nine patients in the control group responded to delay ed antibiotics but five had to undergo surgery: Of those receiving antibiot ics, 2 (8%) of 25 in the early antibiotic (imipenem) group needed surgery c ompared to 5 (36%) of 14 in the delayed antibiotic (control) group (P = 0.0 4). Tyro (8%) of 25 patients in the imipenem group and 5 (15%) of 13 patien ts in the control group died (P = NS [no significant difference]). Seven (2 8%) of 25 in the imipenem group and 25 (76%) of 33 in the control group had major organ complications (P = 0.0003). Based on the preceding criteria, e arly imipenem-cilastatin therapy appears to significantly reduce the need f or surgery and the overall number of major organ complications in acute nec rotizing pancreatitis, and reduces by half the mortality rate; this is not, however, statistically significant in a series of this size.