Pancreatic Concentrations of Cefepime in Experimental Necrotizing Pancreatitis

Abstract

To evaluate the penetration of cefepime in the inflamed pancreas, three doses of 50 mg/kg were administered intramuscularly at 8-h intervals after induction of acute necrotizing pancreatitis using intraperitoneal injection of DL-ethionine in 35 rabbits and in 33 controls. Animals were sacrificed and concentrations of cefepime were determined by a microbiological assay. Cefepime reached its peak concentrations 60 min after the last drug dose when mean values of 46.05 microg/ml, 22.34 microg/g and 34.74 microg/ml were found in serum, pancreas and bile, respectively, in rabbits with acute necrotizing pancreatitis and 45.19 microg/ml, 12.68 microg/g and 20.77 microg/ml respectively in controls. Tissue/serum ratios of cefepime were 0.48, 0.23, 0.15 and 0.09 at 60, 90, 120 and 180 min, respectively, after the last dose of cefepime in rabbits with acute necrotizing pancreatitis and 0.28, 0.18, 0.16 and 0.16, respectively at 60, 90, 120 and 180 min in controls. It is concluded that the administration of cefepime in rabbits with acute necrotizing pancreatitis resulted in pancreatic tissue levels well above the MIC90s of the common pathogens involved in pancreatic superinfection, so that its administration might be proposed for the therapy of superinfection following acute necrotizing pancreatitis in humans.

Impact of prior antibiotics on infected pancreatic necrosis microbiology in ICU patients: a retrospective cohort study

“…In two studies, after a single intravenous dose of ertapenem or imipenem, concentrations in pancreatic tissue and juice, respectively, were low but above the minimum inhibitory concentrations for the main pathogens responsible for intra-abdominal infections [22,43,44]. Several studies of animal models of acute pancreatitis [24][25][26] showed penetration within necrotic tissue to levels above the minimal inhibitory concentrations of common pathogens, and a single study [23] demonstrated good cefepime concentrations in pancreatic pseudocyst fluid or pancreatic resection specimens for cancer. However, pancreatic necrotic tissue during acute pancreatitis was not studied.…”

“…Furthermore, patients with IPN may require immediate antibiotic therapy for a co-existing infection at another site. The penetration of antibiotics within foci of pancreatic necrosis has been poorly evaluated but may be limited [18][19][20][21][22][23][24][25][26]. Thus, whether antibiotic exposure before the collection of pancreatic samples sterilizes the microbiological findings is unclear.…”

Rethinking Carbapenems: A Pharmacokinetic Approach for Antimicrobial Selection in Infected Necrotizing Pancreatitis

“…59 Cefepime was also studied in animal models with simulated INP and peak cefepime concentrations between 22.34 and 75 mg/kg, and 6-hour levels were 11.75 mg/kg. 11,18,40 It appears that higher doses and longer infusion times may be necessary to achieve PK/PD targets for an MIC of 8 µg/mL.…”