Cefepime tissue penetration in experimental acute pancreatitis.
BACKGROUND
Antibiotic treatment represents a cornerstone in the management of severe acute pancreatitis. However, different antibiotic substances are currently used. In this study, we analyzed penetration of cefepime into pancreatic tissue in two models of acute pancreatitis.


OBJECTIVE
Following induction of acute pancreatitis, animals were treated with a single intravenous dose of cefepime (0.1 mg/g of body weight). At two different time points, blood and tissue samples were obtained for determination of cefepime concentration and microbiologic analysis.


RESULTS
Mean pancreatic tissue concentrations +/- SEM 30 minutes after drug administration were significantly higher in animals with either mild acute pancreatitis (113 +/- 22 mg/kg) or severe acute pancreatitis (75 +/- 22 mg/kg) than in control animals (30 +/- 6 mg/kg) (p < 0.005). The minimal inhibitory concentrations (MIC90) for organisms usually isolated from infected pancreatic necrosis vary between 0.05 and 8 mg/L, which is between nine and 1,500 times lower than the mean peak concentration found in necrotic pancreatic tissue. Seven hours 30 minutes after antibiotic administration, pancreatic cefepime concentrations were still above the MIC90 in 100% and 83% of animals with mild and severe disease, respectively. The infection rate of pancreatic tissue was significantly lower after antibiotic treatment and was similar after imipenem/cilastatin or cefepime treatment.


CONCLUSIONS
Because of its antibacterial coverage and proven tissue penetration in acute pancreatitis, cefepime should be studied in patients with severe acute pancreatitis.
Gloor
Beat
B
Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.
Worni
Mathias
M
Strobel
Oliver
O
Uhl
Waldemar
W
Tcholakov
Oleg
O
Müller
Christophe A
CA
Stahel
Philip F
PF
Droz
Sara
S
Büchler
Markus W
MW
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D000077723:Cefepime; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002108:Ceruletide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
D002511:Cephalosporins; D000077723:Cefepime; D002108:Ceruletide