Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis.
OBJECTIVE
To investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.


METHODS
Sterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10(8) CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS.


RESULTS
Moxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10(7) ± 2.4·10(7) vs. AN 4.9·10(4) ± 2.6·10(4) CFU/g; p < 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p < 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p < 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p < 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis.


CONCLUSIONS
In the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Gabriel J
GJ
Seifert
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Philipp J
PJ
Poxleitner
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Sabine C
SC
Richter
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Ulrich T
UT
Hopt
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany. Electronic address: uwe.wittel@uniklinik-freiburg.de.
Uwe A
UA
Wittel
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002756:Cholagogues and Choleretics; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy*; D024841:Fluoroquinolones / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D010179:Pancreas / Q000382:microbiology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013656:Taurocholic Acid; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D002756:Cholagogues and Choleretics; D024841:Fluoroquinolones; D013656:Taurocholic Acid; D000077266:Moxifloxacin
Acute necrotizing pancreatitis; Infected pancreatic necrosis; Moxifloxacin; Severe acute pancreatitis; Therapy of acute necrotizing pancreatitis