Abstract
Background
The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat.
Materials and methods
Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection.
Results
Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8–25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not.
Conclusions
In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.
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References
Beger HG, Rau B, Mayer J, Pralle U (1997) Natural course of acute pancreatitis. World J Surg 21:130–135
Bradley EL (1987) Management of infected pancreatic necrosis by open drainage. Ann Surg 206:542–550
Beger HG, Bittner R, Block S, Büchler M (1986) Bacterial contamination of pancreatic necrosis. Gastroenterology 91:433–438
Lumsden A, Bradley EL (1990) Secondary pancreatic infection. Surg Gynecol Obstet 170:459–467
Rau B, Uhl W, Büchler MW, Beger HG (1997) Surgical treatment of infected necrosis. World J Surg 21:155–161
Craig RM, Dordal E, Myles L (1975) The use of ampicillin in acute pancreatitis. Ann Intern Med 83:831–832
Howes R, Zuidema GD, Cameron JL (1975) Evaluation of prophylactic antibiotics in acute pancreatitis. J Surg Res 18:197–200
Finch WT, Sawyers JL, Schenker S (1976) A prospective study to determine the efficacy of antibiotics in acute pancreatitis. Ann Surg 183:667–671
Büchler M, Malfertheiner P, Frieß H, Isenmann R, Vanek E, Grimm H, Schlegel P, Friess T, Beger HG (1992) Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 103:1902–1908
Finch DRA, Lee E (1974) Acute appendicitis complicating pregnancy in the Oxford region. Br J Surg 61:129–132
Ho HS, Frey CF (1997) The role of antibiotic prophylaxis in severe acute pancreatitis. Arch Surg 132:487–492
Schwarz M, Thomsen J, Meyer H, Buchler MW, Beger HG (2000) Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery 127:427–432
Spormann H, Sokolowski A, Letko G (1989) Experimental acute pancreatitis—a quantification of dynamics at enzymic and histomorphologic levels. Pathol Res Pract 185:358–362
Spormann H, Sokolowski A, Letko G (1989) Effect of temporary ischemia upon development and histological patterns of acute pancreatitis in the rat. Pathol Res Pract 184:507–513
Nevalainen TJ, Aho HJ (1992) Standards of morphological evaluation and histological grading in experimental acute pancreatitis. Eur Surg Res 24(Suppl 1):14–23
Isenmann R, Rau B, Beger HG (1999) Bacterial infection and extent of necrosis are determinants of organ failure in severe acute necrotizing pancreatitis. Br J Surg 86:1020–1024
Pederzoli P, Bassi C, Vesentini S, Campedelli A (1993) A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 176(5):480–483
Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V, Haapiainen R, Schröder T, Kivilaakso E (1995) Early antibiotic treatment in acute necrotising pancreatitis. Lancet 346:663–667
Delcenserie R, Yzet T, Ducroix JP (1996) Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas 13:198–201
Luiten EJT, Hop WCJ, Lange JF, Bruining HA (1995) Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg 222:57–65
Schwarz M, Isenmann R, Meyer H, Beger HG (1997) Antibiotika bei nekrotisierender Pankreatitits. Ergebnisse einer kontrollierten Studie. DMW 122:356–361
Golub R, Siddiqi F, Pohl D (1998) Role of antibiotics in acute pancreatitis: a meta-analysis. J Gastrointest Surg 2:496–503
Isenmann R, Rünzi M, Kron M, Kahl S, Kraus D, Jung N, Maier L, Malfertheiner P, Goebell H, Beger HG (2004) Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis. Gastroenterology 126:977–1004
Foitzik T, Fernandez del Castillo C, Ferraro MJ, Mithofer K, Rattner DW, Warshaw AL (1995) Pathogenesis and prevention of early pancreatic infection in experimental acute necrotizing pancreatitis. Ann Surg 222:179–185
Mithofer K, Fernandez del Castillo C, Ferraro MJ, Lewandrowski K, Rattner DW, Warshaw AL (1996) Antibiotic treatment improves survival in experimental acute necrotizing pancreatitis. Gastroenterology 110:232–240
Heinkel K (1953) Die Ratte als Versuchstier in der experimentellen Pankreasdiagnostik. II. Mitteilung. Die Erzeugung einer akuten hämorrhagischen Pankreatitis durch Injektion von Gallensäure in den Ductus pancreaticus. Klin Wochenschr 31:815
Adler G, Kern HF, Scheele GA (1986) Experimental models and concepts in acute pancreatitis. In: Gardner JD, Brooks FP, Lebenthal E, DiMagno EP, Scheele GA (eds) The exocrine pancreas: biology, pathobiology, and diseases. VLW Go, Raven, New York, pp 407–421
Bilchik AJ, Leach SD, Zucker KA, Modlin IM (1990) Experimental models of acute pancreatitis. J Surg Res 48:639–647
Aho HJ, Koskensalo SML, Nevalainen TJ (1980) Experimental pancreatitis in the rat. Sodium taurocholate-induced acute hemorrhagic pancreatitis. Scand J Gastroenterol 15:411–416
Arora A (1989) Massive lower gastrointestinal bleeding as a presenting feature of Behcet’s disease. Trop Gastroenterol 10:56–61
Aho HJ, Nevalainen TJ (1980) Experimental pancreatitis in the rat: ultrastructure of sodium taurocholate-induced pancreatic lesions. Scand J Gastroenterol 15:417–424
Borner K, Hartwig H, Lode H, Höffken G (1986) Chromatographische Bestimmung von Ofloxacin in Körperflüssigkeiten. Fresenius Z Anal Chem 324:355
Holt DE, de Louvois J, Hurley R, Harvey D (1990) A HPLC system for the simultaneous assay of some antibiotics commonly found in combination in clinical samples. J Antimicrob Chemother 26:107–115
Runkel NSF, Moody FG, Smith GS, Rodriguez LF, LaRocco MT, Miller TA (1991) The role of the gut in the development of sepsis in acute pancreatitis. J Surg Res 51:18–23
Runkel NSF, Moody FG, Smith GS, Rodriguez LF, Chen Y, LaRocco MT, Miller TA (1993) Alterations in rat intestinal transit by morphine promote bacterial translocation. Dig Dis Sci 38:1530–1536
Barber AE, Jones WG II, Minei JP, Fahey TJ III, Lowry SF, Shires GT (1991) Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat. Am J Surg 161:300–304
Brumfitt W, Franklin I, Grady D, Hamilton-Miller JM, Iliffe A (1984) Changes in the pharmacokinetics of ciprofloxacin and fecal flora during administration of a 7-day course to human volunteers. Antimicrob Agents Chemother 26:757–761
Gianotti L, Munda R, Alexander JW, Tchervenkov JI, Babcock GF (1993) Bacterial translocation: a potential source for infection in acute pancreatitis. Pancreas 8:551–558
Gianotti L, Munda R, Gennari R, Pyles R, Alexander JW (1995) Effect of different regimens of gut decontamination on bacterial translocation and mortality in experimental acute pancreatitis. Eur J Surg 161:85–92
Mai (1999) Shift of bacterial spectrum in acute pancreatitis. EPC
Isenmann R, Schwarz M, Rau B, Trautmann M, Schober W, Beger HG (2002) Characteristics of infection with Candida species in patients with necrotizing pancreatitis. World J Surg 26:372–376
Spormann H, Sokolowski A, Letko G (1989) Experimental acute pancreatitis—a quantification of dynamics at enzymic and histomorphologic levels. Pathol Res Pract 185:358–362
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Schwarz, M., Poch, B., Isenmann, R. et al. Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats. Langenbecks Arch Surg 392, 365–370 (2007). https://doi.org/10.1007/s00423-007-0166-5
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DOI: https://doi.org/10.1007/s00423-007-0166-5