The Effectiveness of Continuous Regional Arterial Infusion Therapy with Meropenem in Severe Acute Pancreatitis Compared with Imipenem: A Prospective, Randomized Study

Introduction: We performed a prospective randomized controlled trial in patients with severe acute pancreatitis, comparing one group who were given meropenem (MP group) and another group who received imipenem (IP group) using continuous regional arterial infusion (CRAI), and the effect of meropenem...

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Published inThe Japanese Journal of Gastroenterological Surgery Vol. 41; no. 1; pp. 1 - 11
Main Authors Ogura, Shinji, Tanjou, Katsuhisa, Shinohara, Katsuhiro, Shirai, Kunihiro
Format Journal Article
LanguageJapanese
Published The Japanese Society of Gastroenterological Surgery 2008
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ISSN0386-9768
1348-9372
DOI10.5833/jjgs.41.1

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Abstract Introduction: We performed a prospective randomized controlled trial in patients with severe acute pancreatitis, comparing one group who were given meropenem (MP group) and another group who received imipenem (IP group) using continuous regional arterial infusion (CRAI), and the effect of meropenem was reviewed. Methods: At admission, 30 subjects were randomly allocated to either the MP group (n=16) or the IP group (n=14). We then conducted continuous hemodiafiltration, selective decontamination of the digestive tract, and enteral nutrition. We looked at the start time and duration of CRAI, the catheterization locus, and specific treatment enforcement rates. We also compared our findings to Ministry of Health, Labour and Welfare severity scores, the APACHE II score, the SOFA score, and the CRP level both at admission and two weeks after. We then reviewed the infection rate, pancreatitis-related complications frequency, infected pancreatic necrosis rate, surgical treatment rate, mortality, infection site, and presence of causative organisms. Results: The two groups had no significant differences in age, cause, CRAI start time and duration, catheterization locus, or specific treatment enforcement rates. No significant intragroup differences were seen in any scores or CRP levels either at admission or two weeks after. No significant differences in infection rates were seen between groups (MP group: 37.5%, IP group: 42.9%). No significant intragroup differences were seen, either, in incidence of infection and pancreatitis-related complications, the rate of infected pancreatic necrosis, the surgical treatment rate, or mortality. The infection site had a great deal of expectoration requiring catheterization, and causative bacteria did not differ between the groups. We did, however, observe the presence of isolated antimicrobial resistance pathogens and polymicrobial infection. Conclusions: Meropenem was found to be effective in preventing of infection in severe acute pancreatitis when initiated within 72 hours after onset. Its effectiveness closely parallels that of imipenem.
AbstractList Introduction: We performed a prospective randomized controlled trial in patients with severe acute pancreatitis, comparing one group who were given meropenem (MP group) and another group who received imipenem (IP group) using continuous regional arterial infusion (CRAI), and the effect of meropenem was reviewed. Methods: At admission, 30 subjects were randomly allocated to either the MP group (n=16) or the IP group (n=14). We then conducted continuous hemodiafiltration, selective decontamination of the digestive tract, and enteral nutrition. We looked at the start time and duration of CRAI, the catheterization locus, and specific treatment enforcement rates. We also compared our findings to Ministry of Health, Labour and Welfare severity scores, the APACHE II score, the SOFA score, and the CRP level both at admission and two weeks after. We then reviewed the infection rate, pancreatitis-related complications frequency, infected pancreatic necrosis rate, surgical treatment rate, mortality, infection site, and presence of causative organisms. Results: The two groups had no significant differences in age, cause, CRAI start time and duration, catheterization locus, or specific treatment enforcement rates. No significant intragroup differences were seen in any scores or CRP levels either at admission or two weeks after. No significant differences in infection rates were seen between groups (MP group: 37.5%, IP group: 42.9%). No significant intragroup differences were seen, either, in incidence of infection and pancreatitis-related complications, the rate of infected pancreatic necrosis, the surgical treatment rate, or mortality. The infection site had a great deal of expectoration requiring catheterization, and causative bacteria did not differ between the groups. We did, however, observe the presence of isolated antimicrobial resistance pathogens and polymicrobial infection. Conclusions: Meropenem was found to be effective in preventing of infection in severe acute pancreatitis when initiated within 72 hours after onset. Its effectiveness closely parallels that of imipenem.
Author Tanjou, Katsuhisa
Ogura, Shinji
Shinohara, Katsuhiro
Shirai, Kunihiro
Author_xml – sequence: 1
  fullname: Ogura, Shinji
  organization: Department of Emergency and Disaster Medicine Advanced Critical Care Center, Gifu University
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  fullname: Tanjou, Katsuhisa
  organization: Department of Emergency and Critical Care of Medicine, Nihon University
– sequence: 1
  fullname: Shinohara, Katsuhiro
  organization: Department of Surgery, Kamitomachi Hospital
– sequence: 1
  fullname: Shirai, Kunihiro
  organization: Department of Emergency and Disaster Medicine Advanced Critical Care Center, Gifu University
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References 19) Takeda K, Sunamura M, Shibuya K et al: Role of early continuous regional arterial infusion of protease inhibitor and antibiotic in nonsurgical treatment of acute necrotizing pancreatitis. Digestion 60: 9-13, 1999
5) Bassi C, Falconi M, Talamini G et al: Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis. Gastroenterology 115: 1513-1517, 1998
23) Manes G, Rabitti PG, Menchise A et al: Prophylaxis with meropenem of septic complications in acute pancreatitis: a randomized, controlled trial versus imipenem. Pancreas 27: e79-e83, 2003
4) Bassi C, Mangiante G, Falconi M et al: Prophylaxis for septic complications in acute necrotizing pancreatitis. J Hepatobiliary Pancreat Surg 8: 211-215, 2001
21) Bassi C, Pederzoli P, Vesentini S et al: Behaviour of antibiotics during human necrotizing pancreatitis. Antimicrob Agents Chemother 4: 830-836, 1994
26) Grewe M, Tsiotos CG, Luque de-Leon E et al: Fungal infection in acute necrotizing pancreatitis. J Am Coll Surg 188: 408-414, 1999
6) 急性膵炎の診療ガイドライン作成委員会編: エビデンスに基づいた急性膵炎のガイドライン. 第1版. 金原出版, 東京, 2003, p71-80
32) Manes G, Uomo I, Menchise A et al: Timing of antibiotic prophylaxis in acute pancreatitis: a controlled randomized study with meropenem. Am J Gastroenterol 101: 1348-1353, 2006
1) 大槻眞, 木原康之: 急性膵炎全国疫学調査. 厚生労働省科学研究費補助金難治性疾患克服研究事業難治性膵疾患に関する調査研究班. 平成14-16年度総合研究報告書. 東京, 2005, p31-39
28) Yamaguchi K, Ishi Y, Iwata M et al: Meropenemを含む各種注射用抗菌薬に対する2004年臨床分離株の感受性サーベイランス. Jpn J Antibiotics 58: 655-689, 2005
16) Hayashi J, Kawarada Y, Isaji S et al: Therapeutic effects of continuous intraarterial antibiotic infusion in preventing pancreatic infection in ex perimental acute necrotizing pancreatitis. Pancreas 13: 184-192, 1996
8) 小川道雄, 広田昌彦, 早川哲夫ほか: 重症急性膵炎全国調査-不明例の追加調査を加えた最終報告. 厚生省特定疾患消化器系疾患調査研究班難治性膵疾患分科会平成10年度研究報告書. 厚生省, 東京, 2000, p23-35
34) 砂川洵, 森永正敏: カルバペネム系抗生物質と中枢神経系副作用-メロペネムの構造活性相関の研究より-. BIO Clinica 12: 1074-1077, 1997
35) Wendelin KN, Priscilla AR, Ralph Q et al: Empiric Carbapenem Monotherapy in Pediatric Bone Marrow Transplant Recipients. Ann Pharmacother 36: 1360-1365, 2002
12) Luiten EJ, Hop WC, Lange JF et al: Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg 222: 57-65, 1995
13) 平澤博之, 北村伸哉, 上野博一: 重症急性膵炎におけるhumoral mediatorからみた持続的血液濾過透析(CHDF)の有効性に関する検討. 小川道雄監. 重症急性膵炎の救命率を改善するための研究班平成11年度研究報告書. 厚生省, 東京, 2000, p162-170
11) Kalfarentzos F, Kehagias J, Mead N et al: Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis. Br J Surg 84: 1665-1669, 1997
9) Vincent JL, de Mendonca A, Cantraine F et al: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: result of a multicenter, prospective study. Working group on “sepsis-related problems” of European Society of Intensive Care Medicine. Crit Care Med 26: 1793-1800, 1998
2) Golub R, Siddiqi F, Pohl D: Role of antibiotics in acute pancreatitis: a meta-analysis. J Gastrointest Surg 2: 496-503, 1998
15) Kakugawa Y, Takeda K, Sunamura M et al: Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstuction. Jpn Gastroenterol 87: 1440-1450, 1990
17) Imaizumi H, Kida M, Nishimaki H et al: Efficacy of continuous regional arterial infusion of a protease inhibitor and antibiotic for severe acute pancreatitis in patients admitted to an intensive care unit. Pancreas 28: 369-373, 2004
18) Takeda K, Matsuno S, Ogawa M et al: Continuous regional arterial infusion (CRAI) therapy reduces the mortality rate of acute necrotizing pancreatitis: results of a cooperative survey in Japan. J Hepatobiliary Pancreat Surg 8: 216-220, 2001
3) Pederzoli P, Bassi C, Vesentini S et al: A randomized multicenter clinical trial of antibiotic prophylaxis of septic acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 176: 480-483, 1993
20) Buchler M, Malfertheiner P, Friess H et al: Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 103: 1902-1908, 1992
7) Takeda K, Matsuno S, Sunamura M et al: Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis. Am J Surg 117: 394-398, 1996
14) Satoh H, Harada M, Tashiro S et al: The effect of continuous arterial infusion of gabexate mesilate (FOY-007) on experimental acute pancreatitis. J Med Invest 51: 186-193, 2004
22) Saglamkaya U, Mas MR, Yasar M et al: Penetration of meropenem and cefepim into pancreatic tissue during the course of experimental acute pancreatitis. Pancreas 24: 264-268, 2002
24) Luiten EJ, Hop WC, Endtz HP et al: Prognostic importance of gram-negative in testinal colonization preceding pancreatic infection in severe acute pancreatitis. Result of a controlled clinical trial of selective decontamination. Intensive Care Med 24: 438-445, 1998
30) Zhou YM, Xue ZL, Li YM et al: Antibiotic prophylaxia in patients with severe acute pancreatitis. Hepatobiliary Pancreat Dis Int 4: 23-27, 2005
33) 武田正一郎: 保険薬辞典. 平成18年4月版. じほう出版, 東京, 2006, p515
10) Wilson C, Heath DI, Imrie CW: Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg 77: 1260-1264, 1990
27) Tsuji A, Kobayashi I, Oguri T et al: An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan. J Infect Chemother 11: 64-70, 2005
25) Gloor B, Muller CA, Worni M et al: Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organism. Arch Surg 136: 592-596, 2001
31) Heinrich S, Schafer M, Rousson V et al: Evidence-based treatment of acute pancreatitis: a look at established paradigms. Ann Surg 243: 154-168, 2006
29) Unal S, Masterton R, Goossens H: Bacteraemia in Europe-antimicrobial susceptibility data from MYSTIC surveillance programme. Int J Antimicrob Agents 23: 155-163, 2004
References_xml – reference: 18) Takeda K, Matsuno S, Ogawa M et al: Continuous regional arterial infusion (CRAI) therapy reduces the mortality rate of acute necrotizing pancreatitis: results of a cooperative survey in Japan. J Hepatobiliary Pancreat Surg 8: 216-220, 2001
– reference: 11) Kalfarentzos F, Kehagias J, Mead N et al: Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis. Br J Surg 84: 1665-1669, 1997
– reference: 7) Takeda K, Matsuno S, Sunamura M et al: Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis. Am J Surg 117: 394-398, 1996
– reference: 15) Kakugawa Y, Takeda K, Sunamura M et al: Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstuction. Jpn Gastroenterol 87: 1440-1450, 1990
– reference: 4) Bassi C, Mangiante G, Falconi M et al: Prophylaxis for septic complications in acute necrotizing pancreatitis. J Hepatobiliary Pancreat Surg 8: 211-215, 2001
– reference: 12) Luiten EJ, Hop WC, Lange JF et al: Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg 222: 57-65, 1995
– reference: 20) Buchler M, Malfertheiner P, Friess H et al: Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 103: 1902-1908, 1992
– reference: 28) Yamaguchi K, Ishi Y, Iwata M et al: Meropenemを含む各種注射用抗菌薬に対する2004年臨床分離株の感受性サーベイランス. Jpn J Antibiotics 58: 655-689, 2005
– reference: 14) Satoh H, Harada M, Tashiro S et al: The effect of continuous arterial infusion of gabexate mesilate (FOY-007) on experimental acute pancreatitis. J Med Invest 51: 186-193, 2004
– reference: 19) Takeda K, Sunamura M, Shibuya K et al: Role of early continuous regional arterial infusion of protease inhibitor and antibiotic in nonsurgical treatment of acute necrotizing pancreatitis. Digestion 60: 9-13, 1999
– reference: 24) Luiten EJ, Hop WC, Endtz HP et al: Prognostic importance of gram-negative in testinal colonization preceding pancreatic infection in severe acute pancreatitis. Result of a controlled clinical trial of selective decontamination. Intensive Care Med 24: 438-445, 1998
– reference: 16) Hayashi J, Kawarada Y, Isaji S et al: Therapeutic effects of continuous intraarterial antibiotic infusion in preventing pancreatic infection in ex perimental acute necrotizing pancreatitis. Pancreas 13: 184-192, 1996
– reference: 22) Saglamkaya U, Mas MR, Yasar M et al: Penetration of meropenem and cefepim into pancreatic tissue during the course of experimental acute pancreatitis. Pancreas 24: 264-268, 2002
– reference: 1) 大槻眞, 木原康之: 急性膵炎全国疫学調査. 厚生労働省科学研究費補助金難治性疾患克服研究事業難治性膵疾患に関する調査研究班. 平成14-16年度総合研究報告書. 東京, 2005, p31-39
– reference: 26) Grewe M, Tsiotos CG, Luque de-Leon E et al: Fungal infection in acute necrotizing pancreatitis. J Am Coll Surg 188: 408-414, 1999
– reference: 8) 小川道雄, 広田昌彦, 早川哲夫ほか: 重症急性膵炎全国調査-不明例の追加調査を加えた最終報告. 厚生省特定疾患消化器系疾患調査研究班難治性膵疾患分科会平成10年度研究報告書. 厚生省, 東京, 2000, p23-35
– reference: 34) 砂川洵, 森永正敏: カルバペネム系抗生物質と中枢神経系副作用-メロペネムの構造活性相関の研究より-. BIO Clinica 12: 1074-1077, 1997
– reference: 33) 武田正一郎: 保険薬辞典. 平成18年4月版. じほう出版, 東京, 2006, p515
– reference: 6) 急性膵炎の診療ガイドライン作成委員会編: エビデンスに基づいた急性膵炎のガイドライン. 第1版. 金原出版, 東京, 2003, p71-80
– reference: 5) Bassi C, Falconi M, Talamini G et al: Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis. Gastroenterology 115: 1513-1517, 1998
– reference: 13) 平澤博之, 北村伸哉, 上野博一: 重症急性膵炎におけるhumoral mediatorからみた持続的血液濾過透析(CHDF)の有効性に関する検討. 小川道雄監. 重症急性膵炎の救命率を改善するための研究班平成11年度研究報告書. 厚生省, 東京, 2000, p162-170
– reference: 27) Tsuji A, Kobayashi I, Oguri T et al: An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan. J Infect Chemother 11: 64-70, 2005
– reference: 35) Wendelin KN, Priscilla AR, Ralph Q et al: Empiric Carbapenem Monotherapy in Pediatric Bone Marrow Transplant Recipients. Ann Pharmacother 36: 1360-1365, 2002
– reference: 17) Imaizumi H, Kida M, Nishimaki H et al: Efficacy of continuous regional arterial infusion of a protease inhibitor and antibiotic for severe acute pancreatitis in patients admitted to an intensive care unit. Pancreas 28: 369-373, 2004
– reference: 25) Gloor B, Muller CA, Worni M et al: Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organism. Arch Surg 136: 592-596, 2001
– reference: 29) Unal S, Masterton R, Goossens H: Bacteraemia in Europe-antimicrobial susceptibility data from MYSTIC surveillance programme. Int J Antimicrob Agents 23: 155-163, 2004
– reference: 32) Manes G, Uomo I, Menchise A et al: Timing of antibiotic prophylaxis in acute pancreatitis: a controlled randomized study with meropenem. Am J Gastroenterol 101: 1348-1353, 2006
– reference: 30) Zhou YM, Xue ZL, Li YM et al: Antibiotic prophylaxia in patients with severe acute pancreatitis. Hepatobiliary Pancreat Dis Int 4: 23-27, 2005
– reference: 10) Wilson C, Heath DI, Imrie CW: Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg 77: 1260-1264, 1990
– reference: 2) Golub R, Siddiqi F, Pohl D: Role of antibiotics in acute pancreatitis: a meta-analysis. J Gastrointest Surg 2: 496-503, 1998
– reference: 21) Bassi C, Pederzoli P, Vesentini S et al: Behaviour of antibiotics during human necrotizing pancreatitis. Antimicrob Agents Chemother 4: 830-836, 1994
– reference: 9) Vincent JL, de Mendonca A, Cantraine F et al: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: result of a multicenter, prospective study. Working group on “sepsis-related problems” of European Society of Intensive Care Medicine. Crit Care Med 26: 1793-1800, 1998
– reference: 3) Pederzoli P, Bassi C, Vesentini S et al: A randomized multicenter clinical trial of antibiotic prophylaxis of septic acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 176: 480-483, 1993
– reference: 23) Manes G, Rabitti PG, Menchise A et al: Prophylaxis with meropenem of septic complications in acute pancreatitis: a randomized, controlled trial versus imipenem. Pancreas 27: e79-e83, 2003
– reference: 31) Heinrich S, Schafer M, Rousson V et al: Evidence-based treatment of acute pancreatitis: a look at established paradigms. Ann Surg 243: 154-168, 2006
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Snippet Introduction: We performed a prospective randomized controlled trial in patients with severe acute pancreatitis, comparing one group who were given meropenem...
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SubjectTerms continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI)
imipenem
meropenem
severe acute pancreatitis
Title The Effectiveness of Continuous Regional Arterial Infusion Therapy with Meropenem in Severe Acute Pancreatitis Compared with Imipenem: A Prospective, Randomized Study
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