Trudel J L, Wittnich C, Brown R A
Department of Surgery, Montreal General Hospital, Quebec, Canada.
J Am Coll Surg. 1994 May;178(5):475-9.
Pancreatic sepsis in acute pancreatitis is the most lethal complication of the disease. This study was done to create a rational basis for the choice of antibiotics used in the treatment of severe acute pancreatitis. We postulated that, unless the antibiotics were present in therapeutic concentrations in the pancreatic tissue during pancreatitis, their use was of no value. Six mongrel dogs were used to test each antibiotic, each dog acting as its own control. The doses were based on the weight of the dogs: 15.0 milligrams per kilogram of clindamycin; 50.0 milligrams per kilogram of chloramphenicol; 10.0 milligrams per kilogram of metronidazole; 5.0 milligrams per kilogram of gentamicin; 12.5 milligrams per kilogram of cefazolin, and 50.0 milligrams per kilogram of ampicillin. Baseline serum and pancreatic tissue levels were obtained after intravenous injection of the antibiotics. Bile-trypsin hemorrhagic pancreatitis was induced one week later, and the serum and pancreatic tissue level antibiotics were measured again. The results showed significant differences in bioactive levels of antibiotics between blood and the pancreas. Ampicillin, gentamicin and cefazolin reached therapeutic blood levels, but did not achieve a parallel therapeutic level in the normal pancreatic tissue or during pancreatitis. Only three of the antibiotics tested, clindamycin, metronidazole and chloramphenicol, achieved therapeutic tissue penetrance in the normal and inflamed pancreas. After 1982, based on these results, clindamycin became our prophylactic antibiotic of choice in instances of acute severe pancreatitis. This resulted in the eradication of Bacteroides as a cause of pancreatic sepsis between 1980 and 1985. In 1993, our recommendation is to use a broad-spectrum gram-negative and gram-positive antibiotic with good penetration of the pancreatic tissue, such as cefotaxime or imipenem.
急性胰腺炎中的胰腺脓毒症是该疾病最致命的并发症。本研究旨在为治疗重症急性胰腺炎时抗生素的选择建立合理依据。我们推测，除非在胰腺炎期间抗生素在胰腺组织中达到治疗浓度，否则使用它们毫无价值。使用6只杂种狗来测试每种抗生素，每只狗自身作为对照。剂量根据狗的体重确定：每千克体重15.0毫克克林霉素；每千克体重50.0毫克氯霉素；每千克体重10.0毫克甲硝唑；每千克体重5.0毫克庆大霉素；每千克体重12.5毫克头孢唑林，以及每千克体重50.0毫克氨苄西林。静脉注射抗生素后获取基线血清和胰腺组织水平。一周后诱发胆胰蛋白酶性出血性胰腺炎，再次测量血清和胰腺组织中的抗生素水平。结果显示血液和胰腺中抗生素的生物活性水平存在显著差异。氨苄西林、庆大霉素和头孢唑林达到了治疗性血液水平，但在正常胰腺组织或胰腺炎期间未达到相应的治疗水平。所测试的抗生素中只有三种，即克林霉素、甲硝唑和氯霉素，在正常和发炎的胰腺中实现了治疗性组织穿透。1982年后，基于这些结果，克林霉素成为我们在急性重症胰腺炎病例中预防性使用的首选抗生素。这导致在1980年至1985年间消灭了作为胰腺脓毒症病因的拟杆菌。1993年，我们建议使用一种对胰腺组织有良好穿透性的广谱革兰氏阴性和革兰氏阳性抗生素，如头孢噻肟或亚胺培南。
