The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic samples were collected simultaneously at diferent time intervals after parenteral drug administration by computed tomographyguided needle aspiration, intraoperatively, and from surgical drainages placed during surgery. Drug concentrations were determined by microbiological and high-performance liquid chromatography assays. All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%o) and metronidazole (990%). The concentrations of pefloxacin (13.0 to 23 ,Lg/g) and metronidazole (8.4 ,ug/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 ,ug/g) and mezlocillin (8.0 and 15.0 ,ug/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 p.g/g) were inadequate. Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue. The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.Superinfection of necrotic tissue in the course of acute necrotizing pancreatitis is a decisive prognostic factor with regard to morbidity and mortality (2,3,5,7,20,25,33,34,40).This has prompted attempts to identify the patients at septic risk (3,5,20), the microorganisms responsible for the superinfection (1), the times of infection in the natural history of the disease (3,20), the therapeutic measures to be adopted (1-3, 5, 20, 34), and possible effective prophylaxis (7,9,10,19,23,25,33).The ideal antibiotic for therapy and/or prophylaxis should be targeted at the microorganisms responsible for the septic complications and should reach the infection site in therapeutic concentrations.To date, several studies have been conducted to evaluate the penetration of various different antibiotics into healthy pancreatic tissue and juice (4, 7-11, 28, 35-38). None of these studies has been conducted with humans in the course of disease, and to the best of our knowledge, the effective ability of antibiotics to penetrate the infection risk areas has never been assessed. Such areas of the retroperitoneum are characterized by the presence of necrotic fragments of pa...

Randomized clinical trials of antibiotic prophylaxis in acute pancreatitis are now warranted in the light of recent evidence of pancreatic penetration of certain antibiotics at therapeutic minimal inhibitory concentrations. The aim of the present prospective clinical study was to investigate whether there are detectable risk factors for pancreatic sepsis in acute pancreatitis that would allow better selection of patients for inclusion in clinical trials. Fifty-nine consecutive patients with acute pancreatitis were recruited and submitted to admission baseline and 48-h determinations of Ranson score, and assay of C-reactive protein at admission and weekly intervals thereafter. Contrast-enhanced computed tomography (CT) was also performed within 24 h of admission. Pancreatic sepsis, defined as infection of pancreatic and/or peripancreatic collections, was demonstrated in all cases by culture of samples obtained by needle aspiration and at laparotomy. Although all prognostic indices correlated significantly with sepsis, multivariate logistic regression analysis showed that the only variables predictive of the risk of subsequent sepsis were the presence and extent of necrosis. Early detection of pancreatic necrosis by CT should be the primary inclusion criterion in future clinical trials of antibiotic prophylaxis in acute pancreatitis.

This is a report on 108 cases collected from 1970 to 1987, in the same department, of surgically-detected pancreatic abscesses or pus-harboring collections. The purulent areas were either of a spreading pattern or represented a clearly localized mass. To the spreading pattern belong 47 cases of necrotizing pancreatitis, without discontinuity in the clinical course from the early toxic to the late septic phase, 4 cases of acute pancreatitis, initially in remission and later complicated by septic collections, and 4 cases which developed after an acute attack of chronic pancreatitis. The abscess pattern was made up of 19 each of pseudocysts and predisposing pancreatitis, 10 cases of chronic pancreatitis, and only 5 necrotizing "nonstop" pancreatitis. The surgical treatment in all cases consisted of multiple drainages and postoperative irrigation. We exclude 3 cases of associated open packing. The etiological, clinical, and biochemical features of each group of patients are reported and discussed. Computed tomography availability seems to be the most important improvement reported as regards diagnosis and surgical tactics. The overall mortality rate was 15.7% with a significant difference between the 2 patterns (23.6% for the spreading pattern versus 7.5% for the abscess pattern). On the basis of this experience, it is possible to establish a relationship between the gross appearance of the collection and the underlying pancreatic disease with differences in terms of prognosis, morbidity, and mortality. Finally, a simple nomenclature can be chosen which is capable of distinguishing between the diverse pancreatic purulent collections. While the presence of pus may characterize the course of severe acute pancreatitis in many cases, the low incidence of "true" pancreatic abscess is emphasized.

Seventeen (8.8%) patients died; mortality showed a decreasing trend over the period of years considered and was correlated, among other things, with necrotizing type of pancreatitis, idiopathic etiology, and shock status on admission.

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