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ANTIBIOTICS IN ACUTE PANCREATITIS
Sanjay C Wagle*
*Intensivist, ICCU, Bombay Hospital.
The occurrence of pancreatic infection is a leading cause of morbidity and mortality in acute necrotizing pancreatitis. Approximately 30 per cent of patients with severe acute pancreatitis develop local pancreatic infection. Patients who develop infection tend to have more extensive necrosis compared to those in whom the necrotic tissue remains sterile.
Clinically, pancreatic infection may be suspected on the basis of unresolved organ failure, persisting systemic toxicity, or both. In this case, ultrasound-guided or CT-guided percutaneous aspiration of suspected pancreatic tissue with bacteriologic sampling should be performed. Gram stain has proven to be reliable as an early indicator of pancreatic infection.
The important organisms causing infection in necrotizing pancreatitis are predominantly gut-derived including escherichia coli, pseudomonas, klebsiella, and enterococcus spp. The majority of infections (about 75 per cent) are monomicrobial. Fungal infection and infection with gram positive organisms are uncommon but occur more frequently in the setting of antibiotic use. As a general rule, patients with gram negative and fungal infections have a worse prognosis compared to those with gram positive infections.
Although using antibiotic treatment in the case of proven infection raises no questions, there is considerable discussion concerning antibiotic prophylaxis in acute pancreatitis.
Three approaches have been taken to decrease bacterial infections in acute necrotizing pancreatitis:
•Enteral feeding to avoid central line related infections, maintain gut barrier integrity, and decrease bacterial translocations.
•Selective decontamination of the gut with non-absorbable antibiotics
•Prophylactic systemic antibiotics
Selective decontamination of the gut - As mentioned above, the source of bacterial infections in acute necrotizing pancreatitis is the gut. Thus, reduction of intestinal bacteria through the use of oral - nonabsorbable antibiotics could theoretically reduce the risk of infection. This hypothesis was supported in a controlled trial involving 102 patients with severe acute pancreatitis who were randomly assigned to standard treatment of gut decontamination (using a combination of oral norfloxacin, colistin, and amphotericin). Overall mortality was significantly lower in patients assigned to gut decontamination (22 versus 35 per cent). The reduced mortality was mostly attributable to a reduction in gram negative infections (8 versus 33 per cent). A problem with this study was the use of systemic antibiotics in the patients who received gut decontamination. Thus, the effect of gut decontamination alone is unclear.
Antibiotic prophylaxis in severe acute pancreatitis
A number of studies have evaluated the benefit of administering prophylactic intravenous antibiotics. Initial studies done in the mid-1970s failed to show a benefit, probably because they included patients with mild disease who were at low risk for infection. Furthermore, the selection of antibiotics that had poor penetration into the pancreas, such as ampicillin, may have contributed to the negative results.
In contrast to these older studies, more recent studies have demonstrated improved outcomes associated with the use of prophylactic antibiotics in patients with severe necrotizing pancreatitis.
Pederzoli et al [5] studied imipenem in 74 patients and found that it lead to less pancreatic and nonpancreatic infections but did not have any effect on incidence of multiorgan failure or on mortality rate.
Saino et al6 used cefuroxime in 30 patients and reported that it lead to less infections and resulted in lower mortality.
Declenserie et al [2] used a combination of ceftazidime, amikacin and metronidazole and found that it resulted in less pancreatic infections. The incidence of multiorgan failure and mortality rate did not change.
Schwarz et al [7] used ofloxacin and metronidazole and found that there was no change in incidence of pancreatic infection and multiorgan failure and there was no change in mortality.
A small study of 60 patients with severe acute pancreatitis evaluated the effect of pefloxacin versus imipenem. [8] This nonblinded, non-placebo-controlled, but group-matched study showed that imipenem was superior to pefloxacin with regard to the prevention of pancreatic infection.
A meta-analysis of eight controlled trials concluded that prophylactic antibiotics reduced mortality, but the advantage was limited to patients with severe acute pancreatitis who received broad-spectrum antibiotics that are capable of achieving therapeutic pancreatic tissue levels. [4]
Human and animal studies of the degree of pancreatic penetration of various antibiotics have demonstrated adequate penetration with imipenem, third generation cephalosporins, piperacillin, mezlocillin, fluoroquinolones, and metronidazole, but not with aminoglycosides, amino penicillins, and first generation cephalosporins.
CONCLUSIONS
The choice of antibiotic and the duration of therapy still remain debatable issues. Current recommendations are not uniform. The American Society of Gastroenterology practice guidelines merely state that it is "reasonable to initiate" antibiotic therapy in severe acute pancreatitis. [1] The United Kingdom guidelines for the management of acute pancreatitis simply state that the place of antibiotics in severe acute pancreatitis is unclear. Strongly suspected or confirmed local infective complications (infected necrosis, pancreatic abscess, and infected fluid collections) require appropriate antibiotics in addition to formal drainage by percutaneous or surgical means. Prophylactic antibiotics are recommended before invasive procedures, such as ERCP and surgery. Finally, British workers state that there is a place for prophylactic antibiotics early in an attack of acute pancreatitis predicted as severe. The German Society of Gastroenterology in its consensus conference has stated that there is an indication for antibiotic prophylaxis in acute necrotizing pancreatitis (intrapancreatic and extrapancreatic necrosis) and in those patients with a severe course of the disease (multiorgan failure, C-reactive protein ô 120 mg/L, ranson score ô 3, APACHE II score ô 8).
The duration of antibiotic treatment in necrotizing acute pancreatitis or the duration of an antibiotic prophylaxis depends on the course of the disease; antibiotic prophylaxis or treatment, however, should be given for not less than 7 to 10 days.
Unfortunately, the use of prophylactic antibiotics is not without problems. In addition to the expense, antibiotic prophylaxis can be associated with the selection of resistant organisms and the development of fungal infection. Because of the risk of fungal infections, some authorities advocate the use of prophylactic antifungal therapy, an approach that remains to be validated.
REFERENCES
1.Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997; 92 : 377.
2.Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas 1996; 13 : 198.
3.Glazer G, Mann DV. United Kingdom guidelines for the management of acute pancreatitis. Gut 1998; 42 (Suppl 2) : S1-S13.
4.Golub R, Siddiqi F, Pohl D. Role of antibiotics in acute pancreatitis : A metaanalysis. J Gastrointest Surg 1998; 2 : 496.
5.Pederzoli P. Bassi C, Vesentini S, et al. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 1993; 176 : 480.
6.Saino V, Kemppainen E, Puolakkainen P, et al. Early antibiotic treatment in acute necrotising pancreatitis. Lancet 1995; 346 : 663.
7.Schwarz M, Isenmann R, Meyer H, et al. Antibiotika bei nekrotisierender pankreatitis : Ergebnisse einer kontrollierten studie. Dtsch Med Wochenschr 1997; 122 : 356.
8.Bassi C, Falconi M, Talamini G, et al. Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis. Gastroenterology 1998; 115 : 1513.
9.Luiten EJ, Hop WC, Lange JF, Bruining HA. Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann Surg 1995; 222 : 57.
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