Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.
BACKGROUND
Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection.


OBJECTIVE
To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis.


METHODS
Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched.


METHODS
Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis.


METHODS
Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem).


RESULTS
Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84).


CONCLUSIONS
No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.
Villatoro
Eduardo
E
Academic Division of Surgery, School of Graduate Entry Medicine, University of Nottingham, Derby City General Hospital, Uttoxeter Road, Derby, Derbyshire, UK, DE22 3DT.
Mulla
Mubashir
M
Larvin
Mike
M
D000208:Acute Disease; D019072:Antibiotic Prophylaxis; D001424:Bacterial Infections / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D009336:Necrosis / Q000150:complications; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000150:complications* / Q000401:mortality; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D015163:Superinfection / Q000517:prevention & control*
Gastroenterol Clin North Am. 1999 Sep;28(3):641-59, ix-x
10503141
Arch Surg. 2001 May;136(5):592-6
11343553
Gastroenterology. 2004 Apr;126(4):997-1004
15057739
Acta Gastroenterol Latinoam. 2009 Mar;39(1):24-9
19408736
Antimicrob Agents Chemother. 1994 Apr;38(4):830-6
8031054
Br J Surg. 1999 Mar;86(3):320-2
10201771
Pancreatology. 2007;7(5-6):531-8
17901714
Dig Surg. 2004;21(4):297-304
15365228
Gut. 2005 May;54 Suppl 3:iii1-9
15831893
J Surg Res. 1975 Feb;18(2):197-200
1094193
J Gastroenterol Hepatol. 2001 Sep;16(9):1055-9
11595073
Gastroenterologist. 1997 Jun;5(2):157-64
9193933
Ann Surg. 2006 Feb;243(2):154-68
16432347
Br J Surg. 1998 May;85(5):582-7
9635800
Br J Surg. 2006 Jun;93(6):674-84
16703633
Baillieres Best Pract Res Clin Gastroenterol. 1999 Jul;13(2):317-30
11030609
Gastroenterology. 2004 Apr;126(4):1195-8
15057759
Dig Dis. 2003;21(1):38-45
12837999
Ann Intern Med. 1975 Dec;83(6):831-2
1106281
Pancreas. 2004 May;28(4):369-73
15097852
Gastroenterology. 1992 Dec;103(6):1902-8
1451983
Br J Surg. 1996 Jul;83(7):883-4
8813769
BMJ. 1990 Jun 2;300(6737):1425-8
2379000
Am J Surg. 1986 Feb;151(2):205-8
3946753
Br J Surg. 1999 Feb;86(2):147-8
10100779
Intensive Care Med. 2003 Nov;29(11):1974-80
14551680
Int J Pancreatol. 1994 Aug;16(1):1-10
7806908
BMC Gastroenterol. 2009 Mar 05;9:18
19265519
Surg Gynecol Obstet. 1993 May;176(5):480-3
8480272
J Gastrointest Surg. 2009 Apr;13(4):768-74
19082671
Am J Surg. 1989 Nov;158(5):472-7; discussion 477-8
2683821
J Gastrointest Surg. 2003 Jan;7(1):26-36
12559182
Surg Clin North Am. 1999 Aug;79(4):759-65, ix
10470325
Ann Surg. 1995 Jul;222(1):57-65
7618970
Ann Surg. 2007 May;245(5):674-83
17457158
BMJ. 2004 Apr 24;328(7446):968-9
15105303
Am J Surg. 1996 Apr;171(4):394-8
8604829
Scand J Gastroenterol. 2007 Jun;42(6):771-6
17506001
Int J Pancreatol. 1999 Jun;25(3):195-210
10453421
J Gastrointest Surg. 1998 Nov-Dec;2(6):496-503
10457308
N Engl J Med. 1994 Apr 28;330(17):1198-210
7811319
Aliment Pharmacol Ther. 2002 Dec;16(12):2097-105
12452943
J Antimicrob Chemother. 1996 Aug;38(2):237-43
8877537
Surgery. 1992 Oct;112(4):824-30; discussion 830-1
1411957
Gastroenterology. 1986 Aug;91(2):433-8
3522342
Lancet. 1995 Sep 9;346(8976):663-7
7658819
J Am Coll Surg. 1999 Apr;188(4):408-14
10195725
Pancreas. 1996 Aug;13(2):198-201
8829189
J Gastroenterol Hepatol. 2009 May;24(5):736-42
19220676
J Am Coll Surg. 2002 Dec;195(6):759-67
12495307
Gastroenterology. 1998 Dec;115(6):1513-7
9834279
Shock. 2000 Sep;14(3):320-3; discussion 323-4
11028550
Pharmacotherapy. 1999 May;19(5):592-602
10331822
Cochrane Database Syst Rev. 2003;(4):CD002941
14583957
Clin Infect Dis. 2003 Jul 15;37(2):208-13
12856213
Br J Surg. 1996 Jul;83(7):930-3
8813777
Arch Surg. 1997 May;132(5):487-92; discussion 492-3
9161390
Scand J Gastroenterol. 2007 Jun;42(6):667-72
17505987
Arch Surg. 2004 Dec;139(12):1371-5
15611464
Br J Surg. 1994 Dec;81(12):1707-8
7827923
Ann Surg. 2000 Nov;232(5):619-26
11066131
J Gastrointest Surg. 2001 Mar-Apr;5(2):113-8; discussion 118-20
11331472
BMJ. 2004 Jun 19;328(7454):1466-9
15205290
Gut. 1997 Apr;40(4):526-30
9176083
Dtsch Med Wochenschr. 1997 Mar 21;122(12):356-61
9118789
Antibiot Khimioter. 2001;46(5):24-7
11558450
Arch Surg. 1993 May;128(5):586-90
8489394
Cochrane Database Syst Rev. 2006 Oct 18;(4):CD002941
17054156
Br J Surg. 1989 May;76(5):465-71
2736358
J Gastrointest Surg. 1999 May-Jun;3(3):252-62
10481118
Pancreas. 2001 Jan;22(1):28-31
11138967
Br J Surg. 1993 Dec;80(12):1579-82
8298930
Curr Gastroenterol Rep. 2008 Apr;10(2):107-14
18462595
Am J Surg. 1996 Dec;172(6A):38S-43S
9003689
Gut. 2005 Mar;54(3):426-36
15710995
Am J Gastroenterol. 2006 Jun;101(6):1348-53
16771960
Ann Surg. 1976 Jun;183(6):667-71
788655