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Three Part Question

In [patients with proven pancreatic necrosis on CT scan], can [prophylactic antibiotics] effectively [improve survival and length of hospital stay]?

Clinical Scenario

A 50 year old man presented to the accident and emergency department with epigastric pain. Acute pancreatitis was diagnosed. You wonder if early prophylactic antibiotics will improve survival and length of hospital stay in this patient.

Search Strategy

Medline 1966 to June Week 4 2006 using Ovid Interface.
({[pancreatitis.mp. or exp Pancreatitis, Acute Necrotizing/ or exp Pancreatitis/ or exp Pancreatitis, Alcoholic/] AND [antibiotics.mp. or exp Anti-Bacterial Agents/]} limit to humans and English language and "all adult (19 plus years)")

Search Outcome

299 articles were found, of which 7 were relevant. They are shown below:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Finch, W T. Sawyers, J L. Schenker, S. 1976	58 patients with acute pancreatitis confirmed by amylase admitted to Nashville Metropolitan hospital between 1971-1973	Double blinded evaluation study	Length of hospital stay	Antibiotics: 10.4 days, No treatment: 11.3 days	Ethical approval not mentioned The study only aimed to study alcoholic and idiopathic pancreatitis Different radiographic studies were used to assess the result Not all patients underwent radiographic studies for assessment
			Normal serum amylase by day	Antibiotics: 5.0 days, No treatment: 4.5 days
			Recurrent pancreatitis	Antibiotics: 6 patients, No treatment: 2 patients
			Development of complications	Antibiotics: 6 patients, No treatment: 5 patients
				Conclusion: there is no significant difference between 2 groups except recurrence rate, which was higher in the antibiotics group
Pederzoli, P. Bassi, C. Vesentini, S. Campedelli, A 1993 Italy	74 patients with pancreatic necrosis confirmed by US and CT scan from 6 centres in Italy between 1989 and 1991 33 in control group 41 in antibiotics group	Randomised clinical trial	Pancreatic sepsis	Antibiotic group 12.2%, No treatment 30.3%,P<0.01	Not a blinded study
			Surgery	Antibiotics 29%, No treatment 33%
			Death	Antibiotics 7%, No treatment 12%
				Conclusion: Prophylactic antibiotics significantly reduces sepsis
Sainio, V. Kemppainen, E. Puolakkainen, P 1995 Finland	60 patients with severe necrotic alcohol-induced pancreatitis confirmed by CT scan between the year 1989 and 1993	Randomised clinical trial	Infective pancreatic necrosis	Antibiotics 30%, No treatment 40%	Not blinded Study does not include other causes of acute pancreatitis
			surgery	Antibiotics 23%, No treatment 47%
			Duration of hospital stay	Antibiotics: 33 days, No treatment: 44 days
			Death	Antibiotics 3%, No treatment 23%, P=0.0284
				Conclusion: antibiotics are beneficial and may reduce mortality
Delcenserie, R. Yzet, T. Ducroix, J P 1996 France	23 patients with severe alcoholic acute pancreatitis with fluid collections on CT scan between 1988 and 1993 antibiotics=11 control=12	Randomised control study	Infected pancreatic necrosis	Antibiotics 0%, control 58%, P<0.03	Not blinded Sample size not large enough to show significant statistical difference regarding length of stay and mortality rate Study does not include other causes of acute pancreatitis
			Length of hospitalisation	Antibiotics 22days, control 27.8days, P=not significant (NS)
			Death	Antibiotics 9%, control 25%, P=NS
				Conclusion: antibiotics can reduce the incidence of severe infection
Ho HS. Frey CF. Prinz RA. Weigelt JA, et al. 1997 USA	180 consecutive patients with severe acute pancreatitis from 1982 to 1996 no antibiotic (1982-1989)s=50 non-protocol use of antibiotics(1990-1992)=55 protocol (4-wk course) antibiotics(1993-1996)=75	Retrospective cohort study	Infection	Antibiotics 27%, Non-protocol antibiotics 45% , No treatment 76%, P<0.001	Retrospective Not randomised, not blinded Did not specify no. of patients receiving full 4-wk course of antibiotics (less illness in those who did not?) Patient groups taken from different period of time (differences in quality of care over time?)
			Death	Antibiotics 5%, Non-protocol 7%, No treatment 16%, P=0.11
				Conclusion: antibiotics may reduce incidence of infection
Nordback, I. Paajanen, H. Sand, J 2001 Finland	58 patients with acute necrotising pancreatitis shown on CT antibiotics=25 control=33	Randomised clinical study	Infected necrosis	Antibiotics 8%, control 36%, P=0.04	Not blinded Sample size too small to achieve statistical power Patients who are >70 yrs or required direct intensive care admission were excluded
			Major organ complications	Antibiotics 20%, control 33%, P=NS
			Length of hospital stay	Antibiotics 17days, control 21days, P=NS
			Death	Antibiotics 8%, control 5%, P=NS
				Conclusion: antibiotics significantly reduce the incidence of infected necrosis
R. Isenmann, M. Runzi, M Kron, et al. 2004 Germany	114 patients with acute pancreatitis with CRP>150mg/L and/or necrosis on CT between 1999 and 2002 58 on antibiotics 56 on placebo (random allocation)	Double-blinded controlled trial	Development of infectious complications (e.g., multiple organ failure sepsis)	Antibiotics 28%, PLA 46%	Sample size not large enough
			Development of infective necrosis	Antibiotics: 12%. PLA 9%, P=0.585
			Death	Antibiotics 5%, PLA 7%
				Conclusion: there is no benefit of antibiotic with respect to the risk of developing infected pancreatic necrosis

Comment(s)

Incidence of infection, length of hospital stay and mortality rates were compared between treatment and control group. Three studies concentrated on alcohol-induced acute pancreatitis. Incidence of infective necrosis were reduced in antibiotics group in most studies. However there were no statistical differences in the length of hospital stay and mortality rates between the two groups as the sample size was not large enough in most of the studies.

Clinical Bottom Line

Five out of the 7 papers were in favour of the use of prophylactic antibiotics. Prophylactic antibiotics are effective in reducing the incidence of infections mainly in alcohol-induced acute pancreatitis.

References

1. Finch, W T. Sawyers, J L. Schenker, S. A prospective study to determine the efficacy of antibiotics in acute pancreatitis. Annals of Surgery. 183(6):667-71, 1976 Jun.
2. Pederzoli, P. Bassi, C. Vesentini, S. Campedelli, A A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surgery, Gynecology & Obstetrics 176(5):480-3, 1993 May.
3. Sainio, V. Kemppainen, E. Puolakkainen, P Early antibiotic treatment in acute necrotising pancreatitis. Lancet. 346(8976):663-7, 1995 Sep 9.
4. Delcenserie, R. Yzet, T. Ducroix, J P Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas 13(2):198-201, 1996 Aug.
5. Ho HS. Frey CF. Prinz RA. Weigelt JA, et al. The role of antibiotic prophylaxis in severe acute pancreatitis. Archives of Surgery Vol. 132(5)(pp 487-493), 1997
6. Nordback, I. Paajanen, H. Sand, J Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis--a single-center randomized study. Journal of Gastrointestinal Surgery. 5(2):113-8; discussion 118-20, 2
7. R. Isenmann, M. Runzi, M Kron, et al. Prophylactic Antibiotic Treatment in Patients with Predicted Severe Acute Pancreatitis: A Placebo-Controlled, Double-Blind Trial. Gastroenterology. Vol. 126(4)(pp 997-1004), 2004.