A 65-year-old woman was admitted with a two-day history of feeling non-specifically unwell, severe upper abdominal pain, anorexia and vomiting. On examination she was tachycardic, hypotensive with epigastric tenderness and guarding. Admission amylase was 1024 mmol/L. A diagnosis of acute pancreatitis was made and she was admitted for conservative management with IV fluids and analgaesia. Her initial Ranson score was 3 placing her at moderate risk of of death. Abdominal ultrasound scanning showed a swollen pancreas with a small amount of free fluid but no gallstones or obstruction to the biliary system. Over the next twelve hours she deteriorated on the ward, developing type 1 respiratory failure for which she was referred to intensive care.
On admission to ITU she was semi-electively intubated and ventilated. A low-dose infusion of noradrenaline required to achieve adequate mean arterial pressure. A CT scan showed inflammatory changes and free fluid around the pancreas with possible early pseudocyst formation but no necrotic areas. Two hours after admission she became pyrexial at 39.5°C with a modest increase in her noradrenaline requirements. Peripheral blood cultures were taken and empirical imipenem started following discussion with microbiology. Subsequent repeated microbiological cultures of blood, ascitic fluid, urine and sputum were negative. A nasojejunal tube was passed to allow enteral feeding.
Over the next 48 hours her sedation was weaned and her respiratory function improved. Vasculitis screens, viral serology, lipids, etc. were all negative or normal. Despite her clinical improvement she remained pyrexial with an elevated CRP and white cell count. Further microbiological sampling was unhelpful, serum procalcitonin middling and repeat CT scan showed maturation of her pseduocyst. Fine needle aspiration was performed and subsequently proved culture negative. Her imipenem was stopped after 7 days after gradual resolution of her noradrenaline requirements. Surgical tracheostomy was performed on day 11 to facilitate ventilatory weaning and she was discharged to the ward on day 21.
What is the role for antibiotics in acute pancreatitis?
Pancreatitis is a common acute abdominal emergency due to multicausal inflammation of the pancreatic gland which frequently involves peripancreatic tissue and/or remote organ systems.1 The incidence of this condition appears to be rising over the course of the last half-century.2 Whilst advances in treatment of causative mechanisms have improved, for example ERCP for removal of gallstones blocking the biliary system, there remains no specific treatment for pancreatitis itself, other than supportive care; despite increasing incidence however, mortality has reduced from around 12% to nearer 6%.3
Early pancreatitis is characterised by interstitial oedema and by necrosis of peripancreatic fat through the activation of pancreatic enzymes. This produces both localised and systemic effects for reasons which are not well understood, including increased vascular permeability, coagulopathy and the leak of bacteria from intestinal spaces through translocation or via intervening lymphatics.4 Severe disease may be associated with localised necrosis or the formation of pseudocysts or fistulae.5 Death is usually associated with uncontrolled local and systemic inflammation and the associated organ failure.6
Those patients who develop necrosis and pseudocyst formation are at particular risk of infection between days 7 and 21.7 Most infections appear polymicrobial but gram negative organisms such as Enterobacter species predominate and there is increasing awareness of the role of fungi such as Candida.7,8
The use of prophylactic antibiotics in such cases of acute pancreatitis remains controversial. Empirical treatment with appropriately penetrant antibiotics such as carbapenems or third-generation cephalosporins has been advocated but the benefit and duration of this treatment remains questionable. Broad-spectrum antibiotics are not without side-effects including antimicrobial resistance and the need for vascular access. Guidelines published by the British Gastroenterogy Society suggest antibiotics do not affect outcome in those without extensive necrosis, i.e. greater than 30%.9 No concensus was offered regarding the choice of chemotherapeutic of duration of treatment and as such they recommend that limiting treatment to 7-14 days where they are used prophylactically and that treatment should not be continue beyond this without microbiologically documented evidence of infection through culture.9
However, a more recent Cochrane review concluded that whilst there was a reduction in death and infections including of pancreatic necroses, these differences were not statistically significant and hence genuine benefit could not be confirmed.10 In this meta-analysis, many different regimens were used and there was a tendency for β-lactam antibiotics to work better. Consistent trends towards a benefit were seen and an argument made for further, better designed studies. A similar meta-analysis of Swedish patients however found no benefit to prophylactic administration in severe acute pancreatitis.11 Serum procalcitonin may be of use in predicting the severity of acute pancreatitis and guiding the initiation of treatment for potentially infected necroses.12
The early administration of antibiotics may not have been necessary in this case; whilst certainly evidence of an inflammatory response, the repeatedly negative microbiological sampling may represent true ‘sterility’ or be masked by broad-spectrum antimicriobials. Targeted therapy, perhaps with earlier attempts at fine needle aspiration or serial procalcitonin assays may have been helpful.
- Bradley EL. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg. 1993. pages 586–90.
- Spanier BWM, Dijkgraaf MGW, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Practice & Research Clinical Gastroenterology. 2008 Feb;22(1):45–63.
- Banks PA, Freeman ML, Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am. J. Gastroenterol. 2006. pages 2379–400.
- Bakoyiannis A, Delis S, Dervenis C. Pathophysiology of acute and infected pancreatitis. Infect Disord Drug Targets. 2010 Feb;10(1):2–4.
- Gravante G, Garcea G, Ong SL, Metcalfe MS, Berry DP, Lloyd DM, et al. Prediction of Mortality in Acute Pancreatitis: A Systematic Review of the Published Evidence. Pancreatology. 2009;9(5):601–14.
- Petrov MS, Shanbhag S, Chakraborty M, Phillips ARJ, Windsor JA. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology. 2010 Sep;139(3):813–20.
- Behrman SW, Bahr MH, Dickson PV, Zarzaur BL. The microbiology of secondary and postoperative pancreatic infections: implications for antimicrobial management. Arch. Surg. 2011 May;146(5):613–9.
- Tsui N-C, Zhao E, Li Z, Miao B, Cui Y, Shen Y, et al. Microbiological findings in secondary infection of severe acute pancreatitis: a retrospective clinical study. Pancreas. 2009 Jul;38(5):499–502.
- Working Party of the British Society of Gastroenterology, Association of Surgeons of Great Britain and Ireland, Pancreatic Society of Great Britain and Ireland, Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut. Gut; 2005. pages iii1–9.
- Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010;(5):CD002941.
- Wittau M, Mayer B, Scheele J, Henne-Bruns D, Dellinger EP, Isenmann R. Systematic review and meta-analysis of antibiotic prophylaxis in severe acute pancreatitis. Scand J Gastroenterol. 2011 Mar;46(3):261–70.
- Reza Mofidi MB M, Stuart A Suttie MB B, Pradeep V Patil MB BS, Simon Ogston BA M, MD RWP. The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: Systematic review. Surgery. Mosby, Inc; 2009 Jul 1;146(1):72–81.