Question 1

College Answer

Background / Rationale:

Systemic antibiotics in severe acute pancreatitis (SAP) have a potential role in three areas:

• Infected pancreatic necrosis 
  • Necrotising pancreatitis develops in about 15% and approx. half of these become infected with increased mortality
  • Majority of pancreatic infections are from gut derived organisms and may be polymicrobial. Common organisms include E coli, Klebsiella species, Enterobacter species, Proteus, Pseudomonas aeruginosa, Bacteroides species and Enterococcus
  • Should be suspected in patients with pancreatic necrosis who fail to improve after 7-10 days of hospitalisation
• Extra-pancreatic infections
  • Common (up to 20% of patients with SAP), e.g. bloodstream, pneumonia, UTI and associated with increased mortality
• Prophylaxis
  • Theoretically antibiotics could prevent or decrease infection rates and decrease mortality
  • Use of prophylactic antibiotics in SAP is controversial

Disadvantages:

• Development of resistant strains of bacteria and selection of fungal infections.

Evidence and Practice Guidelines:

• Infected pancreatic necrosis
  • In suspected infected necrosis or pancreatic abscess, use antibiotics in association with minimally invasive drainage or open surgery.
  • Therapeutic guidelines recommend Tazocin OR if allergic to penicillin’s 3^rd generation cephalosporin and metronidazole OR meropenem OR quinolone and metronidazole.
• Extra-pancreatic infections
  • Antibiotics should be prescribed as clinically indicated.
• Use of prophylactic antibiotics in pancreatitis
  • Controversial
  • Cochrane meta-analysis in 2010:
    • Trends towards increased survival and reduced rates of infections of pancreatic necrosis but not statistically significant
    • Trend towards less incidence of non-pancreatic infections
    • Of subgroup analysis regarding antibiotic therapy, only imipenem had statistically decreased infection rates of necrotic pancreas but no mortality benefit
    • Issues with under powering of studies, not limited to necrotic pancreatitis and heterogeneity of patients
    • Prophylactic antibiotics in established necrosis of acute pancreatitis not recommended.

Summary statement:

• In suspected infected pancreatic necrosis treat with surgical/percutaneous/endoscopic drainage and broad-spectrum antibiotics
• Routine use of prophylactic antibiotics with sterile necrosis to prevent infected necrosis is not recommended
• Antibiotics as indicated for extra-pancreatic infections
• Routine use of prophylactic antibiotics in severe acute pancreatitis is not recommended

Discussion

The correct answer to this question is "role? there is none". However, it is a ten-mark SAQ. So, here is an example of how to say "none" using approximately extra 400 words.

Potential uses of antibiotics in pancreatitis

• Prophylaxis to prevent infection of the necrotic pancreas
• Prophylaxis to prevent infection of the pancreatic pseudocyst
• Treatment of infected pancreatic necrosis
• Coincidental use of these antibiotics to treat an unrelated extrapancreatic infection

Coincidental treatment of extrapancreatic infection

• Brown et al (2014): incidence of  infectious complications = 32%
• Commonest infections were respiratory (9.2%) and bacteraemia (8.4%).
• Half of bacterial cultures of pancreatic necrosis are of non-enteric origin.
• Ergo, pancreatic nnecrosis easily gets infected from extrapancreatic sources.
• However, this seems to have no effect on severity or mortality of the pancreatitis.

Treatment of infected pancreatic necrosis

• "Pancreatic necrosis" is non-enhancing areas of the pancreas
• 8-12% of patients develop infected necrosis (Mike Larvin, 2008)
• Infection of the pancreatic necrosis tends to be confirmed late (19-21 days following onset).
• Survivors from early organ system failure may still die if pancreatic necrosis later becomes infected.
• Organ system failure tends to be worse and mortality tends to be higher.
• Confirmation of the diagnosis is invasive, i.e. by samples and culture.
• CT-guided aspiration has pros (Banks, 2005) and cons (Pappas, 2005).
• If the patient is haemodynamically unstable and the infected pancreas is held responsible, CT-guided or gastroscopic drainage offers both a diagnosis (confirming infection) and souirce control.
• If infection is confirmed by Gram stain, the best choice of antibiotics is probably meropenem.

Arguments for the use of prophylactic antibiotics in severe pancreatitis

• Pancreatic necrosis promotes bacterial growth
• Surgical source control is difficult or impossible
• Diagnosis of sepsis is difficult (in the presense of SIRS)
• Sepsis is a major cause of death in severe pancreatitis
• Non-pancreatic infection plays a major role in this mortality.
• Thus, prophylactic antibiotics should reduce mortality, even if by treating extrapancreatic infections
• This practice is common: Baltatziz et al (2016) found antibiotic prophylaxis was used in 44-88% of the surveyed units.

Counterarguments to the routine use of prophylactic of antibiotics

• Penetration into the collection will be poor.
• Treatment of extrapancreatic infections with panreas-penetrating antibiotics results in overuse of meropenem.
• The use of antibiotics will promote the overgrowth of resistant organisms, and select for species which will subsequently be more difficult to eradicate. The college answer mentions fungus as one of the options.

Evidence

• Jafri et al (2009):no improvement in mortality, risk of pancreatic pseudocyst infection or need for surgical intervention.- Hoqwever, the risk of extrapancreatic infection was reduced by 15%, NNT =7.
• Parent et al (2016): meta-analysis; only low quality studies show any treatment effect.
• The Cochrane analysis referred to by the college is Villatoro et al (2010), whose conclusion was also "no benefit". 

Antibiotic choice (if you felt compelled to give them)

• All antibiotics penetrate the necrotic tissue, but most end up not achieving MIC (Bassi et al, 1994).
• Drugs which achieve a high concentration in pancreatic tissue :
  • Imipenem (and thus also meropenem)
  • Metronidazole
  • Fluoroquinolones (specifically, pefloxacin)
• Drugs which are known to penetrate poorly:
  • Aminoglycosides
  • Beta-lactams

Guidelines and "own practice"

• This practice is not supported by the American College of Gastroenterology guidelines (2013)
• Antibiotics should not be routinely given to patients with severe acute pancreatitis
• Clinical evidence of sepsis (including sepsis of other origin, eg. urinary or pulmonary) should be promptly treated with appropriate antibiotics (not pancreas-specific antibiotics)
• It may be possible to sample the collection by CT-guided aspiration; if the Gram-stain is positive this will be the deciding factor

Maheshwari, Rahul, and Ram M. Subramanian. "Severe Acute Pancreatitis and Necrotizing Pancreatitis." Critical care clinics 32.2 (2016): 279-290.

Baltatzis, Minas, et al. "Antibiotic use in acute pancreatitis: Global overview of compliance with international guidelines." Pancreatology (2016).

Parent, Brodie, and E. Patchen Dellinger. "Antibiotic Prophylaxis for Acute Necrotizing Pancreatitis." Difficult Decisions in Hepatobiliary and Pancreatic Surgery. Springer International Publishing, 2016. 433-449.

Tenner, Scott, et al. "American College of Gastroenterology guideline: management of acute pancreatitis." The American journal of gastroenterology 108.9 (2013): 1400-1415.

Jiang, Kun, et al. "Present and future of prophylactic antibiotics for severe acute pancreatitis." World J Gastroenterol 18.3 (2012): 279-84.

Jafri, Nadim S., et al. "Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis." The American Journal of Surgery 197.6 (2009): 806-813.

Bassi, C., et al. "Behavior of antibiotics during human necrotizing pancreatitis." Antimicrobial agents and chemotherapy 38.4 (1994): 830-836.

Brown, Lisa A., et al. "A systematic review of the extra-pancreatic infectious complications in acute pancreatitis." Pancreatology 14.6 (2014): 436-443.

Larvin, Mike. "Management of infected pancreatic necrosis." Current gastroenterology reports 10.2 (2008): 107-114.

Banks, Peter A. "Pro: computerized tomographic fine needle aspiration (CT-FNA) is valuable in the management of infected pancreatic necrosis." The American journal of gastroenterology 100.11 (2005): 2371.

Pappas, Theodore N. "Con: computerized tomographic aspiration of infected pancreatic necrosis: the opinion against its routine use." The American journal of gastroenterology 100.11 (2005): 2373.

Villatoro, Eduardo, Mubashir Mulla, and Mike Larvin. "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis." The Cochrane Library (2010).