Bacterial peritonitis

Is there any evidence that proton pump inhibitors (PPIs) benefit patients with acute pancreatitis?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Despite their widespread use, there is no firm evidence that PPIs should be routinely prescribed in the treatment of acute pancreatitis (AP).1   In fact, current guidelines do not include the use of PPIs as standard therapy in  AP. 1-3

Although a 2023 systematic review and meta-analysis involving 6 randomized controlled trials and 3 cohort studies of patients with AP found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI, no significant difference in the rates of 7-day mortality, length of hospital stay, or acute respiratory distress syndrome was found when compared to control groups.3

Theoretically, PPIs may improve the course of AP through reduction in the incidence of stress-related upper GI hemorrhagic complications.  However, the incidence of such complications in AP is quite low, ranging from 1.2% to 14.5%, with great majority of cases (>85%) unrelated to peptic ulcer disease. 3,4  These findings may help explain why it has been difficult to show any benefit for use of PPIs in reducing the incidence of GI bleed in AP.3,5

Similarly, although PPIs have been shown to reduce secretin-stimulated bicarbonate secretion by the pancreas, the clinical significance of this finding in the overall course of AP—except perhaps a lower risk of pseudocysts—remains unclear.3 Parenthetically, experimental studies have reported contradictory results regarding the inhibition of pancreatic enzyme production by PPIs,  with omeprazole failing to suppress amylase release in isolated pancreatic acini while pantoprazole showing reduced amylase secretion in rats.3

It is also unclear how the reported anti-inflammatory effects of PPIs may benefit the clinical course of AP.3,6 What is clear is that any potential benefits of PPIs in AP should be weighed against their potential adverse effects, including the risk of nosocomial pneumonia, Clostridiodes difficile infection, and spontaneous bacterial peritonitis.7,8 

Bonus Pearl: Did you know that PPIs may not only inhibit acid production by gastric parietal cells but also interfere with bactericidal activity of neutrophils?  One potential mechanism is interference with proton pump-dependent H202 generation within lysosomes necessary to create a highly acidic and bactericidal environment. 9  Fascinating!

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References

  1. Arvanitakis M, Dumonceau JM, Albert J, et al. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guideline. Endoscopy 2018; 50:524-46. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guideline – European Society of Gastrointestinal Endoscopy (ESGE)
  2. Crocket SD, Wani S, Gardner TB, et al. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology 2018;154:1096-1101. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis (gastrojournal.org)
  3. Horvath IL, Bunduc S, Hanko B , et al. No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis. Scientific Reports 2023;13:2791. https://doi.org/10.1038/s41598-023-29939-S
  4. Rana SS, Sharma V, Bhasin Dk, et al. Gastrointestinal bleeding in acute pancreatitis: etiology, clinical features, risk factors and outcome. Tropical Gastroenterology 2015;36:31-35. http://www.tropicalgastro.com/articles/36/1/gastrointestinal-bleeding-in-acute.html
  5. Demcsak A, Soos A, Kincses L, et al. Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis-An international cohort study. Pancreatology 2020;20:1323-31.lyso https://www.sciencedirect.com/science/article/pii/S142439032030658X?via%3Dihub
  6. Hackert T, Tudor S, Felix K, et al. Effects of pantoprazole in experimental acute pancreatitis. Comparative Study 2010;8:551-7. https://pubmed.ncbi.nlm.nih.gov/20851132/
  7. Elzouki AB, Neffati N, Rasoul FA, et al. Increased risk of spontaneous bacterial peritonitis in cirrhotic patients using proton pump inhibitors. GE Port J Gastroenterol 2019; 26:83-89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454390/#:~:text=The%20result%20showed%20that%20PPI,medical%20literature%20confirm%20this%20association.
  8. Yibirin M, De Oliveira D, Valera R, et al. Cureus 2021;13:e12759/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887997/#:~:text=The%20most%20likely%20explanation%20for,incidence%20of%20pneumonia%20%5B2%5D
  9. Ozatik O, Ozatik EY, Tesen Y, et al. Research into the effect of proton pump inhibitors on lungs and leukocytes. Turk J Gastroenterol 2021;32:1003-1011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975296/

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Is there any evidence that proton pump inhibitors (PPIs) benefit patients with acute pancreatitis?

Why are antibiotics routinely administered in patients with cirrhosis and upper gastrointestinal (GI) bleed?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , 1 Comment

Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleed (UGIB) reduce bacterial infections, all-cause mortality, bacterial infection, mortality, rebleeding events and hospitalization.1

A 2011 Cochrane meta-analysis involving 12 trials comparing antibiotic prophylaxis to no prophylaxis or placebo found reduction in bacterial infection (RR 0.35, 95% C.I., 0.26-0.47) and overall mortality (RR 0.79, 95% C.I. 0.63-0.98). It also found a significant reduction in rebleeding and days of hospitalization, based on more limited data. Trials in this meta-analysis involved a variety of antibiotics, including norfloxacin, ciprofloxacin, cefazolin, cefotaxime, ceftriaxone and ampicillin-sulbactam. 1

So why is ceftriaxone the often-favored bacterial prophylaxis in UGIB? First, infections in cirrhotic patients often originate from bacterial translocation through the GI tract with aerobic gram-negative GI flora expected to be susceptible to ceftriaxone.2 Second, the emerging quinolone resistance among aerobic Gram-negative bacteria 2 and frequent use of ciprofloxacin for prophylaxis against spontaneous bacterial peritonitis have made use of ceftriaxone in this setting more desirable than quinolones.

Of note, a 2006 study involving patients with advanced cirrhosis (Child Pugh B or C) and GI hemorrhage receiving either norfloxacin or ceftriaxone for 7 days found a significantly lower risk of suspected or proven infections (11% vs 33%) and bacteremia or spontaneous bacterial peritonitis (2% vs 12%) in the ceftriaxone group; there was no difference in hospital mortality. 3 Although the overall prevalence of quinolone-resistant gram-negatives was unknown, 6 of 7 gram-negative bacilli isolated in the norfloxacin group were quinolone resistant.

Bonus Pearl: Did you know that 30-40% of cirrhotic patients presenting with UGIB will develop a bacterial infection within a week of their admission? 1

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References

  1. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, et al. Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding-an updated Cochrane review. Aliment Pharmacol Ther 2011;34:509-518. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2036.2011.04746.x
  2. Mallet M, Rudler M, Thabut D. Variceal bleeding in cirrhotic patients. Gastroenterology Reports 2017;5:185-192. https://academic.oup.com/gastro/article/5/3/185/4002779
  3. Fernandez J, del Arbo LR, Gomez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006;131:1049-1056. https://www.sciencedirect.com/science/article/abs/pii/S0016508506015356

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why are antibiotics routinely administered in patients with cirrhosis and upper gastrointestinal (GI) bleed?