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

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?

Why is my patient with systemic amyloidosis at higher risk of bleeding?

The major mechanism of bleeding tendency in primary systemic amyloidosis (AL) appears to revolve around amyloid deposit infiltration of the vasculature and musculature, leading to amyloid angiopathy, fragility, impaired vasoconstriction, tears and hemorrhage. 1,2 Other potential mechanisms include:

  • Presence of plasma inhibitors of fibrinogen conversion to fibrin
  • Deficiencies of factor X, IX and V due to their affinity for amyloid substance
  • Presence of circulating heparin-like anticoagulants
  • Uremic platelet dysfunction in the presence of renal involvement

In a study involving 36 patients with AL, ~30% had bleeding symptoms with alterations of 1 or more clotting tests found in ~85%: prolonged prothrombin time (PT) ratio (22%), activated partial thromboplastin time (aPTT) (65%) and thrombin time (85%).

Clinical manifestations of amyloidosis related to its bleeding diathesis include petechiae, ecchymoses, purpura (“raccoon eyes when periorbital), uncontrollable epistaxis, gingival bleeding, and gastrointestinal bleed or submucosal hematomas. 1-6

Due to its convenience and relative safety, a biopsy of abdominal fat or minor salivary glands is often initially performed for definitive diagnosis of amyloidosis, followed by biopsy of specific organs (eg, kidney, liver), if needed. 3,6

Due to the potential risk of bleeding complications, transjugular liver biopsy is preferred over percutaneous approach. This is because the liver capsule is not perforated with transjugular liver biopsy and if bleeding occurs, the blood returns directly into the venous system rather than into the peritoneum. 7-8 

Bonus Pearl: Did you know that AL amyloidosis is the most common type of systemic amyloidosis in western countries? This is because the incidence of the other major type of amyloidosis (AA), often related to chronic infections or inflammatory diseases, has been dropping in these countries.3

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References

  1. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica 2000;85:289-92. https://moh-it.pure.elsevier.com/en/publications/clotting-alterations-in-primary-systemic-amyloidosis
  2. Marconcini LAL, Stewart FM, Sonntag L, et al. AL amyloidosis complicated by persistent oral bleeding. Case Reports in Hematology 2015, Article ID 981346. https://www.hindawi.com/journals/crihem/2015/981346/
  3. Desport E, Bridoux F, Sirac C, et al. AL Amyloidosis. Orphanet Journal of Rare Diseases 2012, 7:54. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-54
  4. Yoshii S, Mabe K, Nosho K, et al. Submucosal hematoma is a highly suggestive finding for amyloid light-chain amyloidosis: Two case reports. W J Gastroenterol 2012;4:434-37. https://www.ncbi.nlm.nih.gov/pubmed/23125904
  5. Kon T, Nakagawa N, Yoshikawa F, et al. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptoms. Clin J Gastroenterol 2016;9:243. http://europepmc.org/article/med/27318996
  6. Petre S, Shah IA, Gilani N. Review article:gastrointestinal amyloidosis-clinical features, diagnosis and therapy. Alim Pharmacol Ther 2008;27:1006-16. https://www.ncbi.nlm.nih.gov/pubmed/18363891
  7. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(Suppl IV):IV1-IV11. https://www.ncbi.nlm.nih.gov/pubmed/10485854
  8. Dohan A, Guerrache Y, Boudiaf M, et al. Transjugular liver biopsy: Indications, technique and results. Diagnostic and Interventional Imaging 2014;95:11-15. https://www.ncbi.nlm.nih.gov/pubmed/24007769
Why is my patient with systemic amyloidosis at higher risk of bleeding?