Why do we often prescribe ceftriaxone in preference to fluoroquinolones for prophylaxis of infections in patients with cirrhosis and upper GI bleed?

Preference of ceftriaxone over fluoroquinolones (FQs) for prophylaxis of infection in patients with cirrhosis and upper GI bleed (UGIB) can often be traced back to a small 2006 Spanish randomized controlled trial (RCT)1 which found a significantly lower rate of proved or possible bacterial infection and lower rate of fermentative Gram-negative bacilli infection in the ceftriaxone group (vs norfloxacin) over a 10-day period (11% vs 33% and 0% vs 11%, respectively). There was no significant difference in the incidence of proved bacterial infection (spontaneous bacterial peritonitis or bacteremia, P=0.07) or 10-day mortality between the 2 groups.   

It’s worth emphasizing that the primary impetus for this study was evaluation of the efficacy of ceftriaxone in patients with cirrhosis and UGIB in a setting where FQ Gram-negative bacilli was thought to be highly prevalent. Parenthetically, a similar RCT performed where the prevalence of FQ resistance was considered low failed to find a significant difference in breakthrough bacterial infection, rebleeding or mortality when ceftriaxone was compared to IV ciprofloxacin.2

Another caveat of the 2006 study was that an IV antibiotic (ceftriaxone) was compared to a oral antibiotic (norfloxacin) which, in the setting of active UGIB, may be problematic.

Despite these limitations, its favorable safety profile compared to FQs coupled with its ease of administration has often made ceftriaxone the drug of choice for prophylaxis of infections in patients with cirrhosis and UGIB. The 2016 Practice Guidance by the American Association for the Study of Liver Diseases considers ceftriaxone as the first choice in patients with advanced cirrhosis, on FQ prophylaxis, and in hospital settings with high prevalence of FQ resistant bacterial infection.3

Bonus Pearl: Did you know that the prevalence of FQ resistant in Enterobacteriaceae may be as high as 30% in certain regions of U.S. and >50% in certain regions of the world? 4

Also see related 2 P4P pearls (1, 2) on the association of UGIB bleed with infections in patients with cirrhosis.

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References

  1. Fernandez J, Del Arbol LR, Gomez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterol 2006;131:1049-1056. https://pubmed.ncbi.nlm.nih.gov/17030175/
  2. Pittayanon R, Reknimir R, Kullavanijaya P, et al. Intravenous ciprofloxacin vs ceftriaxone for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding:A randomized controlled trial. Thai J Gastroenterol 2016;17:24-30. http://www.thaigastro.com/books.php?act=content&content_id=476&book_id=61
  3. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis:risk stratification, diagnosis and management: 2016 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2017;65:310-335. https://pubmed.ncbi.nlm.nih.gov/27786365/
  4. Spellberg B, Doi Y. The rise of fluoroquinolone-resistant Escherichia coli in the community:scarier than we thought. J Infect Dis 2015;212:1853-1855. https://pubmed.ncbi.nlm.nih.gov/25969562/

Disclosures: 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!

Why do we often prescribe ceftriaxone in preference to fluoroquinolones for prophylaxis of infections in patients with cirrhosis and upper GI bleed?