Novel prevention strategies for bacterial infections in cirrhosis

ABSTRACT

Introduction: Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics.

Areas Covered: This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis.

Expert Opinion: Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.

KEYWORDS:

• Cirrhosis
• bacterial infections
• bacterial translocation
• selective intestinal decontamination
• probiotics
• rifaximin
• fecal microbiota transplant
• prokinetics
• beta-blockers
• bile acids
• FXR agonist
• statins
• GCSF

Article highlights

• Bacterial translocation is the main mechanism in the pathogenesis of spontaneous infection in cirrhosis and results from the following physiological alterations in cirrhosis: altered gut microbiota, intestinal dysmotility, gut barrier dysfunction, and immune dysfunction.

• Our current strategy for preventing infections is the method of selective intestinal decontamination, which uses an antibiotic such as norfloxacin to change the taxonomy of gut microbiota. However, it is associated with the development of antibiotic-resistant organisms.

• Novel approaches to preventing bacterial infections include the following strategies: targeting altered gut microbiota using probiotics and rifaximin; targeting intestinal dysmotility with prokinetics, and β-blockers; improving the intestinal barrier with bile acids and farnesoid X receptor agonists; and targeting immune dysfunction with granulocyte colony-stimulating factor and statins.

• Of these approaches, there is most evidence in human studies for probiotics, rifaximin, and β-blockers.

• There is insufficient evidence to officially recommend any of these strategies at this point.

This box summarizes key points contained in the article.

Declaration of interest

The authors were supported by Yale Liver Center NIH P30 DK34989; and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH T35DK104689. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed