What is the role of Neomycin in the management of hyperammonemia?

Neomycin for Hyperammonemia

Neomycin is NOT recommended as a primary treatment for hyperammonemia and should only be considered as a second-line alternative antibiotic for hepatic encephalopathy-related hyperammonemia when rifaximin is unavailable, and even then, only for short-term use due to significant nephrotoxicity and ototoxicity risks. 1

Current Role in Clinical Practice

Primary Indication (FDA-Approved)

• Neomycin is FDA-approved as adjunctive therapy in hepatic coma (portal-systemic encephalopathy) by reducing ammonia-forming bacteria in the intestinal tract, with subsequent reduction in blood ammonia resulting in neurologic improvement 2
• The mechanism involves glutaminase inhibition, which reduces ammonia production from glutamine metabolism 1

Guideline-Based Positioning

• The Korean Association for the Study of the Liver (2020) explicitly states that neomycin is NOT recommended for management of hepatic encephalopathy due to side effects including intestinal malabsorption, nephrotoxicity, and ototoxicity 1
• The American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) classify neomycin only as an alternative choice (GRADE II-1, B, 2) for overt hepatic encephalopathy, not as first-line therapy 1
• Rifaximin added to lactulose carries the highest grade recommendation (GRADE I, A, 1) and is the preferred antibiotic approach, with substantially superior evidence quality compared to neomycin 1

Treatment Algorithm for Hyperammonemia

When Neomycin Should NOT Be Used

• For acute severe hyperammonemia (>300-400 μmol/L): Nitrogen scavengers (sodium benzoate, sodium phenylacetate) and kidney replacement therapy are the appropriate interventions, NOT antibiotics like neomycin 3, 4
• For urea cycle disorders or organic acidemias: Primary treatment involves stopping protein intake, aggressive caloric support, nitrogen scavengers, L-arginine, and L-carnitine—neomycin has no role 3, 4
• For long-term management: The toxicity profile makes neomycin unsuitable for chronic use 1

When Neomycin Might Be Considered (Rare Scenarios)

• Only for hepatic encephalopathy-related hyperammonemia when:
  • Lactulose has been tried as first-line therapy 1
  • Rifaximin is unavailable or contraindicated 1
  • Short-term use only is anticipated 1
  • Patient has no pre-existing renal or hearing impairment 5

Critical Safety Concerns

Major Toxicities

• Nephrotoxicity: Can cause acute renal failure, even when used as an irrigant solution, producing "high output" renal failure that is usually reversible 5
• Ototoxicity: Hearing loss is frequently permanent and irreversible, even after discontinuation 5
• Intestinal malabsorption: Affects nutrient absorption, particularly problematic in already malnourished patients 1
• Systemic absorption: Neomycin can be absorbed systemically despite being intended for local gut action, leading to unsuspected toxicity 5

Comparative Efficacy Data

• Neomycin reduces blood ammonia by approximately 38.2 μmol/L over 4 days in stable chronic liver disease 6
• Ampicillin shows similar efficacy (38.5 μmol/L reduction) with potentially better safety profile 6
• Metronidazole is less effective (8.7 μmol/L reduction) but may be used short-term when other options are unavailable 6, 7

Common Pitfalls to Avoid

• Do not use neomycin as monotherapy: It should never replace lactulose as the foundation of therapy for hepatic encephalopathy 1
• Do not use neomycin for non-hepatic causes of hyperammonemia: Urea cycle disorders, organic acidemias, and acute severe hyperammonemia require entirely different management strategies 3, 4
• Do not prescribe for long-term use: The major limitation preventing routine use is toxicity with prolonged administration 1
• Do not ignore monitoring requirements: If neomycin must be used, monitor renal function and hearing closely 5
• Do not delay definitive therapy: For severe hyperammonemia, hemodialysis or continuous kidney replacement therapy (CKRT) is the most effective intervention, not antibiotics 3, 4

Modern Treatment Hierarchy

For hepatic encephalopathy with hyperammonemia:

1. Lactulose (first-line, GRADE II-1, B, 1) 1
2. Rifaximin added to lactulose (preferred add-on, GRADE I, A, 1) 1
3. Neomycin (alternative only, GRADE II-1, B, 2) 1

For acute severe hyperammonemia (any cause):

1. Stop protein intake immediately 3, 4
2. Provide aggressive caloric support (≥100 kcal/kg/day) 3, 4
3. Administer nitrogen scavengers (sodium benzoate/phenylacetate) 3
4. Initiate hemodialysis or CKRT if ammonia >300-400 μmol/L 3, 4
5. Antibiotics like neomycin have NO role in this acute setting 3, 4