Effect of three antibacterial drugs in lowering blood & stool ammonia production in hepatic encephalopathy

Neomycin (700 mg/8 h), ampicillin (500/6 h) and metronidazole (400 mg/8 h), were compared for their effect, on oral administration for 4 days, in reducing blood ammonia in 27 patients with stable chronic liver disease. It was found that there was 38.2, 38.5 and 8.7 m mol/litre mean reduction in blood ammonia in the neomycin, ampicillin and metronidazole treated groups respectively. The difference in blood ammonia was statistically significant for both neomycin (P = 0.01) and ampicillin (P = 0.03) but there was no significant change after metronidazole treatment (P = 0.6). The total stool enzyme activity at optimum pH was maximally reduced by ampicillin and minimally with metronidazole. The reduction was noted to be 3.51 m mol/1 (P = 0.01), 3.87 m mol/1 (P = 0.08) and 2.8 m mol/1 (P = 0.02) of NH3/g dry weight of stool for neomycin, ampicillin and metronidazole respectively. The main bacterial gut enzymes responsible for ammonia production, urease and protease, were found to be very sensitive to stool pH. At pH 6 their activity was around 20 per cent of what was found in optimum pH of 7.4 and at pH 5 it is only about 8 per cent of optimum activity. None of the three antibacterial agents changed the stool pH significantly. It can be concluded that oral neomycin and ampicillin are superior to oral metronidazole in lowering blood ammonia.