Lactulose therapy in Shigella carrier state and acute dysentery

Abstract

Antibiotic-resistant shigella are increasingly prevalent. Lactulose, a non-absorbable disaccharide, was investigated as an alternative therapy for shigella infection on the hypothesis that the short-chain fatty acids (inhibitory to shigella) resulting from metabolism of lactulose by normal colonic flora would diminish shigella excretion. A long-term antibiotic-refractory carrier (large bowel) excreting 10(4) to 10(7)Shigella sonnei/g of feces was given two courses of lactulose (of 24 and 16 days duration). During lactulose therapy, excretion of shigella was greatly diminished (24-day course) or suppressed below detectable levels (16-day course), but returned to pretreatment levels upon discontinuation of lactulose. The volunteers who developed induced shigellosis during an efficacy test of oral Shigella flexneri 2a vaccine were randomly given oral ampicillin, lactulose, or placebo in double-blind fashion. Daily rectal cultures were taken. After 4 days of therapy, cultures were still positive in four out of four men on lactulose, three of three on placebo and none of three on ampicillin. Mean stool pH of men receiving lactulose (6.1) was significantly lower than those getting ampicillin (7.4), P < 0.01, or placebo (7.0), P < 0.05. Only in the lactulose group was mean stool pH during therapy significantly decreased compared with the level off therapy (6.1 versus 7.1), P < 0.02. Lactulose shows promise for the treatment of shigella carriers but appears ineffective in treatment of acute shigellosis.