Reduction of the intestinal endotoxin pool by three different SDD regimens in human volunteers

Abstract

Aerobic Gram-negative bacilli (AGNB) carried in the gut by healthy individuals generate 1 mg of 'physiological' endotoxin per g of faeces. Successful eradication of AGNB from the gut would be expected to lead to a lowering of the intestinal endotoxin pool. This prompted us to evaluate the reduction of intestinal endotoxin in 6 healthy volunteers who each received 3 different oral antibiotic regimens. Regimen 1 was polymyxin E (600 mg/day), regimen 2 polymyxin E (400 mg/day) combined with tobramycin (320 mg/day) and regimen 3 pefloxacin (800 mg/day). Each regimen was separated by an antibiotic free period of 3 months. A faecal sample (minimally 2 g) was obtained from each volunteer, before treatment began and afterwards 3 times a week on alternating days (Monday, Wednesday, Friday) for 3 weeks. Each volunteer produced 30 samples, 10 each per oral antibiotic. The samples were serially diluted in nutrient broth for the colony count of AGNB, whilst endotoxin was measured using the classical Limulus amoebocyte lysate micro-assay. The base-line value of faecal AGNB was 10 3-4 colony forming units/g of faeces. All samples obtained on day 3 following antibiotic intake were negative for AGNB, and remained negative during antibiotic intake. The AGNB free carrier state was associated with a reduction in gut endotoxin. The reduction was approximately 10 ng (1 log) for polymyxin E and pefloxacin, whilst the combination of polymyxin/tobramycin significantly reduced the intestinal endotoxin concentrations from 1 mg to 100 ng in the gut; a reduction of 104. Although AGNB were killed by the three regimens, the 'free' endotoxin left in the gut was effectively neutralised by the combination polymyxin/tobramycin only. From a clinical point of view, gut-derived endotoxaemia may play a role in the systemic inflammatory response syndrome and hence the outcome, in critically ill intensive care patients. This study supports other work which indicates that mortality is significantly reduced in only those intensive care patients who received oral polymyxin/tobramycin.