Limitations of the Usefulness of the Limulus Assay for Endotoxin

Abstract

Gelation of lysates of amebocytes of the horseshoe crab has been proposed as a highly sensitive and specific bioassay for endotoxin that might be of diagnostic value in infections due to gram-negative bacteria. To assess the diagnostic value of the test and evaluate the role of endotoxin in such infections, limulus assays were performed on 694 specimens collected during 344 episodes of suspected bacteremia and compared with qualitative and quantitative blood cultures. Positive assays were obtained from 28 of 65 patients (43 per cent) with bacteremia due to gram-negative bacilli and in 11 of 43 patients (26 per cent) with localized infections due to gram-negative organisms. However, the occurrence of positive assays in eight of 22 patients (36 per cent) with infections due to gram-positive bacteria, who had no concomitant infections with gram-negative organisms, casts doubt on the diagnostic value of the assay. In addition, no correlation was found between positive assays and the number of circulating gram-negative bacilli or the occurrence of shock or death. (N Engl J Med 288:1261–1264, 1973)