Abstract
The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 μg of polymyxin B per ml, whereas Bacteroides fragilis endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beveridge E. G., Martin A. J. Sodium sulphomethyl derivatives of polymyxins. Br J Pharmacol Chemother. 1967 Feb;29(2):125–135. doi: 10.1111/j.1476-5381.1967.tb01946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caridis D. T., Reinhold R. B., Woodruff P. W., Fine J. Endotoxaemia in man. Lancet. 1972 Jun 24;1(7765):1381–1385. doi: 10.1016/s0140-6736(72)91108-7. [DOI] [PubMed] [Google Scholar]
- Chen C. H., Johnson A. G., Kasai N., Key B. A., Levin J., Nowotny A. Heterogeneity and biological activity of endotoxic glycolipid from Salmonella minnesota R595. J Infect Dis. 1973 Jul;128(Suppl):43–51. doi: 10.1093/infdis/128.supplement_1.s43. [DOI] [PubMed] [Google Scholar]
- Corrigan J. J., Jr, Bell B. M. Comparison between the polymyxins and gentamicin in preventing endotoxin-induced intravascular coagulation and leukopenia. Infect Immun. 1971 Nov;4(5):563–566. doi: 10.1128/iai.4.5.563-566.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corrigan J. J., Jr, Bell B. M. Endotoxin-induced intravascular coagulation: prevention with polymyxin B sulfate. J Lab Clin Med. 1971 May;77(5):802–810. [PubMed] [Google Scholar]
- Das J., Schwartz A. A., Folkman J. Clearance of endotoxin by platelets: role in increasing the accuracy of the Limulus gelation test and in combating experimental endotoxemia. Surgery. 1973 Aug;74(2):235–240. [PubMed] [Google Scholar]
- Davis S. D., Iannetta A., Wedgwood R. J. Paradoxical synergism and antagonism between serum and the antibacterial activity of colistin. J Infect Dis. 1971 Apr;123(4):392–398. doi: 10.1093/infdis/123.4.392. [DOI] [PubMed] [Google Scholar]
- Edwards E. A. Immunological investigations of meningococcal disease. II. Some characteristics of group C antigen of Neisseria meningitidis in the sera of patients with fulminant meningococcemia. J Infect Dis. 1974 May;129(5):538–544. doi: 10.1093/infdis/129.5.538. [DOI] [PubMed] [Google Scholar]
- Garibaldi R. A., Allman G. W., Larsen D. H., Smith C. B., Burke J. P. Detection of endotoxemia by the limulus test in patients with indwelling urinary catheters. J Infect Dis. 1973 Oct;128(4):551–554. doi: 10.1093/infdis/128.4.551. [DOI] [PubMed] [Google Scholar]
- Gruninger R. P., Howe C. W. Temporal protection of chick embryo against endotoxin by isoproterenol, polymyxin B sulfate, and hydrocortisone. Proc Soc Exp Biol Med. 1969 Apr;130(4):1202–1205. doi: 10.3181/00379727-130-33754. [DOI] [PubMed] [Google Scholar]
- Levin J., Bang F. B. Clottable protein in Limulus; its localization and kinetics of its coagulation by endotoxin. Thromb Diath Haemorrh. 1968 Mar 31;19(1):186–197. [PubMed] [Google Scholar]
- Levin J., Poore T. E., Young N. S., Margolis S., Zauber N. P., Townes A. S., Bell W. R. Gram-negative sepsis: detection of endotoxemia with the limulus test. With studies of associated changes in blood coagulation, serum lipids, and complement. Ann Intern Med. 1972 Jan;76(1):1–7. doi: 10.7326/0003-4819-76-1-1. [DOI] [PubMed] [Google Scholar]
- Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
- Lüderitz O., Galanos C., Lehmann V., Nurminen M., Rietschel E. T., Rosenfelder G., Simon M., Westphal O. Lipid A: chemical structure and biological activity. J Infect Dis. 1973 Jul;128(Suppl):17–29. doi: 10.1093/infdis/128.supplement_1.s17. [DOI] [PubMed] [Google Scholar]
- McGill M. W., Porter P. J., Kass E. H. The use of a bioassay for endotoxin in clinical infections. J Infect Dis. 1970 Feb;121(2):103–112. doi: 10.1093/infdis/121.2.103. [DOI] [PubMed] [Google Scholar]
- NEWTON B. A. Site of action of polymyxin on Pseudomonas aeruginosa: antagonism by cations. J Gen Microbiol. 1954 Jun;10(3):491–499. doi: 10.1099/00221287-10-3-491. [DOI] [PubMed] [Google Scholar]
- Rifkind D., Hill R. B., Jr Neutralization of the Shwartzman reactions by polymyxins B. J Immunol. 1967 Sep;99(3):564–569. [PubMed] [Google Scholar]
- Rifkind D., Palmer J. D. Neutralization of endotoxin toxicity in chick embryos by antibiotics. J Bacteriol. 1966 Oct;92(4):815–819. doi: 10.1128/jb.92.4.815-819.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rifkind D. Prevention by polymyxin B of endotoxin lethality in mice. J Bacteriol. 1967 Apr;93(4):1463–1464. doi: 10.1128/jb.93.4.1463-1464.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rifkind D. Studies on the interaction between endotoxin and polymyxin B. J Infect Dis. 1967 Dec;117(5):433–438. doi: 10.1093/infdis/117.5.433. [DOI] [PubMed] [Google Scholar]
- Rojas-Corona R. R., Skarnes R., Tamakuma S., Fine J. The Limulus coagulation test for endotoxin. A comparison with other assay methods. Proc Soc Exp Biol Med. 1969 Nov;132(2):599–601. doi: 10.3181/00379727-132-34268. [DOI] [PubMed] [Google Scholar]
- Stumacher R. J., Kovnat M. J., McCabe W. R. Limitations of the usefulness of the Limulus assay for endotoxin. N Engl J Med. 1973 Jun 14;288(24):1261–1264. doi: 10.1056/NEJM197306142882402. [DOI] [PubMed] [Google Scholar]
- Yin E. T., Galanos C., Kinsky S., Bradshaw R. A., Wessler S., Lüderitz O., Sarmiento M. E. Picogram-sensitive assay for endotoxin: gelation of Limulus polyphemus blood cell lysate induced by purified lipopolysaccharides and lipid A from Gram-negative bacteria. Biochim Biophys Acta. 1972 Jan 28;261(1):284–289. doi: 10.1016/0304-4165(72)90340-6. [DOI] [PubMed] [Google Scholar]