Abstract
Nocardicin A, a monocyclic beta-lactam antibiotic with modest anti-pseudomonal activity in vitro, controlled an otherwise fatal Pseudomonas infection in mice when given in doses which produced blood levels well below the minimum bactericidal concentration. In even smaller doses, it converted the partial protection afforded by modest doses of carbenicillin into full protection. Human polymorphonuclear leucocytes exposed to low concentrations of the drug in vitro and peritoneal macrophages recovered from mice treated with nocardicin A exhibited an unusually specific form of enhanced activity. Chemotaxis and phagocytosis were not affected, but intracellular killing of Ps. aeruginosa was significantly increased. This was shown to be due to an effect on the phagocyte and not to facilitated killing of organisms damaged by extracellular exposure to the antibiotic. It is argued that the effect on phagocyte function is sufficient to contribute materially to the therapeutic effect of nocardicin A.
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Selected References
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- Baltch A. L., Griffin P. E. Pseudomonas aeruginosa bacteremia: a clinical study of 75 patients. Am J Med Sci. 1977 Sep-Oct;274(2):119–129. [PubMed] [Google Scholar]
- Bodey G. P., Buckley M., Sathe Y. S., Freireich E. J. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966 Feb;64(2):328–340. doi: 10.7326/0003-4819-64-2-328. [DOI] [PubMed] [Google Scholar]
- Bridges C. G., Dasilva G. L., Yamamura M., Valdimarsson H. A radiometric assay for the combined measurement of phagocytosis and intracellular killing of Candida albicans. Clin Exp Immunol. 1980 Nov;42(2):226–233. [PMC free article] [PubMed] [Google Scholar]
- Fraser-Smith E. B., Waters R. V., Matthews T. R. Correlation between in vivo anti-Pseudomonas and anti-Candida activities and clearance of carbon by the reticuloendothelial system for various muramyl dipeptide analogs, using normal and immunosuppressed mice. Infect Immun. 1982 Jan;35(1):105–110. doi: 10.1128/iai.35.1.105-110.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jarstrand C., Blomgren H. Increased granulocyte phagocytosis after oral administration of bestatin, a new immunomodulator. J Clin Lab Immunol. 1982 Feb;7(2):115–118. [PubMed] [Google Scholar]
- Lam C., Mathison G. E. Phagocytosis measured as inhibition of uridine uptake: a method that distinguishes between surface adherence and ingestion. J Med Microbiol. 1979 Nov;12(4):459–467. doi: 10.1099/00222615-12-4-459. [DOI] [PubMed] [Google Scholar]
- McDonald P. J., Wetherall B. L., Pruul H. Postantibiotic leukocyte enhancement: increased susceptibility of bacteria pretreated with antibiotics to activity of leukocytes. Rev Infect Dis. 1981 Jan-Feb;3(1):38–44. doi: 10.1093/clinids/3.1.38. [DOI] [PubMed] [Google Scholar]
- Mine Y., Nonoyama S., Kojo H., Fukada S., Nishida M. Nocardicin A, a new monocyclic beta-lactam antibiotic V. In vivo evaluation. J Antibiot (Tokyo) 1977 Nov;30(11):932–937. doi: 10.7164/antibiotics.30.932. [DOI] [PubMed] [Google Scholar]
- Nelson R. D., Quie P. G., Simmons R. L. Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol. 1975 Dec;115(6):1650–1656. [PubMed] [Google Scholar]
- Nishida M., Mine Y., Nonoyama S., Kojo H. Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation. J Antibiot (Tokyo) 1977 Nov;30(11):917–925. doi: 10.7164/antibiotics.30.917. [DOI] [PubMed] [Google Scholar]
- O'Grady F., Murphy B., Pearson N. J. Semiautomated determination of minimum bactericidal concentrations of antibiotics. J Clin Pathol. 1983 Feb;36(2):208–212. doi: 10.1136/jcp.36.2.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sensakovic J. W., Bartell P. F. The slime of Pseudomonas aeruginosa: biological characterization and possible role in experimental infection. J Infect Dis. 1974 Feb;129(2):101–109. doi: 10.1093/infdis/129.2.101. [DOI] [PubMed] [Google Scholar]
- Showell H. J., Freer R. J., Zigmond S. H., Schiffmann E., Aswanikumar S., Corcoran B., Becker E. L. The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med. 1976 May 1;143(5):1154–1169. doi: 10.1084/jem.143.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuart R. K., Pollack M. Pseudomonas aeruginosa exotoxin A inhibits proliferation of human bone marrow progenitor cells in vitro. Infect Immun. 1982 Oct;38(1):206–211. doi: 10.1128/iai.38.1.206-211.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
