Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Jun;36(6):1290–1295. doi: 10.1128/aac.36.6.1290

Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection.

I Uezumi 1, M Terashima 1, T Kohzuki 1, M Kato 1, K Irie 1, H Ochi 1, H Noguchi 1
PMCID: PMC190334  PMID: 1416830

Abstract

The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.

Full text

PDF
1290

Images in this article

1292Image
on p.1292

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames P., DesJardins D., Pier G. B. Opsonophagocytic killing activity of rabbit antibody to Pseudomonas aeruginosa mucoid exopolysaccharide. Infect Immun. 1985 Aug;49(2):281–285. doi: 10.1128/iai.49.2.281-285.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson T. R., Montie T. C. Flagellar antibody stimulated opsonophagocytosis of Pseudomonas aeruginosa associated with response to either a- or b-type flagellar antigen. Can J Microbiol. 1989 Sep;35(9):890–894. doi: 10.1139/m89-148. [DOI] [PubMed] [Google Scholar]
  3. Ansorg R. A., Knoche M. E., Spies A. F., Kraus C. J. Differentiation of the major flagellar antigens of Pseudomonas aeruginosa by the slide coagglutination technique. J Clin Microbiol. 1984 Jul;20(1):84–88. doi: 10.1128/jcm.20.1.84-88.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bodey G. P., Bolivar R., Fainstein V., Jadeja L. Infections caused by Pseudomonas aeruginosa. Rev Infect Dis. 1983 Mar-Apr;5(2):279–313. doi: 10.1093/clinids/5.2.279. [DOI] [PubMed] [Google Scholar]
  5. Bundtzen R. W., Gerber A. U., Cohn D. L., Craig W. A. Postantibiotic suppression of bacterial growth. Rev Infect Dis. 1981 Jan-Feb;3(1):28–37. doi: 10.1093/clinids/3.1.28. [DOI] [PubMed] [Google Scholar]
  6. Collins M. S., Roby R. E. Protective activity of an intravenous immune globulin (human) enriched in antibody against lipopolysaccharide antigens of Pseudomonas aeruginosa. Am J Med. 1984 Mar 30;76(3A):168–174. doi: 10.1016/0002-9343(84)90337-1. [DOI] [PubMed] [Google Scholar]
  7. Cryz S. J., Jr, Fürer E., Germanier R. Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antielastase, and antilipopolysaccharide. Infect Immun. 1983 Mar;39(3):1072–1079. doi: 10.1128/iai.39.3.1072-1079.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cryz S. J., Jr, Pitt T. L., Fürer E., Germanier R. Role of lipopolysaccharide in virulence of Pseudomonas aeruginosa. Infect Immun. 1984 May;44(2):508–513. doi: 10.1128/iai.44.2.508-513.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drake D., Montie T. C. Flagella, motility and invasive virulence of Pseudomonas aeruginosa. J Gen Microbiol. 1988 Jan;134(1):43–52. doi: 10.1099/00221287-134-1-43. [DOI] [PubMed] [Google Scholar]
  10. Drake D., Montie T. C. Protection against Pseudomonas aeruginosa infection by passive transfer of anti-flagellar serum. Can J Microbiol. 1987 Sep;33(9):755–763. doi: 10.1139/m87-130. [DOI] [PubMed] [Google Scholar]
  11. Holder I. A., Wheeler R., Montie T. C. Flagellar preparations from Pseudomonas aeruginosa: animal protection studies. Infect Immun. 1982 Jan;35(1):276–280. doi: 10.1128/iai.35.1.276-280.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kropp H., Sundelof J. G., Kahan J. S., Kahan F. M., Birnbaum J. MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities. Antimicrob Agents Chemother. 1980 Jun;17(6):993–1000. doi: 10.1128/aac.17.6.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MacIntyre S., Lucken R., Owen P. Smooth lipopolysaccharide is the major protective antigen for mice in the surface extract from IATS serotype 6 contributing to the polyvalent Pseudomonas aeruginosa vaccine PEV. Infect Immun. 1986 Apr;52(1):76–84. doi: 10.1128/iai.52.1.76-84.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matthews-Greer J. M., Gilleland H. E., Jr Outer membrane protein F (porin) preparation of Pseudomonas aeruginosa as a protective vaccine against heterologous immunotype strains in a burned mouse model. J Infect Dis. 1987 Jun;155(6):1282–1291. doi: 10.1093/infdis/155.6.1282. [DOI] [PubMed] [Google Scholar]
  15. Montie T. C., Doyle-Huntzinger D., Craven R. C., Holder I. A. Loss of virulence associated with absence of flagellum in an isogenic mutant of Pseudomonas aeruginosa in the burned-mouse model. Infect Immun. 1982 Dec;38(3):1296–1298. doi: 10.1128/iai.38.3.1296-1298.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Núez R. M., Rodriguez A. B., Barriga C., De la Fuente M. In vitro and in vivo effects of Imipenem on phagocytic activity of murine peritoneal macrophages. APMIS. 1989 Oct;97(10):879–886. [PubMed] [Google Scholar]
  17. Ochi H., Ohtsuka H., Yokota S., Uezumi I., Terashima M., Irie K., Noguchi H. Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa. Infect Immun. 1991 Feb;59(2):550–554. doi: 10.1128/iai.59.2.550-554.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pennington J. E. Lipopolysaccharide pseudomonas vaccine: efficacy against pulmonary infection with Pseudomonas aeruginosa. J Infect Dis. 1979 Jul;140(1):73–80. doi: 10.1093/infdis/140.1.73. [DOI] [PubMed] [Google Scholar]
  19. Pennington J. E., Reynolds H. Y., Carbone P. P. Pseudomonas pneumonia. A retrospective study of 36 cases. Am J Med. 1973 Aug;55(2):155–160. doi: 10.1016/0002-9343(73)90163-0. [DOI] [PubMed] [Google Scholar]
  20. Pennington J. E., Small G. J., Lostrom M. E., Pier G. B. Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia. Infect Immun. 1986 Oct;54(1):239–244. doi: 10.1128/iai.54.1.239-244.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pennington J. E., Small G. J. Passive immune therapy for experimental Pseudomonas aeruginosa pneumonia in the neutropenic host. J Infect Dis. 1987 May;155(5):973–978. doi: 10.1093/infdis/155.5.973. [DOI] [PubMed] [Google Scholar]
  22. Pier G. B., Thomas D. M. Characterization of the human immune response to a polysaccharide vaccine from Pseudomonas aeruginosa. J Infect Dis. 1983 Aug;148(2):206–213. doi: 10.1093/infdis/148.2.206. [DOI] [PubMed] [Google Scholar]
  23. Pier G. B., Thomas D., Small G., Siadak A., Zweerink H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1989 Jan;57(1):174–179. doi: 10.1128/iai.57.1.174-179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rosok M. J., Stebbins M. R., Connelly K., Lostrom M. E., Siadak A. W. Generation and characterization of murine antiflagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa. Infect Immun. 1990 Dec;58(12):3819–3828. doi: 10.1128/iai.58.12.3819-3828.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sawada S., Kawamura T., Masuho Y. Immunoprotective human monoclonal antibodies against five major serotypes of Pseudomonas aeruginosa. J Gen Microbiol. 1987 Dec;133(12):3581–3590. doi: 10.1099/00221287-133-12-3581. [DOI] [PubMed] [Google Scholar]
  26. Stieritz D. D., Holder I. A. Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: description of a burned mouse model. J Infect Dis. 1975 Jun;131(6):688–691. doi: 10.1093/infdis/131.6.688. [DOI] [PubMed] [Google Scholar]
  27. Stoll B. J., Pollack M., Young L. S., Koles N., Gascon R., Pier G. B. Functionally active monoclonal antibody that recognizes an epitope on the O side chain of Pseudomonas aeruginosa immunotype-1 lipopolysaccharide. Infect Immun. 1986 Sep;53(3):656–662. doi: 10.1128/iai.53.3.656-662.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zweerink H. J., Gammon M. C., Hutchison C. F., Jackson J. J., Lombardo D., Miner K. M., Puckett J. M., Sewell T. J., Sigal N. H. Human monoclonal antibodies that protect mice against challenge with Pseudomonas aeruginosa. Infect Immun. 1988 Aug;56(8):1873–1879. doi: 10.1128/iai.56.8.1873-1879.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. van den Broek P. J. Antimicrobial drugs, microorganisms, and phagocytes. Rev Infect Dis. 1989 Mar-Apr;11(2):213–245. doi: 10.1093/clinids/11.2.213. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES