Summary
Using a model of an experimentalKlebsiella pneumoniae septicemia in mice, we examined the therapeutic effect of passively administered specific antibacterial antibodies from rabbits. Both specific IgM and IgG antibody proved to be therapeutically effective. However, the effect of IgG was markedly superior to that of IgM with regard both to the degree of protection and the time interval allowing efficient therapy after infection. The effect of IgG was due to a marked enhancement ofin vivo phagocytosis, as demonstrated by monitoring bacterial numbers in the liver, spleen, lungs and kidneys. In mice immunocompromised with cyclophosphamide, treatment with IgG still exerted protection against low challenge inocula. When higher inocula were used, treatment with IgG ceased to influence the final mortality rates but delayed the course of the disease for several days by transient reduction of bacterial numbers in the parenchymal organs. In both normal and immunocompromised mice, concomitant treatment with gentamicin resulted in a marked synergistic enhancement of survival.
Zusammenfassung
Am Modell einer experimentellenKlebsiella pneumoniae-Sepsis der Maus wurde der therapeutische Effekt spezifischer antibakterieller Antikörper vom Kaninchen untersucht. Sowohl IgG- als auch IgM-Antikörper erwiesen sich als therapeutisch effektiv, jedoch war der durch IgM vermittelte Schutzeffekt deutlich geringer als derjenige von IgG. Das nach der Infektion für eine effiziente Therapie zur Verfügung stehende Zeitintervall war bei Anwendung von IgM wesentlich kürzer als bei Therapie mit IgG. Wie Keimzahlbestimmungen in Leber, Milz, Lungen und Nieren zeigten, beruhte der Effekt von IgG auf einer ausgeprägten phagozytosefördernden Wirkungin vivo. Bei mit Cyclophosphamid immunsupprimierten Mäusen führte die Gabe von IgG nur dann zu einer Senkung der Letalität, wenn niedrige Infektionsdosen verabreicht wurden. Bei höheren Infektionsdosen führte die IgG-Behandlung lediglich zu einer passageren Keimzahlreduktion in den parenchymatösen Organen sowie zu einer Verzögerung des letalen Verlaufes der Sepsis um einige Tage. Die Kombinationstherapie mit IgG und Gentamicin hatte sowohl bei normalen als auch bei immunsupprimierten Mäusen einen ausgeprägten synergistischen Effekt.
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Literature
Young, L. S., Stevens, P., Kaijser, B. Gram-negative pathogens in septicemic infections. Scand. J. Infect. Dis. 31 Suppl. (1982) 78–94.
Kreger, B. E., Craven, D. E., McCabe, W. R. Gram-negative bacteremia IV: Re-evaluation of clinical features and treatment in 612 patients. Am. J. Med. 68 (1980) 344–355.
Daschner, F. Bakterielle Erreger von Krankenhausinfektionen. Immun. Infekt. 12 (1984) 139–142.
Cryz, S. J. Progress in immunization againstKlebsiella infections. Eur. J. Clin. Microbiol. 2 (1983) 523–528.
Cryz, S. J., Fürer, E., Germanier, R.: Immunization against experimentalKlebsiella pneumoniae burn wound sepsis. Third International Symposium on Infections in the Immunocompromised Host. Toronto, Canada, Juni 24–28, 1984, Abstract No. 155.
Umsawasdi, T., Middleman, E. A., Luna, M., Bodey, G. P. Klebsiella bacteremia in cancer patients. Am. J. Med. Sci. 265 (1973) 473–482.
Neter, E., Bertram, L. F., Arbesman, C. E. Demonstration ofEscherichia coli O 55 and O 111 antigens by means of hemagglutination test. Proc. Soc. Exp. Biol. Med. 79 (1952) 255–257.
Young, L. S., Stevens, P., Ingram, J. Functional role of antibody against “core” glycolipid ofEnterobacteriaceae. J. Clin. Invest. 56 (1975) 850–861.
Cooper, J. M., Rowley, D. Resistance toKlebsiella pneumoniae and the importance of two bacterial antigens. Austr. J. Exp. Biol. Med. Sci. 60 (1982) 629–641.
Riottot, M. M., Fournier, J. M., Pillot, J. Capsular serotypic specificity of the protection conferred on mice byKlebsiella pneumoniae ribosomal preparations. Infect. Immun. 24 (1979) 476–482.
Greisman, S. E., DuBuy, J. B., Woodward, C. L. Experimental gram-negative bacterial sepsis: Prevention of mortality not preventable by antibiotics alone. Infect. Immun. 25 (1979) 538–557.
Chedid, L., Parant, M., Parant, F., Boyer, F. A proposed mechanism for natural immunity to enterobacterial pathogens. J. Immunol. 100 (1968) 292–301.
McCabe, W. R. Immunization with R mutants ofS. minnesota. I. Protection against challenge with heterologous gram-negative bacilli. J. Immunol. 108 (1972) 601–610.
Kawaharajo, K., Homma, J. Y. Synergistic effect of immune gamma-globulin fraction on protection by antibiotic against corneal ulcers in experimental mice infected withPseudomonas aeruginosa. Jpn. J. Exp. Med. 46 (1976) 155–165.
Dalhoff, A., Brunner, H. Mode of interaction between immunoglobulin G and mezlocillin against β-lactamase producing bacteria. Arzneimittelforsch./Drug Res. 33 (1983) 1666–1671.
Dalhoff, A. Synergy between acylureidopenicillins and immunoglobulin G in experimental animals. Am. J. Med. 76 (1984) 91–100.
Stendahl, O., Tagesson, C., Magnusson, K. E., Edebo, L. Physicochemical consequences of opsonization ofSalmonella typhimurium with hyperimmune IgG and complement. Immunology 32 (1977) 11–18.
Dalhoff, A. In vitro andin vivo effect of immunoglobulin G on the integrity of bacterial membranes. Infection 12 (1984) 214–220.
Katsunuma, H. Zur Immunglobulinwirkung auf Bakterienzellen. Die gelben Hefte 24 (1984) 21–25.
Seklecki, M. M., Quintiliani, R., Maderazo, E. G. Aminoglycoside antibiotics moderately impair granulocyte function. Antimicrob. Agents Chemother. 13 (1978) 552–554.
Mandell, L. A. The effects of antibacterial, antiviral, and antifungal drugs on the phagocytic, microbicidal, and chemotactic function of the human polymorphonuclear leukocyte. In:Eickenberg, H. U., Hahn, H., Opferkuch, W. (eds.): The influence of antibiotics on the host-parasite relationship. Springer, Berlin — Heidelberg — New York 1982, pp. 40–54.
Undeutsch, Ch., Brunner, H. Einfluß von Antibiotika auf die Phagozytose vonKlebsiella pneumoniae durch Alveolarmakrophagen. Zbl. Bakt. Hyg. I. Abt. Orig. A 249 (1981) 53–62.
Adam, D. Enhancedin vitro phagocytosis of different pathogens by human monocytes in the presence of antibiotics. InEickenberg, H. U., Hahn, H., Opferkuch, W. (eds.): The influence of antibiotics on the host-parasite relationship, Springer, Berlin — Heidelberg — New York 1982, pp. 67–73.
Trautmann, M., Brückner, O., Hahn, H. Schutzeffekt von pseudomonas-spezifischem Hyperimmunglobulin vom Kaninchen und von aktiver Immunisierung bei experimenteller Pseudomonassepsis der Maus. Zbl. Bakt. Hyg. I. Abt. Orig. A 252 (1982) 370–383.
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Trautmann, M., Müller-Leutloff, Y., Hahn, H. et al. Experimental klebsiella septicemia in mice: Treatment with specific antibodies from the rabbit alone and in combination with gentamicin. Infection 13, 29–34 (1985). https://doi.org/10.1007/BF01643618
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DOI: https://doi.org/10.1007/BF01643618