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Prophylaxe gramnegativer und grampositiver Infektionen mit drei intravenösen Immunglobulin-Präparaten und Therapie der experimentellen polymikrobiellen Verbrennungssepsis mit intravenösem Pseudomonas-Immunglobulin G und Ciprofloxacin im Tiermodell

Prophylaxis of gram-negative and gram-positive infections in rodents with three intravenous immunoglobulins and therapy of experimental polymicrobial burn wound sepsis with pseudomonas immunoglobulin and ciprofloxacin

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Zusammenfassung

Drei Immunglobulin-Präparate zur intravenösen Infusion wurdenin vivo hinsichtlich ihrer relativen Schutzwirkung gegen verschiedene gramnegative und grampositive Erreger verglichen. Polyglobin®N* ist ein polyvalentes IgG-Präparat. Psomaglobin®N** ist nach seiner Zubereitung identisch mit Polyglobin®N, es stammt jedoch von Plasmaspendern mit hohen natürlichen Antikörperspiegeln gegen Lipopolysaccharid-Antigene vonPseudomonas aeruginosa. Beim dritten Präparat handelte es sich um ein polyvalentes IgG-Präparat mit 12% IgM und 16% IgA (IgGMA). Im Mausmodell der Verbrennungssepsis zeigten alle drei IgG-Präparate gegen drei von zehnP. aeruginosa-Stämmen eine ähnliche Schutzwirkung. Psomaglobin®N und Polyglobin®N besaßen im Vergleich zu IgGMA eine signifikant höhere Schutzwirkung gegen sechs bzw. drei von zehnP. aeruginosa-Stämmen (p ≤ 0,015). Im Mausmodell der Pneumonie durchStreptococcus pneumoniae Typ 3 erwiesen sich alle drei IgG-Präparate als ähnlich protektiv wirksam. IgGMA bot einen signifikant höheren Schutz als Psomaglobin®N und Polyglobin®N gegenSalmonella typhimurium bei der Peritonitis der Maus (p ≤ 0,025). Die mittlere protektive Dosis (PD50) der beiden letztgenannten Präparate lag allerdings ebenfalls unter 20 mg/kg Körpergewicht. In Peritonitismodellen waren sowohl Psomaglobin®N als auch Polyglobin®N gegenHaemophilus influenzae b,Klebsiella pneumoniae, Serratia marcescens 06:H3 undStreptococcus Gruppe B Typ 1b und 1c stärker protektiv wirksam als IgGMA (p ≤ 0,004). Psomaglobin®N und Ciprofloxacin*** wurden zur Behandlung der manifesten, polymikrobiellen Verbrennungssepsis der Maus eingesetzt, die durch Kontamination der Brandwunde mit Mischkulturen vonP. aeruginosa undStaphylococcus aureus ausgelöst wurde. Psomaglobin®N oder Albumin wurden 16 h nach der Exposition als Einmaldosis verabreicht. Ciprofloxacin wurde drei Tage lang zweimal täglich oral gegeben, beginnend 16 h nach der Exposition. Bei Albumin-behandelten Mäusen betrug die PD50 von Ciprofloxacin 5,0 mg/kg. Bei Mäussen, die mit 100 bzw. 500 mg Psomaglobin®N/kg behandelt worden waren, reduzierte sich die PD50 von Ciprofloxacin auf 1,5 bzw. 0,1 mg/kg. Dies weist auf eine synergistische Interaktion dieser beiden Medikamente in der Therapie der polymikrobiellen Verbrennungssepsis hin.

Summary

Three immunoglobulin preparations for intravenous infusion were comparedin vivo to determine their relative protective capacity against several gram-negative and gram-positive pathogens. Polyglobin®N is a conventional IgG concentrate. Psomaglobin®N is identical in formulation to Polyglobin®N but is prepared from the plasma of donors who have naturally high levels of antibody to lipopolysaccharide antigens ofPseudomonas aeruginosa. IgGMA is a conventional IgG concentrate containing 12% IgG and 16% IgA. In a murine model of burn wound sepsis the three IgG preparations were similarly protective against three or ten strains ofP. aeruginosa. Psomaglobin®N and Polyglobin®N were significantly (p ≤ 0.015) more protective than IgGMA against six of ten and three of ten strains ofP. aeruginosa, respectively. In a murine model ofStreptococcus pneumoniae type 3 pneumonia, the three Ig preparations were similarly protective. IgGMA was significantly more protective (p ≤ 0.025) than Psomaglobin®N and Polyglobin®N againstSalmonella typhimurium in murine peritonitis. However, the mean protective dose (PD50) of the two later preparations was ≤ 20 mg/kg body weight. In models of peritonitis both Psomaglobin®N and Polyglobin®N were more protective than IgGMA (p ≤ 0.004) againstHaemophilus influenzae b,Klebsiella pneumoniae, Serratia marcescens 06:H3 and group BStreptococcus types 1b and 1c. Psomaglobin®N and ciprofloxacin were employed to treat established polymicrobial murine burn wound sepsis resulting from contamination of the burn site with mixtures ofP. aeruginosa andStaphylococcus aureus. Psomaglobin®N or albumin was given once 16 h after challenge. Ciprofloxacin was given orally twice daily for three days beginning 16 h after challenge. The PD50 of ciprofloxacin was 5.0 mg/kg in albumin treated mice. In mice treated with 100 or 500 mg Psomaglobin®N, the PD50 of ciprofloxacin was reduced to 1.5 and 0.1 mg/kg respectively, thus, suggesting synergistic interaction between the two agents in the therapy of polymicrobial burn wound sepsis.

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Authors and Affiliations

  1. Abteilung für mikrobiologische Forschung, Cutter Laboratories, Division of Miles Laboratories, Inc., P.O. Box 1986, 94701, Berkeley, California, U.S.A.

    M. S. Collins Ph.D., R. F. Hector Ph.D., R. E. Roby B.A., A. A. Edwards M.S. & D. K. Ladehoff B.A.

  2. Abteilung für Statistik, Cutter Laboratories, Division of Miles Laboratories, Inc., P.O. Box 1986, 94701, Berkeley, California, U.S.A.

    J. H. Dorsey M.A.

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  1. M. S. Collins Ph.D.
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  2. R. F. Hector Ph.D.
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  3. R. E. Roby B.A.
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  4. A. A. Edwards M.S.
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  5. D. K. Ladehoff B.A.
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  6. J. H. Dorsey M.A.
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Collins, M.S., Hector, R.F., Roby, R.E. et al. Prophylaxe gramnegativer und grampositiver Infektionen mit drei intravenösen Immunglobulin-Präparaten und Therapie der experimentellen polymikrobiellen Verbrennungssepsis mit intravenösem Pseudomonas-Immunglobulin G und Ciprofloxacin im Tiermodell. Infection 15 (Suppl 2), S51–S59 (1987). https://doi.org/10.1007/BF01644193

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