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Antibacterial Properties of Pseudomonas aeruginosa Immunotype 1 Lipopolysaccharide‐Specific Monoclonal Antibody (MAb) in a Murine Thigh Infection Model: Combined Effects of MAb and Ceftazidime
Author(s) -
Akiyama Moritoshi,
Oishi Kazunori,
Tao Misao,
Matsumoto Keizo,
Pollack Matthew
Publication year - 2000
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2000.tb02543.x
Subject(s) - ceftazidime , microbiology and biotechnology , monoclonal antibody , biology , in vivo , antibody opsonization , pseudomonas aeruginosa , lipopolysaccharide , antibody , antibiotics , in vitro , opsonin , bacteria , immunology , phagocytosis , biochemistry , genetics
A murine monoclonal antibody (MAb) specific for the Pseudomonas aeruginosa immunotype 1 (It‐1) lipopolysaccharide (LPS) O‐side chain was evaluated in terms of its in vitro bactericidal opsonophagocytic activity and in vivo bacterial killing in a mouse thigh infection model. An immunoglobulin (Ig) G2a MAb Ld3–2F2, specific for It‐1 LPS, mediated in vitro complement‐dependent opsonophagocytic killing at a concentration of 10 μg/ml. MAb‐mediated, complement‐dependent killing also occurred in the absence of neutrophils at serum concentrations in excess of 20%. A remarkable synergy was observed in opsonophagocytic assays between MAb Ld3–2F2 (0.5 μg/ml) and ceftazidime (1/4 MIC). The administration of MAb Ld3–2F2 at a level of 1 μg resulted in a significant decrease in the number of bacteria in the thigh muscles of normal mice, while 100 μg of the same MAb was required for one log of reduction in the number of bacteria at the same site in neutropenic mice. The combined therapy with MAb Ld3–2F2 and ceftazidime provided a significant reduction in the density of bacteria in the thigh muscle at 9 hr post‐infection in normal and neutropenic mice as compared with those after treatment alone or with no treatment ( P < 0.01). These favorable in vitro and in vivo interactions of an LPS‐specific IgG MAb and ceftazidime strongly support their potential for use in therapy, combined with an LPS‐reactive MAb and parenteral antipseudomonas β‐lactam antibiotics in the therapy of systemic Pseudomonas infections in normal and neutropenic hosts.