Antibacterial properties of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide-specific monoclonal antibody (MAb) in a murine thigh infection model: Combined effects of MAb and ceftazidime
M. Akiyama et al., Antibacterial properties of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide-specific monoclonal antibody (MAb) in a murine thigh infection model: Combined effects of MAb and ceftazidime, MICROB IMMU, 44(8), 2000, pp. 629-635
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 ba
cterial killing in a mouse thigh infection model. An immunoglobulin (Ig) G2
a MAb Ld3-2F2, specific for It-1 LPS, mediated in vitro complement-dependen
t opsonophagocytic killing at a concentration of 10 mu g/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 i
n opsonophagocytic assays between MAb Ld3-2F2 (0.5 mu g/ml) and ceftazidime
(1/4 MIC). The administration of MAb Ld3-2F2 at a level of 1 mu g resulted
in a significant decrease in the number of bacteria in the thigh muscles o
f normal mice, while 100 mu g of the same MAb was required for one log of r
eduction in the number of bacteria at the same site in neutropenic mice, Th
e 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-infec
tion 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 i
nteractions of an LPS-specific IgG MAb and ceftazidime strongly support the
ir potential for use in therapy, combined with an LPS-reactive MAb and pare
nteral antipseudomonas beta-lactam antibiotics in the therapy of systemic P
seudomonas infections in normal and neutropenic hosts.