Combination therapy of Pseudomonas aeruginosa pyelonephritis in neutropenic mice with human antilipopolysaccharide monoclonal antibody and cefsulodin.

PURPOSE

These studies were designed to determine the combined inhibitory effect of a human monoclonal antibody (MAb) and cefsulodin on Pseudomonas aeruginosa renal infection in a neutropenic condition.

MATERIALS AND METHODS

Protection against the infection of mice was estimated by survival rate and bacterial numbers in the kidney and blood. Opsonophagocytic assay by human polymorphonuclear neutrophils (PMNs) and fluorescence activated cell sorter (FACS) analysis were also examined.

RESULTS

Treatment of infected mice with MAb combined with a suboptimal dose of cefsulodin prevented the mice from developing pyelonephritis and bacteremia and resulted in a significantly higher survival rate than treatment with either MAb or cefsulodin alone (p < 0.01). When bacteria were preexposed to cefsulodin, a significant enhancement in opsonophagocytic killing with MAb was observed. Fluorescence activated cell sorter analysis suggested that the bacteria incubated with 1/4 minimal inhibitory concentration (MIC) of cefsulodin showed greater binding of MAb to bacteria than the control.

CONCLUSION

The combination therapy with human antilipopolysaccharide MAb and cefsulodin is useful for P. aeruginosa pyelonephritis in neutropenic hosts.