Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa peritonitis in a murine model

Infectious peritonitis results from bacterial contamination of the abdomina l cavity, Conventional antibiotic treatment is complicated both by the emer gence of antibiotic-resistant bacteria and by increased patient populations intrinsically at risk for nosocomial infections. To complement antibiotic therapies, the efficacy of direct, locally applied pooled human immunoglobu lin G (IgG) was assessed in a murine model (strains CF-1, CD-1, and CFW) of peritonitis caused by intraperitoneal inoculations of 10(6) or 10(7) CFU o f Pseudomonas aeruginosa (strains IFO-3455, M-2, and MSRI-7072), Various do ses of Ige (0.005 to 10 mg/mouse) administered intraperitoneally simultaneo usly with local bacterial challenge significantly increased survival in a d ose-dependent manner, Local intraperitoneal application of 10 mg of IgG inc reased animal survival independent of either the P. aeruginosa or the murin e strains used. A local dose of 10 mg of IgG administered up to 6 h prophyl actically or at the time of bacterial challenge resulted in 100% survival. Therapeutic 10-mg Ige treatment given up to 12 h postinfection also signifi cantly increased survival. Human IgG administered to the mouse peritoneal c avity was rapidly detected systemically in serum. Additionally, administere d Ige in peritoneal lavage fluid samples actively opsonized and decreased t he bacterial burden via phagocytosis at 2 and 4 h post-bacterial challenge. Tissue microbial quantification studies showed that 1.0 mg of locally appl ied IgG significantly reduced the bacterial burden in the liver, peritoneal cavity, and blood and correlated with reduced levels of interleukin-6 in s erum.