Efficacy of Locally Delivered Polyclonal Immunoglobulin against Pseudomonas aeruginosa Peritonitis in a Murine Model

Abstract

Infectious peritonitis results from bacterial contamination of the abdominal cavity. Conventional antibiotic treatment is complicated both by the emergence 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 immunoglobulin G (IgG) was assessed in a murine model (strains CF-1, CD-1, and CFW) of peritonitis caused by intraperitoneal inoculations of 106 or 107 CFU of Pseudomonas aeruginosa (strains IFO-3455, M-2, and MSRI-7072). Various doses of IgG (0.005 to 10 mg/mouse) administered intraperitoneally simultaneously with local bacterial challenge significantly increased survival in a dose-dependent manner. Local intraperitoneal application of 10 mg of IgG increased animal survival independent of either the P. aeruginosa or the murine strains used. A local dose of 10 mg of IgG administered up to 6 h prophylactically or at the time of bacterial challenge resulted in 100% survival. Therapeutic 10-mg IgG treatment given up to 12 h postinfection also significantly increased survival. Human IgG administered to the mouse peritoneal cavity was rapidly detected systemically in serum. Additionally, administered IgG in peritoneal lavage fluid samples actively opsonized and decreased the bacterial burden via phagocytosis at 2 and 4 h post-bacterial challenge. Tissue microbial quantification studies showed that 1.0 mg of locally applied IgG significantly reduced the bacterial burden in the liver, peritoneal cavity, and blood and correlated with reduced levels of interleukin-6 in serum.

Treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen ofBacillus anthracis

“…Our IgG treatment schedule was chosen based on the fact that clearance rates for i.p. administered IgG in mice are rather rapid (∼3 h) [11–13].…”

Quantification of Staphylococcus aureus Adhesion to Equine Bone Surfaces Passivated with Plasmalyte™ and Hyperimmune Plasma

“…High‐powered pulsatile lavage is superior to low‐pressure lavage, but causes more bone damage 28 . Most recently, the use of plasma proteins including specific immunoglobulins directed at decreasing bacterial adhesion molecules have had promising results 12–14,23–25 …”

“…The most common methods used are perioperative systemic antibiotics and intraoperative lavage with sterile fluids (often containing antimicrobials), but they do not eliminate infection in all situations 4 . In human and experimental orthopedics, several additives to lavage to increase bacterial removal and killing lavage have been investigated, including antimicrobials, soap, and immunoglobulins 12,20–25 . Our long‐term goal is to develop an ideal lavage solution that would be inexpensive, non‐toxic to tissues, and rapidly (<1 hour) bactericidal on all bone and tissue surfaces.…”

Prophylactic treatment of gram‐positive and gram‐negative abdominal implant infections using locally delivered polyclonal antibodies

“…Reduced, highly selective antibody doses could also exploit sophisticated delivery strategies21 to reduce initial pathogen adhesion, biofilm formation, and severity of infections. Recent work has shown that commercial human pooled polyclonal IgG injected intraperitoneally effectively protected mice against lethal peritonitis induced by virulent Pseudomonads 41. Infection survival was independent of either the mouse or Pseudomonas aeruginosa strain 41.…”

“…Recent work has shown that commercial human pooled polyclonal IgG injected intraperitoneally effectively protected mice against lethal peritonitis induced by virulent Pseudomonads 41. Infection survival was independent of either the mouse or Pseudomonas aeruginosa strain 41. The timing of locally delivered polyclonal IgG was important for optimizing the survival benefit, with prophylactic local antibody applications producing the highest survival 41, 42…”