Compositions for the treatment of peritonitis

Abstract

The present invention provides compositions comprising granulocyte-macrophage colony-stimulating factor and antimicrobial agents for the treatment, pre-emptive treatment or prevention of infectious peritonitis or intra-abdominal infection by intraperitoneal administration of the compositions.

Description

FIELD OF INVENTION[0001]The present invention provides compositions comprising granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with one or more antimicrobial agents for the prophylaxis, pre-emptive treatment or treatment of peritonitis of microbial causation by direct instillation into the peritoneal cavity. As such, it will be useful in the fields of abdominal surgery, gastroenterology and even nephrology, for patients receiving peritoneal dialysis.BACKGROUND OF INVENTION[0002]Peritonitis is defined as inflammation of the peritoneum, the serosal membrane that lines the abdominal cavity and covers the organs within it. The peritoneum, which is normally sterile, reacts to various pathologic stimuli with a fairly uniform inflammatory response. Depending on the underlying pathology, the resulting peritonitis may be infectious or sterile in origin (Daley 2013).[0003]Sterile or aseptic peritonitis may be caused by irritants such as foreign bodies, bile from a per...

AI Technical Summary

Benefits of technology

The present invention provides a pharmaceutical composition for intraperitoneal administration that includes granulocyte-macrophage colony-stimulating factor (GM-CSF) and one or more antimicrobial or antibiotic agents for the treatment, pre-emptive treatment, or prophylaxis of infectious peritonitis or intra-abdominal infection. The composition is effective in restoring defective peritoneal macrophage function and recruiting further primed macrophages into the peritoneum without inducing systemic inflammation. The invention also provides a kit-of-parts for use in the treatment, pre-emptive treatment, or prophylaxis of infectious peritonitis or intra-abdominal infection. The therapeutical effects of the invention include high local bactericidal or fungicidal concentrations, effective treatment of bacterial peritonitis caused by bacteria of the Bacteroides fragilis group, and reduced risk of systemic inflammation.

Problems solved by technology

The incidence of secondary peritonitis is similarly difficult to assess.

In severe infections such as bacterial peritonitis, the normal immuno-inflammatory defense mechanisms involving macrophages, neutrophils and lymphocytes may not always function optimally for the patient's recovery.

However, attempting to restore monocyte / macrophage function in bacterial peritonitis by giving systemic GM-CSF has given rise to contradictory results.

The survival rate did not improve and animals died earlier than in the control group.

Antibiotic regimens with little or no activity against Gram-negative rods or anaerobic Gram-negative rods are not considered acceptable (Holzheimer 2001).