Abstract
PurposeWe compared different immunoglobulin preparations containing IgG (Intraglobin/Intratect) or a mixture of IgG, IgA, and IgM (Pentaglobin) to assess the opsonic and protective efficacy of human immunoglobulin preparations against multiresistent nosocomial pathogens.Materials and methodsClinical isolates of E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, Enterococcus faecium, and Staphylococcus aureus were tested by opsonophagocytic assay using immunologobulin preparations at dilutions usually obtained in patients. The target antigens of opsonic antibodies were characterized by opsonophagocytic inhibition assays, and the protective efficacy in vivo was tested in a mouse bacteremia model as previously described.ResultsAll strains were killed to at least 50 % by Pentaglobin. One P. aeruginosa strain was not efficiently killed by Intraglobin (23 %) but the other strains were killed by Intraglobin to a similar degree compared to Pentaglobin. Opsonic IgG antibodies against E. faecalis were directed against LTA, while opsonic antibodies in Pentaglobin were primarily directed against other cell wall carbohydrates. In a mouse bacteremia model, Pentaglobin was more protective than Intratect against Staphylococcus aureus, while Intratect reduced colony counts better than normal rabbit serum or saline.ConclusionsAll tested human immunoglobulin preparations contain opsonic and protective antibodies against targets present on multiresistant Gram-positive and Gram-negative bacteria. Enrichment of these preparations with IgM increases the protective efficacy against some strains, probably due to antibodies directed against cell wall carbohydrates.
Highlights
Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics and are one of the most serious problems in modern medicine
IgM increases the protective efficacy against some strains, probably due to antibodies directed against cell wall carbohydrates
A recent report from the Centers for Disease Control and Prevention (CDC) estimates that in the US about two million people acquire infections with resistant bacteria, and that probably about 23,000 patients die each year as a direct consequence of these infections [1]
Summary
Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics and are one of the most serious problems in modern medicine. A recent report from the Centers for Disease Control and Prevention (CDC) estimates that in the US about two million people acquire infections with resistant bacteria, and that probably about 23,000 patients die each year as a direct consequence of these infections [1]. Multiresistant Staphylococcus aureus cause pneumonia, skin, wound, bloodstream and surgical site infections. About 80,000 S. aureus infections have been reported in the US per year with about 12,000 deaths caused by bacteria resistant to methicillin (MRSA) [1]. High rates are seen for enterococci, mainly Enterococcus faecium resistant to vancomycin (VRE) causing bloodstream infections, urinary tract infections, and foreign-body infections (e.g., catheters, stents, CNS shunts, artificial heart valves, etc.) mostly in immunocompromised patients [2,3,4]. For the US, it is estimated that about 66,000 enterococcal infections occur each year, and about 20,000 of these are due to multiple-drug resistant (i.e., VRE) with about 1,300 deaths per year [1]
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