title: Influence of antibiotic and E5 monoclonal immunoglobulin M interactions on endotoxin release from Escherichia coli and Pseudomonas aeruginosa.
abstract: Recent controversy surrounding the activity of monoclonal antibodies against endotoxin highlights the necessity of identifying all factors associated with increased mortality, one of which is endotoxin concentrations. Antibiotics may induce different patterns of endotoxin release. We compared the release of free endotoxin (in endotoxin units per milliliter) over 6 h and changes in numbers of CFU of exponentially growing Escherichia coli and Pseudomonas aeruginosa (10(6) to 10(7) CFU/ml) cultured in chemically defined endotoxin-free broth combined with pooled human serum and/or 10 micrograms of E5 immunoglobulin M monoclonal antibody per ml. MICs and MBCs were tested in each medium at the same inoculum. The inoculum was exposed to antibiotics at a single fixed multiple of the MIC for each medium (range, two to eight times the MIC). E5 antibody had no effect on MICs, MBCs, bactericidal activity, or endotoxin release. In the presence of 50% serum, amikacin, ceftazidime, imipenem, and ofloxacin each killed equivalent amounts of E. coli over 6 h; however, ceftazidime induced the highest release of endotoxin. Amikacin and ofloxacin produced the most favorable ratio of endotoxin release to amount of bacterial killing. In the presence of 50% serum, ceftazidime and imipenem reduced the P. aeruginosa inoculum to the greatest extent over 6 h. Although its bactericidal activity was diminished, ofloxacin caused the lowest release of free endotoxin. Imipenem and ofloxacin showed similar low ratios of endotoxin release to bacterial killing. In summary, antibiotic class, presence of serum, and type of organism influenced bactericidal activity and endotoxin release.
authors.affiliation: School of Pharmacy, University of Missouri, Kansas City 64110, USA. kclamp@cctr.umkc.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Lamp
authors.forename: M J
authors.initials: MJ
authors.lastname: Rybak
authors.forename: B J
authors.initials: BJ
authors.lastname: McGrath
authors.forename: K K
authors.initials: KK
authors.lastname: Summers
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects; D004347:Drug Interactions; D004731:Endotoxins / Q000276:immunology / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007075:Immunoglobulin M; C044101:endotoxin, Escherichia coli