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.

Zingerone Suppresses Liver Inflammation Induced by Antibiotic Mediated Endotoxemia through Down Regulating Hepatic mRNA Expression of Inflammatory Markers in Pseudomonas aeruginosa Peritonitis Mouse Model

“…Ciprofloxacin acts on the A subunit of DNA gyrase, which inhibits DNA supercoiling, resulting in the inhibition of DNA replication [27] without causing cell lysis. Amikacin and gentamicin that inhibit protein synthesis are also known to release low amounts of endotoxin as compared to beta lactam antibiotics [28]. Whereas, cefotaxime (7-[2-(2-amino-4-thiazolyl)-2-methoximino]-acetamido cephalosporanate) has high affinity for penicillin-binding proteins (PBPs) and induces formation of filamentous cells leading to cell lysis [29].…”

Biological Characterization of Endotoxins Released from Antibiotic-TreatedPseudomonas aeruginosaandEscherichia coli

“…However, a pathway of LPS-induced cell activation that does not require CD14 has been suggested (16). The CD14 dependency of CAZ-released P. aeruginosa endotoxin was examined with a CD14-positive murine macrophage-like cell line (J774.1 cells) and its LPS-resistant mutant (J7.DEF3 cells) (18,19). J7.DEF3 cells do not express CD14 antigen (unpublished observation).…”

“…Endotoxin or LPS is a component of the outer membrane of gram-negative bacteria, and cell wall-active antibiotics (such as ␤-lactams) are considered to be most responsible for the liberation of excess amounts of endotoxin. The amounts of endotoxin released from bacteria by antibiotics can vary depending on the bacterial strains, the types and efficacies of the antibiotics, the concentrations of the antibiotics, the length of time that the bacteria are exposed to the antibiotic (9,14), and the presence of antibody and/or other serum constituents that can interact with endotoxin (18). Among the ␤-lactam antibiotics, the capabilities for releasing endotoxin vary greatly depending on the antibiotics used, and the difference can partly be explained by the binding affinities of the antibiotics to the different kinds of penicillin-binding proteins (PBPs).…”

Opinion of the Scientific Panel on Animal Health and Welfare on a request from the Commission related to animal health and welfare in fattening pigs in relation to housing and husbandry

“…However, the cell wall components of dead (or non-Viable) bacteria are just as capable of engaging the immune system of pigs and humans as viable bacteria. Bacterial lipopolysaccharide (LPS) or endotoxins are released in high concentrations in the lungs upon infection with Gram-negative bacteria (Lamp et al, 1996;Kadurugamuwa and Beveridge, 1997) and these endotoxins are present in varying concentrations in dust in swine buildings (Zejda et al, 1994). The release of LPS by Gram-negative bacteria, such as H. parasuis, P. multocida, B. bronchiseptica may explain the more severe disease in the experimental dual infections with PRRS and these bacteria (Brockmeier et al, 2000).…”