title: No increase in endotoxin release during antibiotic killing of meningococci.
abstract: Endotoxin is liberated following antibiotic killing of Gram-negative rods, and antibiotics may differ in this respect. Although the amount of filterable endotoxin has also been reported to increase following antibiotic killing of meningococci, it is unknown how this influences the host response. We investigated the influence of three antibiotics on levels of free endotoxin in culture medium and cytokine production in whole blood ex vivo during killing of four strains of meningococci. Bacterial killing was significantly more efficient with penicillin or ceftriaxone than with chloramphenicol, and free endotoxin levels were lower after exposure to antibiotics as compared with no treatment (ANOVA, P < 0.001). Endotoxin levels were lowest after exposure to chloramphenicol. In three of the four strains exposure to antibiotics resulted in considerably lower cytokine levels (ANOVA, P < 0.001), and TNF-alpha levels were significantly lower after exposure to penicillin or ceftriaxone than after chloramphenicol treatment. Only in the strain that induced the lowest levels of TNF-alpha were cytokine levels comparable for untreated and treated samples. We conclude that fear of excessive endotoxin release or cytokine production caused by effective antibiotics is not justified in the treatment of meningococcal infections.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Prins
authors.forename: P
authors.initials: P
authors.lastname: Speelman
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuijper
authors.forename: J
authors.initials: J
authors.lastname: Dankert
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D009345:Neisseria meningitidis / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D016207:Cytokines; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha