title: Endotoxin release after antibiotic treatment and its potential pathogenetic role in coagulative disorders of patients with gram-negative sepsis.
abstract: The liberation of endotoxin by gram-negative bacteria upon antibiotic treatment might be of clinical relevance in terms of adverse effects of antibiotic therapy in patients with gram-negative infections. In this paper we have taken into consideration the endotoxic material released by Salmonella typhimurium SH9178 after treatment with either ofloxacin and norfloxacin (which act as DNA-gyrase inhibitors) or imipenem (which affects the bacterial cell wall) in its capacity to induce in-vitro production of procoagulant activity, tissue factor-like, by human mononuclear cells. Endotoxin released from Salmonella typhimurium after treatment with the above antibiotics behaves as the typical endotoxin of gram-negative bacteria in its capacity to induce procoagulant production. Indeed human mononuclear cells after prolonged incubation with supernatants of antibiotic-treated Salmonella were able to shorten the recalcification time of normal but not Factor VII deficient plasma (tissue factor-like activity). On this basis we hypothesize that this mechanism, leading to the activation of blood coagulation through the extrinsic pathway, might be closely involved in thrombohemorrhagic disorders sometimes complicating the antimicrobial therapy of gram-negative sepsis.
authors.affiliation: Istituto di Microbiologia Medica, Università di Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Miragliotta
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology*; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000382:microbiology / Q000503:physiopathology; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D009643:Norfloxacin / Q000009:adverse effects / Q000494:pharmacology*; D015242:Ofloxacin / Q000009:adverse effects / Q000494:pharmacology*; D012480:Salmonella Infections / Q000150:complications*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000472:pathogenicity*; D012772:Shock, Septic / Q000503:physiopathology
chemical_list: D000890:Anti-Infective Agents; D004731:Endotoxins; D015242:Ofloxacin; D009643:Norfloxacin