These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Species specificity of 2-aryl carbapenem-induced immune-mediated hemolytic anemia in primates.
    Author: Lankas GR, Coleman JB, Klein HJ, Bailly Y.
    Journal: Toxicology; 1996 Apr 30; 108(3):207-15. PubMed ID: 8658540.
    Abstract:
    L-695,256 is a novel 2-fluorenonyl carbapenem antibiotic with significant antimicrobial activity against strains of methicillin-resistant Staphylococci. This prototype compound was administered intravenously to rhesus monkeys (Macaca mulatta) at does of 50 or 200 mg/kg/day for 2 weeks to assess toxicity and found to induce a hemolytic anemia characterized by extravascular hemolysis and splenomegaly. A subsequent study in this species in which 100 mg/kg/day was administered i.v. for 4 weeks showed that all animals were direct antiglobulin test (Coombs' test) positive for IgG with 20-25% reductions in the erythron. Following 3 weeks of recovery, the erythron had returned to normal, although it took an additional 2 months for the Coombs' test to become negative. Challenge of these same animals with 0.5 million U/kg (300 mg/kg/day) of penicillin intravenously indicated no apparent cross-reactivity. Since attempts to establish a model for this immune-mediated hemolytic anemia with this drug in rats or mice were unsuccessful, a 2-week i.v. study in squirrel monkeys (Saimiri sciureus) was conducted at a dose of 200 mg/kg/day. All animals in this study remained Coombs' test negative with no changes in the erythron, suggesting an increased sensitivity to beta-lactam-induced anemia in rhesus monkeys compared to other species. Further support for this hypothesis was obtained using the cephalosporin antibiotic, cefotetan. This compound induced a high incidence of Coombs' test positive hemolytic anemia at clinically relevant doses in rhesus monkeys, despite a very low incidence of this adverse effect in patients with many years of clinical use. These data suggest that although rhesus monkeys respond in a qualitatively similar manner to humans with regard to high doses of beta-lactam antibiotics, their sensitivity may overestimate the risk of immune-mediated hemolytic anemia for clinical use.
    [Abstract] [Full Text] [Related] [New Search]