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Journal of Antimicrobial Chemotherapy (1992) 30, 839-842
© 1992 The British Society for Antimicrobial Chemotherapy

research-article

Inhibition of nitric oxide synthesis improves survival in a murine peritonitis model of sepsis that is not cured by antibiotics alone

David M. Teale and Annie M. Atkinson

ICI Pharmaceuticals, Bioscience 1, Mereside Alderly Park, Macclesfield, Cheshire SK10 4TG, UK

Received 8 May 1992; returned 10 August 1992; accepted 10 August 1992

Inhibition of nitric oxide synthesis was investigated in a murine model of advanced sepsis in which antibiotic therapy alone did not improve survival. Seven hours after receiving a lethal intraperitoneal challenge with live Escherichia coli, mice were given either NG-monomethyl-L-arginine (L-NMMA) intravenously, imipenem-cilastatin subcutaneously or a combination of both. L-NMMA (3–300 mg/kg) or imipenemcilastatin (10 or 50 mg/kg) given alone did not improve survival; co-administration of L-NMMA and either 10 or 50 mg imipenem-cilastatin/kg improved survival significantly. These findings suggest that nitric oxide contributes to the morbidity associated with advanced sepsis and that nitric oxide synthase inhibition may improve the efficacy of conventional antimicrobial treatment of severe infections.


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