2255. The Comparative Efficacy of Antibiotics against Experimental Clostridium septicum Infection
Session: Poster Abstract Session: New Antibiotics in Development
Saturday, October 29, 2016
Room: Poster Hall
Background: Clostridium septicum is a highly pathogenic microbe that causes gas gangrene in humans and is the principal cause of spontaneous gas gangrene in patients with gastrointestinal maladies, including adenocarcinoma of the colon. Despite modern approaches to manage C. septicum infections, morbidity and mortality remain high (>50%). At present, no objective in vivo data exists supporting the current antibiotic treatment recommendations for C. septicum infection.

Methods: Utilizing our established murine model of clostridial myonecrosis, we investigated the efficacy of standard antibiotics for anaerobic Gram positive soft-tissue infections (penicillin, clindamycin, tetracycline, vancomycin) in treating C. septicum gas gangrene. Following intramuscular challenge with 1x106 colony forming units of C. septicum, antibiotics were administered by intraperitoneal injection every four hours for a total of four doses.

Results: At 30 hours, all animals in all treatment groups survived the C. septicum challenge, compared to no survivors in the untreated controls (100% mortality by 10 hours). By 60 hours, mice treated with vancomycin exhibited 40% mortality, with no mortality observed in any other antibiotic treatment group. Additionally, microbroth dilution MIC analysis for three strains of C. septicum collectively demonstrated high susceptibility to penicillin, clindamycin and tetracycline, but considerably lower susceptibility to vancomycin.

Conclusion: These studies corroborate that penicillin, clindamycin and tetracycline may be suitable alternatives for the treatment of C. septicum infection in humans.

Michael Aldape, PhD, Clifford Bayer, BS, Savannah Rice, BS, Amy Bryant, PhD and Dennis Stevens, MD, PhD, Infectious Diseases, Veterans Affairs Medical Center, Boise, ID

Disclosures:

M. Aldape, None

C. Bayer, None

S. Rice, None

A. Bryant, Merck & Co.: Grant Investigator , Research grant

D. Stevens, None

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