Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)
- Armed Forces Radiobiology Research Institute, Bethesda, MD (USA)
Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area (TBSA)) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.
- OSTI ID:
- 5838540
- Journal Information:
- Journal of Trauma; (USA), Vol. 31:3; ISSN 0022-5282
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIBIOTICS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
EFFICIENCY
BACTERIAL DISEASES
FISSION NEUTRONS
GAMMA RADIATION
IMMUNITY
MICE
SURVIVAL CURVES
WHOLE-BODY IRRADIATION
ANIMALS
ANTI-INFECTIVE AGENTS
BARYONS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTARY PARTICLES
EXTERNAL IRRADIATION
FERMIONS
HADRONS
INFECTIOUS DISEASES
IONIZING RADIATIONS
IRRADIATION
MAMMALS
NEUTRONS
NUCLEONS
RADIATIONS
RODENTS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals