Synthetic trehalose dicorynomycolate and antimicrobials increase survival from sepsis in mice immunocompromised by radiation and trauma.
When mammalian antimicrobial defenses are compromised by radiation, death from sepsis may occur. Tissue trauma in irradiated hosts significantly increases mortality from bacterial infections and makes antimicrobial treatments more difficult than when individuals are subjected to trauma or radiation alone. We determined that postirradiation therapy with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) and antimicrobials increases survival in mice after lethal irradiation and tissue trauma. Single agent therapy with systemic oxacillin, gentamicin, ofloxacin, and S-TDCM did not increase survival. Topical treatment of the injury with gentamicin cream in addition to systemic therapy with oxacillin or S-TDCM was necessary to enhance survival. Therapy with gentamicin and S-TDCM had a synergistic effect on survival. Therapies combining augmentation of non-specific host defense mechanisms with antimicrobials may be valuable in treating irradiated patients also sustaining tissue trauma.
Ledney
G D
GD
Department of Experimental Hematology Armed Forces, Radiobiology Research Institute, Bethesda, MD 20889-5145.
Madonna
G S
GS
Moore
M M
MM
Elliott
T B
TB
Brook
I
I
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology; D003311:Cord Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D016867:Immunocompromised Host; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000150:complications; D014946:Wound Infection / Q000188:drug therapy / Q000209:etiology; D014947:Wounds and Injuries / Q000150:complications
D000890:Anti-Infective Agents; D003311:Cord Factors; C043399:6,6'-dicorynomycolyl trehalose