Nonspecific enhancement of resistance to bacterial infection: evidence of an effect supplemental to antibiotics.

Experiments have been undertaken to further characterize the actions of the synthetic immunoadjuvant compound, muramyl dipeptide (MDP), in an animal model simulating surgical infection. When used prophylactically in combination with antibiotics, MDP proved to be significantly additive in terms of local and systemic effects, and survival, to both chloramphenicol (p less than 0.01) and cephaloridine (p less than 0.05). The combined use of MDP and cephaloridine therapy, initiated four or six hours following infectious challenge and including a surgical foreign body in starved and refed animals, showed statistically significant decreases in bacteremia during early time periods, as well an increased early survival (p less than 0.02), compared with the use of cephaloridine alone. Benefits observed in the therapeutic mode were of lesser magnitude than those observed following prophylactic use, but the model used was a much more significant physiologic challenge. Evidence indicating additive effects to those of antibiotics is essential prior to the use of MDP in clinical trials.