The anti-infective activity of
romurtide, a synthetic
muramyl dipeptide (MDP) derivative, was evaluated in experimental
pneumococcal pneumonia in mice deficient in the third component of
complement (C3). The compound was found to be effective against the
pneumonia in combination with subcutaneous
ampicillin (ABPC). This synergistic effect of
romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before
infection.
Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent
pneumonia. In contrast, the combination treatment of
romurtide with ABPC successfully prevented most of the mice from the purulent
pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with
romurtide in combination with ABPC. Thus,
romurtide was suggested to promote recovery of the mice with
pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.