Synergistic Effect of Romurtide with Ampicillin against Pneumococcal Pneumonia in Mice

Abstract

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.