SYNERGISTIC EFFECTS OF A MACROLIDE AND A CELL WALL-AFFECTING ANTIBIOTIC ON PSEUDOMONAS AERUGINOSA IN VITRO AND IN VIVO

1. COMBINED EFFECTS OF A MACROLIDE AND A PEPTIDE ANTIBIOTIC

Abstract

Synergistic effects of peptide and macrolide antibiotics against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals in the logarithmic growth phase. These bacteria were treated concurrently with polymyxin B (PL) at the final concentration of 1.56 U/ml and with 9, 3"-di-O-acetylmidecamycin (MOM) at varying concentrations. Synergistic effect was observed when PL was used with MOM at 3.13 and 12.5 μg/ml respectively. When MOM at 50 μg/ml was used with PL, the viable bacterial count was reduced to below 1/300 of the control to which PL alone had been added. Thus, the synergistic effect was remarkable. Similar results were obtained when colistin methanesulfonate (CL) was used instead of PL. Subsequently, attempts were made to determine if this action could also be found in in vivo experiments using mice. PL or CL was injected intramuscularly and midecamycin (MDM) or MOM was administered once or repeatedly by the oral route. Simultaneously, Pseudomonas aeruginosa strain IFO 3455 was inoculated intraperitoneally to mice. In the case of treatment once or repeatedly using both PL and MDM or MOM, the survival rate of infected mice increased significantly compared to single treatment by PL alone. Thus, the synergistic effects were demonstrated in four experiments. (The significance levels for the experiments were P=0.070, 0.015, 0.042 and 0.024). Similar results were obtained when strain No. 5 was used to infect mice (P=0.0096, 0.0027). When CL and MOM were given to mice once prior to infection with strain No. 5, synergistic effects were obtained as well (P=0.010, 0.034).