title: Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 2. Combined effects of a macrolide with a fosfomycin and an aminoglycoside antibiotic.
abstract: Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D003864:Depression, Chemical; D003982:Dibekacin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology* / Q000627:therapeutic use; D007612:Kanamycin / Q000031:analogs & derivatives*; D007933:Leucomycins / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D007933:Leucomycins; D005578:Fosfomycin; D003982:Dibekacin; D007612:Kanamycin; C026483:midecamycin