Combination effect of fosfomycin to beta-lactam, aminoglycoside, and macrolide antibiotics against clinical isolates of Klebsiella pneumoniae]

It is well known that fosfomycin (FOM) shows the combination effects with some other antibiotics. Suck effects have not been known against Klebsiella pneumoniae, however. In this report, combination effects of FOM with beta-lactam, aminoglycoside, and macrolide antibiotics were investigated against clinical isolates of both FOM-susceptible and resistant Klebsiella pneumoniae. FOM had synergistic activities with beta-lactams such as ampicillin (ABPC) and cefminox (CMNX), and macrolide antibiotics as erythromycin (EM) and midecamycin (MDM) against all strains tested. Among beta-lactams, penicillin V showed synergistic actions against FOM-susceptible strain of Tf341A and additive actions against FOM-resistant 3 strains with FOM. Pheneticillin was synergistic with FOM against FOM-highly susceptible strain Tf341A and the additive or nearly synergistic effects against other strains. FOM with amoxicillin was synergistic against Tf341A, and FOM-resistant strain of Tf170B and additive against other strains. While the activities of combination of FOM with kanamycin or dibekacin against FOM-susceptible 2 strains were additive, those with amikacin were synergistic. Five different aminoglycosides tested showed antagonistic activities with FOM against 3 FOM-resistant strains. From these results, FOM appears to be clinically useful in treating FOM-susceptible and resistant strains of Klebsiella pneumoniae in combination of 4 antibiotics such as ABPC, CMNX, EM, and MDM.