SYNERGY OF MECILLINAM WITH PENICILLINS AND CEPHALOSPORINS AGAINST <I>E. COLI</I> AND OTHER BACTERIAL SPECIES
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Mecillinam (MPC) is reported not to inhibit transpeptidase, D-alanine carboxypeptidase and endopeptidase which are enzymes related to the synthesis of bacterial cell walls. Synergism was therefore examined between MPC and other penicillins and cephalosporins which inhibit these enzymes as well as between MPC and fosfomycin (FOM) which inhibits the mucopeptide biosynthesis of the cell walls. The results obtained were : <BR>1) A potentializing synergism of the antimicrobial activity against E. coli was combined with ampicillin (ABPC), sulbenicillin (SBPC), cephalexin (CEX), cefazolin (CEZ) and FOM.<BR>2) The antimicrobial effect of MPC against <I>Klebsiella</I> was potentiated by combination with CEX and CEZ. The potentiation was especially marked in case of the combinations of MPC and CEX.No.remarkable synergism, however, was noted between MPC and ABPC, SBPC or FOM.<BR>3) Synergistic effect on <I>Proteus mirabilis</I> was approximately the same as that on <I>Klebsiella</I>. Against <I>Proteus morganii</I> and <I>Pseudomonas aeruginosa</I>, combinations of MPC with CEZ or SBPC were not so synergistically effective.<BR>4) Combinations of MPC and CEX which showed the most potentializing synergism against <I>E. coli</I>, <I>Klebsiella</I> and <I>Proteus mirabilis</I> were examined for their bactericidal effect on the organisms. The combinations were found bactericidal at a concentration lower than MIC of each agent. Especially, they markedly suppressed regrowth of <I>Klebsiella</I>.<BR>5) The suppressing effect on regrowth of <I>Klebsiella</I> exerted by combination of MPC and CEX was also confirmed by the morphological changes of the organism observed by a phase contrast microscope. Division and growth of the organism were immediately suppressed by the combined use of MPC and CEX, producing a giant spherical form of the bacterial cells in which vacuoles formed to result into the suppressed regrowth without bacteriolysis.<BR>6) The above results suggest that some combinations of MPC having a different mode of action with other penicillins and cephalosporins have a synergistic effect. A discussion is made on the necessity of a theoretical approach for attaining an ideal synergism by examining, for example, which part of the bacterial cell wall structure is inhibited by each drug, whether a competition against protein binding exists there, and what is the behavior of each drug to β-lactamase.
- 公益社団法人 日本化学療法学会の論文
公益社団法人 日本化学療法学会 | 論文
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