Odenholt Inga, Walder Mats, Wullt Marlene
Infectious Diseases Research Unit, Department of Clinical Sciences, Malmö, Sweden.
Chemotherapy. 2007;53(4):267-74. doi: 10.1159/000104471. Epub 2007 Jun 25.
Pharmacodynamic studies of antibiotics have attracted great interest in recent years. However, studies on the pharmacodynamics of different antibiotics against Clostridium difficile are scarce.
The postantibiotic effects (PAE) and the postantibiotic sub-minimum inhibitory concentration (MIC) effects (PA SME) of vancomycin, metronidazole and fusidic acid were investigated by viable counts against three different strains of C. difficile. The killing rate and extent of the three antibiotics against the same strains were also studied by adding 2, 4, 8, 16 and 32x MIC of the three antibiotics, respectively.
Metronidazole exerted a very rapid bactericidal effect at concentrations of 8x MIC and above against all three strains investigated. Vancomycin gave overall less kill in comparison to metronidazole and was bacteriostatic against two of the three strains. Fusidic acid exerted a concentration-dependent killing against two of the strains. Vancomycin exerted short PAEs and PA SMEs against all three strains. Significantly longer PAEs and PA SMEs were noted for fusidic acid. Metronidazole gave similar short PAEs like vancomycin but longer PA SMEs were noted against two of the investigated strains.
Metronidazole exerted the most prominent bactericidal effect greater than fusidic acid and greater than vancomycin. Fusidic acid gave overall the longest PAEs and PA SMEs greater than metronidazole and greater than vancomycin.
近年来，抗生素的药效学研究备受关注。然而，针对艰难梭菌的不同抗生素药效学研究却很匮乏。
通过活菌计数法，研究了万古霉素、甲硝唑和夫西地酸对三株不同艰难梭菌菌株的抗生素后效应（PAE）及抗生素后亚最低抑菌浓度（MIC）效应（PA SME）。同时，分别加入三种抗生素的2、4、8、16和32倍MIC，研究这三种抗生素对同一菌株的杀菌率和杀菌程度。
甲硝唑在8倍MIC及以上浓度时，对所有三株受试菌株均呈现出非常快速的杀菌作用。与甲硝唑相比，万古霉素的总体杀菌效果较差，且对三株菌株中的两株具有抑菌作用。夫西地酸对其中两株菌株呈现浓度依赖性杀菌作用。万古霉素对所有三株菌株的PAE和PA SME均较短。夫西地酸的PAE和PA SME明显更长。甲硝唑的PAE与万古霉素相似，但对两株受试菌株的PA SME更长。
甲硝唑的杀菌作用最为显著，大于夫西地酸且大于万古霉素。夫西地酸的PAE和PA SME总体最长，大于甲硝唑且大于万古霉素。
