Pharmacodynamic studies of vancomycin, metronidazole and fusidic acid against Clostridium difficile.
BACKGROUND
Pharmacodynamic studies of antibiotics have attracted great interest in recent years. However, studies on the pharmacodynamics of different antibiotics against Clostridium difficile are scarce.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Odenholt
Inga
I
Infectious Diseases Research Unit, Department of Clinical Sciences, Malmö, Sweden. odenholt@med.lu.se <odenholt@med.lu.se>
Walder
Mats
M
Wullt
Marlene
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005672:Fusidic Acid / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014640:Vancomycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D008795:Metronidazole; D005672:Fusidic Acid; D014640:Vancomycin