Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3348104 | Diagnostic Microbiology and Infectious Disease | 2010 | 7 Pages |
Fusidic acid (CEM-102) is a steroidal antimicrobial agent with focused Gram-positive activity that acts by preventing bacterial protein synthesis via interacting with elongation factor G. A collection of 114 wild-type isolates (>80 species) was used to define the contemporary limits of fusidic acid spectrum against Gram-positive and Gram-negative species. Reference broth microdilution and anaerobic agar dilution methods were performed. Modifications of standardized test methods included adding 10% human serum and adjusting the medium pH to 5, 6, and 8. Synergy was assessed by the checkerboard method and time-kill studies. Mutational rates to resistance were determined at 4×, 8×, and 16× MIC. Against Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 μg/mL with the greatest potency against Staphylococcus aureus, Corynebacterium spp., and Micrococcus luteus (MIC results, 0.25, ≤0.12, and ≤0.5 μg/mL, respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2–8 and 16–32 μg/mL, respectively). Fusidic acid activity against Gram-negative species was more limited (all MIC values, ≥2 μg/mL) except for Empedobacter brevis, Moraxella catarrhalis and Neisseria meningitidis. A 4-fold increase in fusidic acid MIC results was observed when 10% serum was added to the broth. Decreasing medium pH to 5.0 to 6.0 negated the protein binding effects. Among the 8 antimicrobial combinations tested, gentamicin and rifampin enhanced the activity when combined with fusidic acid (no antagonism). Fusidic acid in vitro activity was most improved when combined with rifampin. Single-step mutational rates ranged from 1.2 × 10−6 for 4× MIC to 9.8 × 10−8 for 16× MIC. In conclusion, these in vitro results for fusidic acid tested against contemporary strains confirm a persisting antimicrobial spectrum, especially against staphylococci and some other Gram-positive species.