Document Detail


Spectrum of activity, mutation rates, synergistic interactions, and the effects of pH and serum proteins for fusidic acid (CEM-102).
MedLine Citation:
PMID:  20159376     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 x, 8 x, and 16 x MIC. Against Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 microg/mL with the greatest potency against Staphylococcus aureus, Corynebacterium spp., and Micrococcus luteus (MIC results, 0.25, < or = 0.12, and < or = 0.5 microg/mL, respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2-8 and 16-32 microg/mL, respectively). Fusidic acid activity against Gram-negative species was more limited (all MIC values, > or = 2 microg/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 x 10(-6) for 4x MIC to 9.8 x 10(-8) for 16 x 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.
Authors:
Douglas J Biedenbach; Paul R Rhomberg; Rodrigo E Mendes; Ronald N Jones
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diagnostic microbiology and infectious disease     Volume:  66     ISSN:  1879-0070     ISO Abbreviation:  Diagn. Microbiol. Infect. Dis.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-05-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8305899     Medline TA:  Diagn Microbiol Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  301-7     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
JMI Laboratories, North Liberty, IA 52317, USA. douglas-biedenbach@jmilabs.com
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MeSH Terms
Descriptor/Qualifier:
Anti-Infective Agents / pharmacology*
Blood Proteins / metabolism*
Culture Media / chemistry
Drug Synergism
Fusidic Acid / pharmacology*
Gram-Negative Bacteria / drug effects,  genetics
Gram-Positive Bacteria / drug effects*,  genetics
Humans
Hydrogen-Ion Concentration
Microbial Sensitivity Tests / methods*
Microbial Viability / drug effects
Mutation
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Blood Proteins; 0/Culture Media; 6990-06-3/Fusidic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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