In vitro antimicrobial findings for fusidic acid tested against contemporary (2008-2009) gram-positive organisms collected in the United States.
ABSTRACT Fusidic acid has a long history of consistent activity against staphylococcal pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid (CEM-102) was susceptibility tested against a surveillance study collection of 12,707 Gram-positive pathogens (2008-2009) from the United States. Reference broth microdilution method results demonstrated the following MIC(50/90) results: S. aureus (.12/.25 μg/mL), coagulase-negative staphylococci (.12/.25 μg/mL), enterococci (4/4 μg/mL), Streptococcus pyogenes (4/8 μg/mL), and viridans group Streptococcus spp. (>8/>8 μg/mL). At a proposed susceptible breakpoint (≤1 μg/mL), fusidic acid inhibited 99.7% of MRSA strains and 99.3% to 99.9% of multidrug-resistant phenotypes of S. aureus. Furthermore, S. aureus strains nonsusceptible to fusidic acid (.35%) generally had detectable resistance mechanisms (fusA, B, C, and E). Reviews of in vitro susceptibility test development confirm the accuracy and intermethod reproducibility of various fusidic acid methods. Fusidic acid is a promising oral therapy for staphylococcal skin and skin structure infections in the United States, where the contemporary S. aureus population remains without significant resistance.
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ABSTRACT: tInhibition of growth of the malaria parasite Plasmodium falciparum by known translation-inhibitoryantibiotics has generated interest in understanding their action on the translation apparatus of thetwo genome containing organelles of the malaria parasite: the mitochondrion and the relic plastid (api-coplast). We report GTPase activity of recombinant EF-G proteins that are targeted to the organelles andfurther use these to test the effect of the EF-G inhibitor fusidic acid (FA) on the factor–ribosome interface.Our results monitoring locking of EF-G·GDP onto surrogate Escherichia coli ribosomes as well as multi-turnover GTP hydrolysis by the factor indicate that FA has a greater effect on apicoplast EF-G comparedto the mitochondrial counterpart. Deletion of a three amino acid (GVG) sequence in the switch I loop thatis conserved in proteins of the mitochondrial EF-G1 family and the Plasmodium mitochondrial factor, butis absent in apicoplast EF-G, demonstrated that this motif contributes to differential inhibition of the twoEF-Gs by FA. Additionally, the drug thiostrepton, that is known to target the apicoplast and proteasome,enhanced retention of only mitochondrial EF-G on ribosomes providing support for the reported effectof the drug on parasite mitochondrial translation.Molecular and Biochemical Parasitology 01/2013; · 2.73 Impact Factor
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ABSTRACT: Protostane triterpenes belong to a group of tetracyclic triterpene that exhibit unique structural characteristics. Their natural distribution is primarily limited to the genus Alisma of the Alismataceae family, but they have also been occasionally found in other plant genera such as Lobelia, Garcinia, and Leucas. To date, there are 59 known protostane structures. Many of them have been reported to possess biological properties such as improving lipotropism, hepatoprotection, anti-viral activity against hepatitis B and HIV-I virus, anti-cancer activity, as well as reversal of multidrug resistance in cancer cells. On the other hand, fusidanes are fungal products characterized by 29-nor protostane structures. They possess antibiotic properties against staphylococci, including the methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid is a representative member which has found clinical applications. This review covers plant sources of the protostanes, their structure elucidation, characteristic structural and spectral properties, as well as biological activities. The fungal sources, structural features, biological activities of fusidanes are also covered in this review. Additionally, the biogenesis of these two types of triterpenes is discussed and a refined pathway is proposed.Molecules 01/2013; 18(4):4054-80. · 2.43 Impact Factor
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ABSTRACT: Clinical development of CEM-102 (fusidic acid) has recently begun in the United States for chronic oral treatment of prosthetic joint infections. To support this development, the in vitro activity of fusidic acid against important Staphylococcus aureus clones and resistance phenotypes was determined. Against 51 such isolates, the modal fusidic acid MIC was 0.12 μg/ml (range, 0.06 to 0.25 μg/ml for 49 isolates). This level of in vitro fusidic acid activity underscores the potential clinical utility of this compound in the United States.Antimicrobial Agents and Chemotherapy 09/2013; 57(9). · 4.57 Impact Factor