In Vitro Antimicrobial Findings for Fusidic Acid Tested Against Contemporary (2008–2009) Gram-Positive Organisms Collected in the United States

JMI Laboratories, North Liberty, Iowa, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 06/2011; 52 Suppl 7(suppl 7):S477-86. DOI: 10.1093/cid/cir163
Source: PubMed


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 MIC50/90 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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    • "FA inhibits protein synthesis in bacteria and acts against many pathogens including Staphylococcus aureus, gram-positive anaerobic bacteria, Neisseria spp., and Bordetella pertussis [19]. It is used clinically as a topical application or systemic treatment, particularly in case of bone and joint infections or skin and soft tissue infections [19]. EF-G has five structural domains (DI–DV). "
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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.
    Full-text · Article · Jan 2013 · Molecular and Biochemical Parasitology
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    • "Some authors have proposed that isolates with MIC ≤ 1.0 μg/mL are susceptible (S) and those with MIC ≥ 2.0 μg/mL are resistant (R) while others have proposed an MIC ≤ 0.5 μg/mL as the susceptible breakpoint [10] [12]. Most recently Jones et al. compared broth dilution, Etest MIC, and disk diffusion, and they proposed an MIC ≥ 4.0 μg/mL as the interpretive break point for resistance and ≤1.0 μg/mL for susceptibility [13]. For disk diffusion testing, EUCAST has set the 10 μg fusidic acid zone size for resistance at 24 mm, while Skov et al. recently proposed ≤18 mm for resistance and ≥21 mm as susceptible interpretive break points [10] [12]. "
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    ABSTRACT: Fusidic acid is a common therapy for staphylococcal infections in Saudi Arabia, but reports have suggested high rates of resistance among clinical isolates. Susceptibility testing of S. aureus to fusidic acid is further complicated by the lack of consensus on mean inhibitory concentrations (MIC) and disk diffusion cutoffs to determine resistance. The purpose of this study was to determine the correlation between disk diffusion and Etest determined MIC susceptibility results in clinical isolates of S. aureus from a large academic hospital in Riyadh, Saudi Arabia. Our data demonstrate excellent correlation between Etest determined MIC and disk diffusion susceptibility data, using either previously proposed zone sizes of ≥21 mm as susceptible and ≤18 mm as resistant or the EUCAST recommended zone size of ≤24 mm for resistance, in an area with relatively high rates of fusidic acid resistance.
    Full-text · Article · Jul 2012 · International Journal of Microbiology
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    • "Fusidic acid offers a potentially valuable systemic treatment option for ABSSSI, including for medically complex patients. It has a broad gram-positive antimicrobial spectrum [10, 21]; oral bioavailability [22]; a long safety history, including in patients receiving prolonged courses of treatment [23, 24] ; and a mechanism of action that is not shared with any other available antibacterial agent [9]. As shown inTable 3, there are some imbalances between the 2 treatment groups. "
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    ABSTRACT: Fusidic acid (CEM-102), an orally bioavailable fusidane antibiotic with a unique mode of action, is under development for treatment of acute gram-positive bacterial skin and skin structure infections, including those caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus and streptococci. A phase 2, adaptive design, randomized, double-blind, multiple-center study of 198 adult patients with cellulitis or wound infections was conducted to evaluate an oral CEM-102 loading-dose regimen (1500 mg twice per day on day 1 followed by 600 mg twice per day) compared with oral linezolid (600 mg twice per day) administered for 10–14 days. The CEM-102 loading-dose regimen demonstrated efficacy, safety, and tolerability that was comparable to linezolid for the treatment of acute gram-positive bacterial skin and skin structure infections. Clinical Trials registration. NCT00948142.
    Preview · Article · Jun 2011 · Clinical Infectious Diseases
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