Fusidic Acid - Resistance

Resistance

Because the drug is not licensed for use in the U.S., there are no Clinical and Laboratory Standards Institute standard definitions of fusidic acid resistance. However, in vitro susceptibility studies of U.S. strains of several bacterial species such as S. aureus, including MRSA and coagulase negative Staphylococcus, indicate potent activity against these pathogens

In the UK and Australia, susceptibility is defined as a minimum inhibitory concentration (MIC) of 0.25 mg/l or 0.5 mg/l or less. Resistance is defined as an MIC of 2 mg/l or more. In laboratories using disc diffusion methods, susceptibility for a 2.5 µg disc is defined as a zone of 22 mm or more, and resistance is defined as a zone of 17 mm or less; intermediate values are defined as intermediate resistance. These susceptibility criteria are based on lower dosing regimens used outside of the U.S. Clinical trials in the U.S. incorporate a different dosing regimen that results in higher blood levels. Therefore, the U.S. dosing regimen may warrant different susceptibility criteria.

Mechanisms of resistance have been extensively studied only in Staphylococcus aureus. The most important mechanism is the development of point mutations in fusA, the chromosomal gene that codes for EF-G. The mutation alters EF-G so that fusidic acid is no longer able to bind to it. Resistance is readily acquired when fusidic acid is used alone and commonly develops during the course of treatment. As with most other antibiotics, resistance to fusidic acid arises less frequently when used in combination with other drugs. For this reason, fusidic acid should not be used on its own to treat serious Staph. aureus infections. However, at least in Canadian hospitals, data collected between 1999-2005 showed rather low rate of resistance of MSSA and MRSA to fusidic acid, and mupirocin was found to be the more problematic topical antibiotic for the aforementioned conditions.

Some bacteria also mediate resistance via the fusB gene, which is carried on a plasmid; the mechanism by which fusB causes resistance is unknown.