Abstract
Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n=23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.
Highlights
The emergence and dissemination of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) lineages in the community [1] and hospital settings [2] pose a significant clin-ical problem due to the lack of response to first-line empirical antimicrobials (-lactams)
MRSA bacteraemia isolates that were only resistant to fusidic acid but were otherwise susceptible were not detected in 2002 but steadily increased in number to reach to 2.4% of MRSA bacteraemia isolates by 2012 and 3.9% in 2013 (Fig. 1B)
The heaviest use of fusidic acid occurred in the community, where diverse MRSA that were only resistant to fusidic acid were emerging rapidly, with both known and novel staphylococcal cassette chromosome (SCC)
Summary
The emergence and dissemination of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) lineages in the community [1] and hospital settings [2] pose a significant clin-ical problem due to the lack of response to first-line empirical antimicrobials (-lactams). The emergence and dissemination of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) lineages in the community [1] and hospital settings [2] pose a significant clin-. M.J. Ellington et al / International Journal of Antimicrobial Agents 45 (2015) 477–484 resistance among S. aureus in 2007–2008 in the USA was only 0.3% compared with 7% in Canada and Australia and 11.8% in the UK [4,5]. Fusidic acid inhibits protein synthesis by preventing the turnover of elongation factor G (EF-G) from the ribosome, and resistance usually emerges through point mutation(s) in the chromosomal gene encoding EF-G (fusA), which typically confers high-level resistance [6]. Lower-level resistance can arise via the acquisition of factors that protect the translational machinery (encoded by plasmid-borne genes fusB or fusC) [5,7]
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