1. Clin Infect Dis. 2011 Jun;52 Suppl 7:S493-503.

Activity of fusidic acid against extracellular and intracellular Staphylococcus
aureus: influence of pH and comparison with linezolid and clindamycin.

Lemaire S, Van Bambeke F, Pierard D, Appelbaum PC, Tulkens PM.

Cellular and Molecular Pharmacology, Louvain Drug Research Institute, Université 
Catholique de Louvain, Brussels, Belgium.

BACKGROUND: Emergence of multidrug-resistant Staphylococcus aureus has triggered 
a reassessment of fusidic acid (CEM-102, sodium fusidate).
METHODS: Fusidic acid was examined for (1) activity against recent
methicillin-resistant S. aureus (MRSA) isolates; (2) modulation of activity by
acidic pH; and (3) accumulation by phagocytic cells and intracellular activity
against methicillin-susceptible S. aureus (MSSA) and MRSA.
RESULTS: About 96% of strains (N = 94) were susceptible (European Committee on
Antimicrobial Susceptibility Testing breakpoint [≤ 1 mg/L]). Activity was
enhanced at pH 5.5 (6 dilutions decrease for minimum inhibitory concentration) in
parallel with an increase of drug bacterial accumulation (opposite effects for
clindamycin; linezolid remained unaffected). Fusidic acid accumulated in THP-1
cells (about 5.5 fold), with further accumulation at pH 5.5 vs pH 7.4. The
intracellular activity of Fusidic acid was similar to that of clindamycin and
linezolid (maximal relative activity, 0.4-0.6 log(10) colony-forming unit
decrease). No cross-resistance to vancomycin or daptomycin was observed.
CONCLUSIONS: Fusidic acid is active against S. aureus in broth as well as
intracellularly, with no cross-resistance to other antibiotics.

PMID: 21546626  [PubMed - in process]