In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide
Chuard, C. ; Rohner, P. ; Dunand, V. ; Auckenthaler, R. ; Lew, D.P.
In: Journal of Antimicrobial Chemotherapy, 1992, vol. 30, no. 3, p. 327-337
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- During recent years, a resurgence of interest in the macrolides had led to the discovery of new derivatives of erythromycin with improved antibacterial activity and pharmacokinetic properties. In this study the in-vitro and in-vivo antistaphylococcal activity of S-5556, a 16-membered macrolide, was evaluated. In vitro, S-5556 was slightly less active than erythromycin against methicillin-susceptible Staphylococcus aureus. In contrast, it had superior activity for methicillin-resistant S. aureus (MRSA); several of these strains with inducible resistance to the macrolides-lincosamides-streptogramins group were susceptible to S-5556 whereas erythromycin was inactive. The combination of S-5556 with oxatillin was synergic for most MRSA strains tested. In vivo, a single prophylactic dose of S-5556 prevented 75%-100% of the cases of acute staphylococcal subcutaneous foreign body infection in a guinea pig-model. In a rat-model of chronic implant infection due to a methicillin- and erythromycin-resistant S. aureus strain, S-5556 significantly decreased the bacteria] concentration around the foreign material, however resistant mutants emerged