In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide.
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 oxacillin 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 bacterial concentration around the foreign material, however resistant mutants emerged.
Chuard
C
C
Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
Rohner
P
P
Dunand
V
V
Auckenthaler
R
R
Lew
D P
DP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003030:Coagulase / Q000032:analysis; D004195:Disease Models, Animal; D004357:Drug Synergism; D005547:Foreign Bodies / Q000150:complications; D006168:Guinea Pigs; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D051381:Rats; D012867:Skin; D013045:Species Specificity; D013207:Staphylococcal Skin Infections / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D015645:Tylosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003030:Coagulase; C078575:para-nitrobenzyl-oxime-tylosine; D015645:Tylosin