In vitro and in vivo antibacterial activities of the tricyclic ketolide TE-802 and its analogs.

The in vitro and in vivo antibacterial activities of tricyclic ketolides (TKs: TE-802, TE-806, TE-935, TE-943) have been compared with those of clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM). TKs were active against not only erythromycin (EM)-susceptible organisms; aerobic gram-positive bacteria, some gram-negative bacteria, anaerobic bacteria and Mycoplasma pneumoniae, but also EM-resistant Staphylococcus aureus (inducible macrolide-resistant strains) as well as EM-resistant Streptococcus pneumoniae (efflux-resistant strains). The therapeutic efficacies of TKs against systemic infections and respiratory tract infection (RTI) caused by gram-positive bacteria in mice are superior to those of CAM and AZM.

Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives.

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae.

Recent developments in macrolide antimicrobial research.

Clarithromycin and azithromycin, which are more acid-stable than erythromycin A (EM), have been widely prescribed for the treatment of respiratory tract infections because of their high efficacy and safety. However, these macrolide antibiotics are only weakly active against pathogens with an efflux gene (mef) and are inactive against pathogens with a methyltransferase-inducible gene (erm) and constitutively resistant organisms. To address the drug resistance issue, tremendous efforts have been devoted to the modification of the macrolide structure.