Recent progress in novel macrolides, quinolones, and 2-pyridones to overcome bacterial resistance

Macrolides, such as clarithromycin and azithromycin, having good activity a gainst pathogens such as Legionella, Chlamydia, Campylobacter spp, Branhame lla spp, Pasteurella multocida and streptococci, have gained wide acceptanc e for the treatment of both upper and lower respiratory tracts, as well as cutaneous infections. Emergence of bacterial resistance, particularly in gr am-positive bacteria, has been observed. Macrolide-resistant Streptococcus pneumoniae and S. pyogenes are found in France and many other countries, re sulting in failure of therapy for pneumonia, pharyngitis, and skin infectio n. RU 004, HMR 3647, and TE 802 were reported to be active against these re sistant strains. Research at Abbott produced several macrolide derivatives in the anhydrolide, tricyclic and tetracyclic ketolides as well as 6-O-alky l ketolides series having potent activity against macrolide resistant S. py ogenes and S. pneumoniae. Research on streptogramins to overcome bacterial resistance in gram-positive bacteria has produced interesting compounds. An other class of antibacterial agent called quinolones is useful for the trea tment of bacterial infections of respiratory tract, urinary tract, skin and soft tissues, as well as sexually transmitted diseases. Ciprofloxacin, the market leader, however, has low potency against anaerobes. Bacterial resis tance( such as Pseudomonas aeruginosa and methicillin- resistant Staphyloco ccus aureus) to ciprofloxacin is increasing rapidly. Many quinolone compoun ds are being synthesized to address these drawbacks. The new quinolones cur rently under development are characterized by enhanced activities against s treptococci, staphylococci, enterococci, and anaerobes. This presentation r eviews the current research in the identification of agents to overcome the macrolide and quinolone resistance. (C) 1999 John Wiley & Sons, Inc.