Advances in the research and development of chemotherapeutic agents for respiratory tract bacterial infections.
The activity of existing antibiotics is diminishing due to the increasing number of resistant strains and by the increase of infections with naturally resistant microorganisms. New agents are urgently needed to meet this challenge and the molecular strategies adopted for the discovery of these compounds must focus on minimizing the emergence of future resistance to them. Novel compounds can be grouped on the basis of their mechanism of action: inhibitors of nucleic acid synthesis (fluoroquinolones), inhibitors of protein synthesis (ketolides, oxazolidinones, streptogramins, and glycylcyclines), inhibitors of peptidoglycan synthesis (beta-lactams and glycopeptides), and agents interfering with membrane function (cationic peptides, and lipopeptides). Regarding the agents that are already in the research and development pipeline, only the oxazolidinones, the cationic peptides and the lipopeptide antibiotics can be truly considered as structurally novel inhibitors because the other agents are analogues of existing compounds that have been in use for many years.
Cazzola
M
M
A. Cardarelli Hospital, Department of Respiratory Medicine, Naples, Italy. mcazzola@qubisoft.it
Blasi
F
F
Centanni
S
S
Donner
C F
CF
Allegra
L
L
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D004352:Drug Resistance, Microbial; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010457:Peptidoglycan; D012106:Research / Q000639:trends; D012141:Respiratory Tract Infections / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D019384:Nucleic Acid Synthesis Inhibitors; D010457:Peptidoglycan