Newer antibacterial drugs for a new century.
BACKGROUND
Antibacterial drug discovery and development has slowed considerably in recent years, with novel classes discovered decades ago and regulatory approvals tougher to get. Traditional approaches and the newer genomic mining approaches have not yielded novel classes of antibacterial compounds. Instead, improved analogues of existing classes of antibacterial drugs have been developed by improving potency, minimizing resistance and alleviating toxicity.


METHODS
This article is a comprehensive review of newer classes of antibacterial drugs introduced or approved after year 2000.


RESULTS
It describes their mechanisms of action/resistance, improved analogues, spectrum of activity and clinical trials. It also discusses new compounds in development with novel mechanisms of action, as well as novel unexploited bacterial targets and strategies that may pave the way for combating drug resistance and emerging pathogens in the twenty-first century.


CONCLUSIONS
The outlook of antibacterial drug discovery, though challenging, may not be insurmountable in the years ahead, with legislation on incentives and funding introduced for developing an antimicrobial discovery program and efforts to conserve antibacterial drug use.
Devasahayam
Gina
G
University of Virginia, Department of Medicine, Room 2146 MR4 Bldg, 409 Lane Rd, Charlottesville, VA 22908, USA. psh2n@virginia.edu
Scheld
William M
WM
Hoffman
Paul S
PS
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000187:drug effects; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006020:Glycopeptides / Q000494:pharmacology / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D015507:Drugs, Investigational; D006020:Glycopeptides; D018942:Macrolides; D023303:Oxazolidinones; D000078304:Tigecycline; D008911:Minocycline