Production Of Novel Agents Research Articles

Shooting At the DARC: Potential Issues with Species-Specific Antimalarials

Scientific drug design enables the production of novel agents that may be specific for individual malaria species, particularly by targeting their methods of cellular entry. Though there are practical and theoretical barriers to introducing novel agents into clinical practice, there may also be theoretical benefits to encourage further investigation of such agents, including a reduction in the rate of development of falciparum resistance. This paper discusses the potential risks and benefits such agents using the example of CCR5 blockers, drugs which are already in use for HIV treatment, but may be able to block DARC, the site of Plasmodium vivax into the human red blood cell.

Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens

Guided antibiotic adjustment for the treatment of multidrug-resistant, gram-negative pathogens is explored. Multidrug-resistant pathogens are being isolated with increasing frequency, while the production of novel agents to circumvent resistance has slowed to a near halt. Hence, antimicrobial adjustment based on drug pharmacokinetic and pharmacodynamic properties has moved to the forefront of treatment. Pharmacodynamic principles for major classes of antimicrobials are reviewed, and the use of susceptibility reports to optimize pharmacodynamics to treat gram-negative infections is described. The need for the application of antimicrobial pharmacodynamics continues to grow as resistance to the agents becomes more common. Susceptibility reports, including antibiograms, and their limitations are briefly discussed. The resistance profiles of the beta-lactams (including carbapenems), aminoglycosides, fluoroquinolones, tetracyclines and glycylcyclines, and the polymyxins are reviewed, and the pharmacodynamic optimization of these profiles is explored. Various mechanisms account for resistance of bacteria to antibiotics. The appropriate use of pharmacokinetics and pharmacodynamics can guide antibiotic therapy and enhance the likelihood of success.