Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens

Purpose. Guided antibiotic adjustment for the treatment of multidrug-resistant, gram-negative pathogens is explored. Summary. 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 β-lactams (including carbapenems), aminoglycosides, fluoroquinolones, tetracyclines and glycylcyclines, and the polymyxins are reviewed, and the pharmacodynamic optimization of these profiles is explored. Conclusion. 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.