Pharmacokinetic and Pharmacodynamic Issues in the Treatment of Bacterial Infectious Diseases

  title={Pharmacokinetic and Pharmacodynamic Issues in the Treatment of Bacterial Infectious Diseases},
  author={Peggy S. McKinnon and Susan L. Davis},
  journal={European Journal of Clinical Microbiology and Infectious Diseases},
  • P. McKinnon, S. Davis
  • Published 10 March 2004
  • Medicine, Biology
  • European Journal of Clinical Microbiology and Infectious Diseases
This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection. Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic. For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal… 

Pharmacologic Considerations in Antimicrobial Therapy, with Emphasis on Pharmacokinetics and Pharmacodynamics: Reviews for the Practicing Clinician

  • P. McKinnonV. Yu
  • Medicine, Biology
    European Journal of Clinical Microbiology and Infectious Diseases
  • 2004
This series of four review articles by authorities in the field is designed to address the many factors a clinician must consider when selecting an antimicrobial agent and appropriate dosing regimen for the treatment of various infections.

What should be considered in the treatment of bacterial infections by multi-drug therapies: a mathematical perspective?

Pharmacodynamic Evaluation: Infectious Diseases

The present chapter provides a comprehensive overview of different models citing their advantages and limitations, along with simulations for optimizing treatment regimens and the pathophysiological conditions leading to treatment failures and strategies to overcome them.

Pharmacology of Drug Resistance

This chapter reviews the available preclinical and clinical data on antimicrobial PK–PD relationships, and assesses how they can be used to effectively treat infections and epidemiologically conserve active antimicrobials.

Integration of pharmacokinetic/pharmacodynamic modeling and simulation in the development of new anti-infective agents – minimum inhibitory concentration versus time-kill curves

An overview of the present PK/PD approaches used in anti-infective therapy is provided and their role in improving drug therapy is discussed.

Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives.

It appears important to evaluate the intracellular activity of antibiotics in appropriate models, despite the fact that all antibiotics reach intrACEllular concentrations that are at least equal to, and more often higher than, the extracellular concentrations.

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

The pharmacokinetic and pharmacodynamics characteristics of these agents are considered to optimize treatment regimens for CRE infections and this review will focus on the PK-PD challenges of the current treatment options.

Optimizing Antimicrobial Chemotherapy in the ICU—A Review

The author reviews the various strategies that can be employed to improve the quality of antibiotic prescribing in order to both improve patient outcome and reduce the selection of resistant strains.

Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens.

  • M. ScheetzK. HurtG. NoskinC. Oliphant
  • Medicine, Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2006
Various mechanisms account for resistance of bacteria to antibiotics, and the appropriate use of pharmacokinetics and pharmacodynamics can guide antibiotic therapy and enhance the likelihood of success.



Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model.

This study is the first to successfully minimize the interdependence between pharmacokinetic parameters and determine that the time that serum levels exceeded the minimum inhibitory concentration was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides.

Pharmacodynamic Evaluation of Factors Associated with the Development of Bacterial Resistance in Acutely Ill Patients during Therapy

The selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUC0–24/MIC ratio of less than 100.

Potential impact of quantitative susceptibility tests on the design of aminoglycoside dosing regimens.

Simulations were performed to examine the consequences of designing aminoglycoside regimens considering both disease effects on excretion and bacterial susceptibility, and argue for a wider range of dosage requirements than observed with regimens that maintain desired peaks and troughs.

Dosing of Aminoglycosides To Rapidly Attain Pharmacodynamic Goals and Hasten Therapeutic Response by Using Individualized Pharmacokinetic Monitoring of Patients with Pneumonia Caused by Gram-Negative Organisms

Individualized pharmacokinetic monitoring coupled with MIC data should determine subsequent dosing regimens to minimize the potential for toxicity and maximize the probability of clinical response.

Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials.

Exposure to levofloxacin was significantly associated with successful clinical and microbiological outcomes and occurrence of adverse events in infected patients and could be used to determine optimal treatment dose in clinical trials in a shorter time frame with fewer patients.

Clinical Pharmacokinetics of Newer Antibacterial Agents in Liver Disease

When renal function is impaired and there is an increased volume of distribution due to ascites, the elimination half-life of most antibiotics is markedly prolonged, resulting in potential side effects due to drug accumulation, and dosage adjustment applies to all drugs.

Pharmacodynamics and pharmacokinetics of antibiotics with special reference to the fluoroquinolones.

  • M. Dudley
  • Biology, Medicine
    The American journal of medicine
  • 1991

Antimicrobial therapy in the elderly.

Pharmacodynamics of cefepime in patients with Gram-negative infections.

In vitro data support in vitro data that suggest bactericidal activity of beta-lactams is optimized at concentrations approximately 4 x MIC, and should be validated by large prospective clinical trials.

Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients

The rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities are provided and shown to be more precise than current guidelines.