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Infection in the intensive care unit: beta-lactamase-mediated resistance among Enterobacteriaceae and optimal

G L Drusano1

  • 1Department of Medicine, Albany Medical Center, New York 12202-3479, USA.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|August 26, 1998
PubMed

Insights

Beta-lactamase resistance in Enterobacteriaceae is rising, leading to multiresistance and higher patient mortality. Optimizing antimicrobial dosing based on pharmacodynamics is crucial for effective treatment and preventing further resistance.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Class I beta-lactamase-mediated resistance in Enterobacteriaceae is a growing clinical concern.
  • This resistance is often linked to prior use of third-generation cephalosporins and is associated with increased patient mortality.
  • The spread of extended-spectrum beta-lactamases further exacerbates antimicrobial resistance.

Purpose of the Study:

  • To review the pharmacodynamic principles governing antimicrobial activity and resistance suppression.
  • To highlight the importance of tailoring antimicrobial dosage regimens to optimize clinical outcomes.
  • To emphasize strategies for combating the rise of beta-lactamase-mediated resistance.

Main Methods:

  • Review of existing literature on beta-lactamase resistance and antimicrobial pharmacodynamics.
  • Analysis of key pharmacokinetic/pharmacodynamic (PK/PD) indices, including time above minimum inhibitory concentration (MIC) and area under the concentration-time curve (AUC):MIC ratio.
  • Discussion of the role of peak concentration:MIC ratio in suppressing resistance.

Main Results:

  • For beta-lactams, antibacterial activity is primarily determined by the time plasma concentration exceeds the MIC.
  • For concentration-dependent drugs like aminoglycosides and fluoroquinolones, the AUC:MIC ratio is critical, especially at lower peak:MIC values.
  • High peak:MIC ratios (≥10:1) are linked to improved outcomes and resistance suppression.

Conclusions:

  • Antimicrobial resistance, particularly beta-lactamase-mediated resistance, poses a significant threat.
  • Understanding and applying pharmacodynamic principles in dosage regimen design is essential.
  • Optimizing PK/PD targets can maximize therapeutic efficacy and minimize the emergence of bacterial resistance.

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