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Synergism and antagonism.

G M Eliopoulos1

  • 1Harvard Medical School, Massachusetts.

Infectious Disease Clinics of North America
|September 1, 1989
PubMed
Summary

Antimicrobial drug combinations aim for synergistic effects, but testing methods are often time-consuming. While some combinations show promise, clinical evidence for synergism

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Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Antimicrobial combinations are used to achieve synergistic effects, enhancing inhibitory or bactericidal activity against pathogens.
  • Existing methods for testing antimicrobial synergism are often time-consuming and lack standardization.
  • Synergistic interactions can occur through various mechanisms, including enhanced drug uptake and targeting sequential metabolic pathways.

Purpose of the Study:

  • To review the rationale and methods for assessing synergistic antimicrobial activity.
  • To highlight examples of successful and potentially synergistic antimicrobial combinations.
  • To discuss the challenges and clinical significance of antimicrobial synergism.

Main Methods:

  • Review of literature on antimicrobial combination therapy and synergy testing.
  • Analysis of documented synergistic interactions between different classes of antimicrobial agents.
  • Discussion of theoretical frameworks for predicting synergistic effects.

Main Results:

  • Bactericidal synergism with cell wall-active agents and aminoglycosides is linked to increased aminoglycoside uptake.
  • Combinations of beta-lactamase inhibitors with susceptible beta-lactams demonstrate synergistic activity against common pathogens.
  • The combination of trimethoprim-sulfamethoxazole exemplifies synergy by targeting sequential steps in a metabolic pathway.

Conclusions:

  • Antimicrobial combinations offer potential for enhanced efficacy, particularly when targeting sequential metabolic pathways or improving drug uptake.
  • Despite documented successes, the clinical importance of synergism is established in limited circumstances.
  • Further research is needed to develop standardized, efficient methods for synergy testing and to broaden the clinical application of synergistic antimicrobial combinations.

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