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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
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Aminoglycoside/beta-lactam combinations in clinical practice.

Leonard Leibovici1, Mical Paul

  • 1Department of Medicine E, Beilinson Campus, Petah-Tiqva 49100, Israel. leibovic@post.tau.ac.il

The Journal of Antimicrobial Chemotherapy
|September 25, 2007
PubMed
Summary

Adding aminoglycosides to broad-spectrum beta-lactams offers no advantage for bacteraemic patients. Combination therapy does not improve outcomes and increases side effects, particularly where broad-spectrum agents are common.

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Area of Science:

  • Infectious Diseases
  • Clinical Pharmacology
  • Microbiology

Background:

  • Randomized controlled trials (RCTs) have not demonstrated a benefit of adding aminoglycosides to broad-spectrum beta-lactams.
  • Aminoglycoside addition to beta-lactams is a common treatment strategy for bacterial infections.
  • Concerns exist regarding the added toxicity and potential for resistance development with combination therapy.

Purpose of the Study:

  • To evaluate the efficacy of narrow-spectrum beta-lactams compared to combination therapy (beta-lactam plus aminoglycoside) in bacteraemic patients.
  • To assess whether adding aminoglycosides to broad-spectrum beta-lactams improves patient outcomes.
  • To investigate the role of combination therapy in antimicrobial resistance.

Main Methods:

  • Analysis of a large series of bacteraemic patients from Denmark.
  • Comparison of treatment outcomes between patients receiving narrow-spectrum beta-lactams and those receiving beta-lactam/aminoglycoside combinations.
  • Review of existing randomized controlled trial data.

Main Results:

  • Comparable outcomes were observed between patients treated with narrow-spectrum beta-lactams and those receiving beta-lactam/aminoglycoside combinations.
  • In settings with high use of broad-spectrum beta-lactams, aminoglycoside addition did not enhance efficacy and increased side effects.
  • Evidence supporting the efficacy of combination treatment and its role in resistance mitigation is lacking in certain contexts.

Conclusions:

  • The addition of aminoglycosides to broad-spectrum beta-lactams is not beneficial for bacteraemic patients and may increase toxicity.
  • In regions where narrow-spectrum beta-lactams are viable and broad-spectrum agents are used judiciously, combination therapy offers no proven advantage.
  • Further evidence is needed to support the use of combination therapy for antimicrobial resistance containment.