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Interactions of rifampin and trimethoprim in vitro
Abstract:
Combination of rifampin and trimethoprim (TMP) has been suggested as a means of preventing the emergence of bacterial resistance to the individual agents and of achieving synergistic antimicrobial activity. By means of standard techniques of antimicrobial susceptibility testing, combinations of rifampin and TMP were tested against clinical isolates of a variety of aerobic bacteria. Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration (MIC) of the more active agent in the combination. Antagonism was defined as a fourfold or greater increase in the MIC of the more active agent. No change or, at most, a twofold change was considered to represent indifference. Combinations of rifampin and TMP in ratios of 7:1, 7:2, and 1:1 demonstrated synergistic activity against 12%, 13%, and 28% of 440 isolates, respectively. Antagonism was observed in 10%, 9%, and 8% of strains tested against the above ratios. Killing curves determined with selected organisms failed to demonstrate synergistic antibacterial activity. Combinations of rifampin and TMP failed to prevent the emergence of resistance to both drugs when selected strains of various bacteria were exposed to serial, subinhibitory concentrations. Thus, synergism of rifampin and TMP was observed in only a minority of strains tested, and combination of the two agents failed to prevent the emergence of drug resistance in vitro.
Insights
The combination of rifampin and trimethoprim (TMP) showed limited synergistic activity against aerobic bacteria. This combination also failed to prevent the emergence of drug resistance in vitro.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Bacterial resistance to antibiotics is a growing global health concern.
- Combination therapy is explored to enhance efficacy and combat resistance.
- Rifampin and trimethoprim (TMP) are antibiotics with distinct mechanisms of action.
Purpose of the Study:
- To evaluate the synergistic and antagonistic effects of rifampin-TMP combinations against clinical isolates of aerobic bacteria.
- To determine if rifampin-TMP combinations can prevent the emergence of bacterial resistance in vitro.
Main Methods:
- Antimicrobial susceptibility testing using standard techniques.
- Determination of minimal inhibitory concentrations (MICs) for rifampin and TMP alone and in combination.
- Evaluation of synergistic, antagonistic, and indifferent interactions based on MIC changes.
- Assessment of resistance emergence using serial, subinhibitory concentrations and killing curves.
Main Results:
- Synergistic activity was observed in a minority of bacterial isolates (12-28% depending on the ratio).
- Antagonistic effects were noted in 8-10% of tested strains.
- Killing curve analyses did not demonstrate synergistic antibacterial activity.
- The rifampin-TMP combination failed to prevent the emergence of resistance to either drug in vitro.
Conclusions:
- Rifampin and TMP combinations exhibit limited synergistic potential against a broad range of aerobic bacteria.
- The combination therapy does not appear to be effective in preventing the in vitro development of antibiotic resistance.
- Further research may be needed to identify specific bacterial species or conditions where this combination could be beneficial.