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Published on: May 2, 2018
Trimethoprim-resistant bacteria: cross-resistance patterns
Abstract:
One hundred and eighty one strains (clinically isolated) of trimethoprim-resistant bacteria were tested for sensitivity to proguanil, pyrimethamine, methotrexate and methasquin. All these agents had less intrinsic antibacterial activity than trimethoprim, and there was marked cross-resistance between trimethoprim on the one hand and pyrimethamine and methasquin on the other. Methotrexate was of very low activity against Gram-negative bacilli, but was highly inhibitory for streptococci. Proguanil had approximately the same activity for all the organisms tested, and appears not to act as an anti-folate agent.
Insights
Trimethoprim-resistant bacteria showed cross-resistance to pyrimethamine and methasquin. Proguanil exhibited consistent activity, suggesting it may not be an anti-folate agent.
Area of Science:
- Microbiology
- Pharmacology
- Antimicrobial Resistance
Background:
- Trimethoprim is a widely used antibiotic.
- Emerging resistance to trimethoprim necessitates the investigation of alternative antimicrobial agents.
- Understanding cross-resistance patterns is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate the sensitivity of trimethoprim-resistant bacteria to other dihydrofolate reductase inhibitors.
- To determine the antibacterial activity spectrum of proguanil, pyrimethamine, methotrexate, and methasquin against resistant strains.
- To investigate potential cross-resistance between trimethoprim and these agents.
Main Methods:
- Testing 181 clinically isolated trimethoprim-resistant bacterial strains.
- Assessing bacterial sensitivity to proguanil, pyrimethamine, methotrexate, and methasquin.
- Comparing the intrinsic antibacterial activity of tested agents with trimethoprim.
Main Results:
- All tested agents demonstrated lower intrinsic antibacterial activity than trimethoprim.
- Significant cross-resistance was observed between trimethoprim and pyrimethamine/methasquin.
- Methotrexate showed minimal activity against Gram-negative bacilli but was inhibitory to streptococci.
- Proguanil displayed consistent activity across all tested organisms and may not function as an anti-folate agent.
Conclusions:
- Trimethoprim resistance is associated with cross-resistance to pyrimethamine and methasquin.
- Proguanil's consistent activity suggests a different mechanism of action, distinct from folate antagonism.
- Further research into proguanil's efficacy and mechanism is warranted for clinical applications.
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