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Mechanisms of in vitro sensitivity to sulfadiazine silver
Abstract:
Sulfonamide-resistant organisms have been reported as a frequent consequence of the clinical use of sulfadiazine silver. At this burn center, sulfonamide resistance occurred in more than 80% of gram-negative isolates. We tested the requirement for the individual antimicrobial activities of sulfadiazine and silver for the vitro activity of sulfadiazine silver. The sulfadiazine component is not necessary for in vitro sensitivity. In vitro sensitivity to sulfadiazine silver does not consistently predict the presence of therapeutic activity in Pseudomonas aeruginosa-infected rats with burns. We describe an example of a transferable multiple-antibiotic resistance plasmid that contains selectable sulfonamide resistance. The use of sulfadiazine silver can, therefore, lead to the selection of organisms that are resistant not only to sulfonamides but to antibiotics of clinical consequence, and this possible risk must be considered in electing to use the agent.
Insights
Sulfadiazine silver use frequently leads to sulfonamide resistance in bacteria. This resistance can extend to other antibiotics, posing a significant clinical risk that warrants careful consideration.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Sulfadiazine silver is clinically used for burn wound infections.
- High rates of sulfonamide resistance have been observed in gram-negative isolates following its use.
Purpose of the Study:
- To determine the necessity of sulfadiazine and silver components for the in vitro activity of sulfadiazine silver.
- To assess the correlation between in vitro sensitivity and in vivo therapeutic activity.
- To investigate the potential for selecting transferable antibiotic resistance.
Main Methods:
- In vitro antimicrobial sensitivity testing of sulfadiazine silver.
- In vivo efficacy studies in Pseudomonas aeruginosa-infected burn models in rats.
- Plasmid analysis to identify transferable resistance mechanisms.
Main Results:
- Sulfadiazine component is not essential for in vitro sensitivity to sulfadiazine silver.
- In vitro sensitivity does not reliably predict therapeutic effectiveness in vivo.
- A transferable plasmid conferring sulfonamide resistance was identified.
Conclusions:
- Sulfadiazine silver can select for organisms resistant to sulfonamides and potentially other clinically important antibiotics.
- The risk of promoting multidrug resistance necessitates careful evaluation of sulfadiazine silver's clinical application.