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[Experimental models: interaction of Synercid with other anti-Gram positive agents]
1INSERM EMI 9933, Paris.
Experimental Data:
In case of resistance to quinupristin, the bacteriostatic synergism is preserved but the in vivo bactericidal effect of Synercid declines. On the other hand, no selection of resistant mutants has been observed. In case of isolated resistance to dafopristin, there is no reduction in the bactericidal effect of Synercid; there is however a possible risk of selecting resistant mutants. To become resistant to Synercid, S. aureus strains have to become resistant to both quinupristin and dafopristin, a highly unlikely situation. POTENTIAL COMBINATIONS: Among the combinations of Synercid with other antibiotics, the combination with vancomycin would have particular interest for clinical applications, increasing bactericidal activity. This would be the case for severe S. aureus infections with a large inoculum and even more so for meti-R resistant strains with a C-MLSB phenotype. Combination with rifampicin would be another possibility, but only for strains not resistant to quinupristin.
Insights
Synercid retains bacteriostatic effects against quinupristin-resistant bacteria but loses in vivo killing power. Resistance to Synercid requires dual resistance, a rare event, with vancomycin showing promise for enhanced bactericidal activity.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Synercid, a combination antibiotic, exhibits bacteriostatic and bactericidal properties.
- Understanding resistance mechanisms to Synercid is crucial for effective treatment of Staphylococcus aureus infections.
Purpose of the Study:
- To investigate the effects of resistance to individual components of Synercid (quinupristin and dalfopristin) on its overall efficacy.
- To explore potential synergistic antibiotic combinations with Synercid for treating severe S. aureus infections.
Main Methods:
- Evaluating the in vitro and in vivo effects of Synercid in the presence of resistance to quinupristin or dalfopristin.
- Assessing the potential of combining Synercid with vancomycin or rifampicin.
Main Results:
- Resistance to quinupristin preserves bacteriostatic synergism but reduces in vivo bactericidal activity of Synercid without selecting resistant mutants.
- Isolated resistance to dalfopristin does not diminish Synercid's bactericidal effect but may risk selecting resistant mutants.
- Synercid resistance in S. aureus requires dual resistance to both components, a highly improbable scenario.
- Combining Synercid with vancomycin enhances bactericidal activity, particularly for severe infections and methicillin-resistant S. aureus (MRSA) with C-MLSB phenotype.
- Combining Synercid with rifampicin is viable only for strains not resistant to quinupristin.
Conclusions:
- Synercid maintains some efficacy even with partial resistance, and dual resistance is unlikely.
- Combination therapy, especially with vancomycin, holds significant clinical potential for enhancing Synercid's bactericidal action against challenging S. aureus infections.