[Experimental models: interactions Synercid and beta-lactam antibiotics]

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Context:

• Experimental endocarditis models are crucial for evaluating antibiotic efficacy against Staphylococcus aureus.
• Synercid (quinupristin/dalfopristin) demonstrated limited efficacy against certain resistant strains.
• Venous toxicity of Synercid restricts dose escalation, necessitating combination therapy.

Purpose:

• To investigate the efficacy of Synercid alone and in combination with beta-lactam antibiotics against Staphylococcus aureus endocarditis in a rat model.
• To assess the potential of antibiotic combinations to overcome Synercid's limitations and prevent resistance development.

Summary:

• Synercid monotherapy achieved rapid cure in rats infected with methicillin-resistant Staphylococcus aureus (MRSA) sensitive to erythromycin but failed against clindamycin, erythromycin, and other macrolides, lincosamides, and streptogramins B resistant (C-MLSB-R) strains.
• In vitro studies revealed additive or synergistic effects of several beta-lactams when combined with Synercid against both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains.
• In vivo, the Synercid + cefepime combination enhanced cefepime activity and prevented the selection of highly resistant strains in rats infected with C-MLSB-R MRSA. The Synercid + cefpirome combination yielded even more potent results. Crucially, Synercid, alone or combined with these cephalosporins, did not select for resistant strains.

Impact:

• Combination therapy with Synercid and specific beta-lactams offers a promising strategy to enhance treatment outcomes for Staphylococcus aureus endocarditis, particularly against resistant strains.
• This approach may help mitigate the emergence of antibiotic resistance, a significant global health concern.
• The findings support the development of novel therapeutic regimens for complex bacterial infections where monotherapy is insufficient.