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

P Moreillon1

  • 1CHUV Lausanne.

Presse Medicale (Paris, France : 1983)
|October 18, 2001
PubMed
Abstract

Insights

Synercid effectively treated experimental endocarditis in rats caused by certain Staphylococcus aureus strains. However, combinations with beta-lactam antibiotics like cefepime and cefpirome showed improved efficacy and prevented resistance development.

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.

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