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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
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Combinations of (lipo)glycopeptides with β-lactams against MRSA: susceptibility insights

Razieh Kebriaei1, Seth A Rice1, Nivedita B Singh1

  • 1Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA.

The Journal of Antimicrobial Chemotherapy
|June 28, 2020
PubMed
Abstract

Insights

Combining lipoglycopeptides (LGPs) with beta-lactams shows significant synergy against resistant Staphylococcus aureus strains, including VISA and hVISA. These combinations offer a promising alternative therapy for challenging MRSA infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Rising prevalence of Methicillin-Resistant Staphylococcus aureus (MRSA) infections necessitates alternative therapies.
  • Emergence of vancomycin intermediate-resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) strains limits treatment options.

Purpose of the Study:

  • To evaluate the synergistic efficacy of (lipo)glycopeptides (LGPs) combined with beta-lactams against various resistant Staphylococcus aureus phenotypes.
  • To assess the activity of specific LGP/beta-lactam combinations against MRSA, hVISA, VISA, and daptomycin non-susceptible (DNS) strains.

Main Methods:

  • Microbroth dilution (MBD) method was used to determine Minimum Inhibitory Concentrations (MICs).
  • Twenty clinical MRSA strains (5 each of MRSA, hVISA, VISA, DNS) were tested against individual agents and combinations.
  • Modified assay conditions were considered for optimal antibiotic activity assessment.

Main Results:

  • Addition of beta-lactams significantly reduced LGP MIC values, with reductions up to 160-fold.
  • Lipoglycopeptides (dalbavancin, oritavancin, telavancin) demonstrated superior activity compared to vancomycin and teicoplanin.
  • Most LGP/beta-lactam combinations exhibited bactericidal activity, outperforming single agents.

Conclusions:

  • LGP and beta-lactam combinations show significant synergistic activity against resistant Staphylococcus aureus.
  • The study highlights the potential of these combinations as effective therapeutic strategies.
  • Further clinical research is warranted to confirm the in vitro findings in patient populations.

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