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Updated: Mar 1, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus
Fumiaki Tabuchi1, Yasuhiko Matsumoto2, Masaki Ishii2,3
1Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
D-cycloserine enhances vancomycin effectiveness against vancomycin-resistant Staphylococcus aureus (VRSA). Combined treatment showed therapeutic effects in silkworm infection models, unlike single-drug treatments.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Vancomycin is a critical antibiotic for treating methicillin-resistant Staphylococcus aureus (MRSA) infections.
- Some patients exhibit poor responses to vancomycin, necessitating alternative therapeutic strategies.
- Previous research indicated that β-lactams can increase vancomycin susceptibility in highly resistant strains.
Purpose of the Study:
- To investigate the potential of D-cycloserine in combination with vancomycin to overcome vancomycin resistance in Staphylococcus aureus.
- To evaluate the efficacy of vancomycin and D-cycloserine combination therapy against vancomycin-resistant Staphylococcus aureus (VRSA) in vitro and in vivo.
Main Methods:
- Generating vancomycin-highly resistant Staphylococcus aureus (VRSA) strains through in vitro mutagenesis and selection.
- Assessing the in vitro susceptibility of VRSA strains to vancomycin in combination with various other antibiotics, including D-cycloserine.
- Evaluating the therapeutic effects of combined vancomycin and D-cycloserine treatment in a silkworm infection model.
Main Results:
- D-cycloserine significantly increased the susceptibility of VRSA strains to vancomycin.
- Combinations of vancomycin with bacitracin, fosfomycin, erythromycin, lincomycin, gentamicin, levofloxacin, or nisin did not enhance vancomycin susceptibility.
- Combined vancomycin and D-cycloserine treatment demonstrated therapeutic efficacy in a silkworm model, while individual treatments were ineffective.
Conclusions:
- Combined vancomycin and D-cycloserine therapy shows promise for treating infections caused by vancomycin-resistant Staphylococcus aureus.
- D-cycloserine represents a potential synergistic agent to restore vancomycin efficacy against resistant bacterial strains.
- This combination therapy warrants further investigation for clinical application against VRSA infections.
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