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Related Concept Videos

Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
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Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds
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Daptomycin In Vitro Activity against Methicillin-Resistant Staphylococcus aureus Is Enhanced by d-Cycloserine in a

O Gasch1,2,3, S K Pillai4,2, J Dakos4

  • 1Beth Israel Deaconess Medical Center ogasch@bellvitgehospital.cat.

Antimicrobial Agents and Chemotherapy
|June 26, 2013
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Summary

Daptomycin showed enhanced killing of methicillin-resistant Staphylococcus aureus (MRSA) with cell wall agents. However, high bacterial loads reduced effectiveness, with d-cycloserine altering cell surface charge.

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat due to antibiotic resistance.
  • Daptomycin is a crucial antibiotic for treating MRSA infections.
  • Understanding factors affecting daptomycin activity is vital for optimizing treatment.

Purpose of the Study:

  • To investigate the impact of cell wall agents on daptomycin activity against susceptible and non-susceptible MRSA strains.
  • To evaluate the effect of bacterial inoculum size on daptomycin efficacy.
  • To explore the mechanism of action, specifically cell surface charge alterations.

Main Methods:

  • Comparative analysis of daptomycin killing activity against isogenic MRSA strains.
  • Testing daptomycin in combination with various cell wall agents at 1x Minimum Inhibitory Concentration (MIC).
  • Assessment of bacterial killing at different inoculum sizes.
  • Cytochrome c binding assays to determine cell surface charge.

Main Results:

  • Certain cell wall agents enhanced daptomycin's killing activity against both daptomycin-susceptible and daptomycin-nonsusceptible (DNS) MRSA strains.
  • High bacterial inocula significantly reduced daptomycin's killing efficacy, particularly against the DNS strain.
  • D-cycloserine was identified as the sole agent that reduced cell surface charge in both MRSA strains at tested concentrations.

Conclusions:

  • Combination therapy with cell wall agents may improve daptomycin efficacy against certain MRSA strains.
  • Bacterial load is a critical factor influencing daptomycin treatment outcomes.
  • D-cycloserine's ability to modify cell surface charge warrants further investigation for its role in daptomycin synergy.