Combination therapy using low-concentration oxacillin with palmitic acid and span85 to control clinical methicillin-resistant staphylococcus aureus

Hun Suk Song, Tae Rim Choi, Shashi Kant Bhatia, Sun Mi Lee, Sol Lee Park, Hye Soo Lee, Yun Gon Kim, Jae Seok Kim, Wooseong Kim, Yung Hun Yang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 µg/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 µg/mL; moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.

Original languageEnglish
Article number682
Pages (from-to)1-11
Number of pages11
JournalAntibiotics
Volume9
Issue number10
DOIs
StatePublished - 2020

Keywords

  • Drug combination therapy
  • MRSA
  • Palmitic acid
  • Span85

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