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<p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) poses a significant challenge, necessitating novel therapeutic strategies. This study demonstrates the synergistic bactericidal activity of citral, a phytochemical, and azithromycin against clinical MRSA isolates. Checkerboard assays confirmed synergy with a fractional inhibitory concentration index (FICI) of 0.093, while time-kill kinetics showed a reduction in bacterial viability from 5.39 to 2.94 log<sub>10</sub> CFU/ml, outperforming monotherapy. Scanning electron microscopy revealed severe cellular damage, indicative of membrane disruption and protein leakage. Notably, the combination extended post-antibiotic effects (PAE) by 4.26&#xa0;h at MIC, suggesting prolonged antibacterial action. Cytotoxicity assays on normal human fibroblasts demonstrated 93.7% viability at the combined MIC, underscoring its biocompatibility. These findings highlight citral-azithromycin synergy as a promising strategy to enhance antibiotic efficacy against MRSA while minimizing cytotoxicity, supporting the potential of phytochemical-adjuvant combinations in combating antimicrobial resistance.</p>

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Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月15日

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  • Hitesh K. Sharma,
  • Ibha Singh,
  • Amarnath Karna,
  • Puneet Gupta,
  • Taru Singh,
  • Anoop Kumar,
  • Deepti Pandita,
  • Monalisa Mukherjee,
  • Virinder S. Parmar,
  • Pallavi Agarwal,
  • Viney Lather

摘要

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge, necessitating novel therapeutic strategies. This study demonstrates the synergistic bactericidal activity of citral, a phytochemical, and azithromycin against clinical MRSA isolates. Checkerboard assays confirmed synergy with a fractional inhibitory concentration index (FICI) of 0.093, while time-kill kinetics showed a reduction in bacterial viability from 5.39 to 2.94 log10 CFU/ml, outperforming monotherapy. Scanning electron microscopy revealed severe cellular damage, indicative of membrane disruption and protein leakage. Notably, the combination extended post-antibiotic effects (PAE) by 4.26 h at MIC, suggesting prolonged antibacterial action. Cytotoxicity assays on normal human fibroblasts demonstrated 93.7% viability at the combined MIC, underscoring its biocompatibility. These findings highlight citral-azithromycin synergy as a promising strategy to enhance antibiotic efficacy against MRSA while minimizing cytotoxicity, supporting the potential of phytochemical-adjuvant combinations in combating antimicrobial resistance.