Abstract
Background Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA.MethodologyA total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays.Principal FindingsSNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log10 CFU/mL.Conclusions/SignificanceSNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.
Highlights
Over the past few decades, antimicrobial resistance has been recognized as a major public health problem
We examined the in vitro activity of Sodium new houttuyfonate (SNH) and its potential for synergy when combined with antibiotics against a collection of hospital-associated methicillinresistant Staphylococcus aureus (MRSA) (HAMRSA) isolates recovered from various clinical samples in recent years
Antibacterial mechanism of SNH remains unknown, it was indicated that SNH exerted its antimicrobial effect mainly through binding of non-polar tail group to bacterial hydrophobic membrane proteins or cytoplasmic enzymes [18,25,26]
Summary
Over the past few decades, antimicrobial resistance has been recognized as a major public health problem. Since it was first recovered from patients in southern England in 1961 [1], methicillin-resistant Staphylococcus aureus (MRSA) has been reported worldwide and has become one of the leading causes of hospitalassociated and community-acquired infections [2]. Treatment options for MRSA are limited and less effective than options available for methicillin-susceptible Staphylococcus aureus (MSSA) infections [4]. This emphasizes the importance of developing more therapeutic options including novel antimicrobials and combinations of existing drugs to combat MRSA.
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