Abstract
As bacteria are becoming more resistant to commonly used antibiotics, alternative therapies are being sought. whISOBAX (WH) is a witch hazel extract that is highly stable (tested up to 2 months in 37 °C) and contains a high phenolic content, where 75% of it is hamamelitannin and traces of gallic acid. Phenolic compounds like gallic acid are known to inhibit bacterial growth, while hamamelitannin is known to inhibit staphylococcal pathogenesis (biofilm formation and toxin production). WH was tested in vitro for its antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, and its synergy with antibiotics determined using checkerboard assays followed by isobologram analysis. WH was also tested for its ability to suppress staphylococcal pathogenesis, which is the cause of a myriad of resistant infections. Here we show that WH inhibits the growth of all bacteria tested, with variable efficacy levels. The most WH-sensitive bacteria tested were Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis, followed by Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Streptococcus agalactiae and Streptococcus pneumoniae. Furthermore, WH was shown on S. aureus to be synergistic to linezolid and chloramphenicol and cumulative to vancomycin and amikacin. The effect of WH was tested on staphylococcal pathogenesis and shown here to inhibit biofilm formation (tested on S. epidermidis) and toxin production (tested on S. aureus Enterotoxin A (SEA)). Toxin inhibition was also evident in the presence of subinhibitory concentrations of ciprofloxacin that induces pathogenesis. Put together, our study indicates that WH is very effective in inhibiting the growth of multiple types of bacteria, is synergistic to antibiotics, and is also effective against staphylococcal pathogenesis, often the cause of persistent infections. Our study thus suggests the benefits of using WH to combat various types of bacterial infections, especially those that involve resistant persistent bacterial pathogens.
Highlights
Community and healthcare-acquired bacterial infections (CAI and HAI) are becoming harder to treat because of bacterial resistance to antibiotics [1]
Gallic Acid Equivalent (GAE), where 75% of that is due to HAMA [29]
The remaining 25% is due to other phenolic compounds naturally present in witch hazel extract, such as gallic acid [24]
Summary
Community and healthcare-acquired bacterial infections (CAI and HAI) are becoming harder to treat because of bacterial resistance to antibiotics [1]. 2 million HAIs occur, which result in about 100,000 deaths. The cost to treat such infections is about. According to the Center of Disease Control (CDC) in 2014, of the infected individuals, pneumonia (21.8%) and surgical site infections (21.8%) were the leading infections, followed by gastrointestinal infections (17.1%), urinary tract infection (12.9%) and primary bloodstream infection (9.9%) [5]. Bacteria most frequently associated with HAIs include Gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, as well as Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa. Clostridium difficile infections are common in healthcare settings, but those mostly result from extensive antibiotic use needed to treat initial infections caused by other bacteria [6]
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