Abstract
Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey synergy.
Highlights
Staphylococcus aureus is a major causative agent of chronic wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers (Eady and Cove, 2003; Dowd et al, 2008; DeLeo and Chambers, 2009)
MINIMUM INHIBITORY CONCENTRATIONS OF HONEYS AND ANTIBIOTICS AGAINST S. aureus STRAINS DURING PLANKTONIC GROWTH The in vitro antibacterial activity against planktonic growth for Medihoney, manuka honey, and for each of the antibiotics was established by determining the MICs against the various S. aureus strains
To address the urgent problem of antibiotic resistance, this study evaluated the antimicrobial activity of combinations of New Zealand (NZ) manuka-type honeys with four antibiotics commonly used to treat S. aureus-related skin infections
Summary
Staphylococcus aureus is a major causative agent of chronic wounds such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers (Eady and Cove, 2003; Dowd et al, 2008; DeLeo and Chambers, 2009) These slow- or non-healing wounds pose a significant risk of sepsis and can result in invasive inflammatory disease such as infective endocarditis, which is associated with high mortality and morbidity (Orsi et al, 2002). Combinations of antimicrobials are synergistic, where the effect of two drugs in combination is significantly greater than the sum of each drug alone This has the additional benefits of reducing both the treatment costs and the risk of possible side effects due to the lower concentrations of both agents used (Leibovici et al, 2010)
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