Research Summary: Plant based interventions for drug resistant infections.

Growing antimicrobial drug resistance is a significant global health problem (Weber, 2005).   There is a need for both novel antimicrobial interventions as well as methods for preserving the efficacy of existing interventions to address this issue.  Clinically, this rise in bacterial resistance has prompted recommendations that allopathic doctors prescribe fewer antibiotics. This in turn, has led to a search for alternatives (MacKay, 2003).  Research using current drug discovery technologies has provided evidence to support the traditional claims for many plant based interventions (Graziose, Lila, & Raskin, 2010).   Garlic (Allium sativum L.) has been used in traditional medicine to treat infections for millennia (Koch & Lawson, 1996).

A recent literature search of controlled clinical trials provided scant and conflicting results on garlic’s efficacy as an antimicrobial. Some trials provide preliminary evidence that garlic is effective against salivary Streptococcus mutans (Chavan, Shetty, & Kanuri, 2010) and chronic oral candidiasis (Bakhshi, Taheri, Basir Shabestari, Tanik, & Pahlevan, 2012).  Yet, an earlier systematic review of controlled clinical trials found that garlic provided no significant effect against Helicobacter Pylori (Martin & Ernst, 2003).   Furthermore, no human trials looking for a synergistic effect between garlic and the existing complement of pharmaceutical antibiotics were found in the literature.  This gap in the literature was unexpected primarily due to an increasing body of basic science on the efficacy of garlic as an antimicrobial both independently and in synergy with existing antimicrobial interventions.

In disk diffusion tests of Candida albicans, the antimicrobials fluconazole and itraconazole combined with Fresh Garlic Extract (FGE) showed greater inhibition zones against multi drug resistant C. albicans than the drugs alone (P<0.01) (Li et al., 2015).   Disk diffusion tests with methicillin-resistant Staphylococcus aureus and the drugs cefoxitin, oxacillin, and piperacillin showed larger inhibition zones (P <0.01) but the factorial analysis showed no positive interaction effects (P>0.05) (Li et al., 2015).   Applying the same test methodology to Pseudomonas aeruginosa resulted in a strong positive interaction between FGE and the anti-microbials cefotaxime & ceftriaxone (P < 0.01) (Li et al., 2015).   Despite larger inhibition zones, the anti-microbials levofloxacin, cefazolin and ampicillin did not show positive interaction effects with FGE on P. Aeruginosa (P>0.05) (Li et al., 2015).

An in-vitro disk/well diffusion study focused on Staphylococcus aureus isolates resistant to ampicillin with a mean minimum inhibitory concentration (MIC) of 24 μg/ml.  In all samples S. aureus showed statistically significant dose dependent increase in the zone of inhibition at FGE concentration 12.5 mg/ml and higher compared with the control (P>0.05).  The addition of 30-60 mg/ml of FGE reduced the MIC of ampicillin to 0.6-1.2 μg/ml (Pillai, Trivedi, & Bhatt, 2013).   Other well diffusion tests with the species Escherichia coli, Klebsiellosis pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus all showed dose-dependent increases (P <0.05) in the zone of inhibition at FGJ concentration of 10% and higher compared to control (Yadav, Trivedi, & Bhatt, 2015).

Based on the increasing body of evidence for garlic’s bactericidal effects, a call for further research is justified.  Research is needed that more fully explores the phytochemical mechanisms that contribute to the possible synergistic effects of garlic with our existing antimicrobial arsenal.  Further clinical trial research is also needed to discover if there are replicable and generalizable garlic interventions that could be relevant to current clinical practice.

    

References:

Bakhshi, M., Taheri, J.-B., Basir Shabestari, S., Tanik, A., & Pahlevan, R. (2012). Comparison of therapeutic effect of aqueous extract of garlic and nystatin mouthwash in denture stomatitis. Gerodontology, 29(2), e680–e684. https://doi.org/10.1111/j.1741-2358.2011.00544.x

Chavan, S. D., Shetty, N. L., & Kanuri, M. (2010). Comparative evaluation of garlic extract mouthwash and chlorhexidine mouthwash on salivary Streptococcus mutans count – an in vitro study. Oral Health & Preventive Dentistry, 8(4), 369–374.

Graziose, R., Lila, M. A., & Raskin, I. (2010). Merging traditional Chinese medicine with modern drug discovery technologies to find novel drugs and functional foods. Current Drug Discovery Technologies, 7(1), 2–12.

Koch, H. P., & Lawson, L. D. (1996). Garlic: the science and therapeutic application of Allium sativum L. and related species (2nd ed). Baltimore: Williams & Wilkins.

MacKay, D. (2003). Can CAM therapies help reduce antibiotic resistance? Alternative Medicine Review: A Journal of Clinical Therapeutic, 8(1), 28–42.

Martin, K. W., & Ernst, E. (2003). Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. Journal of Antimicrobial Chemotherapy, 51(2), 241–246. https://doi.org/10.1093/jac/dkg087

Pillai, R., Trivedi, N. A., & Bhatt, J. D. (2013). Studies on in vitro interaction of ampicillin and fresh garlic extract against Staphylococcus aureus by checkerboard method. Ancient Science of Life, 33(2), 114–118. https://doi.org/10.4103/0257-7941.139053

Li, G., Ma, X., Deng, L., Zhao, X., Wei, Y., Gao, Z., … Sun, C. (2015). Fresh Garlic Extract Enhances the Antimicrobial Activities of Antibiotics on Resistant Strains in Vitro. Jundishapur Journal of Microbiology, 8(5). https://doi.org/10.5812/jjm.14814

Yadav, S., Trivedi, N. A., & Bhatt, J. D. (2015). Antimicrobial activity of fresh garlic juice: An in vitro study. AYU: An International Quarterly Journal of Research in Ayurveda, 36(2), 203–207. https://doi.org/10.4103/0974-8520.175548

Weber, C. J. (2005). Update on Antimicrobial Resistance. Urologic Nursing, 25(1), 55–57.