The potential impact of antibiotic resistance on health in the UK 

Antibiotics were a major medical breakthrough – significantly reducing deaths during childbirth, during surgery and from common infections, including TB. They have also enhanced the effectiveness of treatments such as chemotherapy and radiotherapy[1]

That’s why antibiotic resistance has been declared one of the biggest threats to global health by the WHO[2]. If no action is taken, bacteria will continue to develop resistance - risking death rates rising again.

How can we reduce the risk of antibiotic resistance?

An important first step is to reduce opportunities for bacteria to develop resistance by: 

  • minimising the risk of infection (through vaccinations and good hygiene)[2,3]
  • prescribing antibiotics in a targeted and responsible way – including determining whether infections are viral or bacterial[2]
  • developing more rapid and accurate diagnostic tools, to ensure targeted prescribing[2]
  • using antibiotics with farm animals only where strictly necessary[2] 

However, because no new classes of antibiotic have been developed in recent decades, it makes sense to have a contingency plan in case current antibiotics begin to lose their effectiveness. Here are three options that may be worth exploring: 

Phage Therapy 

Bacteriophages or ‘phages’ are viruses which infect and kill bacteria. The first clinical use of phage therapy was in the 1910s[4]. However, following the discovery of penicillin, interest in phage therapy diminished as focus shifted to the development of antibiotics. Recently, phage therapy has resurfaced as a potential alternative to antibiotics amidst the growing threat of antibiotic resistance. For example, phage therapy has been used to treat a multidrug resistant infection in the US and helped manage a multidrug resistant lung infection in a cystic fibrosis patient in Great Ormond Street[5,6]. However, the vast majority of phage therapy studies lack sufficient evidence of safety and effectiveness, or only exist as small case studies. 

Why Phage Therapy is worth considering 

  • Phages can kill antibiotic resistant bacteria[7].
  • Broad-spectrum antibiotics often kill ‘good’ bacteria. Phages only kill target bacteria, leaving ‘good’ bacteria unharmed and thus reducing the risk of side effects and additional infections[8].
  • Phages replicate at the site of infection. This is known as ‘autodosing.’ It presents potential for single dose administration of phages, which could reduce treatment cost[8].
  • Due to the wide abundance of phages in the gut and the environment, it is assumed that phages themselves are non-toxic to humans[9,10]

What concerns and limitations need to be addressed 

  • Phages are specific to certain bacteria and so cannot be prescribed with the ease of broad-spectrum antibiotics. The bacteria causing the infection must be diagnosed first before target phages can be selected and administered[8].
  • Phages may potentially trigger an immune response, which could reduce the effectiveness of the therapy or induce adverse effects[11].
  • Over time bacteria may develop resistance to phages[12,13].
  • Some phages can facilitate transfer of genes between bacteria, including antibiotic resistance genes - which could contribute to antibiotic resistance[14,15]

What next for Phage Therapy 

Large-scale double-blind placebo-controlled clinical trials are needed to thoroughly investigate phage therapy before it can be considered a viable alternative to antibiotics[16]. If safety and efficacy are confirmed, large-scale commercialisation of phage therapy would require: 

  • A regulatory framework to be developed for phage use[17,18].
  • Significantly more data - to guide decisions such as: whether to use natural or genetically modified phages, whether to develop a one size fits all therapy or personalised therapy, and whether to focus on treatment of acute or chronic infections[19]

Natural products with antibacterial qualities 

Garlic possesses antimicrobial properties, which are thought to be attributed to a compound called allicin[20]. At times in history it has been used to treat infections and wounds[21,22]. Over the last few decades, garlic’s potential as an antibacterial has therefore stirred interest amongst those seeking to reduce reliance on antibiotics. 

Garlic extract has been observed to enhance the antibacterial activity of antibiotics[23]. It can also inhibit the growth of antibiotic resistant bacteria[24,25]. However, results have sometimes been inconsistent[26]. Before widespread use is considered: 

  • Good quality research is needed to identify how best to prepare and administer garlic[27]
  • Safety concerns need to be addressed – in particular, that topical application of garlic can result in a contact dermatitis or even chemical burns[28,29]; and that garlic consumption may result in adverse effects such as dizziness or gastrointestinal disturbance[30]. 

Honey has a long history as a topical treatment for wounds in many civilisations, due to its antibacterial properties[31]. Honey has a low pH and high sugar content, which create unfavourable conditions for bacterial growth[32]. Honey has also been noted to modulate the immune system to assist healing and can enzymatically produce hydrogen peroxide, an antibacterial compound[32,33]. As the threat of antibiotic resistance continues to grow, these properties have resulted in renewed interest in medical-grade honey[34]

There is a need for large scale clinical trials to confirm whether or not, as some studies suggest: 

  • Honey can accelerate wound healing, disrupt bacterial virulence and growth and treat antibiotic resistant infections[35-38].
  • The use of honey to treat wounds is safe[39,40]. 

‘Contact killing’ of Bacteria on Copper Surfaces 

Copper and its alloys can kill micro-organisms within hours by a process known as ‘contact killing’ as copper is a metallic antimicrobial agent[41]. This antimicrobial activity may reduce transmission of bacterial infections. In healthcare environments, bacteria can survive on surfaces such as door handles, arm rests and bed frames for days[42,43]. This increases the number of healthcare acquired infections, including antibiotic resistant infections, and increases the demand for antibiotics. 

Some studies in hospitals have found that substantially fewer bacterial colonies grow on copper and copper alloy surfaces than control surfaces[44,45]. In addition to current hygiene practices, copper surfaces may therefore reduce healthcare acquired infections and subsequently the demand for antibiotics. 

Copper tolerance has been observed in some bacteria in niche environments like marine sediment but not yet in healthcare settings[46]. This suggests that copper fittings may have a role to play in reducing hospital acquired infections but that the position should be kept under review, in case its effectiveness reduces over time. 

 Alex Ellicott   June 2020

 

References 

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/
  2. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
  3. https://www.health.harvard.edu/staying-healthy/how-to-prevent-infections
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460490/
  6. https://www.nature.com/articles/s41591-019-0437-z.epdf?sharing_token=zgdniNNUc-V9dzRhuKBKmNRgN0jAjWel9jnR3ZoTv0PGEeyZNRBV-VGoINtEdCcWOdX1knGcdOj_PFB4GW6BI5cctIWNx5FPi-C82CMQCaBr3dHh7Q490vMLVt1OtIqatjCc6vGRzAvi9FuAtfxx1l6gdlnP-3_4VFSkwSY6E_3ibEjHuzvzcdUwoKvHLAdtQ5oe-dwOr1FOYAb-PVk8m7N1DLQxtmQfxiSXrZ4myW4D1GHG0uJ12jPHVAKHfP1UWxrqU_6rXXBrCabNDbkaosVyUGjZ4LEgAocyLP_44bBABSNAiaENx0IyaHgGxWCHIYELV-lrJASKdCOWglvKtg%3D%3D&tracking_referrer=www.theguardian.com
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954843/#S0007title
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278648/
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418462/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783874/
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356784/#sec5-viruses-11-00010title
  12. https://www.frontiersin.org/articles/10.3389/fphar.2019.00513
  13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070868/
  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615212/
  15. https://pubmed.ncbi.nlm.nih.gov/28096488/
  16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490400/
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205996/
  18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286392/
  19. https://dl.airtable.com/.attachments/6f2f820acb332c78fed8ff158518cae3/ccf22f02/PhageDirectoryReport1.pdf
  20. https://www.sciencedirect.com/science/article/pii/0306987783900403
  21. https://www.tandfonline.com/doi/full/10.1080/10942910601113327
  22. https://academic.oup.com/jn/article/131/3/951S/4687053
  23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458355/
  24. https://www.sciencedirect.com/science/article/pii/S1319016419300751
  25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217283/
  26. https://www.sciencedirect.com/science/article/abs/pii/S0924224416300073?via%3Dihub
  27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073756/
  28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798796/
  29. https://www.researchgate.net/publication/332019348_RARE_BURN_CASES_TREATED_TRADITIONALLY_FOLK_MEDICINE_REVIEW_OF_8_CASES
  30. https://www.sciencedirect.com/science/article/abs/pii/S0924224418307398
  31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758027/
  32. https://pubmed.ncbi.nlm.nih.gov/23569748/
  33. https://pubmed.ncbi.nlm.nih.gov/24612472/
  34. https://pubmed.ncbi.nlm.nih.gov/24199801/
  35. https://www.frontiersin.org/articles/10.3389/fmicb.2012.00144/
  36. https://pubmed.ncbi.nlm.nih.gov/6837863/
  37. https://www.bjoms.com/article/S0266-4356(06)00186-0/fulltext
  38. https://pubmed.ncbi.nlm.nih.gov/18666717/
  39. https://www.sciencedirect.com/science/article/abs/pii/S1744388116300482
  40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613335/
  41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067274/
  42. https://pubmed.ncbi.nlm.nih.gov/20569853/
  43. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224065
  44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405627/
  45. https://pubmed.ncbi.nlm.nih.gov/19931938/
  46. https://pubmed.ncbi.nlm.nih.gov/30906996/