When antibiotics don’t work any more what can we do?


Search for alternatives is focusing on antimicrobial properties of honey and certain metals

The introduction of penicillin in the 1940s heralded the antibiotic era. We are now in the era of antimicrobial resistance (AMR). Can we fight back?

Penicillin resistant Staphylococcus aureus – a common cause of bacterial infection – was reported as early as 1942 after only months of limited clinical trials. In 1960, celbenin – known today as methicillin – a drug effective against penicillin-resistant Staphylococcus aureus strains, became widely available. Yet in 1961, M Patricia Jevons of London’s Central Public Health Laboratory wrote to the British Medical Journal, reporting the isolation of methicillin-resistant Staphylococcus aureus.

Today, economist Jim O’Neill’s 2016 Review on Antimicrobial Resistance for the UK government, states that 700,000 people worldwide die annually from AMR-related infections, and a predicted death toll of 10 million by 2050 will make AMR the world’s biggest cause of death, above cancer.

‘Significant threat’

Prof Colum Dunne – director of research at the University of Limerick’s Graduate Entry Medical School, told The Irish Times: “I’ve heard it said that microbiologists are looking too hard for bacteria that may cause outbreaks. This attitude is akin to an ostrich sticking its head in the sand. The problems and the microbes exist, and failing to resource vigilance in this area means that when outbreaks occur the resulting actions are reactionary ‘firefighting’ rather than planned for, as threats are identified through monitoring.

“Infection prevention and control teams, along with effective antimicrobial stewardship or, in plain English, the use of antibiotics etc in a particular way so that development of resistance is less likely, help in this setting. But this isn’t enough. AMR is a significant threat.”

And Prof Jonathan Cooke – visiting professor at the Department of Medicine, Imperial College London and honorary professor at Manchester Pharmacy School, University of Manchester – told me AMR was a global healthcare and economic problem. It should be a priority for all governments around the world: “Given the direct relationship between antibiotic use and AMR, if antibiotic use is reduced then resistance will fall. Clearly, we should consider adopting any practice that reduces the unnecessary use of antimicrobials.”

One practice has seen Irish researchers modify an ancient wound remedy: honey. In most honeys, the bee enzyme glucose oxidase acts upon the sugar glucose to produce hydrogen peroxide, a potent antimicrobial agent.

Researchers at the Sligo Institute, renowned for its apiary research, have applied a proprietary bioengineering process to honey, ensuring consistently high levels of antibacterial activity through the prolonged release of hydrogen peroxide. The hydrogen peroxide breaks down, releasing reactive oxygen, which is delivered at safe concentrations to the infection site for a sustained period.

This is also the principle behind SurgihoneyRO (SHRO) – reactiveoxygen.co.uk – from British biotech company Matoke Holdings Ltd.

In January 2017, the first randomised controlled trial of SHRO as a dressing for non-healing vascular leg ulcers began at University Hospitals Birmingham NHS Foundation Trust. Consultant microbiologist Beryl Oppenheim, of the Trust, told The Irish Times: “We will study patients with chronic venous ulcers that are failing to heal on both legs and will treat one leg with standard treatment – Aquacel Ag silver dressing – and the other with SHRO. This is a small pilot study but it is hoped that the results, if encouraging, will be used to take the product forward into a much larger multi-centre study, and we hope to have preliminary results available, perhaps by spring 2017.”

Precious metals

Another promising approach to the problem of AMR is “antimicrobial coating innovations to prevent healthcare-associated infection”. That is the title of a recent article in the Journal of Hospital Infection pointing out that healthcare-associated infection (HCAI) affects up to 80,000 patients in European hospitals on any given day.

The article, co-authored by Prof Dunne, notes that the European Commission has funded a four-year initiative to establish a stakeholder network to develop, regulate and use novel antimicrobial coatings for the prevention of HCAI. The use of antimicrobial coatings, containing metals such as copper, silver and gold, and applied to surfaces in healthcare environments, has prompted stakeholders at over 60 universities and other institutes in 29 European countries to focus on these emergent technologies.

Prof Dunne said: “There has been a historical focus on copper-coated antimicrobial surfaces, which work well but are expensive. And new emerging technologies use titanium or silver ions, amongst others. But these won’t work everywhere. For example, there’s little point in applying an antimicrobial coating on a floor travelled by thousands of feet every day. But use in operating theatre tables or equipment coverings may make great sense.”

In the context of global AMR, Prof Dunne has a clear-eyed view on the extent to which individual technologies can address the problem: “We published a piece a year ago,” he said, “stating that the war against certain problematic bacteria was being lost on the Irish front. In light of the tidal wave of AMR, healthcare facility managers are searching for ‘silver bullets’ to help avoid outbreaks and HCAIs.”

Prof Dunne’s overall perspective is tempered by practicality. He points out that hospitals and other healthcare facilities often deal with more patients than they were designed for, and he detects an element of playing catch-up through investing in building, equipment and staff.

“However, in the meantime, and due to a focus on this by the media, hospital managers concentrate on reducing patient numbers in corridors and on trolleys. By doing that, they place pressure on wards to accommodate more patients. This process limits the available space to isolate patients who may be suspected or known to carry particular pathogens.”

Dunne says the hierarchy of hospital management can also be problematic. Clinical managers focus on clinical problems and clinical staff, while hospital managers focus on hygiene or health and safety.

“Both have the potential to impact a patient’s experience in their hospital, and the potential to either spread or solve hospital acquired infections is arguably shared equally. But they may never consult with each other, nor [do they] understand the tactics used or even the jargon/language used by the other. If HCAI challenges are to be overcome, there needs to be a combined strategy.”