WHO warns of drug resistant superbugs

Two major stories on ‘superbugs’ appeared in today’s press. One originates from the World Health Organization, which dedicated this year’s World Health Day to addressing the issue of the rise of antibiotic resistant infections. According to WHO, drug resistance is now becoming so severe that many infections are no longer easily cured, leading to prolonged and expensive treatment and greater risk of death.

The seriousness of the situation regarding antibiotics was summed up by the WHO director-general Dr Margaret Chan, who said that if no action is taken, “the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated”.

The launch of the WHO campaign coincides with a study published in The Lancet , which found that bacteria that are highly resistant to even the strongest antibiotics have been found in public water supplies in New Delhi, India. The study tested water samples for the gene NDM-1. This gene, which can be passed between different bacteria, produces an enzyme that renders antibiotics ineffective.

In 12 out of 171 seepage water samples and two of 50 tap water samples the researchers managed to grow a variety of bacteria that carried this gene, including those that cause cholera and dysentery. The findings demonstrate the spread of the gene to a wider variety of bacterial strains than previously thought, and highlight the need for global action to limit the worldwide spread of NDM-1 producing bacteria.

The emergence of antibiotic resistance is a major public health concern. In the UK, the public is advised to adhere to doctors’ advice on the correct use of antibiotics, not store any unused antibiotics, and ensure that they are taken for the recommended length of time as prescribed by their doctor.

What are the news stories based on?

One news story is from the World Health Organization, which dedicated this year’s World Health Day to addressing the issue of the rise of antibiotic resistant infections.

The second story on superbugs is based on a study that was published in The Lancet . Researchers found that bacteria that are highly resistant to even the strongest antibiotics (ones normally reserved for use against more resistant bacteria) have been found in a small number of public water supplies in New Delhi, India.

Why has WHO dedicated World Health Day to superbugs?

Antimicrobial resistance (AMR) occurs when a microorganism that can harm human health, such as a bacterium, virus, fungus or even parasite, becomes resistant to a medicine to which it was previously vulnerable. This means that standard treatments become ineffective and serious infections persist and become harder to treat. This is a major public health concern, and WHO has selected the fight against AMR as its theme for World Health Day 2011.

On this day, WHO issues a global call for action to halt the spread of antimicrobial resistance and recommends government policies to put this in place. WHO is requesting key stakeholders, policy-makers and planners, the general public, health practitioners and prescribers, pharmacists and dispensers, and the pharmaceutical industry, to act and take responsibility for combating antimicrobial resistance.

The introduction of antibiotics in the 1940s was a medical revolution. Bacteria that had previously caused the death of millions through diseases such as syphilis, gonorrhoea, leprosy, and tuberculosis could now be treated. Yet over the passing decades the increasingly widespread use of antibiotics (and other antimicrobials), population growth, and international travel have contributed to the emergence of bacteria and other microorganisms that are resistant to these drugs.

As WHO Director-General Dr Margaret Chan says, we could now be on the brink of losing these “miracle cures”, and with the “therapeutic arsenal” shrinking, the speed at which drug resistance is developing is far outpacing the speed at which new replacement drugs can be developed.

Dr Chan said:

“The world is heading towards a post-antibiotic era, in which many common infections no longer have a cure and once again, kill unabated.”

What is the current state of affairs regarding resistance?

A summary of facts given by the WHO:

• Last year at least 440,000 new cases of multidrug-resistant tuberculosis were detected worldwide, causing at least 150,000 deaths.
• The malaria parasite is acquiring resistance to even the latest generation of medicines.
• Resistant strains of bacteria that cause gonorrhoea and dysentery are limiting treatment options.
• A high proportion of serious infections acquired in hospital are caused by highly resistant bacteria such as MRSA.
• Drug resistant strains of microorganisms are spreading internationally.
• Resistance is also emerging in antiretroviral medicines used to treat people living with HIV.

WHO also says that because hospitals are now the “hotbeds” of highly-resistant pathogens, the implications also threaten many other lifesaving interventions, such as cancer treatments, surgery and organ transplants.

In Europe, according to reports from the WHO regional office, 25,000 people die each year from superbugs, i.e. bacterial infections that can resist even the newest antibiotics.

How does antimicrobial resistance develop?

AMR develops when a microorganism mutates, or in other words has a random change in its genetic material which produces a new gene that gives it special new properties – in this case coding for an enzyme that allows it to ‘resist’ antimicrobial drugs. The resistance may occur through a number of different mechanisms, depending on the organism and the mutation, such as allowing the organism to inactivate chemicals in the drug, preventing the drug from penetrating the bacterial cell wall. With each new generation of bacteria or other organism, the microorganisms carrying the resistant gene become more dominant until drug treatment is totally ineffective.

The WHO reports that AMR is thought to be caused or exacerbated by many factors, but the largest contributing factor is the misuse and overuse of medicines, including those used in animal husbandry.

As Dr Chan explains:

“This natural process has been vastly accelerated and amplified by a number of human practices, behaviours and policy failures. Collectively, the world has failed to handle these fragile cures with appropriate care. We have assumed that miracle cures will last forever, with older drugs eventually failing only to be replaced by newer, better and more powerful ones. This is not at all the trend we are seeing.”

What does WHO recommend?

WHO has published a policy package of measures that governments and their national partners need to take to combat drug resistance. They recommend that governments:

• develop a comprehensive financed national plan
• strengthen surveillance and laboratory capacity
• regulate and promote the rational use of medicines
• enhance infection prevention and control
• foster innovation and research to develop new tools

The WHO also says that, although governments should take the lead in the fight against drug resistance, health professionals, civil society and patients themselves can also make important contributions, such as:

• doctors and pharmacists only prescribing and dispensing drugs that are required to treat a patient, rather than automatically giving the newest or best-known medicines
• patients not ‘demanding’ that doctors give them antibiotics when they may not be appropriate
• health professionals in healthcare facilities taking appropriate measures to reduce the spread of infection
• collaboration between human and animal health and agriculture professionals, due to the use of antibiotics in food animal production contributing to drug resistance
• governments and partners working closely with industry to encourage greater investment in research and development of new drugs and new diagnostic methods that can improve decision-making

What is the news on resistant bacteria in New Delhi about?

This news story is based on a study in The Lancet , which found that bacteria that are highly resistant to even the strongest antibiotics (those normally reserved for more severe infections by bacteria resistant to other drugs) have been found in a small number of public water supplies in New Delhi, India. The bacteria are known as NDM-1-positive bacteria, because they all carry a gene called NDM-1.

This gene codes for an enzyme (carbapenemase) that makes them resistant to carbapenem antibiotics – one of the strongest antibiotics in current use and normally used for only severe infections. Until recently, bacteria carrying this gene had only been detected in some patients hospitalised in India and this had only first been observed a few years ago.

The researchers took a number of water samples, and in a small number of these were able to culture bacteria that carried the gene, including bacteria that cause cholera and dysentery. The NDM-1 gene alone was isolated from a slightly larger number of water samples. As a control, the study also tested 70 sewage samples from a Wastewater Treatment Works in Cardiff, but did not detect the gene.

What are NDM-1-positive bacteria?

The enzyme NDM-1 is encoded for in sections of bacterial DNA known as plasmids, which can be transferred between types of bacteria. This means that more than one type of bacteria can acquire this kind of resistance. This makes NDM-1 positive bacteria even more hazardous as it means that a variety of different bacteria that are known to cause various serious illnesses may be capable of quickly acquiring this antibiotic resistance.

This is demonstrated by the fact that the researchers were able to culture bacteria that were resistant to cholera and dysentery. Previous research had most often isolated NDM-1 from Klebsiella pneumonia and E.coli bacteria, so the identification of this gene in different types of bacteria such as Shigella boydii and Vibrio cholera (causes of dysentery and cholera) suggests that it is spreading.

The first case of a bacterial infection having this resistance was identified in January 2008 in a patient who had travelled to New Delhi. Scientists began monitoring infections related to this resistance in 2009 as more cases were identified. Cases of infections with NDM-1-positive bacteria are more prevalent on the Indian sub-continent than elsewhere in the world. Many, though not all, patients from other parts of the world (including the UK) who contracted an NDM-1 resistant infection, had been in hospital in India.

What did the Lancet study find?

In this study, researchers from Cardiff University in the UK, together with journalists from Channel 4, investigated how common NDM-1 producing bacteria are in community waste seepage (water pools in streets or rivulets) and tap water in urban New Delhi. They found the NDM-1 gene in two of the 50 drinking water samples, and 51 of 171 seepage samples. Bacteria that were positive for NDM-1 were grown from two drinking water samples and 12 seepage samples. Fourteen different types of bacteria were grown, including 11 bacteria in which NDM-1 had not previously been reported, such as Shigella boydii and Vibrio cholera.

As a control, the researchers also tested 70 sewage samples taken from Cardiff Wastewater Treatment Works in Wales. The NDM-1 gene was not detected in any of these samples.

The presence of NDM-1 positive bacteria in the environment is worrying because of the risk of it spreading through public water and sanitation facilities in India, and the ability of the gene to cross into other types of bacteria. The findings highlight the need for global action to limit the worldwide spread of NDM-1 producing bacteria.

Is there a health risk for travellers to India?

According to the Health Protection Agency, there is minimal risk to travellers who are not treated in hospital. It advises that members of the pubic travelling for surgery overseas should ensure appropriate infection control measures are in place.

In The Lancet study, bacteria carrying the gene were isolated from two out of 50 tap water samples and 12 out of 171 seepage water samples (e.g. water in streets and rivulets). As with any foreign travel, due care should be given to the source and safety of any water used for drinking, cooking or washing.