A “new superbug” could make antibiotics redundant, according to The Daily Telegraph. It reported 37 cases of patients having surgery in India or Pakistan and returning to the UK with infections that do not respond to antibiotics.
The research behind these headlines has identified a range of bacteria (such as salmonella and E. coli) that have developed resistance to many powerful antibiotics, including the carbapenem antibiotics usually reserved for severe infections. This new resistance is due to the bacteria carrying a gene that produces an enzyme called NDM-1. Bacteria can acquire resistance by receiving the gene from other bacteria.
While this may sound worrying, the public should not be alarmed by this news. So far there has only been a small number of cases and it is not clear how serious the infections were. However, it does highlight the important message that antibiotics should only be used when absolutely necessary, because the more they are used the more likely it is that bacteria will develop a resistance against them. Regular hand-washing will also help to prevent infections in the first place.
What is the basis for these current reports?
International researchers investigated the prevalence of the NDM-1 enzyme in multidrug-resistant bacteria in India, Pakistan and the UK. The bacteria studied were Enterobacteriaceae, a large group of bacteria that include the gut bug E. coli, which is a common cause of urinary tract infections. They used bacteria samples taken from patients arriving in hospital with an infection (mostly urinary tract or respiratory infections) in Chennai and Haryana in India, and a number of other locations in Bangladesh, India and Pakistan. These patient samples (such as blood and urine samples) had been cultured in the lab to grow the bacteria, known as “bacterial isolates”. They also collected laboratory bacterial isolates from patients referred to the UK’s Antibiotic Resistance Monitoring and Reference Laboratory, between 2003 and 2009.
The researchers then assessed the presence of the gene coding for the NDM-1 enzyme and tested for antibiotic susceptibility, particularly resistance to carbapenem antibiotics. Carbapenems are a particular type of antibiotic used to treat severe bacterial infections that would be resistant to other antibiotics. For UK patients they also reviewed their history of travel abroad and any admission to hospitals in India and Pakistan.
What were the basic findings?
Of the 3,521 samples that the researchers analysed from Chennai in 2009, 141 (4%) were resistant to carbapenem antibiotics: 75 E. coli samples, 60 Klebsiella pneumoniae samples and six other Enterobacteriaceae samples. Of these 141 carbapenem-resistant bacteria, 44 of them (1.5% of the total bacterial samples) were NDM-1-positive, i.e. contained this newly identified enzyme. Of 198 samples from Haryana, 26 samples (13%) were NDM-1-positive. The researchers also reported that 37 resistant samples had been detected in the UK, along with 73 from other locations in Bangladesh, India and Pakistan.
Overall, NDM-1 was identified mostly in E. coli (36 of the positive samples) and Klebsiella pneumoniae (111 of the positive samples). The bacteria producing NDM-1 were highly resistant to all antibiotics except tigecycline and colistin, and in some cases isolates were resistant to all antibiotics. In most cases, the NDM-1 gene was identified on plasmids, which are circular strands of bacterial DNA that can be easily copied and replicated in the host and transferred between different bacteria.
From the UK laboratory, the researchers noted a dramatic rise in the number of Enterobacteriaceae that were carbapenem-resistant in 2008 and 2009 compared to the preceding five years. The 37 NDM-1 positive samples detected in the UK since 2008 came from 29 patients with an average age of 60. Seventeen of these people had travelled to India or Pakistan within the past year and 14 had been admitted to hospital whilst abroad. Reasons for admission abroad were various and included: kidney or bone marrow transplantation, dialysis, stroke, chronic obstructive pulmonary disease, pregnancy, burns, road traffic accidents and cosmetic surgery.
What is the significance of the findings?
Antibiotics are one of medicine’s most powerful tools for fighting infection and disease: as such, antibiotic resistance is a potentially serious problem and a long-standing concern within public health. The growing problem of antibiotic resistance has arisen due to the widespread use of antibiotics and the natural diversity of microbes, which have the ability to adapt and transform into new strains with new properties. As part of this adaptation process, new strains can develop resistance against antibiotics that they would previously have been susceptible to (cured by).
The findings of this research are highly important because the presence of NDM-1 made these Enterobacteria resistant to most antibiotics they would normally be susceptible to (including β-lactam, fluoroquinolone and aminoglycoside drugs). Most notably, the presence of NDM-1 conveyed resistance against the types of antibiotics that would normally be reserved for fighting severe infections caused by bacteria normally resistant to these more common types of antibiotic.
The NDM-1-positive samples from the UK and India also came from a diverse range of bacterial strains, which means the presence of NDM-1 was not confined to a few common strains of E. coli and Klebsiella pneumonia (the most common types of Enterobacteria carrying NDM-1). Worryingly, this suggests that this was not just a single international outbreak with the same strain of a particular bacterium. This finding supports the fact that the NDM-1 gene, being located on the bacterial plasmid, can be easily transferred to other bacteria. As one of the researchers says, the NDM-1 gene may have “an alarming potential to spread and diversify among bacterial populations.”
The authors say that the emergence of NDM-1 positive bacteria could be a serious global public health concern as there are few antibiotics that are effective against NDM-1. It is also worrying that the isolates in India came from people presenting with common community-acquired infections, suggesting the bacteria with this enzyme may be widespread in the environment, in India at least.
As the researchers conclude, there is the potential of NDM-1 to be a worldwide public health problem, and coordinated international surveillance is necessary.
How does NDM-1 affect you?
The current introduction of NDM-1 into the UK could be an important public health concern. However, there is no immediate cause for concern given the small number of samples detected (37) and the lack of information on how serious the cases were. Instead, it is sensible to remind the public of the importance of awareness, vigilance and taking due precautions to prevent the spread of infection.
In particular, patients should talk to their doctor if they are planning to have any elective surgery in India or Pakistan, where NDM-1-resistant bacteria may be prevalent. Those who have received any form of healthcare abroad, particularly in India, Pakistan or Bangladesh, should inform their healthcare professionals when receiving medical care in their home country.
The Department of Health, on the advice of the Health Protection Agency, has released a National Resistance Alert 3 for NDM-1 bacteria. This alerts microbiologists to the increase in Enterobacteriaceae that produce this enzyme, and to the fact that exposure to healthcare in India in Pakistan may be an additional risk factor. The Health Protection Agency advises that patients with these bacterial isolates should be nursed in isolation with consideration given to screening of their close contacts. All identified cases must be referred to the HPA’s Antibiotic Resistance Monitoring and Reference Laboratory.
This research also highlights the important role individuals can play in preventing and containing infections, with regular hand-washing remaining a simple but effective way to stop bacteria and other microbes from spreading. This is of particular importance when visiting hospitals and other healthcare centres.
Further to this, additional clinical precautions should be taken when visiting patients who are receiving barrier nursing, or treatment in isolated rooms, whatever the cause (either because they have an infection or are at particular risk of infection). For these patients, visitors and all healthcare providers should take extra care with the use of disposable gloves and aprons, ensuring hands are washed before and after entering the room, and ensuring that items from the room, including healthcare equipment, are not transferred without adequate sanitisation.
The general public should also be aware of the growing problem of antibiotic resistance in general, and recognise that antibiotics and other antimicrobials should only be used when there is a clear need. The more often we use antibiotics to fight infection, the more likely it is that bacteria will grow resistant to them in the future.