The rise of drug-resistant E. coli

Behind the Headlines

Tuesday February 19 2008

SEM image of Escherichia coli bacteria (E. coli) x4,700 (Colour Enhanced)

E. coli are common and usually harmless bacteria

Scientists have warned that E. coli, a frequent cause of  infection, is becoming resistant to antibiotics and the reistance problem could become as big as MRSA, the Daily Mail and other newspapers report. According to the newspapers, experts say there is growing concern as healthy non-hospitalised people have become infected with the antibiotic-resistant form of the bug. They highlight the need to restrict the overuse of antibiotics when treating coughs and colds.

This story is not based on a new study, but on a review of the current knowledge in this area. E. coli occurs naturally in the human gut; however, certain strains can lead to infections. As has happened with other bacteria, such as MRSA, there have been cases where strains of E. coli develop resistance to commonly used antibacterial drugs. At present, infections from virulent forms of E. coli in the community are rare.

This story highlights again the dangers of overusing antibiotics, and suggests caution when using them to treat minor infections that would clear up naturally in the course of time.

Where did the story come from?

The article was written by Dr Johann Pitout and Kevin Laupland of University of Calgary, Canada. The authors have previously received research grants from Merck Frosst Ltd Canada and AstraZeneca Canada Inc, and Wyeth Pharmaceuticals Canada, Ltd. The study was published in the peer-reviewed medical journal: The Lancet Infectious Diseases.

What kind of scientific study was this?

This narrative review discusses different methods of diagnosing and treating infections caused by multi-drug resistant E. coli and other bacteria within the same group. These bacteria are able to produce enzymes called Extended-Spectrum Beta-Lactamases (ESBLs) that stop certain antibiotics from working, among which are some of the most widely used in hospitals.

In particular, the authors discuss a need for doctors in the community to be aware of these resistant bugs and that the infections caused by them could fail to respond to normal treatment.

The authors discuss methods of laboratory detection of the bacteria and specific treatment issues. They also carry out a search of an electronic database to identify clinical trials that have investigated the effectiveness of certain antibacterial drugs.

What were the results of the study?

The authors initially discuss a particularly virulent form of bacteria that produce a distinct group of ESBLs (CTX-M enzymes). These bacteria are resistant to the groups of antibiotics that are commonly used to treat these types of infections (penicillins and cephalosporins) and also to certain higher classes of antibiotics normally reserved for more severe infections (e.g. fluoroquinolones, co-trimoxazole and gentamicin). Infections from bacteria that produce these enzymes have not been restricted to vulnerable people in hospital, but have also been found in the community, particularly in certain European and South American countries.

They state that infection with CTX-M producing E. coli in the community normally causes urinary infections. The most vulnerable people are those with kidney or liver problems, diabetics, the elderly, those with repeat infections, and those who have recently been hospitalised or in nursing home care. Less commonly, cases of stomach and blood infection have also been recorded. In Israel, 14% of patients admitted to hospital with blood poisoning were found to have been infected with CTX-M E. coli, with resistance to the higher classes of antibiotics in 61-64% of cases. Similar findings were obtained in another small number of cases that occurred in Spain over a four-year period.

The authors also report on the different laboratory methods that are available to detect ESBL producing bacteria, and report that following US Clinical and Laboratory Standards Institute and UK Health Protection Agency guidelines gives a high lovel of accuracy (above 90%) of detecting these infections.

They also say that the treatment of multi-drug resistant bacterial infection is difficult. Serious community infections are usually treated based on clinical symptoms rather than following laboratory confirmation of the exact organism and its drug sensitivities, and the antibiotics that are normally used (e.g. cephalosporins) are ineffective for multi-drug resistant infection.

The standard antibiotic regimens that are used vary between different health trusts and countries. Failed treatment or a delay in effective treatment is associated with a poorer outcome of the infection and a more prolonged illness. Additional problems can occur when antibiotics found to be effective against the bacteria in the laboratory are not actually effective in the patient.

Due to the resistance of ESBL-producing E. coli and other bacteria of the same group to a variety of drugs tested, the carbapenems (antibiotics usually reserved for infection in seriously ill or immunocompromised people) are used. However, these drugs are expensive, intravenous, and have not been tested in carefully controlled trials against other drugs for the treatment of ESBL bacteria.

The authors’ database search identified 10 articles that investigated the difference in efficacy between antibiotic agents. All trials were generally small, observational (i.e. not a clinical trial), unblinded and with the potential for bias. A few of the trials reported good results following treatment with carbapenems and reduced efficacy with some other agents. One trial in Hong Kong found that 80% of ESBL E. coli infections failed to respond to initial standard antibiotics, compared to 6% of non-ESBL E. coli infections.

What interpretations did the researchers draw from these results?

The authors highlight antibiotic resistance as a public health concern and say that prompt laboratory recognition of resistant organisms is essential. They say that ESBL-producing bacteria are being found in the community and that although infections caused by these bacteria in the community are rare, “it is possible that, in the near future, clinicians will be regularly confronted with the hospital types of bacteria causing infections in patients in the community, a scenario very similar to that of community-acquired MRSA”.

They recommend that further research is done to determine whether there are differences in effectiveness between the carbapenems, and whether this is the best therapy with which to tackle community infections.

What does the NHS Knowledge Service make of this study?

This is an in-depth narrative review of the current level of knowledge and awareness about multi-drug resistant E. coli and other bacteria within the same group. At present, infections from virulent forms of E. coli in the community are rare and the few cases reported by the article occurred predominantly in other areas of Europe and South America.

Rather than being a failure of the healthcare system, the development of drug-resistant bacteria is an unfortunate, but inevitable, consequence of high antibiotic use over time. This story again highlights the dangers of overusing antibiotics and the need for their judicious use in the future.

 

Sir Muir Gray adds...

Antibiotics create resistant bacteria and that is why we should take fewer antibiotics.

 

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

E.coli bug "will rival MRSA threat". The Daily Telegraph, February 19 2008

Deadly e.coli bug spreads beyond hospitals and into the community. Daily Mail, February 19 2008

Warning on the rise of 'super' E coli bugs. The Scotsman, February 19 2008

Links to the science

Pitout J, Laupland  KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 2008; 8: 159-166

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