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The rising incidence of antibiotic-resistant ESBL-producing E. Coli

VOL: 100, ISSUE: 31, PAGE NO: 30

Ann Shuttleworth, BA, is a freelance health care journalist

There has been growing concern about the rising incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in UK hospitals. However, the Health Protection Agency (2004) has now reported an increase in the incidence of urinary tract infections (UTIs) and cases of blood poisoning caused by another bacterium with resistance to most antibiotics (NT News, 27 July, p8).

There has been growing concern about the rising incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in UK hospitals. However, the Health Protection Agency (2004) has now reported an increase in the incidence of urinary tract infections (UTIs) and cases of blood poisoning caused by another bacterium with resistance to most antibiotics (NT News, 27 July, p8).

This bacterium is a strain of Escherichia coli that produces enzymes known as extended-spectrum beta-lactamases (ESBLs). It is commonly associated with UTIs, and is different from E. coli 0157, which has been responsible for outbreaks of food poisoning in recent years. ESBL enzymes can destroy, and therefore develop resistance to, a range of antibiotics, including those listed in Box 1 (Kang et al, 2004; Jones et al, 2003; Iqbal et al, 2002; Watanabe, 2002; Bradford, 2001).

ESBL-producing E. coli
ESBLs have so far only been found in Gram-negative bacteria. They are most commonly associated with E. coli and Klebsiella pneumoniae, although they can also be transferred to Proteus mirabilis, citrobacter, serratia and other enteric bacilli. They were first recognised in Germany in the 1980s, and have been reported in many other countries, including those in Box 2. In some of these 10-40 per cent of strains of E. coli and K. pneumoniae produce ESBLs.

These bacteria have been responsible for numerous hospital outbreaks of infection worldwide (Rupp and Fey, 2003), although they are found most frequently in long-term care settings and are usually identified when someone is admitted to hospital with an infection.

The department of anaesthesia at the Chinese University of Hong Kong (CUHK) suggests worldwide prevalence is underestimated, as a significant proportion of laboratories do not perform tests for ESBLs. Since 2000 a new class of ESBL-producing bacteria has begun to spread across the globe, and appears to be spreading more widely in the community as well as in hospitals.

The exact incidence of ESBL-producing E. coli in the UK is not known, as there is no mandatory requirement to report these infections or UTIs in general. However, voluntary reports to the HPA have increased from only a few per year before 2003 to over 400 in the past year. These reports have come from 60 different laboratories, indicating that the bacterium has widespread prevalence.

Surveillance has shown cases of blood poisoning caused by E. coli have also risen, from 7,833 in 1993 to 14,509 in 2003. The HPA estimates that 3.5 per cent of those in 2003 will have been ESBL-producers. Scientists believe that they will generate a host of therapeutic challenges in the coming years (Bradford, 2001).

Although it stresses that the number of infections caused by ESBL-producers is still small, the HPA is concerned because it is known that some infected people have subsequently died. As these patients may have had underlying medical conditions it is difficult to say whether the infection was a direct cause of their deaths, but the agency has launched an investigation with its own specialists working alongside those in the NHS. It plans to publish its report in the autumn.

Risk factors
Most people are at no risk from ESBL-producing E. coli and may be asymptomatic carriers. The bacterium only poses a threat when it causes an infection. Patients at greatest risk include the very young and the very old. Other risk factors include (CUHK, 2004; Farkosh, 2004):

- Previous prolonged or multiple antibiotic use;

- Urinary, central venous or central arterial catheter in situ;

- Gastrostomy or jejunostomy;

- Gastrointestinal colonisation;

- Prolonged hospital or intensive care stay;

- Previous nursing home stay;

- Severe illness or generally frail health;

- Mechanical ventilation.

Transmission
E. coli is found in normal bowel flora and is necessary for digestion. Infection occurs when it transfers to other tissues or organs where it does not belong and multiplies. Being found in the bowel, it is easily transmitted to the urinary tract and is a common cause of UTIs. These infections range from uncomplicated cystitis to infections that affect the kidneys and those that progress to blood poisoning (HPA, 2004). Unlike those caused by ESBL-producers, most are easily treated with antibiotics.

The bacterium is spread from person to person by faecal contamination of the hands. Faecal/oral spread occurs if the bacterium is introduced to the mouth. Environmental contamination occurs if soiled linen is not disposed of safely and cleanliness is not maintained.

Diagnosis and treatment
Laboratory detection of ESBL-producing bacteria can be difficult, as they can appear sensitive to some antibiotics if too low a number is used in developing laboratory cultures. Infection with ESBL-producing bacteria should be suspected if infections increasingly fail to respond to broad-spectrum cephalosporins (Farkosh, 2004).

Although no randomised controlled trials on the treatment of ESBL-producing bacteria have been performed, in vitro and observational studies have been conducted (Patterson, 2000). These suggest antibiotics of choice for serious infections are the carbapenems (imipenem and meropenem) as they are highly stable against ESBL. However, there are concerns that ESBLs may develop resistance to this class of antibiotic. Their use has been associated with the emergence of carbapenem-resistant strains of stentrophomona and pseudomonas (Rupp and Fey, 2003). Patients in the community may require hospital admission for intravenous antibiotics.

Infection control
In addition to handwashing with antibacterial soap and/or alcohol gel after using the toilet, frequent cleaning and disinfection is vital in hospitals and other health care facilities. Specific attention should be paid to taps, door handles, bedrails and bathrooms.

ESBL-producing bacteria have been isolated from abscesses, blood, catheter tips, peritoneal fluid, and sputum and throat cultures (Farkosh, 2004).

Health professionals should therefore use gloves and gowns as appropriate during clinical procedures, and remove them and wash their hands between patients.

Equipment that is shared between patients, particularly items such as bedpans and commodes, should be cleaned and disinfected thoroughly. Patients should be made aware of the importance of thorough handwashing after using the toilet.

Visitors should also wash their hands before entering and after leaving wards or patients' rooms in all health care facilities.

Since inter-hospital spread has been reported (CUHK, 2004), notification when transferring infected patients is advisable. With the increased incidence of ESBL-producers in the community, the HPA has alerted GPs to the need to send a patient's specimens to a laboratory if an infection is not responding to first-line antibiotic therapy.

Preventing increased resistance
There is a possibility that ESBL-producing bacteria may develop resistance to carbapenems, presenting serious problems in treating these infections. Antibiotics should therefore only be used for people who have symptomatic infections - no treatment is necessary for asymptomatic carriers of ESBL-producing E. coli.

In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic use, measures to monitor and restrict this use may be an important intervention in controlling the spread of ESBLs (Patterson, 2000). Regular surveillance and efforts to decrease the empirical use of antibiotics for patients with mild symptoms in whom infection has not been confirmed are also advisable (Farkosh, 2004).

Conclusion
Although still low, prevalence of ESBL-producing E. coli in the UK is increasing in both hospital and community settings and may have contributed to a number of deaths. It, along with other ESBL-producing bacteria, is likely to present significant therapeutic challenges in the future, particularly if antibiotic resistance increases further.

Excellent infection control procedures are essential in health and residential facilities to prevent the spread of the bacteria, while in the primary setting, ESBL-producing bacteria should be suspected in infections that do not respond to first-line antibiotic therapy.

This article has been double-blind peer-reviewed.

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