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The waiting game

In the spotlight: shoring up defences against c difficile

The surge in Clostridium difficile cases has led to it being dubbed the MRSA of primary care ­ Dr Lance Saker looks at the extent of the problem and advises what GPs can do

The surge in Clostridium difficile cases has led to it being dubbed the MRSA of primary care ­ Dr Lance Saker looks at the extent of the problem and advises what GPs can do

Clostridium difficile is an anaerobic, gram-positive, spore-forming bacterium which produces exotoxins that are pathogenic to humans. It spreads by direct faecal-oral contact, or by contact with bacteria and spores on the hands of contaminated people or in the environment. C difficile is responsible for a spectrum of clinical conditions ranging from asymptomatic carriage to diarrhoea, colitis, toxic megacolon and sometimes death.

C difficile infection (CDI) is strongly associated with the use of antibiotics, particularly ­ but not only ­ broad-spectrum antibiotics such as cephalosporins, clindamycin and quinolones. These disrupt normal bowel flora and promote C difficile overgrowth. The elderly, people who have recently undergone surgery, and people with serious underlying disease are particularly at risk.

Like MRSA, C difficile incidence is related to the prior use of antibiotics. However, the organism is only rarely 'antibiotic-resistant' in the sense that it is not sensitive to common antibiotic treatments. Nevertheless, recurrent disease is common. This may be due either to inadequate treatment or to a new infection in the same person.

The mounting problem

Between 1990 and 2004, the number of positive C difficile stool samples ­ from people of all ages ­ voluntarily reported by microbiology laboratories in England and Wales to the Health Protection Agency (HPA) increased from 1,194 to 42,328 per year. In 2004, mandatory reporting of new cases of C difficile in people aged over 65 was introduced. During the following 12 months, 44,488 cases were reported.

This rise stems partly from a growing awareness of C difficile among clinicians and microbiologists, which leads to greater laboratory testing and reporting of samples. Concurrently, laboratory diagnostic tests have improved.

Nevertheless, the incidence of C difficile is very likely to have shown a real and significant rise during the past decade. Similar increases in other countries have been reported. In Quebec, Canada, incidence of CDI rose from 35.6 per 100,000 population in 1991 to 156.3 per 100,000 in 2003.

In some areas, rates in people over 65 have reached as high as 850 per 100,000. In the US, unpublished evidence suggests rates increased from 31 per 100,000 in 1996 to 61 per 100,000 in 2003.

When we recently surveyed directors of infection prevention and control in England, 67 per cent said they thought the incidence of C difficile at their trust had risen in the past three years.

Why has incidence increased?

It is difficult to be certain. It is likely there are several causes. These include:

  • increases in the numbers of elderly and immunocompromised people
  • greater use of broad-spectrum antibiotics.

Other possible factors are:

  • increased use of proton pump inhibitors which may predispose to CDI
  • the finding of an uncommon human strain in pigs in North Americal the appearance of C difficile strains that are not only more virulent but can also spread more easily between humans.

Increased mortality

Recently, greater than expected increases in mortality have been reported in association with outbreak of CDI. These incidents are probably primarily related to the occurrence of hypervirulent strains of C difficile, such as ribotype 027 ­ also known as NAP1 and North American PFGE type 1.

Microbiological testing of type 027 isolates indicate this strain may produce more than 10 times as much toxin as 'ordinary' strains of C difficile. In one outbreak in Montreal, 23 per cent of people with 027 infection died within 30 days. This contrasts with previous outbreaks in which mortality attributable to CDI was usually between 1 and 4 per cent.

Infections with type 027 were first reported from hospitals in Quebec and have subsequently been discovered in the US and Europe. The strain has now reached the UK and caused several hospital outbreaks, including one at Stoke Mande-ville Hospital that was widely reported in the media after causing several deaths.

Theoretically, proton pump inhibitors (PPIs) predispose to CDI by knocking off one of our best defences against C difficile spores ­ stomach acid. Several studies suggest that this is a real issue. For instance, a recent Canadian analysis found 55/591 (9.3 per cent) of inpatients on a PPI, compared with 26/596 (4.4 per cent) of people not receiving a PPI, developed CDI while in hospital.

However, other research has failed to identify increased numbers of CDIs in people treated with PPIs, and studies have not examined these associations in primary care settings.

A primary care problem?

In contrast to MRSA, most iatrogenic risk factors for CDI, such as prior treatment with antibiotics such as ciprofloxacin or proton pump inhibitors, are common in general practice ­ although as a group, hospital patients are more predisposed to CDI owing to their greater likelihood of having chronic illnesses, immunodeficiency, and prolonged treatment with broad-spectrum antibiotics.

Nevertheless, evidence on how widespread C difficile is in the community is still insufficient. Anecdotally, about 7 per cent of cases reported through national surveillance come from the primary care sector.The overall burden is likely to be higher because people in the community are less likely to be tested than those in hospitals.

If you don't make a diagnosis, your patient will be deprived of appropriate treatment ­ most importantly, antibiotics. This means they may not recover, or at least will probably have a longer clinical course. When CDI is protracted, severe complications tend to develop, so they will be at greater risk here too. Also, undiagnosed patients may not be appropriately isolated, so there is a risk of spreading the disease to others, especially in care home settings.

GPs should consider the diagnosis in people in high-risk groups who have recently received antibiotics, been discharged from hospital, had a previous diagnosis of CDI, or had contact with a known case of CDI. It's also important to realise that people with CGI often do not have severe diarrhoea, particularly in the early stages of the infection, although prolonged or severe clinical disease should always sound a warning bell.In future, our index of suspicion may need to be lowered ­ a recent article described cases of severe and fulminant CDI in a 12-year-old girl and a 31- year-old pregnant woman, neither of whom had obvious predisposing risk factors for C difficile.

Whether these events represent a ripple or the first signs of an approaching flood remains to be seen.

CDI can usually be diagnosed by a simple toxin test on stool. Although microbiology laboratories are supposed to routinely test all diarrhoeal samples on patients aged 65 and over for C difficile, GPs should specifically ask for this test on the request form. This should ensure that toxin testing is performed (particularly in those under 65), and that the result will be included in the microbiology report.

What GPs can do

·Antibiotic prescribing: Probably the most important thing GPs can do to reduce incidence of CDI in the community is to minimise their prescribing of broad-spectrum antibiotics in people at obvious risk of CDI.

In particular, GP prescribing of ciprofloxacin has increased substantially in the past decade. This is worrying, as North American studies have shown that quinolones have taken over from antibiotics more traditionally associated with C difficile ­ such as clindamycin and cephalosporins ­ as the commonest predisposing factor for developing CDI. General practices should draw up prescribing policies for common conditions requiring antibiotics such as urinary tract infections, and carry out regular audits of adherence to these.

·Prescribing of proton pump inhibitors: Although the jury is still out on this issue, the evidence is mounting.

For GPs to curtail the prescribing of acid suppressants, where possible, seems reasonable.

·Staff hygiene and environmental cleaning: These are just as important in primary care as in acute hospital settings. C difficile spores can survive for long periods in the environment.

Alcohol hand rubs are ineffective as spores are resistant to alcohol. It is important that with the current drive to encourage use of these ­ to reduce incidence of MRSA ­ health care staff continue to follow the appropriate procedures to decontaminate themselves against C difficile. Where C difficile is suspected, or hands or surfaces are soiled, soap and water should be used. As well as ensuring good hygiene standards themselves and at their surgeries, GPs should encourage nursing and residential homes, and community hospitals where they have responsibilities, to follow similar standards of hygiene.

Lance Saker is consultant epidemiologist, Centre for Infections, Health Protection AgencyCompeting interests None declared

Bottom line

There are several steps GPs can take now relating to antibiotics, proton pump inhibitors and hygiene to help stem the mounting problem of C difficile.

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