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EDITORIALS:
John Starr
Hospital acquired infection
BMJ 2007; 334: 708 [Full text]
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Rapid Responses published:

[Read Rapid Response] Clostridium difficile: difficult also in handwashing?
Nicola Petrosillo, Alessandro Capone   (10 April 2007)
[Read Rapid Response] Understanding Clostridium difficile infection – much room for improvement
Pankaj Lal, RPD Cooke (Consultant Microbiologist ),MM Rothburn (Consultant Microbiologist )   (20 April 2007)

Clostridium difficile: difficult also in handwashing? 10 April 2007
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Nicola Petrosillo,
Director, 2nd Infectious Diseases Division
National Institute for Infectious Diseases,
Alessandro Capone

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Re: Clostridium difficile: difficult also in handwashing?

In his recent editorial (1), John Starr raised several issues on the increasing importance of Clostridium difficile infections in the hospital setting, and on the need for an urgent multiple policy that includes hand hygiene and environmental cleaning, prudent antibiotic prescribing, isolation, and use of protective equipment. However, one of the main measures to minimize the risk of C. difficile patient-to-patient transmission could be ineffective when alcohol hand scrubs are used, because these formulations are likely ineffective against spores.

This point is of particular interest nowadays that alcohol-based formulations are becoming the “standard” of hand hygiene (2) in several hospitals and, particularly, in those wards where C. difficile is more common and patients are more susceptible to this infection, such as intensive care, surgery, and long term care facilities. However, data on alcohol hand rub and C. difficile are scant and controversial. In 1994, Bettin et al. evaluated the efficacy of liquid soap vs. chlorhexidine gluconate in 4% alcohol to decontaminate bare or gloved hands inoculated with an epidemic strain of C. difficile, and they found that the two agents did not differ significantly in residual counts of C. difficile on bare hands, but on gloved hands soap wash was more effective (3). Studies on the impact of the introduction of alcohol hand rub policy on C. difficile incidence are controversial. In 2002, Gopal Rao et al found a consistent reduction of methicillin-resistant Staphylococcus aureus (MRSA) infection and C. difficile associated diarrea, even though not statistically significant (4). On the contrary, King S. found a reduction of MRSA incidence and an increased C. difficile incidence (5). Finally, Gordin et al. (6) and Boyce et al. (7) found that the incidence of C. difficile infection was essentially unchanged after the introduction of alcohol hand rub.

As C. difficile cases are increasing worldwide, and the use of alcohol hand rub is become more common, we think that further studies are needed to better clarify whether current “standard measures” for hand hygiene should be modified in case of C. difficile occurrence in a healthcare facility.

References

1. Starr J. Hospital acquired infection. BMJ 2007;334:708

2. Pittet D, Allegranzi B, Storr J, Donaldson L. ‘Clean Care is Safer Care’: the Global Patient Safety Challenge 2005-2006. Int J Infect Dis 2006;10:419-24.

3. Bettin K, Clabots C, Mathie P, Willard K, Gerding DN. Effectiveness of liquid soap vs. chlorhexidine gluconate for the removal of Clostridium difficile from bare hands and gloved hands. Infect Control Hosp Epidemiol 1994;15:697-702.

4. Gopal Rao G, Jeanes A, Osman M, Aylott C, Green J. Marketing hand hygiene in hospitals--a case study. J Hosp Infect 2002;50:42-7.

5. King S. Provision of alcohol hand rub at the hospital bedside: a case study. J Hosp Infect 2004;56 Suppl 2:S10-2.

6. Gordin FM, Schultz ME, Huber RA, Gill JA. Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol- based handrub. Infect Control Hosp Epidemiol 2005;26:650-3.

7. Boyce JM, Ligi C, Kohan C, Dumigan D, Havill NL. Lack of association between the increased incidence of Clostridium difficile- associated disease and the increasing use of alcohol-based hand rubs. Infect Control Hosp Epidemiol 2006;27:479-83.

Competing interests: None declared

Understanding Clostridium difficile infection – much room for improvement 20 April 2007
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Pankaj Lal,
specialist registrar
Department of Clinical Microbiology ,University Hospital Aintree NHS Trust(L9 7AL),
RPD Cooke (Consultant Microbiologist ),MM Rothburn (Consultant Microbiologist )

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Re: Understanding Clostridium difficile infection – much room for improvement

Although meticillin-resistant Staphylococcus aureus (MRSA) has dominated the debate on healthcare-associated infections in the UK in recent years, there is now growing concern that with Clostridium difficile infection (CDI) also poses a significant risk to public health. 1,2 As highlighted in Starr’s editorial,3 three commonly cited reasons for this include a real and rapid rise in the incidence of disease, the emergence of highly-virulent bacterial strains and anecdotal evidence that infections in lower risk patients groups are increasing.

However, these possible explanations for increasing CDI rates may reflect more complex causalities including increased professional awareness, improved laboratory diagnosis combined with increased laboratory workload due to norovirus infection, increasing numbers of people at risk, changes in antibiotic prescribing patterns (such as the overuse of quinolones), increased use of proton pump inhibitors, high bed occupancy within hospitals, increasing transit in healthcare institutions , perceived lower standards of hygiene and environmental cleaning following reductions in housecleaning staff, outsourcing of hospital cleaning contracts and increased incidence of C. difficile in farm animals and hence the food chain. 4

To date, several hundred strains of C. difficile have been identified. Nevertheless, our understanding of the epidemiological significance of individual strains is very limited. Strains sometimes produce different amounts of toxin in-vitro, raising the possibility that virulence and communicability may vary. It has been demonstrated in an animal model that not all toxigenic strains are equally virulent. Data from the Anaerobic Reference Laboratory (ARL) in Wales provide information about the changing distribution of C. difficile strains, including ribotype 027, in England and Wales. However, anecdotal evidence from the ARL and Health Protection Agency suggests that infections with ribotype 027 are not always associated with greater mortality, and that other genomic factors play a role in determining whether particular strains cause an “average” or “severe” clinical course. Furthermore, the 027 strain does not always produce excessive amounts of toxin when tested in- vitro.

Better scientific information than is currently available is clearly required to accurately evaluate the above concerns. In particular, information on the incidence of CDI in people under 65 years and those living in the community, trends in CDI mortality, basic markers of clinical severity, the link between strain type and clinical severity, and more research into which factors are actually responsible for the reported changes in CDI incidence, distribution and severity, are much needed. This information gap should probably be addressed through a combination of improved surveillance programmes and dedicated research projects but comes with financial resource implications.

The Clostridium difficile Standards Group recommended that laboratories should test specimens for C. difficile toxin using either an immunoassay (detecting both toxin A and toxin B) or a neutralised cytotoxicity assay. 5 The use of diagnostic tests for C. difficile based on combined testing for toxins A and B is now almost universal and is a substantial improvement from a few years ago. 4 However, some kit toxin assay methods have the potential for higher false positive results than previously supposed 6 and toxin tests may not diagnose a proportion of cases. 7 Some have suggested that stool culture should be considered if toxin tests are negative, but CDI is strongly suspected on clinical grounds. 7 Overall, routine use of culture varies considerably throughout Europe, with more than 90% of the laboratories in Denmark and Belgium performing it, but only 28% in Spain and 25% in England. It appears essential that guidelines on the use of C. difficile culture and strain identification should be reviewed and disseminated across Europe. Laboratory methods for detecting C. difficile should be harmonised and the literature critically appraised to ascertain the accuracy and reliability of currently recommended diagnostic tests for C. difficile. Local assessments of the positive and negative predictive values of the current widely used commercial immunoassays would be a good starting point.

Pankaj Lal, Specialist Registrar RPD Cooke Consultant Microbiologist MM Rothburn Consultant Microbiologist Department of Clinical Microbiology University Hospital, Aintree Liverpool L9 7AL

1.Carvel, J. 45,000 patients infected with hospital superbug. The Guardian . 27-8-2005.

2.Lawrence, J. Deaths from 'dirty hospital bug' double in five years. The Independent . 26-5-2006.

3.Starr J. Hospital acquired infection: control measures for Clostridium difficile need to extend into the community. BMJ 2007; 334: 708 (7 April).

4.Health Protection Agency. Clostridium difficile findings and recommendations from a review of the epidemiology and a survey of directors of infection. Prevention and control in England 2006. www.hpa.org.uk/infections/topics.az/clostridium.difficile

5.National Clostridium difficile Standards Group: Report to the Department of Health. J Hosp Infect 2004; 56 suppl 1:1-38.

6.Mohon SS, McDermott BP, Parachuri S, Cunha BA. Lack of value of report stool testing for Clostridium difficile toxin. Am J Med 2006; 119: 356-8.

7.Delmee M, Van Broeck J, Simon A, Jonssens M, Avensani V. Laboratory diagnosis of Clostridium difficile – associated diarrhoea: a plea for culture. J Med Microbiol 2005; 54: 187-91.

Competing interests: None declared