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Clostridium difficile: a challenge for hospitals

Figure 1. Clostridium difficile.

A dramatic increase in the frequency and in severity of nosocomial Clostridium difficile-associated disease has been noted worldwide. In addition, a new and hypervirulent clone has emerged, causing large outbreaks in many countries. This article summarises the recommendations on infection control measures from the European Center for Disease Prevention and Control (ECDC).

by Dr Ralf-Peter Vonberg



Microbiological background: 30 years of antibiotic-associated diarrhoea

Clostridium difficile (CD) is an anaerobic, spore-forming, gram-positive rod bacterium. It is part of the physiological gut flora in about 20% of humans, and some CD strains are capable of producing enterotoxins (e.g., toxins A and B).


CD was first described in 1978 as the cause of intestinal diseases following antimicrobial therapy. Meanwhile, various antibiotic substances have been identified as risk factors for the occurrence of C. difficile-associated disease (CDAD), for example clindamycin, broad spectrum cephalosporins, and fluoroquinolones. Most patients affected by CDAD will only develop rather mild diarrhoea. However, more severe courses of disease, ending up in pseudo membranous colitis, toxic megacolon or even a fatal outcome, are also well documented. In addition to the above mentioned clinical consequences for the individual there is also an economical impact of this disease on hospitals and health care systems. Depending upon the kind of patient population the attributable costs of CDAD may range from $3,000 to $10,000 per case.

Changing epidemiology:
an increase in incidence and virulence

In 2003, a rapid and dramatic increase in the number of CDAD cases, as well as the severity of disease, was noticed – even in otherwise healthy young individuals who had previously not been receiving antimicrobial therapy. Many of these unusual CDAD cases were due to the emergence of a new and hypervirulent CD strain with increased toxin production. This clone (often referred to as ribotype 027/NAP1/toxinotype III) was first recognised in Canada and the US where it caused large nosocomial outbreaks. Shortly thereafter the pathogen was transmitted to Europe and Asia [1-3]. National and local health departments enforced or implemented infection control guidelines, but despite these efforts the strain continued to spread.


That is why the European Centre for Disease Prevention and Control (ECDC) finally decided to develop evidence-based guidelines for the prevention of nosocomial transmission of CD and acquisition of CDAD [4].


These guidelines are primarily meant to serve as a basis for local infection control protocols. They resulted from a systematic search of the literature relating to diagnosis, surveillance, education, isolation precautions, hand hygiene, protective clothing, environmental cleaning, use and reprocessing of medical equipment, antimicrobial stewardship and specific measures in outbreaks. The corresponding recommendations for each topic are presented below.


Early diagnosis of CDAD

Each case of nosocomial diarrhoea should raise suspicion of CDAD and the appropriate microbiological diagnostic test should be performed. This includes toxin ELISA and/or culturing of CD. It may also be necessary to retain cultured isolates in case retrospective typing of the strains is required. There is no need for repeated testing of stool samples once CD has been diagnosed.


Because CD is part of the normal gut flora, screening cultures should only be carried out in symptomatic patients (with diarrhoea). For the same reason, a “test of cure” after symptoms are resolved is not recommended.


Surveillance of CDAD

Routine surveillance of CDAD cases should be carried out in all hospitals. As patients’ underlying disease may influence the likelihood of CDAD, wards should determine their unit-specific baseline incidence of CDAD and should also define a threshold that would trigger additional control interventions. Hospital staff should be especially aware of any rapid changes in the incidence rate, the frequency of complications due to CDAD, or the number of extraordinarily severe CDAD cases. All of these signs may indicate the introduction of a hypervirulent CD strain.

Education of staff, patients and visitors

As is true for many other nosocomial infectious agents, proper education of all players involved is also highly effective in order to limit the spread of CD. This should include physicians, nurses, cleaning personnel, any other staff that enter the patient’s room, visitors of the patient, and the patient him/herself. All of these people need to know the basics of spore transmission and the appropriate precautions to take, with an emphasis on hand hygiene.

Isolation precautions

Symptomatic patients with CDAD should be isolated in single rooms whenever possible. During an episode of diarrhoea, a large numbers of vegetative bacteria and bacterial spores are excreted. Thus, a designated toilet for the CDAD patient only should also be provided. If the number of affected patients is too high to provide single patient rooms, isolation in cohorts should be undertaken. Sometimes the implementation of a complete CDAD ward that is run by designated staff may be helpful in order to prevent further transmission.


Isolation precautions may be discontinued 48 hours after the symptoms of CDAD have resolved and bowel movements have returned to normal.


Hand hygiene

As already mentioned CD is a spore forming bacterium. Bacterial spores are highly resistant in the environment. It is important to note that alcohol does not kill bacterial spores. Therefore, alcohol-based hand rubs should not be the only hand hygiene measure employed when dealing with CDAD patients. Instead meticulous hand washing with soap and water is recommended for all staff after a potential contamination of their hands by CD spores. At present there is no recommendation for the use of antiseptic-containing soap formulae.


Protective clothing

It is part of standard precautionary measures to wear gloves and gowns or aprons when managing patients who have diarrhoea. Of course this is also true when caring for patients suffering from CDAD. Once again, it should be remembered that the immediate vicinity of the patient is often highly
contaminated by spores.


Cleaning the immediate environment

Rooms of CDAD patients should be disinfected regularly using sporocidal agents. Other parts of the ward should also be cleaned at least on a daily basis, concentrating on frequently touched areas. In addition immediate cleaning should occur when obvious environmental contamination has occurred. Toilets, bed pans  and commodes are especially likely to become contaminated with faeces. Thus these items must be scrupulously cleaned. After the discharge of a CDAD patient, a thorough disinfection of the patient’s room is recommended before admission of the next patient takes place.


Use of medical equipment

Patient-specific use of all medical equipment such as blood pressure cuffs is strongly recommended. In particular, electronic thermometers should not be shared between different patients, even if disposable sheaths have been employed. All such devices should always be carefully cleaned and disinfected using a sporocidal agent immediately after use with a CDAD patient. The use of disposable materials should be considered whenever possible instead of reprocessing multiple-use items.


Antimicrobial stewardship

The use of “high-risk” substances that somehow select for CD, such as broad spectrum cephalosporins, clindamycin and fluoroquinolones should be avoided. If possible, any antimicrobial treatment that does not cover CD as soon as possible after the onset of CDAD should be stopped. Specific guidelines on the treatment of CDAD (e.g., the application of metronidazole and/or oral vancomycin) are currently being discussed and should be published soon. At present there is no recommendation that favours the use of probiotics with  CDAD patients.


Specific measures in outbreaks

Infection control staff should always be informed immediately an outbreak of CDAD is suspected, and all infection control measures should then be reinforced. When doing so, the standard of cleaning the immediate environment should be particularly reviewed. A critical review of the current antimicrobial treatment policy of the patients on the ward should also be performed. CD can be cultured at the same time as microbiological diagnostic tests are performed, and the samples can be stored for subsequent molecular typing of the strains involved. This can help to elucidate the epidemiology of the outbreak.


Interim policies for patient admissions, placement and (dedicated) staffing should be administered. Sometimes the entire unit must be closed for new admissions or even vacated for an intensive environmental cleaning before re-opening.



We have to face the fact that, more than ever, CDAD represents an emerging threat in all kinds of medical departments. Because of the clinical and financial burden resulting from this disease, all efforts should be made to minimise the risk of nosocomial CD spread. Already existing infection control protocols should therefore be carefully reviewed and modified if necessary. In addition, the staff on the ward must always be aware of the possibility of CDAD in diarrhoeal patients, and strict adherence to infection control measures is highly recommended as soon as CDAD is diagnosed.



1. Pepin J, Valiquette L, Cossette B. Mortality attributable to
nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 2005;173:1037-42.

2. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079-84.

3. Kuijper EJ, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006;12 Suppl 6:2-18.

4. Vonberg RP, Kuijper EJ, Wilcox MH, Barbut F, Tull P, Gastmeier P et al. Infection control measures to limit the spread of Clostridium difficile. Clin Microbiol Infect 2008;14 Suppl 5:2-20.


The author

Ralf-Peter Vonberg, MD

Institute for Medical Microbiology and Hospital Epidemiology

Medical School Hanover

Carl-Neuberg-Str. 1

D-30625 Hanover


Tel: +49 511 532 4431



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