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Clostridium Difficile-Associated Disease a Growing Threat to US Public Health: Presented at ECCMID

By Chris Berrie

NICE, FRANCE -- April 7, 2006 -- Recent evidence indicates the emergence of one major new epidemic strain of Clostridium difficile that is responsible for the recent increases in cases and severity of C. difficile-associated diarrhea (CDAD) across many US states of the US, according to an analysis presented here at the 16^th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Clostridium difficile is an anaerobic, spore-forming bacillus that can lead to CDAD, which in turn can lead to pseudomembraneous colitis, toxic megacolon, sepsis and death.

L. Clifford McDonald, MD, Principal Investigator and Medical Officer, Division of Healthcare Quality Promotion, National Centre for Infectious Disease, Centres for Disease Control and Prevention, Atlanta, United States, presented the findings, based on the annual National Hospital Discharge Survey (NHDS) data.

Transmission of C. difficile occurs through a fecal-oral pathway from the contaminated environment and the hands of healthcare personnel. Antimicrobial exposure has been implicated as a major risk factor for disease, as this can lead to the acquisition and growth of C. difficile when the normal flora of the colon are suppressed.

However, in the United States, C. difficile-associated disease is not a reportable condition, so there is a lack of good national surveillance data, Dr. McDonald said in his presentation on April 2^nd.

Dr. McDonald and colleagues used available hospital discharge coding data to the incidence of CDAD in US acute care hospitals. The data was obtained through the annual NHDS that is conducted by the National Centre for Health Statistics. The researchers also analyzed NHDS public use data sets and reports.

This collected data (McDonald et al., Emerg. Infect. Dis. 2006, Mar: 12(3):409-15) from 1996-2003 initially indicated a slight increase in the US acute care hospital discharges with CDAD as primary diagnosis.

However, when analyzed for any diagnosis, the researchers found a large and sudden increase from the year 2000 that was associated almost exclusively with the >64 years age group. This increase was happening in all regions included in the analysis data, and tended to be slightly worse in smaller hospitals (<100 beds).

Dr. McDonald and colleagues also analyzed data from the Emerging Infections Network Surveys, 2004, derived from 2 surveys conducted 6 months apart and involving 531 infectious disease clinicians.

Respondents to his survey felt that, as Dr. McDonald said, "They were either seeing more refractory cases, more recurrent cases, or more severe cases, that were accompanied by an increase in the case load, and this was not geographically isolated in one area, but was throughout the United States."

This thus suggests the potential for changes in the underlying host susceptibility, antimicrobial prescribing and/or infection control practices, or the presence of a new and more virulent strain.

This evidence arising from a number of analyses appears to indicate that the emergence of a new epidemic strain in the US is responsible for these increases in both cases and disease severity, Dr. McDonald said. This is the new toxinotype III, or BI/NAP1 strain, as distinct from the J strain of 1989-92, he said.

The strain shows indications of a binary toxin as an increased virulence factor and the potential of increased toxin production as a result of an 18 base-pair loss-of-function deletion in the tcdC gene of the pathogenicity locus of C. difficile. Finally, there is the appearance of a significant increase (P <.001) in the resistance of the BI/NAP1 strain to the fluoroquinolones gatifloxacin and moxifloxacin, in particular.

As highlighted by the increase in the number of US states that have revealed the epidemic strain that was confirmed by the National Centre for Health Statistics in late 2005, there is also evidence of severe CDAD in populations that were previously at low risk in at least four US states.

With this in mind, and while noting a report of increases in both total and community-acquired cases of CDAD in England, Dr. McDonald made immediate recommendations for CDAD in these previously low-risk populations: the need for further investigation and surveillance, the widening of the target diagnostic population in the eyes of clinicians, the increased population awareness for the need to seek medical attention, and the continued emphasis on judicious antimicrobial use.


[Presentation title: Clostridium Difficile-Associated Disease: a Growing Threat to US Public Health. Abstract S108]

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