How big is C. difficile infection in the USA?

Clostridium-difficileThe New England Journal of Medicine recently published an article evaluating the burden of CDI in the USA. The huge CDC-led initiative collected data from 10 geographically distinct regions, identifying more than 15,000 cases. Around two-thirds of cases were classified as healthcare-associated (although only 25% were hospital-onset). This means that, prima facie, a third of CDI cases were community-associated. I find this proportion difficult to believe: I strongly suspect that many of these cases would have had healthcare-associated risk factors if the team were able to look hard enough. For example, they used a fairly standard 12 week look-back period to evaluate previous hospitalisation, but how would the data look if they’d used 12 months? Also, it’s usually only possible to evaluate previous hospitalisation in a single healthcare system, but many patients commute between various healthcare systems. The authors acknowledge in the discussion that this designation of “community-acquired” may be inaccurate based on the finding from a previous study whether healthcare-associated risk factors were identified in most patients, but only be a detailed phone interview.

Scaling up from the figures from the 10 regions, national estimates were around 500,000 cases and 29,000 deaths due to CDI per annum in the US. This estimate is approximately double previous estimates for the national CDI burden in the USA, probably reflecting the adoption of molecular methods for the detection of CDI. This scaling up included an interesting statistical adjustment to see how prevalence varied depending on how many sites use sensitive molecular methods to detect CDI.

A sub-study included the culture of C. difficile from 1625 patients. More than 15% of stool specimens from patients diagnosed as CDI failed to grow C. difficile, probably illustrating the limitations of culture methods more than anything else. NAP1 (027) represented around half of cases, and was significantly more common in healthcare-associated CDI. I think it’s fair to say that the initial fears that NAP1 was a super-strain have been allayed by the fact that it’s now so common and there hasn’t been a surge in CDI mortality.

Finally, around 21% of healthcare-associated cases suffered at least one recurrence. Thus, there is a real need to the roll out of the uber successful faecal microbiota transplantation for recurrent CDI. In fact, there should be around 70,000 faecal microbiota transplantations each year in the US right now (500,000 x 0.66 x 0.21); I suspect there are far fewer.

Carbapenem-Resistant Enterobacteriaceae (CRE) in US hospitals

Enterobacteriaceae are a family of bacteria that commonly cause infections in health-care settings as well as in the community. The family includes more than 70 genera but Escherichia coli, Klebsiella species, and Enterobacter species are the most common in healthcare settings. Until recently, carbapenems have been the treatment of choice for serious infections due to these organisms. However, resistance to these agents has emerged in the Enterobacteriaceae family by various mechanisms and is now a major concern worldwide as infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are difficult to treat and are associated with significant morbidity and mortality.


A recent CDC MMWR report used three different surveillance systems to describe the extent of CRE spread among acute-care hospitals in the US as well as the proportion of clinical isolates resistant to carbapenems. They found that while CRE are relatively uncommon, they have spread throughout the US and their rates have increased during the past decade. During the first 6 months of 2012, 4.6% of the 3,918 US acute-care hospitals performing surveillance for either CAUTIs or CLABSIs reported at least once CRE to the National Healthcare Safety Network (NHSN). CRE were more often reported from long-term acute-care hospitals (17.8%) and the percentage of hospitals reporting CRE was highest in the Northeast of the US and among larger and teaching hospitals. Data from NHSN and the Nosocomial Infection Surveillance system (NNIS) showed that the rate of carbapenem resistance among Enterobacteriaceae increased from 1.2% in 2001 to 4.2% in 2011, most of this increase was among Klebsiella species (from 1.6% to 10.4%).

Data from population based surveillance suggest that most (96%) clinical CRE isolates came from cultures collected outside of the hospital from patient with substantial health-care exposure, particularly recent hospitalization (72%). Although nearly all patients with CRE were currently or recently treated in a healthcare setting, these organisms have the potential to spread into the community among healthy individuals.

A combination of infection control strategies applied on national level are needed to control the rise of carbapenem resistance among the Enterobacteriaceae and the spread of CRE. These include active case detection, contact precautions for colonized or infected patients and patient, and staff cohorting as well as strict antibiotic stewardship in all settings. Particular attention should be given to long-term acute-care hospitals which have historically had less developed infection prevention programs. Such coordinated infection prevention and control programs implemented on a national level have been shown to be effective for controlling the rise of CRE, for instance the containment of KPC-producing strains which emerged in 2006 in Israel.

Article citation

Centers for Disease Control and Prevention (CDC): Vital Signs: Carbapenem-Resistant Enterobacteriaceae. MMWR. 2013;62:165-170.