Clostridium difficile: The More We Learn, the Less We Know

(See the article by Kamboj et al on pages 8–15.) Clostridium difficile has become known as a pathogen responsible for a considerable number of avoidable healthcare-acquired infections. Acquisition is traditionally thought to involve the ingestion of spores from the contaminated healthcare environment by patients whose normal bowel flora is altered by antibiotics. While the majority of these patients remain asymptomatic, some develop diarrhea, further contaminating the environment and serving as a source of ongoing transmission. Clabots et al demonstrated that the rate of C. difficile acquisition is linearly correlated with length of hospital stay, lending further support to the role of the hospital environment as an important reservoir of C. difficile. Thus, prevention efforts have relied largely on measures aimed toward reducing the risk of environmental spreadwithin the healthcare setting such as contact precautions and environmental disinfection, as well as antimicrobial stewardship. For many years, C. difficile was generally regarded as an inconvenient but readily treatable cause of antibiotic-associated diarrhea. In 2003, however, this organism was afforded new respect with the recognition of the North American Pulsed Field type 1 (NAP1)/PCR ribotype 027 strain. This strain became epidemic in several countries and was associated with dramatic increases in healthcare-acquired infection, morbidity, mortality, and metronidazole treatment failures compared with previously described with C. difficile. Public inquiries attributed patient deaths during these epidemics to deficiencies in nursing and medical care, infection control practices, administrative responsiveness, and resource allocation. Media reports of these outbreaks used harsh and litigious language, describing the pathogen as deadly, healthcare providers as villains, and patients as victims. These reports were followed by demands for transparency around C. difficile infection in hospitals. In the wake of these events,C. difficile has become synonymous in the public perception with dirty hospitals, poor management, and noncompliant healthcare providers. Outbreaks have led to successful litigation against healthcare organizations, and criminal charges have been considered in at least one instance. The threat of sanctions and loss of financial reimbursement for patients who develop C. difficile infection during their hospital stay has led to a heightened focus by healthcare administrators on unit-level healthcare-onset C. difficile infection (HO-CDI) rates and accountability. One study found that public reporting was associated with a substantial reduction HO-CDI rates and attributed this reduction to quality improvement efforts by individual healthcare organizations. Consumer groups are now using HO-CDI data to rate hospital performance. In this issue of Infection Control and Hospital Epidemiology, an article by Kamboj et al serves as a caution against using HO-CDI rates as a healthcare system performance measure. Using multilocus sequence typing (MSLT), the authors characterized toxigenic strains of C. difficile from the stools of a large cohort of patients admitted to a stem-cell transplant unit. In this high-risk patient population, 26% of patients were found to be colonized with a toxigenic strain ofC. difficile at the time of admission; 75% of these colonized patients later developed C. difficile infection with an identical strain to the one they were carrying at the time of admission. Considerable diversity was observed among C. difficile isolates in this population, suggesting multiple potential sources of acquisition. The HO-CDI rate, as defined by standard surveillance definitions, was very high on the study unit (3.6 per 1,000 patient days). Conversely, this study found microbiologic evidence of nosocomial acquisition in only 21% of cases, and only half of those had an epidemiologic link to an earlier patient with identical strain type. Thus, healthcare acquisition could be established in only a very small proportion of cases. The authors conclude that most cases of C. difficile infection in this inpatient population represent development of disease in asymptomatic carriers rather than transmission within the inpatient setting. This is not the first study to call into question the belief that C. difficile infection is largely acquired through environmental reservoirs within the healthcare setting. Eyre et al used whole-genome sequencing of isolates from a large cohort of inpatients with C. difficile infection to demonstrate that only 35% of patients were genetically related to an earlier case of C. difficile infection. Furthermore, in nearly half of these genetically related cases (46%), there was no epidemiologic evidence of hospital transmission. These authors also identified a diversity of strains suggesting multiple sources of transmission. A large population-based study in the United