Jessica Cohen

Burden of Clostridium difficile Infection in the United States

BACKGROUND The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. METHODS In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥ 1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. RESULTS A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001). CONCLUSIONS C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

Prevalence of Healthcare-Associated Infections in Acute Care Hospitals in Jacksonville, Florida

OBJECTIVE To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey. DESIGN Point prevalence survey. PATIENTS Acute care inpatients of any age. METHODS HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection. RESULTS Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%-7.7%). Surgical site infections ([Formula: see text]), urinary tract infections ([Formula: see text]), pneumonia ([Formula: see text]), and bloodstream infections ([Formula: see text]) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs. CONCLUSIONS HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Preventions Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale.

NAP1 Strain Type Predicts Outcomes from Clostridium difficile Infection

BACKGROUND Studies are conflicting regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. METHODS CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15 000 cells/µL within 1 day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. RESULTS Strain typing results were available for 2057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%), and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [AOR], 1.74; 95% confidence interval [CI], 1.36-2.22), severe outcome (AOR, 1.66; 95% CI, 1.09-2.54), and death within 14 days (AOR, 2.12; 95% CI, 1.22-3.68). CONCLUSIONS NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.

Clostridium difficile Infection Among Children Across Diverse US Geographic Locations

OBJECTIVE: Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children ≤3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups. METHODS: Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010–2011 were used to identify cases (ie, residents with C difficile–positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or ≤3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. RESULTS: Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100 000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks. CONCLUSIONS: Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized.

Effect of Nucleic Acid Amplification Testing on Population-based Incidence Rates of Clostridium difficile Infection

Nucleic acid amplification testing (NAAT) is increasingly being adopted for diagnosis of Clostridium difficile infection (CDI). Data from 3 states conducting population-based CDI surveillance showed increases ranging from 43% to 67% in CDI incidence attributable to changing from toxin enzyme immunoassays to NAAT. CDI surveillance requires adjustment for testing methods.

Burden of Nursing Home-Onset Clostridium difficile Infection in the United States: Estimates of Incidence and Patient Outcomes

Background. Approximately 4 million Americans receive nursing home (NH) care annually. Nursing home residents commonly have risk factors for Clostridium difficile infection (CDI), including advanced age and antibiotic exposures. We estimated national incidence of NH-onset (NHO) CDI and patient outcomes. Methods. We identified NHO-CDI cases from population-based surveillance of 10 geographic areas in the United States. Cases were defined by C difficile-positive stool collected in an NH (or from NH residents in outpatient settings or ≤3 days after hospital admission) without a positive stool in the prior 8 weeks. Medical records were reviewed on a sample of cases. Incidence was estimated using regression models accounting for age and laboratory testing method; sampling weights were applied to estimate hospitalizations, recurrences, and deaths. Results. A total of 3503 NHO-CDI cases were identified. Among 262 sampled cases, median age was 82 years, 76% received antibiotics in the 12 weeks prior to the C difficile-positive specimen, and 57% were discharged from a hospital in the month before specimen collection. After adjusting for age and testing method, the 2012 national estimate for NHO-CDI incidence was 112 800 cases (95% confidence interval [CI], 93 400–131 800); 31 400 (28%) were hospitalized within 7 days after a positive specimen (95% CI, 25 500–37 300), 20 900 (19%) recurred within 14–60 days (95% CI, 14 600–27 100), and 8700 (8%) died within 30 days (95% CI, 6600–10 700). Conclusions. Nursing home onset CDI is associated with substantial morbidity and mortality. Strategies focused on infection prevention in NHs and appropriate antibiotic use in both NHs and acute care settings may decrease the burden of NHO CDI.

Impact of Changes in Clostridium difficile Testing Practices on Stool Rejection Policies and C. difficile Positivity Rates across Multiple Laboratories in the United States

ABSTRACT We describe the adoption of nucleic acid amplification tests (NAAT) for Clostridium difficile diagnosis and their impact on stool rejection policies and C. difficile positivity rates. Of the laboratories with complete surveys, 51 (43%) reported using NAAT in 2011. Laboratories using NAAT had stricter rejection policies and increased positivity rates.

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations

Nucleic acid amplification test, age, race and sex are associated with increased community-associated Clostridium difficile infection (CDI) incidence, while age and number of inpatient-days are associated with increased healthcare-associated CDI incidence. Comparison of CDI incidence across regions should account for these factors.

Association between Outpatient Antibiotic Prescribing Practices and Community- Associated Clostridium difficile Infection

A modest, 10% reduction in outpatient antibiotic prescribing among U.S. adults could result in a substantial 17% reduction in Clostridium difficile infections that originate in the community.

Identification of population at risk for future Clostridium difficile infection following hospital discharge to be targeted for vaccine trials

BACKGROUND Efforts to develop a Clostridium difficile vaccine are underway; identification of patients at risk for C. difficile infection (CDI) is critical to inform vaccine trials. We identified groups at high risk of CDI ≥ 2 8 days after hospital discharge. METHODS Hospital discharge data and pharmacy data from two large academic centers, in New York and Connecticut, were linked to active population-based CDI surveillance data from the Emerging Infections Program (EIP). Adult residents of the EIP surveillance area were included if they had an inpatient stay at a study hospital without prior history of CDI. The primary outcome was CDI by either toxin or molecular assay ≥ 28 days after an index hospitalization. Important predictors of CDI ≥ 28 days post discharge were initially identified through a Cox proportional hazards model (stepwise backward selection) using a derivation cohort; final model parameters were used to develop a risk score evaluated in the validation cohort. RESULTS Of the 35,186 index hospitalizations, 288 (0.82%) had CDI ≥ 28 days post discharge. After parameter selection, age, number of hospitalizations in the prior 90 days, admission diagnosis, and the use of 3rd/4th generation cephalosporin, clindamycin or fluoroquinolone antibiotic classes remained in the model. Using the validation cohort, the risk score was predictive (p<0.001) with a c-score of 0.75. Based on the distribution of scores in the derivation cohort, we divided the patients into low and high risk groups. In the high risk group, 1.6% experienced CDI ≥ 28 days post discharge compared to 0.3% among our low risk group. CONCLUSIONS Our study identified specific parameters for a risk score that can be applied at discharge to identify a patient population whose risk of CDI ≥ 28 days following an acute care hospitalization was 5 times greater than other patients.