Fernanda C. Lessa

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.).

Current Status of Clostridium difficile Infection Epidemiology

The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions.

National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011.

IMPORTANCE Estimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies. OBJECTIVE To describe updated national estimates and characteristics of health care- and community-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in 2011. DESIGN, SETTING, AND PARTICIPANTS Active laboratory-based case finding identified MRSA cultures in 9 US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured from normally sterile body sites) were classified as health care-associated community-onset (HACO) infections (cultured ≤ 3 days after admission and/or prior year dialysis, hospitalization, surgery, long-term care residence, or central vascular catheter presence ≤ 2 days before culture); hospital-onset infections (cultured >3 days after admission); or community-associated infections if no other criteria were met. National estimates were adjusted using US census and US Renal Data System data. MAIN OUTCOMES AND MEASURES National estimates of invasive HACO, hospital-onset, and community-associated MRSA infections using US census and US Renal Data System data as the denominator. RESULTS An estimated 80,461 (95% CI, 69,515-93,914) invasive MRSA infections occurred nationally in 2011. Of these, 48,353 (95% CI, 40,195-58,642) were HACO infections; 14,156 (95% CI, 10,096-20,440) were hospital-onset infections; and 16,560 (95% CI, 12,806-21,811) were community-associated infections. Since 2005, adjusted national estimated incidence rates decreased among HACO infections by 27.7% and hospital-onset infections decreased by 54.2%; community-associated infections decreased by only 5.0%. Among recently hospitalized community-onset (nondialysis) infections, 64% occurred 3 months or less after discharge, and 32% of these were admitted from long-term care facilities. CONCLUSIONS AND RELEVANCE An estimated 30,800 fewer invasive MRSA infections occurred in the United States in 2011 compared with 2005; in 2011 fewer infections occurred among patients during hospitalization than among persons in the community without recent health care exposures. Effective strategies for preventing infections outside acute care settings will have the greatest impact on further reducing invasive MRSA infections nationally.

Epidemiology of Community-Associated Clostridium difficile Infection, 2009 Through 2011

IMPORTANCE Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. OBJECTIVES To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. DESIGN AND SETTING Active population-based and laboratory-based CDI surveillance in 8 US states. PARTICIPANTS Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). MAIN OUTCOMES AND MEASURES Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. RESULTS Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). CONCLUSIONS AND RELEVANCE Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

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.

Trends in Invasive Methicillin-Resistant Staphylococcus aureus Infections

OBJECTIVE: To describe trends in the incidence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children during 2005–2010. METHODS: We evaluated reports of invasive MRSA infections in pediatric patients identified from population-based surveillance during 2005–2010. Cases were defined as isolation of MRSA from a normally sterile site and classified on the basis of the setting of the positive culture and presence or absence of health care exposures. Estimated annual changes in incidence were determined by using regression models. National age- and race-specific incidences for 2010 were estimated by using US census data. RESULTS: A total of 876 pediatric cases were reported; 340 (39%) were among infants. Overall, 35% of cases were hospital-onset, 23% were health care–associated community-onset, and 42% were community-associated (CA). The incidence of invasive CA-MRSA infection per 100 000 children increased from 1.1 in 2005 to 1.7 in 2010 (modeled yearly increase: 10.2%; 95% confidence interval: 2.7%–18.2%). No significant trends were observed for health care–associated community-onset and hospital-onset cases. Nationally, estimated invasive MRSA incidence in 2010 was higher among infants aged <90 days compared with older infants and children (43.9 vs 2.0 per 100 000) and among black children compared with other races (6.7 vs 1.6 per 100 000). CONCLUSIONS: Invasive MRSA infection in children disproportionately affects young infants and black children. In contrast to reports of declining incidence among adults, there were no significant reductions in health care–associated MRSA infections in children. Concurrently, the incidence of CA-MRSA infections has increased, underscoring the need for defining optimal strategies to prevent MRSA infections among children with and without health care exposures.

Trends in incidence of late-onset methicillin-resistant Staphylococcus aureus infection in neonatal intensive care units: data from the National Nosocomial Infections Surveillance System, 1995-2004.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly being reported to cause outbreaks in neonatal intensive care units (NICUs). We assessed the scope and magnitude of MRSA infections with disease onset after 3 days of age (late-onset MRSA infections) in NICUs. Methods: We analyzed data reported by NICUs participating in the National Nosocomial Infections Surveillance system from 1995 through 2004. For each surveillance month, all healthcare-associated infections as defined by National Nosocomial Infections Surveillance criteria were reported, along with antimicrobial susceptibility patterns of the isolates. We pooled the data from all NICUs by birth weight category and calendar year. Poisson regression was used to assess changes in incidence of late-onset MRSA infections per 10,000 patient-days. Results: Overall, 149 NICUs reported 4831 S. aureus infections and 5,878,139 patient-days. Methicillin testing data were available for 4302 S. aureus isolates, of which 975 (23%) were MRSA. Incidence of late-onset MRSA infection per 10,000 patient-days, combining all birthweight categories, increased 308% from 0.7 in 1995 to 3.1 in 2004 (P < 0.001). A significant increase in incidence of MRSA infections was observed among all 4 birthweight categories analyzed separately (≤1000 g, 1001–1500 g, 1501–2500 g, and >2500 g). The distribution of MRSA infection by type of infection did not vary during the study period; 299 (31%) of MRSA infections were bloodstream infections, 174 (18%) were pneumonia, and 161 (17%) were conjunctivitis. Conclusion: The incidence of late-onset MRSA infections increased substantially between 1995 and 2004, indicating a need to reinforce infection control recommendations and to explore potential sources and routes of transmission.

Complete Restriction of Fluoroquinolone Use to Control an Outbreak of Clostridium difficile Infection at a Community Hospital

OBJECTIVE To review the effect of interventions, including a complete restriction in the use of fluoroquinolones (FQs), used to control an outbreak of hospital-onset Clostridium difficile infection (HO-CDI) caused primarily by the epidemic North American pulsed-field gel electrophoresis type 1 strain. DESIGN Retrospective cohort and case-control study of all episodes of HO-CDI both before and after 2 interventions. SETTING Community hospital; January 1, 2005, through March 31, 2007. Interventions. Complete, 5-month, facility-wide restriction of fluoroquinolone use, during which a change in the environmental-services contractor occurred. RESULTS During a 27-month period, 319 episodes of HO-CDI occurred. The hospital-wide mean defined daily doses of antimicrobials decreased 22% after restricting FQ use, primarily because of a 66% decrease in the use of FQs. The interventions were also associated with a significant change in the HO-CDI incidence trends and with an absolute decrease of 22% in HO-CDI cases caused by the epidemic strain (from 66% before the intervention period to 44% during and after the intervention period; P=.02). Univariate analysis revealed that case patients with HO-CDI due to the epidemic strain were more likely than control patients, who did not have diarrhea, to receive a FQ, whereas case patients with HO-CDI due to a nonepidemic strain were not. However, FQ use was not significantly associated with HO-CDI in multivariable analysis. CONCLUSIONS An outbreak of epidemic-strain HO-CDI was controlled at a community hospital after an overall decrease in antimicrobial use, primarily because of a restriction of FQ use and a change in environmental-services contractors. The restriction of FQ use may be useful as an adjunct control measure in a healthcare facilities during outbreaks of epidemic-strain HO-CDI.

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.

Device-Associated Infections among Neonatal Intensive Care Unit Patients: Incidence and Associated Pathogens Reported to the National Healthcare Safety Network, 2006–2008

OBJECTIVE To describe rates and pathogen distribution of device-associated infections (DAIs) in neonatal intensive care unit (NICU) patients and compare differences in infection rates by hospital type (childrens vs general hospitals). PATIENTS AND SETTING Neonates in NICUs participating in the National Healthcare Safety Network from 2006 through 2008. METHODS We analyzed central line-associated bloodstream infections (CLABSIs), umbilical catheter-associated bloodstream infections (UCABs), and ventilator-associated pneumonia (VAP) among 304 NICUs. Differences in pooled mean incidence rates were examined using Poisson regression; nonparametric tests for comparing medians and rate distributions were used. RESULTS Pooled mean incidence rates by birth weight category (750 g or less, 751-1,000 g, 1,001-1,500 g, 1,501-2,500 g, and more than 2,500 g, respectively) were 3.94, 3.09, 2.25, 1.90, and 1.60 for CLABSI; 4.52, 2.77, 1.70, 0.91, and 0.92 for UCAB; and 2.36, 2.08, 1.28, 0.86, and 0.72 for VAP. When rates of infection between hospital types were compared, only pooled mean VAP rates were significantly lower in childrens hospitals than in general hospitals among neonates weighing 1,000 g or less; no significant differences in medians or rate distributions were noted. Pathogen frequencies were coagulase-negative staphylococci (28%), Staphylococcus aureus (19%), and Candida species (13%) for bloodstream infections and Pseudomonas species (16%), S. aureus (15%), and Klebsiella species (14%) for VAP. Of 673 S. aureus isolates with susceptibility results, 33% were methicillin resistant. CONCLUSIONS Neonates weighing 750 g or less had the highest DAI incidence. With the exception of VAP, pooled mean NICU incidence rates did not differ between childrens and general hospitals. Pathogens associated with these infections can pose treatment challenges; continued efforts at prevention need to be applied to all NICU settings.