Zintars G. Beldavs

Multistate Point-Prevalence Survey of Health Care–Associated Infections

BACKGROUND Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care-associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care-associated infections in acute care hospitals and generate updated estimates of the national burden of such infections. METHODS We defined health care-associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care-associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care-associated infections and of inpatients with such infections in U.S. acute care hospitals in 2011. RESULTS Surveys were conducted in 183 hospitals. Of 11,282 patients, 452 had 1 or more health care-associated infections (4.0%; 95% confidence interval, 3.7 to 4.4). Of 504 such infections, the most common types were pneumonia (21.8%), surgical-site infections (21.8%), and gastrointestinal infections (17.1%). Clostridium difficile was the most commonly reported pathogen (causing 12.1% of health care-associated infections). Device-associated infections (i.e., central-catheter-associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia), which have traditionally been the focus of programs to prevent health care-associated infections, accounted for 25.6% of such infections. We estimated that there were 648,000 patients with 721,800 health care-associated infections in U.S. acute care hospitals in 2011. CONCLUSIONS Results of this multistate prevalence survey of health care-associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections. As device- and procedure-associated infections decrease, consideration should be given to expanding surveillance and prevention activities to include other health care-associated infections.

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.).

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.

Prevalence of Antimicrobial Use in US Acute Care Hospitals, May-September 2011

IMPORTANCE Inappropriate antimicrobial drug use is associated with adverse events in hospitalized patients and contributes to the emergence and spread of resistant pathogens. Targeting effective interventions to improve antimicrobial use in the acute care setting requires understanding hospital prescribing practices. OBJECTIVE To determine the prevalence of and describe the rationale for antimicrobial use in participating hospitals. DESIGN, SETTING, AND PARTICIPANTS One-day prevalence surveys were conducted in acute care hospitals in 10 states between May and September 2011. Patients were randomly selected from each hospitals morning census on the survey date. Data collectors reviewed medical records retrospectively to gather data on antimicrobial drugs administered to patients on the survey date and the day prior to the survey date, including reasons for administration, infection sites treated, and whether treated infections began in community or health care settings. MAIN OUTCOMES AND MEASURES Antimicrobial use prevalence, defined as the number of patients receiving antimicrobial drugs at the time of the survey divided by the total number of surveyed patients. RESULTS Of 11,282 patients in 183 hospitals, 5635 (49.9%; 95% CI, 49.0%-50.9%) were administered at least 1 antimicrobial drug; 77.5% (95% CI, 76.6%-78.3%) of antimicrobial drugs were used to treat infections, most commonly involving the lower respiratory tract, urinary tract, or skin and soft tissues, whereas 12.2% (95% CI, 11.5%-12.8%) were given for surgical and 5.9% (95% CI, 5.5%-6.4%) for medical prophylaxis. Of 7641 drugs to treat infections, the most common were parenteral vancomycin (1103, 14.4%; 95% CI, 13.7%-15.2%), ceftriaxone (825, 10.8%; 95% CI, 10.1%-11.5%), piperacillin-tazobactam (788, 10.3%; 95% CI, 9.6%-11.0%), and levofloxacin (694, 9.1%; 95% CI, 8.5%-9.7%). Most drugs administered to treat infections were given for community-onset infections (69.0%; 95% CI, 68.0%-70.1%) and to patients outside critical care units (81.6%; 95% CI, 80.4%-82.7%). The 4 most common treatment antimicrobial drugs overall were also the most common drugs used for both community-onset and health care facility-onset infections and for infections in patients in critical care and noncritical care locations. CONCLUSIONS AND RELEVANCE In this cross-sectional evaluation of antimicrobial use in US hospitals, use of broad-spectrum antimicrobial drugs such as piperacillin-tazobactam and drugs such as vancomycin for resistant pathogens was common, including for treatment of community-onset infections and among patients outside critical care units. Further work is needed to understand the settings and indications for which reducing antimicrobial use can be most effectively and safely accomplished.

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.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013

IMPORTANCE Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance

ABSTRACT Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in FKS1 and 35 in FKS2. All of the isolates with an FKS mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S. C. glabrata isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata isolates for echinocandin resistance is warranted.

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.