Lisa G. Winston

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.

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.

Clinical failures of appropriately-treated methicillin-resistant Staphylococcus aureus infections

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) infections can be difficult to treat. We evaluated the rate of clinical failure in appropriately-treated patients and determined risk factors for failure. METHODS We retrospectively studied a cohort of patients with invasive MRSA infections who completed recommended therapy at one hospital over a 7 year period. RESULTS Two-hundred and fifteen cases were included. Vancomycin monotherapy was given in 73%. Failure rates by infection site were as follows: osteomyelitis 37/81 (46%), epidural abscess five/18 (28%), surgical wound four/15 (27%), pneumonia eight/45 (18%), endocarditis five/32 (16%), bloodstream five/42 (12%), joint one/23 (4%), and meningitis zero/one (0%). In multivariate analysis, only a diagnosis of osteomyelitis was independently associated with relapse (p<0.001). CONCLUSIONS We found a high rate of treatment failure in an urban population among patients who completed recommended therapy, largely with vancomycin alone. Failure in osteomyelitis was particularly common. High quality comparative studies of antibiotic regimens for MRSA infections, particularly osteomyelitis, are needed.

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.

Penicillin-Nonsusceptible Streptococcus pneumoniae at San Francisco General Hospital

Positive pneumococcal cultures of specimens from adult inpatients at San Francisco General Hospital (SFGH) during the period of 11 August 1994 through 31 December 1996 were identified retrospectively. Of the isolates recovered, 15.5% were not penicillin-susceptible (MIC, > or =.1 microg/mL). A case-control study was performed to evaluate risk factors for colonization or infection with penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) and outcomes. Cases (n = 65) were adult inpatients with a positive culture for PNSP, and controls (n = 411) were adult inpatients with a positive culture for penicillin-susceptible pneumococci (PSSP) and no evidence of PNSP. Cases were less likely to have pneumococcal bacteremia (15.4% versus 39.4%; P<.001) and less likely to have pneumonia (50.8% versus 68.9%; P = .006). In a multiple logistic regression model, recent hospital admission and absence of bacteremia were independent predictors of penicillin-nonsusceptibility. Human immunodeficiency virus infection, mortality, and length of hospitalization were not significantly different among cases and controls. These data suggest that PNSP may be less virulent (cause less pulmonary infection) and/or less invasive (cause fewer bloodstream infections) than PSSP at SFGH.

Infective endocarditis in an urban medical center: Association of individual drugs with valvular involvement

OBJECTIVES Injection drug users (IDUs) develop more right-sided infective endocarditis (IE) than non-IDUs, but it is not known whether this risk is specific to any particular injected drug. This study reviews the clinical characteristics of IE in an urban population and examines the association of drug type with manifestations of IE. METHODS A retrospective cohort of 247 cases of IE was analyzed. Demographic, clinical, microbiologic, and echocardiographic data were collected. RESULTS Our cohort featured a 74% IDU rate, most with heroin. Staphylococcus aureus was the most prevalent organism. S. aureus IE was more likely to occur in IDUs versus non-IDUs (OR 5.5, p<0.0001). Enterococcus faecalis IE was less likely to occur in IDUs (OR 0.21, p=0.02). Tricuspid valve (TV) IE was more likely to occur in IDUs (OR 4.37, p=0.001), while mitral valve (MV) IE occurred less commonly in IDUs (OR 0.40, p=0.005). TV IE occurred more frequently in heroin users vs. IDUs not using heroin (OR 4.03, p=0.033). CONCLUSIONS The epidemiology of IE in this cohort is different from that reported recently in other cohorts, likely due to the high prevalence of IDU. Heroin use may underlie the association between IDU and right-sided endocarditis.

Impact of a Piperacillin‐Tazobactam Shortage on Antimicrobial Prescribing and the Rate of Vancomycin‐Resistant Enterococci and Clostridium difficile Infections

Study Objective. To evaluate the impact of a shortage of piperacillintazobactam in the United States in 2002 on antimicrobial prescribing and associated rates of vancomycin‐resistant enterococci (VRE) and Clostridium difficile infections.

Does Doxycycline Protect Against Development of Clostridium difficile Infection

BACKGROUND Receipt of antibiotics is a major risk factor for Clostridium difficile infection (CDI). Doxycycline has been associated with a lower risk for CDI than other antibiotics. We investigated whether doxycycline protected against development of CDI in hospitalized patients receiving ceftriaxone, a high-risk antibiotic for CDI. METHODS We studied adults admitted to an academic county hospital between 1 June 2005 and 31 December 2010 who received ceftriaxone to determine whether the additional receipt of doxycycline decreased the risk of CDI. Patients were followed from first administration of ceftriaxone to occurrence of CDI or administrative closure 30 days later. RESULTS Two thousand three hundred five unique patients comprising 2734 hospitalizations were studied. Overall, 43 patients developed CDI within 30 days of ceftriaxone receipt, an incidence of 5.60 cases per 10 000 patient-days. The incidence of CDI was 1.67 cases per 10 000 patient-days in those receiving doxycycline, compared to 8.11 per 10 000 patient-days in those who did not receive doxycycline. In a multivariable model adjusted for age, gender, race, comorbidities, hospital duration, pneumonia diagnosis, surgical admission, and duration of ceftriaxone and other antibiotics, for each day of doxycycline receipt the rate of CDI was 27% lower than a patient who did not receive doxycycline (hazard ratio, 0.73; 95% confidence interval, .56-.96). CONCLUSIONS In this cohort of patients receiving ceftriaxone, doxycycline was associated with lower risk of CDI. Guidelines recommend this combination as a second-line regimen for some patients with community-acquired pneumonia (CAP). Further clinical studies would help define whether doxycycline-containing regimens should be a preferred therapy for CAP.