Tiffany Hink

Prevalence and Risk Factors for Asymptomatic Clostridium difficile Carriage

BACKGROUND Clostridium difficile infection (CDI) incidence has increased dramatically over the last decade. Recent studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We sought to identify the prevalence and risk factors for asymptomatic C. difficile carriage on admission to the hospital. METHODS Patients admitted to Barnes-Jewish Hospital without diarrhea were enrolled from June 2010 through October 2011. Demographic information and healthcare and medication exposures 90 days prior to admission were collected. Stool specimens or rectal swabs were collected within 48 hours of admission and stored at -30°C until cultured. Clostridium difficile isolates were typed and compared with isolates from patients with CDI. RESULTS A stool/swab specimen was obtained for 259 enrolled subjects on admission. Two hundred four (79%) were not colonized, 40 (15%) had toxigenic C. difficile (TCD), and 15 (6%) had nontoxigenic C. difficile. There were no differences between TCD-colonized and -uncolonized subjects for age (mean, 56 vs 58 years; P = .46), comorbidities, admission from another healthcare facility (33% vs 24%; P = .23), or recent hospitalization (50% vs 50%; P = .43). There were no differences in antimicrobial exposures in the 90 days prior to admission (55% vs 56%; P = .91). Asymptomatic carriers were colonized with strains similar to strains from patients with CDI, but the relative proportions were different. CONCLUSIONS There was a high prevalence of TCD colonization on admission. In contrast to past studies, TCD colonization was not associated with recent antimicrobial or healthcare exposures. Additional investigation is needed to determine the role of asymptomatic TCD carriers on hospital-onset CDI incidence.

A systematic evaluation of methods to optimize culture-based recovery of Clostridium difficile from stool specimens.

With the increasing prevalence of Clostridium difficile infection among hospitalized patients, a clear understanding of C. difficile epidemiology is needed to evaluate current prevention policies, and to create new and effective policies. To determine the epidemiology of C. difficile, the most sensitive methods for detection of C. difficile are required. The purpose of this study was to systematically assess multiple methods to determine the most sensitive method to recover C. difficile from stool and rectal swabs. Stool samples from healthy asymptomatic individuals that were collected and confirmed to be culture negative for C. difficile were spiked with known concentrations of C. difficile ranging from 10(4) CFU of C. difficile per ml of stool to 10 CFU per ml. Two sets of experiments (A and B) were performed and each involved multiple combinations of untreated and treated stool/rectal swab specimens and selective and non-selective broth and agar. Overall, recovery of C. difficile was increased with the use of an initial broth enrichment followed by plating to solid medium. The most sensitive method of C. difficile detection for both stools and swab specimens was heat shock prior to inoculation of cycloserine-cefoxitin mannitol broth with taurocholate lysozyme cysteine (CCMB, Anaerobe Systems, Morgan Hill, CA) followed by isolation from pre-reduced TSA II with 5% sheep blood (BAP, BBL BD and Co., Sparks, MD). Identifying the most sensitive method of recovery will allow for further study of asymptomatic C. difficile carriers and their role in the epidemiology of C. difficile.

Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in Hospitalized Patients

ABSTRACT Asymptomatic colonization may contribute to Clostridium difficile transmission. Few data identify which patients are at risk for colonization. We performed a prospective cohort study of C. difficile colonization and risk factors for C. difficile acquisition and loss in hospitalized patients. Patients admitted to medical or surgical wards at a tertiary care hospital were enrolled; interviews and chart review were performed to determine patient demographics, C. difficile infection (CDI) history, medications, and health care exposures. Stool samples/rectal swabs were collected at enrollment and discharge; stool samples from clinical laboratory tests were also included. Samples were cultured for C. difficile, and the isolates were tested for toxins A and B and ribotyped. Chi-square tests and univariate logistic regression were used for the analyses. Two hundred thirty-five patients were enrolled. Of the patients, 21% were colonized with C. difficile (toxigenic and nontoxigenic) at admission and 24% at discharge. Ribotype 027 accounted for 6% of the strains at admission and 12% at discharge. Of the patients colonized at admission, 78% were also colonized at discharge. Cephalosporin use was associated with C. difficile acquisition (47% of patients who acquired C. difficile versus 25% of patients who did not; P = 0.03). β-lactam–β-lactamase inhibitor combinations were associated with a loss of C. difficile colonization (36% of patients who lost C. difficile colonization versus 8% of patients colonized at both admission and discharge; P = 0.04), as was metronidazole (27% versus 3%; P = 0.03). Antibiotic use affects the epidemiology of asymptomatic C. difficile colonization, including acquisition and loss, and it requires additional study.

Phenotypic and genotypic analysis of Clostridium difficile isolates: A single-center study

ABSTRACT Clostridium difficile infections (CDI) are a growing concern in North America, because of their increasing incidence and severity. Using integrated approaches, we correlated pathogen genotypes and host clinical characteristics for 46 C. difficile infections in a tertiary care medical center during a 6-month interval from January to June 2010. Multilocus sequence typing (MLST) demonstrated 21 known and 2 novel sequence types (STs), suggesting that the institutions C. difficile strains are genetically diverse. ST-1 (which corresponds to pulsed-field gel electrophoresis strain type NAP1/ribotype 027) was the most prevalent (32.6%); 43.5% of the isolates were binary toxin gene positive, of which 75% were ST-1. All strains were ciprofloxacin resistant and metronidazole susceptible, and 8.3% and 13.0% of the isolates were resistant to clindamycin and tetracycline, respectively. The corresponding resistance loci, including potential novel mutations, were identified from the whole-genome sequencing (WGS) of the resistant strains. Core genome single nucleotide polymorphisms (SNPs) determining the phylogenetic relatedness of the 46 strains recapitulated MLST types and provided greater interstrain differentiation. The disease severity was greatest in patients infected with ST-1 and/or binary gene-positive strains, but genome-wide SNP analysis failed to provide additional associations with CDI severity within the same STs. We conclude that MLST and core genome SNP typing result in the same phylogenetic grouping of the 46 C. difficile strains collected in a single hospital. WGS also has the capacity to differentiate those strains within STs and allows the comparison of strains at the individual gene level and at the whole-genome level.

Assessment of healthcare worker protocol deviations and self-contamination during personal protective equipment donning and doffing

OBJECTIVE To evaluate healthcare worker (HCW) risk of self-contamination when donning and doffing personal protective equipment (PPE) using fluorescence and MS2 bacteriophage. DESIGN Prospective pilot study. SETTING Tertiary-care hospital. PARTICIPANTS A total of 36 HCWs were included in this study: 18 donned/doffed contact precaution (CP) PPE and 18 donned/doffed Ebola virus disease (EVD) PPE. INTERVENTIONS HCWs donned PPE according to standard protocols. Fluorescent liquid and MS2 bacteriophage were applied to HCWs. HCWs then doffed their PPE. After doffing, HCWs were scanned for fluorescence and swabbed for MS2. MS2 detection was performed using reverse transcriptase PCR. The donning and doffing processes were videotaped, and protocol deviations were recorded. RESULTS Overall, 27% of EVD PPE HCWs and 50% of CP PPE HCWs made ≥1 protocol deviation while donning, and 100% of EVD PPE HCWs and 67% of CP PPE HCWs made ≥1 protocol deviation while doffing (P=.02). The median number of doffing protocol deviations among EVD PPE HCWs was 4, versus 1 among CP PPE HCWs. Also, 15 EVD PPE protocol deviations were committed by doffing assistants and/or trained observers. Fluorescence was detected on 8 EVD PPE HCWs (44%) and 5 CP PPE HCWs (28%), most commonly on hands. MS2 was recovered from 2 EVD PPE HCWs (11%) and 3 CP PPE HCWs (17%). CONCLUSIONS Protocol deviations were common during both EVD and CP PPE doffing, and some deviations during EVD PPE doffing were committed by the HCW doffing assistant and/or the trained observer. Self-contamination was common. PPE donning/doffing are complex and deserve additional study. Infect Control Hosp Epidemiol 2017;38:1077-1083.

Randomized Controlled Trial to Determine the Impact of Probiotic Administration on Colonization With Multidrug-Resistant Organisms in Critically Ill Patients.

This was a randomized controlled pilot study of Lactobacillus rhamnosus GG versus standard of care to prevent gastrointestinal multidrug-resistant organism colonization in intensive care unit patients. Among 70 subjects, there were no significant differences in acquisition or loss of any multidrug-resistant organisms (P>.05) and no probiotic-associated adverse events.

Comparison of Chromogenic Media for Recovery of Carbapenemase-Producing Enterobacteriaceae (CPE) and Evaluation of CPE Prevalence at a Tertiary Care Academic Medical Center

ABSTRACT We evaluated the performance characteristics of chromID CARBA and HardyCHROM Carbapenemase for the detection of carbapenemase-producing Enterobacteriaceae (CPE). A CPE prevalence study was conducted using chromID CARBA; this demonstrated that in low-prevalence settings, CPE screening agars may lack specificity, and confirmation of putative isolates is necessary.

Evaluation of correlation between pretest probability for Clostridium difficile infection and Clostridium difficile enzyme immunoassay results

ABSTRACT The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI.

An evaluation of the prevalence of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in hospital food

This prospective cohort study evaluated the presence of MRSA and VRE in the food of hospitalized patients. 149 patients were enrolled and 910 food specimens cultured; 3.2% were positive for MRSA and 2.4% positive for VRE, from a variety of food types.

Ceftolozane-tazobactam activity against phylogenetically diverse Clostridium difficile strains.

ABSTRACT Ceftolozane-tazobactam (C/T) is approved for the treatment of complicated intra-abdominal and urinary tract infections and has varied activity against anaerobic bacteria. Here, we evaluate the activity of C/T against a phylogenetically diverse collection of Clostridium difficile isolates and report uniformly high MICs (≥256 μg/ml) to C/T.