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Key Points Increased risk of SARS-CoV-2 infection was associated with community prevalence. Increased risk of SARS-CoV-2 infection was associated with exposure to infected family members and personal infection prevention measures

Objective:Alteration of the colonic microbiota following antimicrobial exposure allows colonization by antimicrobial-resistant organisms (AROs). Ingestion of a probiotic, such as Lactobacillus rhamnosus GG (LGG), could prevent colonization or infection with AROs by promoting healthy colonic microbiota. The purpose of this trial was to determine the effect of LGG administration on ARO colonization in hospitalized patients receiving antibiotics.Design:Prospective, double-blinded, randomized controlled trial of LGG versus placebo among patients receiving broad-spectrum antibiotics.Setting:Tertiary care center.Patients:In total, 88 inpatients receiving broad-spectrum antibiotics were enrolled.Intervention:Patients were randomized to receive 1 capsule containing 1×1010 cells of LGG twice daily (n = 44) or placebo (n = 44), stratified by ward type. Stool or rectal-swab specimens were collected for culture at enrollment, during admission, and at discharge. Using selective media, specimens were cultured for Clostridioides difficile, vancomycin-resistant Enterococcus spp (VRE), and antibiotic-resistant gram-negative bacteria. The primary outcome was any ARO acquisition. Secondary outcomes included loss of any ARO if colonized at enrollment, and acquisition or loss of individual ARO.Results:ARO colonization prevalence at study enrollment was similar (LGG 39% vs placebo 39%). We detected no difference in any ARO acquisition (LGG 30% vs placebo 33%; OR,1.19; 95% CI, 0.38–3.75) nor for any individual ARO acquisition. There was no difference in the loss of any ARO (LGG 18% vs placebo 24%; OR, 1.44; 95% CI, 0.27–7.68) nor for any individual ARO.Conclusion:LGG administration neither prevented acquisition of ARO nor accelerated loss of ARO colonization.

Introduction: Clostridioides difficile remains the most common cause of healthcare-associated infections in the US, and it disproportionately affects the elderly. Older patients are more susceptible and have a greater risk of adverse outcomes from C. difficile infection (CDI), despite advances in treatment and prevention.Areas covered: The epidemiology and pathogenesis of CDI, as well as risk factors in the aging host, will be reviewed. The importance of antimicrobial stewardship and infection prevention in order to avoid acquisition and transmission will be discussed, as well as strategies to prevent adverse outcomes and recurrent CDI, through optimization of CDI treatment s,election.Expert opinion: Appropriate CDI-prevention strategies to avoid adverse outcomes in this susceptible population involve antimicrobial stewardship and methods to prevent C. difficile transmission in healthcare settings. Management strategies to prevent adverse outcomes include initiation of supportive therapy and proper selection of CDI specific treatments. Many patients may also benefit from adjunctive therapies or additional procedures.

Objective:To assess potential transmission of antibiotic-resistant organisms (AROs) using surrogate markers and bacterial cultures.Design:Pilot study.Setting:A 1,260-bed tertiary-care academic medical center.Participants:The study included 25 patients (17 of whom were on contact precautions for AROs) and 77 healthcare personnel (HCP).Methods:Fluorescent powder (FP) and MS2 bacteriophage were applied in patient rooms. HCP visits to each room were observed for 2–4 hours; hand hygiene (HH) compliance was recorded. Surfaces inside and outside the room and HCP skin and clothing were assessed for fluorescence, and swabs were collected for MS2 detection by polymerase chain reaction (PCR) and selective bacterial cultures.Results:Transfer of FP was observed for 20 rooms (80%) and 26 HCP (34%). Transfer of MS2 was detected for 10 rooms (40%) and 15 HCP (19%). Bacterial cultures were positive for 1 room and 8 HCP (10%). Interactions with patients on contact precautions resulted in fewer FP detections than interactions with patients not on precautions (P < .001); MS2 detections did not differ by patient isolation status. Fluorescent powder detections did not differ by HCP type, but MS2 was recovered more frequently from physicians than from nurses (P = .03). Overall, HH compliance was better among HCP caring for patients on contact precautions than among HCP caring for patients not on precautions (P = .003), among nurses than among other nonphysician HCP at room entry (P = .002), and among nurses than among physicians at room exit (P = .03). Moreover, HCP who performed HH prior to assessment had fewer fluorescence detections (P = .008).Conclusions:Contact precautions were associated with greater HCP HH compliance and reduced detection of FP and MS2.

Background Hospitalized patients with diarrhea who have a negative Clostridoides difficile (C. difficile) test are not routinely evaluated for alternative causes of infectious diarrhea. This study assessed for potential infectious causes of diarrhea in hospitalized patients with an order for repeat C. difficile toxin enzyme immunoassay (tEIA) testing after an initial tEIA test was negative. Methods For patients age ≥18 years who had a second C. difficile tEIA test ordered within 96 h after a negative tEIA test, remnant fecal specimens from the first (negative) tEIA test were evaluated using the BioFire FilmArray Gastrointestinal Panel PCR, C. difficile toxigenic culture, and culture on a blood agar plate (BAP) to identify other potential causes of infectious diarrhea. Growth of organisms on the BAP was also used to assess potential disruptions in the gastrointestinal microbiota. Results Among 84 remnant specimens, toxigenic C. difficile was identified in 9 (11%) by culture or PCR, while potential alternative causes of infectious diarrhea, including norovirus, rotavirus, enteropathogenic Escherichia coli, and Salmonella, were identified in 11 specimens (13%) by PCR. For the majority of patients, no infectious cause of diarrhea was identified, but 84% exhibited disrupted gastrointestinal microbiota, which may contribute to diarrhea. Conclusions When a hospitalized patient has a negative C. difficile tEIA test but continues to have diarrhea, alternative infectious and noninfectious causes of diarrhea should be considered. If the patient has clinical signs and symptoms suggestive of infection or risk factors for gastrointestinal infection, laboratory testing for other etiologic agents may be appropriate.

A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay., Clostridioides difficile infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with C. difficile unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin (n = 8) or placebo (n = 7). C. difficile and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with C. difficile posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity (P = 0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes (P = 0.037) increased after treatment; C. difficile and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear C. difficile, and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.) IMPORTANCE A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease C. difficile shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of C. difficile, perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of C. difficile/ARO-related outcomes and transmission.

Background. Intestinal microbiota restoration can be achieved by replacing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is depletion of antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. Results. All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards healthier configurations were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel ‘transplantation index’ metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. Conclusions. Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.

Accurate and timely diagnosis of Clostridioides difficile infection (CDI) is imperative to prevent C. difficile transmission and reduce morbidity and mortality due to CDI, but CDI laboratory diagnostics are complex. The purpose of this article is to review the role of laboratory tests in the diagnosis of CDI and the role of diagnostic stewardship in optimization of C. difficile testing. Results from C. difficile diagnostic tests should be interpreted with an understanding of the strengths and limitations inherent in each testing approach. Use of highly sensitive molecular diagnostic tests without accounting for clinical signs and symptoms may lead to over-diagnosis of CDI and increased facility CDI rates. Current guidelines recommend a two-step, algorithmic approach for testing. Diagnostic stewardship interventions, such as education, order sets, order search menus, reflex orders, hard and soft stop alerts, electronic references, feedback and benchmarking, decision algorithms, and predictive analytics, may help improve use of C. difficile laboratory tests and CDI diagnosis. The diagnostic stewardship approaches with the highest reported success rates include computerized clinical decision support (CCDS) interventions, face-to-face feedback, and real-time evaluations. CDI is a clinical diagnosis supported by laboratory findings. Together, clinical evaluation combined with diagnostic stewardship can optimize the accurate diagnosis of CDI.

A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.

ObjectiveTo determine the prevalence of Clostridium difficile colonization among patients who meet the 2017 IDSA/SHEA C. difficile infection (CDI) Clinical Guideline Update criteria for the preferred patient population for C. difficile testing.DesignRetrospective cohort.SettingTertiary-care hospital in St. Louis, Missouri.PatientsPatients whose diarrheal stool samples were submitted to the hospital’s clinical microbiology laboratory for C. difficile testing (toxin EIA) from August 2014 to September 2016.InterventionsElectronic and manual chart review were used to determine whether patients tested for C. difficile toxin had clinically significant diarrhea and/or any alternate cause for diarrhea. Toxigenic C. difficile culture was performed on all stool specimens from patients with clinically significant diarrhea and no known alternate cause for their diarrhea.ResultsA total of 8,931 patients with stool specimens submitted were evaluated: 570 stool specimens were EIA positive (+) and 8,361 stool specimens were EIA negative (−). Among the EIA+stool specimens, 107 (19% of total) were deemed eligible for culture. Among the EIA− stool specimens, 515 (6%) were eligible for culture. One EIA+stool specimen (1%) was toxigenic culture negative. Among the EIA− stool specimens that underwent culture, toxigenic C. difficile was isolated from 63 (12%).ConclusionsMost patients tested for C. difficile do not have clinically significant diarrhea and/or potential alternate causes for diarrhea. The prevalence of toxigenic C. difficile colonization among EIA− patients who met the IDSA/SHEA CDI guideline criteria for preferred patient population for C. difficile testing was 12%.

OBJECTIVETo evaluate healthcare worker (HCW) risk of self-contamination when donning and doffing personal protective equipment (PPE) using fluorescence and MS2 bacteriophage.DESIGNProspective pilot study.SETTINGTertiary-care hospital.PARTICIPANTSA 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.INTERVENTIONSHCWs 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.RESULTSOverall, 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%).CONCLUSIONSProtocol 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

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.

The increasing antimicrobial resistance of uropathogens is challenging the continued efficacy of empiric antibiotic therapy for UTIs, which are among the most frequent bacterial infections worldwide. It has been suggested that drug-resistant uropathogens could persist in the intestine after the resolution of UTI and cause recurrences following periurethral contamination. A better understanding of the transmission dynamics between the intestinal and urinary tracts, combined with phenotypic characterization of the uropathogen populations in both habitats, could inform prudent therapies designed to overcome the rising resistance of uropathogens. Here, we integrate genomic surveillance with clinical microbiology to show that drug-resistant clones persist within and are readily transmitted between the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Thus, our results advocate for understanding persistent intestinal uropathogen colonization as part of the pathophysiology of UTIs, particularly in patients affected by recurrent episodes of symptomatic disease., The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae isolates in the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Clonal tracking of isolates in consecutively collected urine and fecal specimens indicated repeated transmission of uropathogens between the urinary tract and their intestinal reservoir. Our results further implicate three independent routes of recurrence of UTIs: (i) following an intestinal bloom of uropathogenic bacteria and subsequent bladder colonization, (ii) reinfection of the urinary tract from an external source, and (iii) bacterial persistence within the urinary tract. Taken together, our observation of clonal persistence following UTIs and uropathogen transmission between the intestinal and urinary tracts warrants further investigations into the connection between the intestinal microbiome and recurrent UTIs.

Background Multi-drug-resistant organisms (MDRO) have complicated the treatment of urinary tract infections (UTIs), especially in patients with recurrent UTIs (rUTI). The objective of this pilot prospective cohort study is to determine the role of the fecal microbiome in rUTIs. Methods Stool and urine specimens were prospectively collected from patients with MDRO UTIs at 6 time points during and after the UTI, and with any rUTI. Specimens underwent semi-quantitative culture on differential and selective media for MDROs, and isolates underwent phenotypic susceptibility testing and whole-genome sequencing. Comparative genomics and clonal tracking were used to detect clonal uropathogen strains in the urinary and gastrointestinal tracts. Resistance genes, resistance-plasmids, and virulence genes of MDROs were characterized in silico. Results A total of 110 isolates (95 Escherichia coli, 2 Klebsiella pneumoniae, 13 Proteus mirabilis) were cultured from the urine and stool of 15 patients (7 non-rUTI, 8 rUTI). Clonal uropathogens were isolated between the urinary tract and their intestinal reservoir (Figure 1). Integration of clonality information with semiquantitative culturing implicated three potential routes for recurrence of UTIs: (i) bladder colonization following an intestinal bloom of uropathogens, (ii) reinfection from an external source, and (III) bacterial persistence within the urinary tract (Figures 2 and 3). Antibiotic susceptibility testing and genomic profiling indicated that antibiotic-resistant uropathogen populations colonizing the urinary tract and intestinal reservoir at symptomatic and asymptomatic timepoints have similar resistance profiles that are largely determined via a pool of shared resistance plasmids (Figure 3). Conclusion This study provides the first time-resolved analysis of uropathogen persistence following UTIs, showing that clonal antibiotic-resistant uropathogens can be detected in both the urine and stool at varying time points post-initial infection. The study implicates 3 potential routes of rUTI, including uropathogen persistence within the gut microbiota, reinfection from an external source, and persistent bacteriuria. Study findings could be utilized to inform future diagnostics and therapies for treatment of rUTIs. Disclosures Carey-Ann Burnham, PhD, BioFire: Research Grant; bioMerieux: Research Grant; Cepheid: Research Grant; Luminex: Research Grant.

The impact of recurrent Clostridium difficile infections (CDIs) on hospital readmissions is unknown. The objective of this study was to determine whether recurrent CDI was independently associated with the number of hospital readmissions and days readmitted.We performed a retrospective cohort study at an academic, urban, tertiary care hospital. Data were collected from electronic medical records and supplemented with chart review. CDI patients were followed for 180 days to ascertain the number of hospital readmissions and total days readmitted. Univariate and multivariable negative binomial regression models were used to evaluate factors, including CDI recurrence, associated with hospital readmissions.The study included 3,950 patients with CDI from 2003-2009, including 413 patients with recurrent CDI. Recurrent CDI patients were significantly more likely to have at least 1 readmission (85% vs 41%; P.001) and had more days readmitted (mean = 18.6 vs 7.6; P.001) than patients without recurrent CDI. In multivariable analysis, recurrent CDI was independently associated with number of readmissions (rate ratio = 2.54; 95% confidence interval [CI], 2.21-2.91) and days readmitted (rate ratio = 3.97; 95% CI, 3.11-5.08) after adjustment for demographics, comorbidities, and medications.Recurrent CDI patients are significantly more likely than patients without a recurrence to be readmitted and spend increased time readmitted to the hospital.

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.

BACKGROUND Recurrent Clostridium difficile infection (rCDI) affects 10% to 25% of patients with initial CDI (iCDI). Initiation of new therapies that reduce recurrences rests on identifying patients at high risk for rCDI at iCDI onset. OBJECTIVE To develop a predictive model for rCDI based on factors present at iCDI onset. DESIGN Retrospective cohort study. SETTING Large urban academic medical center. PATIENTS All adult patients with an inpatient iCDI from January 1, 2003 to December 31, 2009. INTERVENTION None. MEASUREMENTS Positive toxin assay for C difficile with no C difficile infection in the previous 60 days constituted iCDI. Repeat positive toxin within 42 days of stopping iCDI treatment defined rCDI. Three demographic, 13 chronic, and 12 acute disease characteristics, and 7 processes of care prior to or at the onset of iCDI, were assessed for association with rCDI. A logistic regression model to identify predictors for rCDI was developed and cross-validated. RESULTS Among the 4196 patients enrolled, 425 (10.1%) developed rCDI. Six factors (case status as community-onset healthcare-associated, ≥2 hospitalizations in the prior 60 days, new gastric acid suppression, fluoroquinolone and high-risk antibiotic use at the onset of iCDI, age) predicted rCDI in multivariate analyses, whereas intensive care unit stay appeared protective. The model achieved moderate discrimination (C statistic 0.643) and calibration (Brier score 0.089). Its negative predictive value was 90% or higher across a wide range of risk. CONCLUSIONS Among patients hospitalized with rCDI, multiple factors present at the onset of iCDI increased the risk for rCDI. Recognizing patients at high-risk for rCDI can help clinicians tailor early treatment and prevention. Journal of Hospital Medicine 2014;9:418–423. © 2014 Society of Hospital Medicine

Background Antibiotics (ABX) are frequently inappropriately used to treat nonbacterial causes of respiratory illnesses. The goal of this prospective cohort study was to characterize the impact of ABX used to treat community-acquired pneumonia (CAP) on the fecal microbiome and resistome in healthy volunteers (HV). Methods Twenty HVs were randomized to receive 5 days of levofloxacin (LV), azithromycin (AZ), cefpodoxime (CF), or AZ+CF. Stool was collected before, during, and after ABX, then underwent microbiologic culture and shotgun sequencing. DNA was extracted, then sequenced using the Illumina NextSeq platform. Relative abundance of bacterial taxa was estimated by MetaPhlAn and antibiotic resistance gene (ARG) composition by ShortBRED. Analysis was in R. Results The mean HV age was 37 (range 24–59) and 10 were female. Species diversity measured via Shannon Index and richness were significantly lower in samples taken from all HVs 3 days post-ABX (P < 0.01 for all). While nonmetric multidimensional scaling (NDMS) ordination shows high interpatient dissimilarity (Bray–Curtis) for most samples, the post-ABX intrapatient dissimilarity varies by ABX. The AZ group exhibited chronic alterations in taxa dissimilarity and the CF group had increases in dissimilarity directly post-ABX. The CF+AZ group displayed both acute and persistent perturbations (Figure 1). Although there was no significant change in ARG richness post-ABX, there was a significant increase in overall ARG abundance across all samples (P < 0.003). Within each ABX, there were unique changes in ARG abundance, and groups with CF had increases in ARG abundance (Figure 2). Conclusion ABX used to treat CAP can cause acute microbiome disruptions, as evidenced by decreased microbiome species diversity and richness, and an increase in ARG abundance post-ABX. The duration of this impact is variable. To prevent microbiome disruptions, measures to prevent inappropriate ABX use via ABX stewardship are necessary. Disclosures E. R. Dubberke, Rebiotix: Consultant and Investigator, Consulting fee and Research support. Pfizer: Consultant and Grant Investigator, Consulting fee and Research grant. Synthetic biologics: Consultant, Consulting fee. Merck: Consultant and Investigator, Consulting fee and Research support. Valneva: Consultant, Consulting fee. Achaogen: Consultant, Consulting fee. Alere: webinar, Speaker honorarium. Biofire: webinar, Speaker honorarium.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6–7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9–75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018”/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018” isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Background The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. Methods A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6–7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. Results Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018”, and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. Conclusion The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Background MDRO present a greater threat to public health than ever before, and antimicrobial options are decreasing. Altered colonic microbiota following antimicrobial exposure allows for subsequent colonization by MDRO. Ingestion of prophylactic Lactobacillus rhamnosus GG (LGG) could be an approach to prevent the spread of, and subsequent infection due to MDRO, by promoting a healthy bacterial milieu within the colon. Methods This is a prospective, double-blinded, randomized clinical trial in which a total of 87 subjects on broad-spectrum antibiotics were randomized to receive LGG twice daily (n = 43) vs placebo (n = 44). Stool or rectal swab specimens were collected for culture at enrollment, every 3 days during admission, and at discharge. Selective media were used to detect the following MDRO: Clostridioides difficile (CD), vancomycin-resistant Enterococcus (VRE), and antibiotic-resistant Gram-negatives (GN). The primary outcome was MDRO acquisition. Secondary outcomes included analysis for loss of any MDRO if colonized at enrollment, and acquisition or loss of individual MDRO. Results Subjects in both groups had similar prevalence of colonization with any MDRO at study enrollment (LGG 40% vs. placebo 39%), with similar colonization prevalence for individual MDRO (Figure 1). There was no difference in any MDRO acquisition (LGG 27%, placebo 33%, OR 1.36, 95% CI 0.42–4.41) or any individual MDRO acquisition (Figure 2). There was also no difference in loss of any MDRO (LGG 18%, placebo 24%, OR 1.44, 95% CI 0.27–7.68) or any individual MDRO (Figure 2). Conclusion LGG administration did not prevent acquisition of MDRO or accelerate loss of MDRO colonization. Disclosures All authors: No reported disclosures.

OBJECTIVETo determine whetherClostridium difficileis present in the food of hospitalized patients and to estimate the risk of subsequent colonization associated withC. difficilein food.METHODSThis was a prospective cohort study of inpatients at a university-affiliated tertiary care center, May 9, 2011–July 12, 2012. Enrolled patients submitted a portion of food from each meal. Patient stool specimens and/or rectal swabs were collected at enrollment, every 3 days thereafter, and at discharge, and were cultured forC. difficile. Clinical data were reviewed for evidence of infection due toC. difficile.A stochastic, discrete event model was developed to predict exposure toC. difficilefrom food, and the estimated number of new colonization events from food exposures per 1,000 admissions was determined.RESULTSA total of 149 patients were enrolled and 910 food specimens were obtained. Two food specimens from 2 patients were positive forC. difficile(0.2% of food samples; 1.3% of patients). Neither of the 2 patients was colonized at baseline withC. difficile. Discharge colonization status was available for 1 of the 2 patients and was negative. Neither was diagnosed withC. difficileinfection while hospitalized or during the year before or after study enrollment. Stochastic modeling indicated contaminated hospital food would be responsible for less than 1 newly colonized patient per 1,000 hospital admissions.CONCLUSIONSThe recovery ofC. difficilefrom the food of hospitalized patients was rare. Modeling suggests hospital food is unlikely to be a source ofC. difficileacquisition.Infect Control Hosp Epidemiol2016;1401–1407

The incidence and severity of Clostridium difficile infection (CDI) have been increasing in recent years [1–7], but national surveillance efforts and interhospital comparisons have been limited by the lack of a standard CDI surveillance system. As a result, the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes assigned at hospital discharge have been used as a proxy to estimate CDI prevalence in the United States [8–12]. Using administrative data (ICD-9-CM codes) to compare CDI rates between hospitals has several potential advantages. Administrative discharge data are inexpensive to obtain, are systematically collected, and utilize a single ICD-9-CM code to designate CDI (008.45), thus potentially providing a nationally representative method for tracking CDI rates [8, 13, 14]. Two administrative databases have been used to estimate CDI prevalence in the United States: the National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS). ICD-9-CM code data are collected differently in each database; neither data set collects all potential ICD-9-CM codes assigned at hospital discharge. The NHDS is collected annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention (CDC), and about 90% of a panel of 500 hospitals participate [8]. The NIS, on the other hand, is collected from all states that participate in the Healthcare Cost and Utilization Project and includes information from about 1000 US hospitals [15]. The NHDS collects up to the first 7 ICD-9-CM codes assigned per patient, and the NIS collects up to the first 9–15 codes assigned per patient (the number of codes captured varies by state). Despite their advantages, a recent study suggests that ICD-9-CM codes may not be acceptable for hospital-onset CDI surveillance. A multicenter study performed at the CDC Prevention Epicenters hospitals compared the incidences of hospital-onset CDI as measured by ICD-9-CM codes with toxin assay results. ICD-9-CM codes overestimated the incidence of hospital-onset CDI, compared with toxin assay results, indicating that ICD-9-CM codes are not an acceptable surrogate for hospital-onset CDI surveillance [16]. The degree to which ICD-9-CM codes overreported the incidence of hospital-onset CDI varied by year and by hospital, indicating that ICD-9-CM codes would not have been useful for intrahospital or interhospital CDI surveillance. No previously published CDI prevalence study using ICD-9-CM codes has differentiated between the NHDS and NIS criteria. The data collection discrepancies between these 2 data sets may account for the conflicting results of previous studies of CDI prevalence. It is not known how the differences in the number of ICD-9-CM codes available for prevalence estimation affect the estimated CDI prevalence and how CDI burden estimates based on ICD-9-CM codes compare with toxin assay results. Therefore, we investigated how the NHDS and NIS criteria affect CDI prevalence and how these definitions compare with toxin assay results at multiple healthcare facilities during a 6-year study period.

Objective.To develop and validate a risk prediction model that could identify patients at high risk for Clostridium difficile infection (CDI) before they develop disease.Design and Setting.Retrospective cohort study in a tertiary care medical center.Patients.Patients admitted to the hospital for at least 48 hours during the calendar year 2003.Methods.Data were collected electronically from the hospital's Medical Informatics database and analyzed with logistic regression to determine variables that best predicted patients' risk for development of CDI. Model discrimination and calibration were calculated. The model was bootstrapped 500 times to validate the predictive accuracy. A receiver operating characteristic curve was calculated to evaluate potential risk cutoffs.Results.A total of 35,350 admitted patients, including 329 with CDI, were studied. Variables in the risk prediction model were age, CDI pressure, times admitted to hospital in the previous 60 days, modified Acute Physiology Score, days of treatment with high-risk antibiotics, whether albumin level was low, admission to an intensive care unit, and receipt of laxatives, gastric acid suppressors, or antimotility drugs. The calibration and discrimination of the model were very good to excellent (C index, 0.88; Brier score, 0.009).Conclusions.The CDI risk prediction model performed well. Further study is needed to determine whether it could be used in a clinical setting to prevent CDI-associated outcomes and reduce costs.

Background Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. Methods We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Results Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). Conclusions The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

Objective.To describe a pseudo-outbreak ofClostridium difficileinfection (CDI) caused by a faulty toxin assay lot and to determine the effect of sensitivity, specificity, and repeated testing forC. difficileon perceived CDI burden, positive predictive value, and false-positive results.Design.Outbreak investigation and criterion standard.Patients.Patients hospitalized at a tertiary care hospital who had at least 1 toxin assay for detection ofC. difficileperformed during the period from July 1, 2004, through June 30, 2006.Methods.The run control chart method and thex2test were used to compare CDI rates and the proportion of positive test results before, during, and after the pseudo-outbreak. The effect of repeated testing was evaluated by using 3 hypothetical models with a sample of 10,000 patients and various assay sensitivity and specificity estimates.Results.In November of 2005, the CDI rate at the hospital increased from 1.5 to 2.6 cases per 1,000 patient-days (P< .01), and the proportion of positive test results increased from 13.6% to 22.1% (P< .01). An investigation revealed a pseudo-outbreak caused by a faulty toxin assay lot. A decrease of only 1.2% in the specificity of the toxin assay would result in a 32% increase in perceived incidence of CDI at this institution. When calculated by use of the manufacturer's stated specificity and sensitivity and this institution's testing practices, the positive predictive value of the test decreased from 80.6% to 4.1% for patients who received 3 tests.Conclusion.Specificity is as important as sensitivity when testing for CDI. False-positive CDI cases can drain hospital resources and adversely affect patients. Repeated testing forC. difficileshould be performed with caution.

Objectives.To compare Clostridium difficile infection (CDI) rates determined with use of a traditional definition (ie, with healthcare-onset CDI defined as diagnosis of CDI more than 48 hours after hospital admission) with rates determined with use of expanded definitions, including both healthcare-onset CDI and community-onset CDI, diagnosed within 48 hours after hospital admission in patients who were hospitalized in the previous 30 or 60 days, and to determine whether differences exist between patients with CDI onset in the community and those with CDI onset in a healthcare setting.Design.Prospective cohortSetting.Tertiary acute care facility.Patients.General medicine patients who received a diagnosis of CDI during the period January 1, 2004, through December 31, 2005.Methods.CDI was classified as healthcare-onset CDI, healthcare facility–associated CDI after hospitalization within the previous 30 days, and/or healthcare facility-associated CDI after hospitalization within the previous 60 days. Patient demographic characteristics and medication exposures were obtained. The CDI incidence with use of each definition, CDI rate variability, patient demographic characteristics, and medication exposures were compared.Results.The healthcare-onset CDI rate (1.6 cases per 1,000 patient-days) was significantly lower than the 30-day healthcare facility–associated CDI rate (2.4 cases per 1,000 patient-days; PPPPP = .02) or intravenous vancomycin (P = .01) during hospitalization.Conclusions.Compared with the traditional definition, expanded definitions identify more patients with CDI. There is good correlation between traditional and expanded CDI definitions; therefore, it is unclear whether expanded surveillance is necessary to identify an abnormal change in CDI rates. Cases that met the expanded definitions were less likely to have occurred in patients with fourth-generation cephalosporin and vancomycin exposure.

CDAD led to significantly worse outcomes in these patients., Data are limited on the attributable outcomes of Clostridium difficile–associated disease (CDAD), particularly in CDAD-endemic settings. We conducted a retrospective cohort study of nonsurgical inpatients admitted for >48 hours in 2003 (N = 18,050). The adjusted hazard ratios for readmission (hazard ratio 2.19, 95% confidence interval [CI] 1.87–2.55) and deaths within 180 days (hazard ratio 1.23, 95% CI 1.03–1.46) were significantly different among CDAD case-patients and noncase patients. In a propensity score matched-pairs analysis that used a nested subset of the cohort (N = 706), attributable length of stay attributable to CDAD was 2.8 days, attributable readmission at 180 days was 19.3%, and attributable death at 180 days was 5.7%. CDAD patients were significantly more likely than controls to be discharged to a long-term-care facility or outside hospital. Even in a nonoutbreak setting, CDAD had a statistically significant negative impact on patient illness and death, and the impact of CDAD persisted beyond hospital discharge.

Background & Aims:Clostridium difficile–associated disease (CDAD) rates have been increasing. We sought to determine whether CDAD incidence has increased specifically in hospitalized patients with IBD. We also explored possible differences in the risk for and time to presentation of CDAD between IBD and non-IBD patients. Methods: We analyzed hospital admissions from 1998–2004 for demographics, length of stay, C difficile infections, and time from admission to a positive C difficile test. We calculated CDAD incidence for non-IBD, all IBD, CD, and UC admissions and used logistic regression to estimate the risk for CDAD. Results: CDAD incidence increased in each group and was higher in all IBD than non-IBD groups. During the observation period, CDAD rates approximately doubled in CD (9.5 to 22.3/1000 admissions) and tripled in UC (18.4 to 57.6/1000). Length of stay was similar among the groups. For all years combined, the adjusted odds ratios for CDAD in all IBD, CD, and UC admissions were 2.9 (95% confidence interval, 2.1–4.1), 2.1 (1.3–3.4), and 4.0 (2.4–6.6), respectively. The median times from admission to a positive C difficile test result for non-IBD, CD, and UC were 4.0, 0.8, and 0.5 days, respectively. Conclusions: CDAD incidence in IBD has increased and is higher than in the non-IBD population. IBD and UC patients in particular have a higher risk for CDAD. C difficile infections in IBD are confirmed predominantly within 48 hours of admission, suggesting most were acquired before hospitalization.

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.Infect. Control Hosp. Epidemiol. 2015;36(12):1451–1454

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.

We conducted a retrospective cohort study to compare Clostridium difficile–associated disease rates determined by C. difficile–toxin assays and International Classification of Diseases, 9th Revision (ICD-9) codes. The correlation between toxin assay results and ICD-9 codes was good (κ = 0.72, p

Background The objective of the study was to assay for alternative infectious causes of diarrhea in patients with negative EIA tests for Clostridium difficile. Methods A hard-stop alert was implemented at a tertiary care hospital to limit repeat testing for C. difficile within 96 hours of an initial negative EIA. Stool samples from patients with a negative (–) repeat EIA test for C. difficile within 96 hours in the 3 months pre- and postintervention underwent further evaluation: C. difficile toxigenic culture, GeneXpert C. difficile PCR, Biofire Gastrointestinal (GI) Panel, and culture on a blood agar plate. Results Of the 84 C. difficile EIA stool specimens evaluated, 8% were toxigenic culture positive (+), 8% tested + for C. difficile via the Biofire GI panel, and 5 (7%) + with the GenXpert C. difficile PCR (Table 1). Three of these patients were diagnosed with CDI within 30 days of a + test. Five patients were + for Norovirus via Biofire GI panel; none were tested for or diagnosed with Norovirus. Two patients were + for Enteropathogenic E. coli and one for Enteroaggregative E. coli via Biofire GI panel; none were tested for or diagnosed with E. coli infection. One patient was positive for Salmonella and Salmonella was isolated by stool culture. Conclusion Patients tested for C. difficile may have alternate causes of diarrhea. When evaluating hospitalized patients with diarrhea, C. difficile, along with alternate causes of diarrhea can be considered. Table 1. Alternate infectious causes of diarrhea Result Preintervention (N = 73) Postintervention (N = 11) Biofire GI results Negative 57 (78) 10 (91) Norovirus 5 (7)a 0 C. difficile toxin A/B gene 5 (7) 1 (9) Enteropathogenic E. coli 2 (3)b 0 Campylobacter 1 (1)c 0 C. difficile tox A/B gene and Rotavirus 1 (1) 0 Enteroaggregative E. coli 1 (1)b 0 Salmonella 1 (1)d 0 C. difficile culture positive Nontoxigenic C. difficile 2 (3) 2 (18) Toxigenic C. difficile 5 (7) 2 (18) GenXpert C. difficile PCR positive 5 (7) 0 Blood agar plates Klebsiella oxytoca 1 (1) 0 Staphylococcus aureus 3 (4) 0 aNone received clinical diagnosis of Norovirus. bNo clinical enteric culture performed or diagnosis received. cClinical enteric culture performed >30 days postindex stool collection (negative). dClinical enteric culture in hospital positive for Salmonella. Disclosures E. R. Dubberke, Merck: Consultant, Consulting fee; Biofire: one time talk, Speaker honorarium;; Alere: one-time talk, Speaker honorarium; Sanofi pasteur: Grant Investigator, Grant recipient; Pfizer: Consultant, Consulting fee; Rebiotix: Investigator, Research support; Rebiotix: Consultant, Consulting fee; valneva: Consultant, Consulting fee; C. A. D. Burnham, bioMerieux: Grant Investigator, Research grant; ThermoFisher: Consultant, Salary; Cepheid: Grant Investigator, Research grant

BACKGROUND Clostridium difficile infection (CDI) is a frequent cause of diarrhea among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown whether risk factors for CDI vary by time posttransplant. METHODS We performed a 3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants were enrolled during their transplant hospitalizations. Clinical assessments were performed weekly during hospitalizations and for 12 weeks posttransplant, and monthly for 30 months thereafter. Data were collected through patient interviews and chart review, and included CDI diagnosis, demographics, transplant characteristics, medications, infections, and outcomes. CDI cases were included if they occurred within 1 year of HCT and were stratified by time from transplant. Multivariable logistic regression was used to determine risk factors for CDI. RESULTS One hundred eighty-seven allogeneic HCT recipients were enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%) postengraftment (day >30). Lack of any preexisting comorbid disease was significantly associated with lower risk of CDI preengraftment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR, 6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95% CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were significant independent risk factors for CDI postengraftment. CONCLUSIONS A large portion of CDI cases occurred during the postengraftment period in allogeneic HCT recipients, suggesting that surveillance for CDI should continue beyond the transplant hospitalization and preengraftment period. Patients with continued high underlying severity of illness were at increased risk of CDI postengraftment.

Objective.To determine the attributable inpatient costs of recurrentClostridium difficileinfections (CDIs)Design.Retrospective cohort study.Setting.Academic, urban, tertiary care hospital.Patients.A total of 3,958 patients aged 18 years or more who developed an initial CDI episode from 2003 through 2009.Methods.Data were collected electronically from hospital administrative databases and were supplemented with chart review. Patients with an index CDI episode during the study period were followed up for 180 days from the end of their index hospitalization or the end of their index CDI antibiotic treatment (whichever occurred later). Total hospital costs during the outcome period for patients with recurrent versus a single episode of CDI were analyzed using zero-inflated lognormal models.Results.There were 421 persons with recurrent CDI (recurrence rate, 10.6%). Recurrent CDI case patients were significantly more likely than persons without recurrence to have any hospital costs during the outcome period (P< .001). The estimated attributable cost of recurrent CDI was $11,631 (95% confidence interval, $8,937–$14,588).Conclusions.The attributable costs of recurrent CDI are considerable. Patients with recurrent CDI are significantly more likely to have inpatient hospital costs than patients who do not develop recurrences. Better strategies to predict and prevent CDI recurrences are needed.Infect Control Hosp Epidemiol2014;35(11):1400–1407

Objective.Recent outbreaks ofClostridium difficileinfection (CDI) have been difficult to control, and data indicate that the importance of different sources of transmission may have changed. Our objectives were to evaluate the contributions of asymptomatic and symptomatic C.difficilecarriers to new colonizations and to determine the most important epidemiological factors influencing C.difficiletransmission.Design, Setting, and Patients.Retrospective cohort study of all patients admitted to medical wards at a large tertiary care hospital in the United States in the calendar year 2008.Methods.Data from six medical wards and published literature were used to develop a compartmental model of C.difficiletransmission. Patients could be in one of five transition states in the model: resistant to colonization (R), susceptible to colonization (S), asymptomatically colonized without protection against CDI (C-), asymptomatically colonized with protection against CDI (C+), and diseased (ie, with CDI; D).Results.The contributions of C-, C+, and D patients to new colonizations were similar. The simulated basic reproduction number ranged from 0.55 to 1.99, with a median of 1.04. These values suggest that transmission within the ward alone from patients with CDI cannot sustain new C.difficilecolonizations and therefore that the admission of colonized patients plays an important role in sustaining transmission in the ward. The epidemiological parameters that ranked as the most influential were the proportion of admitted C-patients and the transmission coefficient for asymptomatic carriers.Conclusion.Our study underscores the need to further evaluate the role of asymptomatically colonized patients in C.difficiletransmission in healthcare settings.

The incidence of Clostridium difficile-associated disease (CDAD) is increasing. There are few data on the short-term and long-term attributable costs of CDAD. The objective of this study was to determine the acute and 180-day attributable inpatient costs of CDAD.We performed a retrospective cohort study of all patients without operating room costs who were admitted foror =48 h to Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, Missouri, 1 January 2003-31 December 2003 (n = 24,691). Attributable costs of CDAD were determined by multivariable linear regression and propensity-score matched-pairs analyses (n = 684) for the hospitalization in which CDAD occurred and per patient over a 180-day period, including the initial hospitalization.CDAD was associated with $2454 (95% confidence interval, $2380-$2950; increase in cost, 41%) attributable costs per CDAD episode by linear regression and with $3240 attributable costs (P.001; increase in cost, 33%) by propensity-score matched-pairs analysis. CDAD was associated with $5042 (95% confidence interval, $3797-$6481; increase in cost, 53%) attributable inpatient costs over 180 days by linear regression and with $7179 attributable costs for inpatient care (P.001; 48% increase in costs) by propensity-score matched-pairs analysis.CDAD was associated with a significant increase in costs for inpatient care and increased costs at 180 days after the initial hospitalization when the CDAD episode occurred.

Background. Previous studies of risk factors for Clostridium difficile-associated disease (CDAD) have been limited by small sample sizes and case-control study designs. Many of these studies were performed during outbreaks of CDAD. Colonization pressure and use of fluoroquinolones, vancomycin, and gastric acid suppressors have not been fully evaluated as risk factors for CDAD. The purpose of this study was to determine risk factors for endemic CDAD, including CDAD pressure, a modified version of colonization pressure. Methods. We performed a retrospective cohort study of 36,086 patients admitted to Barnes-Jewish Hospital (St. Louis, MO) during the period from 1 January 2003 through 31 December 2003. Administrative, laboratory, and pharmacy data were collected from electronic hospital databases. Colonization pressure was measured through a surrogate variable (i.e., CDAD pressure). Multivariable pooled logistic regression models were used to evaluate independent risk factors for CDAD. Results. The analysis included 382 CDAD case patient admissions and 35,704 non-case patient admissions. Significant independent risk factors for CDAD included increasing age, admission(s) in the previous 60 days, hypoalbuminemia, leukemia and/or lymphoma, mechanical ventilation, and receipt of antimotility drugs, histamine-2 blockers, proton pump inhibitors, intravenous vancomycin, fluoroquinolones, and first-, third-, or fourth-generation cephalosporins. Increasing CDAD pressure was a strong risk factor for CDAD (for a CDAD pressure >1.4, the odds ratio was 4.0; 95% confidence interval, 2.9-5.6). Receipt of metronidazole was protective against CDAD (odds ratio, 0.5; 95% confidence interval, 0.3-0.6). Conclusions. This study identified the previously underrecognized CDAD risk factors of CDAD pressure and vancomycin. More studies are needed to evaluate the relationship between CDAD, these risk factors, and use of gastric acid suppressors and fluoroquinolones.

Colonization pressure has been identified as an important risk factor in the transmission of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus species, but the role of colonization pressure in the transmission of Clostridium difficile-associated disease (CDAD) is unclear. The purpose of this study was to evaluate CDAD pressure, a modified form of colonization pressure based on symptomatic CDAD cases, as a risk factor for CDAD.Retrospective cohort and nested case-control studies of patients admitted to Barnes-Jewish Hospital from January 1, 2003, through December 31, 2003. Univariate analysis and multivariate logistic regression models were used to evaluate the role of CDAD pressure as a risk factor for CDAD.A total of 36 275 patients were included in the cohort, of which 382 had CDAD. The median CDAD pressure was higher for case patients than noncase patients (1.4 vs 0.3; P.001), and only 1 patient with CDAD had a CDAD pressure of 0. In the nested case-control study, CDAD pressure remained an independent risk factor for CDAD after adjustment for demographics, severity of illness, medications received (chemotherapy, gastric acid suppressors, antidiarrheals or narcotics, and antibiotics), and abdominal procedures or surgery performed.The results of this study suggest that CDAD pressure may be an independent risk factor for CDAD. Future studies that evaluate risk of CDAD should control for CDAD pressure.

Clostridium difficile spores can contaminate the hospital environment. Little is known about the prevalence and strain variability of C. difficile environmental contamination in health care facilities. The objective of this study was to assess C. difficile environmental contamination at various health care facilities in a metropolitan area and determine if the North American pulsed field gel electrophoresis type 1 (NAP1) strain was present.A cross-sectional pilot survey was conducted. Forty-eight environmental samples were collected from six health care facilities. Samples were cultured for the presence of C. difficile, and positive samples underwent pulsed field gel electrophoresis, toxinotyping, and detection of binary toxin and/or tcdC deletion.C. difficile was cultured from 13 of 48 (27%) samples. Rooms housing a patient with C. difficile-associated disease (CDAD) were more likely to be culture positive than non-CDAD patient rooms (100% vs. 33%; P0.01); C. difficile was not isolated outside of patient rooms (0 of 12 samples). The NAP1 epidemic strain was found in 5 out of 6 facilities.C. difficile spores frequently contaminated the hospital environment. Rooms with a CDAD patient were more likely to be contaminated than rooms without a CDAD patient. The NAP1 strain was prevalent throughout the metropolitan area.

The purpose of this study was to develop and test a Clostridium difficile-associated disease (CDAD) grading system based on presenting symptoms in allogeneic stem cell transplant recipients. Patients with severe CDAD had significantly shorter median survival times and more adverse outcomes than patients with mild or moderate CDAD.