Incident Clostridium Research Articles

Relationship Between Remote History of Cholecystectomy and Risk for Incident Clostridium difficile Infection

Introduction:Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea and gastroenteritis-associated death. Secondary bile acids inhibit C. difficile germination in vitro and confer resistance to CDI in animals. Cholecystectomy (CCY) alters gut bile acid composition, with increased fecal levels of secondary bile acids. This study tested the hypothesis that remote CCY confers protection against CDI by increasing gut levels of secondary bile acids. Methods: This was a retrospective case control study. The study population included all adult inpatients tested for the C. difficile toxin B gene by stool PCR between 1 January 2010 and 30 June 2017 at our institution, excluding those with a previous positive test for CDI within 90 days. For patients with multiple stool tests for C. difficile, the first test was selected. Remote CCY was defined as a history of CCY at least 6 months prior to the index test. Cases of CDI were defined as a positive stool PCR followed by anti-CDI treatment and were matched 1:1 with non-CDI controls by gender, age, BMI, and recent antibiotics exposure. Additional clinical factors including demographics, baseline comorbidities, medication exposures, and laboratory values were retrieved using automated queries. Conditional logistic regression modeling was used to estimate the relationship between remote CCY and risk for CDI, after adjusting for other factors. Results: The final study population was 4,918, including 2,459 CDI cases and 2,459 controls. Cases and controls did not differ based on gender, age, BMI, or recent antibiotics exposure. Patients with CDI had higher serum creatinine, more baseline comorbidities, and longer hospital stays. They were more likely to have an abnormal white blood cell count, to be in an intensive care unit, and to have recently received proton pump inhibitors. More patients with remote CCY were obese compared to patients without history of CCY (31% vs 25%, p<0.05) and were female (69% vs 50%, p<0.01). Rates of remote CCY did not differ based on CDI status (8.1% vs 7.9%, p=0.83). This result was unchanged after adjusting for additional clinical factors (adjusted OR 1.05, 95% CI 0.85-1.29, see Table) and also unchanged after adjusting for the matching variables. Conclusion: There was no association between remote CCY and risk for CDI in this large retrospective cohort study. Either gut bile acid content is not a major driver of CDI in humans or CCY impacts gut bile acids less than previously believed.168 Figure 1 No Caption available.

Adherence to Treatment Guidelines for Incident Clostridium difficile Infection in Critically Ill Adults

Adherence to Treatment Guidelines for Incident Clostridium difficile Infection in Critically Ill Adults

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients.

The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults.

Risk Factors for Recurrent Clostridium difficile Infection in Pediatric Inpatients.

The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention. This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children's hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were <18 years of age at admission and had a new diagnosis of CDI. Patients <1 year of age and those with a history of CDI in the previous 60 days were excluded. Age, gender, race, complex chronic conditions, and other information were collected. Multivariable logistic regression was used to evaluate predictors of recurrent CDI. During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2-13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3-4.0) and 2.8 (95% CI: 1.2-6.9) times more likely to experience recurrence, respectively. The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence.

Integrating Time-Varying and Ecological Exposures into Multivariate Analyses of Hospital-Acquired Infection Risk Factors: A Review and Demonstration.

OBJECTIVES Hospital-acquired infections (HAIs) develop rapidly after brief and transient exposures, and ecological exposures are central to their etiology. However, many studies of HAIs risk do not correctly account for the timing of outcomes relative to exposures, and they ignore ecological factors. We aimed to describe statistical practice in the most cited HAI literature as it relates to these issues, and to demonstrate how to implement models that can be used to account for them. METHODS We conducted a literature search to identify 8 frequently cited articles having primary outcomes that were incident HAIs, were based on individual-level data, and used multivariate statistical methods. Next, using an inpatient cohort of incident Clostridium difficile infection (CDI), we compared 3 valid strategies for assessing risk factors for incident infection: a cohort study with time-fixed exposures, a cohort study with time-varying exposures, and a case-control study with time-varying exposures. RESULTS Of the 8 studies identified in the literature scan, 3 did not adjust for time-at-risk, 6 did not assess the timing of exposures in a time-window prior to outcome ascertainment, 6 did not include ecological covariates, and 6 did not account for the clustering of outcomes in time and space. Our 3 modeling strategies yielded similar risk-factor estimates for CDI risk. CONCLUSIONS Several common statistical methods can be used to augment standard regression methods to improve the identification of HAI risk factors. Infect.

Antimicrobial Stewardship Programs in Inpatient Hospital Settings: A Systematic Review

ObjectiveEvaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes.DesignSystematic review.MethodsSearch of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel.ResultsFew intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence ofClostridium difficileinfection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed.ConclusionsNumerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported.

Proton Pump Inhibitors and Risk for Recurrent Clostridium difficile Infection Among Inpatients

Observational studies suggest that proton pump inhibitors (PPIs) are a risk factor for incident Clostridium difficile infection (CDI). Data also suggest an association between PPIs and recurrent CDI, although large-scale studies focusing solely on hospitalized patients are lacking. We therefore performed a retrospective cohort analysis of inpatients with incident CDI to assess receipt of PPIs as a risk factor for CDI recurrence in this population. Using electronic medical records, we identified hospitalized adult patients between 1 December 2009 and 30 June 2012 with incident CDI, defined as a first positive stool test for C. difficile toxin B and who received appropriate treatment. Electronic records were parsed for clinical factors including receipt of PPIs, other acid suppression, non-CDI antibiotics, and comorbidities. The primary exposure was in-hospital PPIs given concurrently with C. difficile treatment. Recurrence was defined as a second positive stool test 15-90 days after the initial positive test. C. difficile recurrence rates in the PPI exposed and unexposed groups were compared with the log-rank test. Multivariable Cox proportional hazards modeling was performed to control for demographics, comorbidities, and other clinical factors. We identified 894 inpatients with incident CDI. The cumulative incidence of CDI recurrence in the cohort was 23%. Receipt of PPIs concurrent with CDI treatment was not associated with C. difficile recurrence (hazard ratio (HR)=0.82; 95% confidence interval (CI)=0.58-1.16). Black race (HR=1.66, 95% CI=1.05-2.63), increased age (HR=1.02, 95% CI=1.01-1.03), and increased comorbidities (HR=1.09, 95% CI=1.04-1.14) were associated with CDI recurrence. In light of a higher 90-day mortality seen among those who received PPIs (log-rank P=0.02), we also analyzed the subset of patients who survived to 90 days of follow-up. Again, there was no association between PPIs and CDI recurrence (HR=0.87; 95% CI=0.60-1.28). Finally, there was no association between recurrent CDI and increased duration or dose of PPIs. Among hospitalized adults with C. difficile, receipt of PPIs concurrent with C. difficile treatment was not associated with CDI recurrence. Black race, increased age, and increased comorbidities significantly predicted recurrence. Future studies should test interventions to prevent CDI recurrence among high-risk inpatients.

Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection

The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Clostridium difficile Outbreak Strain BI Is Highly Endemic in Chicago Area Hospitals

Describe the clinical and molecular epidemiology of incident Clostridium difficile infection (CDI) cases in Chicago area acute healthcare facilities (HCFs). Laboratory, clinical, and epidemiologic information was collected for patients with incident CDI who were admitted to acute HCFs in February 2009. Stool cultures and restriction endonuclease analysis typing of the recovered C. difficile isolates was performed. Two hundred sixty-three patients from 25 acute HCFs. Acute HCF rates ranged from 2 to 7 patients with CDI per 10,000 patient-days. The crude mortality rate was 8%, with 20 deaths occurring in patients with CDI. Forty-two (16%) patients had complications from CDI, including 4 patients who required partial, subtotal, or total colectomy, 3 of whom died. C. difficile was isolated and typed from 129 of 178 available stool specimens. The BI strain was identified in 79 (61%) isolates. Of patients discharged to long-term care who had their isolate typed, 36 (67%) had BI-associated CDI. Severe disease was common and crude mortality was substantial among patients with CDI in Chicago area acute HCFs in February 2009. The outbreak-associated BI strain was the predominant endemic strain identified, accounting for nearly two-thirds of cases. Focal HCF outbreaks were not reported, despite the presence of the BI strain. Transfer of patients between acute and long-term HCFs may have contributed to the high incidence of BI cases in this investigation.

Clostridium difficileInfection and Inflammatory Bowel Disease: A Review

The incidence of Clostridium difficile infection (CDI) has significantly increased in the last decade in the United States adding to the health care burden of the country. Patients with inflammatory bowel disease (IBD) have a higher prevalence of CDI and worse outcomes. In the past, the traditional risk factors for CDI were exposure to antibiotics and hospitalizations in elderly people. Today, it is not uncommon to diagnose CDI in a pregnant women or young adult who has no risk factors. C. difficile can be detected at the initial presentation of IBD, during a relapse or in asymptomatic carriers. It is important to keep a high index of suspicion for CDI in IBD patients and initiate prompt treatment to minimize complications. We summarize here the changing epidemiology, pathogenesis, risk factors, clinical features, and treatment of CDI in IBD.

Comparison of Real-Time PCR Techniques to Cytotoxigenic Culture Methods for Diagnosing Clostridium difficile Infection

In the past decade, the incidence of Clostridium difficile infections (CDI) with a more severe course has increased in Europe and North America. Assays that are capable of rapidly diagnosing CDI are essential. Two real-time PCRs (LUMC and LvI) targeting C. difficile toxin genes (tcdB, and tcdA and tcdB, respectively) were compared with the BD GeneOhm PCR (targeting the tcdB gene), using cytotoxigenic culture as a gold standard. In addition, a real-time PCR targeting the tcdC frameshift mutation at position 117 (Δ117 PCR) was evaluated for detecting toxigenic C. difficile and the presence of PCR ribotype 027 in stool samples. In total, 526 diarrheal samples were prospectively collected and included in the study. Compared with those for cytotoxigenic culture, sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were for PCR LUMC 96.0%, 88.0%, 66.0%, and 98.9%, for PCR LvI 100.0%, 89.4%, 69.7%, and 100.0%, for PCR Δ117 98.0%, 90.7%, 71.9%, and 99.5%, and for PCR BD GeneOhm 88.3%, 96.9%, 86.5%, and 97.4%. Compared to those with feces samples cultured positive for C. difficile type 027, the sensitivity, specificity, PPV, and NPV of the Δ117 PCR were 95.2%, 96.2%, 87.0%, and 98.7%. We conclude that all real-time PCRs can be applied as a first screening test in an algorithm for diagnosing CDI. However, the low PPVs hinder the use of the assays as stand-alone tests. Furthermore, the Δ117 PCR may provide valuable information for minimizing the spread of the epidemic C. difficile PCR ribotype 027.

Epidemiological Patterns and Hospital Characteristics Associated with Increased Incidence ofClostridium difficileInfection in Quebec, Canada, 1998–2006

To explore epidemiological patterns of the incidence of Clostridium difficile infection (CDI) and hospital characteristics associated with increased incidence during nonepidemic and epidemic years. Retrospective and prospective ecological study. Eighty-three acute care hospitals participating in CDI surveillance in the province of Quebec, Canada. A Serfling-type regression model applied to data obtained from an administrative database (1998-2006) and prospective Quebec CDI surveillance (2004-2006) was used to calculate expected CDI baseline incidence and to detect incidence exceeding the defined epidemic threshold at the provincial and hospital level. Multivariable Poisson regression was used to determine hospital characteristics associated with increased incidence during nonepidemic (1998-2001) and epidemic (2003-2005) periods. During the study period (1998-2006), 4,525,847 discharges, including 45,508 with a CDI in any diagnosis field, were reported by 83 hospitals. During 1998-2001, the average Quebec incidence of CDI was 10,304 cases in 1,775,822 discharges (5.8 cases per 1,000 discharges) and presented a pattern of seasonality, with similar patterns at the hospital level for some hospitals. The Quebec epidemic started in October-November 2002 and peaked in March 2004 at 845 cases in 40,852 discharges (20.7 cases per 1,000 discharges). In multivariable analysis, higher incidence was associated with location in Montreal and surrounding regions, greater hospital size, larger proportion of hospitalized elderly patients, longer length of stay, and greater proportion of comorbidities in patients, whereas teaching profile was associated with decreased incidence during both nonepidemic and epidemic periods. The effect of geographical location on incidence was greater during the epidemic. Baseline incidence from nonepidemic years and hospital characteristics associated with CDI incidence should be taken into account when estimating the efficacy of interventions.

Correlations between bed occupancy rates andClostridium difficileinfections: a time-series analysis

A time-series analysis was performed to identify the impact of bed occupancy rates and length of hospital stay on the incidence of Clostridium difficile infections (CDI). Between January 2003 and July 2008, a mean incidence of 0·5 CDI cases/1000 patient days was recorded. Application of a multivariate model (R2=0·50) showed that bed occupancy rates on general wards (P<0·01) and length of stay in intensive care units (ICUs) (P<0·01) influenced the incidence of CDI. Overcrowding on general wards and long periods in ICUs were identified as being positively associated with the incidence of CDI.

Clostridium difficile Testing in the Clinical Laboratory by Use of Multiple Testing Algorithms

The incidence of Clostridium difficile infection (CDI) has risen almost 3-fold in the United States over the past decade, emphasizing the need for rapid and accurate tests for CDI. The Cepheid Xpert C. difficile assay is an integrated, closed, nucleic acid amplification system that automates sample preparation and real-time PCR detection of the toxin B gene (tcdB). A total of 432 stool specimens from symptomatic patients were tested by a glutamate dehydrogenase (GDH) assay, a toxin A and B enzyme immunoassay (EIA), the Xpert C. difficile assay, and a cell culture cytotoxicity neutralization assay (CCCN). The results of these methods, used individually and in combination, were compared to those of toxigenic culture. Results for the Xpert C. difficile assay alone showed a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 94.4, 96.3, 84.0, and 98.8%, while the EIA alone gave corresponding values of 58.3, 94.7, 68.9, and 91.9%, respectively. An algorithm using the GDH assay and the EIA (plus the CCCN if the EIA was negative) showed corresponding values of 83.1, 96.7, 83.1, and 96.1%. The Xpert C. difficile assay was statistically superior to the EIA (P, <0.001 by Fisher's exact test) and to the GDH-EIA-CCCN algorithm (P, 0.0363). Combining the GDH and Xpert C. difficile assays lowered both the sensitivity and the NPV of the Xpert assay. The GDH-EIA-CCCN procedure required, on average, 2 days to complete testing on GDH-positive results, while testing by the Xpert C. difficile assay was completed, on average, in less than 1 h. Xpert C. difficile testing yielded the highest sensitivity and NPV, in the least amount of time, of the individual- and multiple-test algorithms evaluated in this study.

Comparison of Nine Commercially Available Clostridium difficile Toxin Detection Assays, a Real-Time PCR Assay for C . difficile tcdB , and a Glutamate Dehydrogenase Detection Assay to Cytotoxin Testing and Cytotoxigenic Culture Methods

The continuing rise in the incidence of Clostridium difficile infection is a cause for concern, with implications for patients and health care systems. Laboratory diagnosis largely relies on rapid toxin detection kits, although assays detecting alternative targets, including glutamate dehydrogenase (GDH) and toxin genes, are now available. Six hundred routine diagnostic diarrheal samples were tested prospectively using nine commercial toxin detection assays, cytotoxin assay (CYT), and cytotoxigenic culture (CYTGC) and retrospectively using a GDH detection assay and PCR for the toxin B gene. The mean sensitivity and specificity for toxin detection assays were 82.8% (range, 66.7 to 91.7%) and 95.4% (range, 90.9 to 98.8%), respectively, in comparison with CYT and 75.0% (range, 60.0 to 86.4%) and 96.1% (91.4 to 99.4%), respectively, in comparison with CYTGC. The sensitivity and specificity of the GDH assay were 90.1% and 92.9%, respectively, compared to CYT and 87.6% and 94.3%, respectively, compared to CYTGC. The PCR assay had the highest sensitivity of all the tests in comparison with CYT (92.2%) and CYTGC (88.5%), and the specificities of the PCR assay were 94.0% and 95.4% compared to CYT and CYTGC, respectively. All kits had low positive predictive values (range, 48.6 to 86.8%) compared with CYT, assuming a positive sample prevalence of 10% (representing the hospital setting), which compromises the clinical utility of single tests for the laboratory diagnosis of C. difficile infection. The optimum rapid single test was PCR for toxin B gene, as this had the highest negative predictive value. Diagnostic algorithms that optimize test combinations for the laboratory diagnosis of C. difficile infection need to be defined.

Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile -Associated Diarrhea in Hospitalized Patients

The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.02/100 bed-days), fluoroquinolone use (average delay = 3 months; variation of CDAD incidence = 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay = 1 month; variation of CDAD incidence = 0.002/100 bed-days), and macrolide use (average delay = 5 months; variation of CDAD incidence = 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay = 1 month; variation of CDAD incidence = 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect.

Effects of Exposure of Clostridium difficile PCR Ribotypes 027 and 001 to Fluoroquinolones in a Human Gut Model

The incidence of Clostridium difficile infection is increasing, with reports implicating fluoroquinolone use. A three-stage chemostat gut model was used to study the effects of three fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) on the gut microbiota and two epidemic C. difficile strains, strains of PCR ribotypes 027 and 001, in separate experiments. C. difficile total viable counts, spore counts, and cytotoxin titers were determined. The emergence of C. difficile isolates with reduced antibiotic susceptibility was monitored with fluoroquinolone-containing medium, and molecular analysis of the quinolone resistance-determining region was performed. C. difficile spores were quiescent in the absence of fluoroquinolones. Instillation of each fluoroquinolone led to C. difficile spore germination and high-level cytotoxin production. High-level toxin production occurred after detectable spore germination in all experiments except those with C. difficile PCR ribotype 027 and moxifloxacin, in which marked cytotoxin production preceded detectable germination, which coincided with isolate recovery on fluoroquinolone-containing medium. Three C. difficile PCR ribotype 027 isolates and one C. difficile PCR ribotype 001 isolate from fluoroquinolone-containing medium exhibited elevated MICs (80 to > or =180 mg/liter) and possessed mutations in gyrA or gyrB. These in vitro results suggest that all fluoroquinolones have the propensity to induce C. difficile infection, regardless of their antianaerobe activities. Resistant mutants were seen only following moxifloxacin exposure.

Epidemiology of Clostridium species bacteremia in Calgary, Canada, 2000–2006

To define the incidence, risk factors for acquisition, and outcomes associated with clostridial bacteremia in a large Canadian health region. Retrospective population-based surveillance for clostridial bacteremia was conducted among all residents of the Calgary Health Region (population 1.2 million) during 2000-2006. One hundred and thirty-eight residents had incident Clostridium species bacteremia (1.8 per 100,000/year); 45 (33%) were nosocomial, 55 (40%) were healthcare-associated community onset, and 38 (28%) were community acquired. Older age and a number of underlying conditions were risk factors for acquiring Clostridium species bacteremia most importantly hemodialysis [relative risk (RR) 212.3; 95% confidence interval (CI) 106.5-385.5], malignancy (RR 40.2; 95% CI 27.6-58.1), and Crohn's disease (RR 11.2; 95% CI 3.0-29.4). Clostridium perfringens was most commonly identified with 58 (42%) isolates followed by Clostridium septicum (19; 14%), Clostridium ramosum (13; 9%), Clostridium clostridiiforme (8; 6%), and Clostridium difficile (7; 5%). Reduced susceptibility to penicillin occurred in 14/135 (10%), to metronidazole in 2/135 (1%), and to clindamycin in 36/135 (27%) isolates. The median length of stay was 12.7 days and 39/130 (30%) patients died in hospital for mortality rate of 0.5 per 100,000/year. Clostridium species bacteremia is associated with a significant burden of illness and hemodialysis and cancer patients are at highest risk.

Lack of Association Between the Increased Incidence ofClostridium difficile–Associated Disease and the Increasing Use of Alcohol-Based Hand Rubs

To determine whether there is an association between the increasing use of alcohol-based hand rubs (ABHRs) and the increased incidence of Clostridium difficile-associated disease (CDAD). A 500-bed university-affiliated community teaching hospital. Use of ABHRs during the period 2000-2003 was expressed as the number of liters of ABHR used per 1000 patient-days. The proportion of hand hygiene episodes performed by using an ABHR was determined by periodic observational surveys. CDAD was defined as a physician-ordered stool assay positive for C. difficile toxin A or A/B. The incidence of CDAD was expressed as the number of unique patients who had 1 or more positive CDAD test results per 1,000 patient-days. During 2000-2003, the use of ABHR increased 10-fold, from 3 to greater than 30 L/1,000 patient-days (P<.001). The proportion of hand hygiene episodes performed using an ABHR increased from 10% to 85% (P<.001). The incidence of CDAD in 2000, 2001, 2002, and 2003 was 1.74, 2.33, 1.14, and 1.18 cases/1,000 patient-days, respectively. Despite a significant and progressive increase in the use of ABHRs in our facility during a 3-year period, there was no evidence that the incidence of CDAD increased. These findings suggest that factors other than the increased use of ABHRs are responsible for the increasing incidence of CDAD noted since 2000 in other facilities.

D1.1 The incidence of Clostridium difficile-associated diarrhea in the adult intensive care units of the UP-Philippine general hospital: A case-control study

D1.1 The incidence of Clostridium difficile-associated diarrhea in the adult intensive care units of the UP-Philippine general hospital: A case-control study