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The annual incidence rate of community-associated Clostridioides difficile infections in Quebec, Canada, has increased by 33.3%, from 0.51 (2008) to 0.68 (2015) cases/100,000 population, while incidence of healthcare-associated cases remained relatively stable. Possible causes include increased disease severity, increased antimicrobial drug use, emergence of virulent strains, and heightened physician awareness.

Background Asymptomatic patients colonized with Clostridioides difficile are at risk of developing C. difficile infection (CDI), but the factors associated with disease onset are poorly understood. Our aims were to identify predictors of hospital-onset CDI (HO-CDI) among colonized patients and to explore the potential benefits of primary prophylaxis to prevent CDI. Methods We conducted a retrospective cohort study in a tertiary academic institution. Colonized patients were identified by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Univariate and multivariate logistic regression analyses were used to identify predictors of HO-CDI. Results There were 19 112 patients screened, from which 960 (5%) colonized patients were identified: 513 met the inclusion criteria. Overall, 39 (7.6%) developed a HO-CDI, with a 30-day attributable mortality of 15%. An increasing length of stay (adjusted odds ratio [aOR] per day, 1.03; P = .006), exposure to multiple classes of antibiotics (aOR per class, 1.45; P = .02), use of opioids (aOR, 2.78; P = .007), and cirrhosis (aOR 5.49; P = .008) were independently associated with increased risks of HO-CDI, whereas the use of laxatives was associated with a lower risk of CDI (aOR 0.36; P = .01). Among the antimicrobials, B-lactam with B-lactamase inhibitors (OR 3.65; P < .001), first-generation cephalosporins (OR 2.38; P = .03), and carbapenems (OR 2.44; P = .03) correlated with the greatest risk of HO-CDI. By contrast, patient age, the use of proton pump inhibitors, and the use of primary prophylaxis were not significant predictors of HO-CDI. Conclusions This study identifies several factors that are associated with CDI among colonized patients. Whether modifying these variables could decrease the risk of CDI should be investigated.

Cell cytotoxicity neutralization assay (CCNA) is considered to be a gold standard to diagnose Clostridioides difficile infections. We performed CCNA on 77 consecutive admission screening rectal swabs from asymptomatic toxigenic C. difficile carriers. Thirty-nine percent of specimens from asymptomatic carriers were positive. Thus, CCNA specificity may be lower than previously thought.

Background: Choosing Wisely Canada is a forum for health care professional societies to lead system change through identification and reduction of low-value practices. Microbiologic investigations are frequently overused and may contribute to unnecessary health care expenditures as well as patient harm. Methods: A Choosing Wisely Canada top five list in medical microbiology was developed by the Association of Medical Microbiology and Infectious Disease (AMMI) Canada through broad consultation of its members. Following an electronic survey of members, recommendations were developed and ranked by a working group, then further narrowed during a national open forum using the modified Delphi method. Feedback was solicited through an online forum prior to dissemination. Results: The top five declarative statements in medical microbiology are: ( 1 ) Don’t collect urine specimens for culture from adults who lack symptoms localizing to the urinary tract or fever, ( 2 ) Don’t routinely collect or process specimens for Clostridium difficile testing when stool is non-liquid or if the patient has had a prior nucleic acid amplification test result within the past 7 days, ( 3 ) Don’t obtain swabs from superficial ulcers for culture, ( 4 ) Don’t routinely order nucleic acid amplification testing on cerebrospinal fluid in patients without a compatible clinical syndrome, and ( 5 ) Don’t routinely obtain swabs during surgical procedures when fluid and/or tissue samples can be collected. Conclusions: This Choosing Wisely list represents a launching point to reduce low-value practices in microbiology. Strong implementation science around these statements will be needed to improve the value of microbiology testing in Canada.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

Background The isolation of asymptomatic Clostridium difficile (CD) carriers may decrease the incidence of hospital-associated C. difficile infections (CDI), but its impact on isolation precaution needs is unknown. Methods A time series analysis was conducted to investigate the impact of isolating CD carriers on the burden of isolation precautions from 2008 to 2016 in a Canadian hospital. To account for the changes in C. difficile infection control policies, the series was divided into 3 intervention periods: period 1 (2008-2011), isolation of patients with CDI until symptom resolution; period 2 (2011-2013), isolation of patients with CDI until discharge; and period 3 (2013-2016), isolation of patients with CDI and CD carriers until discharge. We compared the prevalence of isolation-days for C. difficile (ie, for either CDI or carriage) per 1000 patient-days between study periods. Changes in trend were analyzed by segmented regression analysis. Results A total of 806357 patient-days and 20455 isolation-days were included. Isolation-day prevalence during periods 1, 2, and 3 were 12.9, 26.2, and 37.8 isolation-days per 1000 patient-days, respectively (P < .001 between periods). Isolating CD carriers was associated with an increase in isolation-days' prevalence compared with period 2 (rate ratio [RR], 1.66; P < .001) followed by a significant decrease in trend (RR per 4-week period, 0.97; P < .001). The downward trend was mainly due to decreasing isolation needs for patients with CDI (RR per 4-week period, 0.94; P < .001) rather than for carriage (RR per 4-week period, 0.996; P = .21). Conclusions Isolating CD carriers led to an initial increase in isolation needs that was partially compensated by a decrease in isolation needs for CDI.

Background Several Clostridium difficile infection (CDI) surveillance programs do not specify laboratory strategies to use. We investigated the evolution in testing strategies used across Quebec, Canada, and its association with incidence rates. Methods Cross-sectional study of 95 hospitals by surveys conducted in 2010 and in 2013-2014. The association between testing strategies and institutional CDI incidence rates was analyzed via multivariate Poisson regressions. Results The most common assays in 2014 were toxin A/B enzyme immunoassays (EIAs) (61 institutions, 64%), glutamate dehydrogenase (GDH) EIAs (51 institutions, 53.7%), and nucleic acid amplification tests (NAATs) (34 institutions, 35.8%). The most frequent algorithm was a single-step NAAT (20 institutions, 21%). Between 2010 and 2014, 35 institutions (37%) modified their algorithm. Institutions detecting toxigenic C difficile instead of C difficile toxin increased from 14 to 37 ( P C difficile had higher CDI rates (7.9 vs 6.6 per 10,000 patient days; P = .01). Institutions using single-step NAATs, GDH plus toxigenic cultures, and GDH plus cytotoxicity assays had higher CDI rates than those using an EIA-based algorithm ( P Conclusions Laboratory detection of CDI has changed since 2010. There is an association between diagnostic algorithms and CDI incidence. Mitigation strategies are warranted.

Background Respiratory tract infections are frequent causes of hospitalization and initiation of empirical antimicrobial therapy. Testing for a broad panel of respiratory viruses has been advocated as a useful tool for antibiotic stewardship. We conducted a prospective observational study to assess the impact of rapid viral test results on antimicrobial prescriptions and clinical outcomes among hospitalized adults. Methods Eight hundred patients admitted with respiratory symptoms were tested by a 12-virus respiratory panel (RVP) during 3 consecutive winters in Montreal, Canada. The primary outcome measure was change in antimicrobial prescriptions (ie, de-escalation of empirical antimicrobial therapy or commencement of new antimicrobial therapy) after RVP results were available. Clinical outcomes were also assessed. Results Influenza virus was identified in 53% of individuals in the study population, and other viruses were identified in 10%. Influenza virus positivity was associated with shorter duration of hospitalization and appropriate antiviral management. Antibiotic management was most significantly correlated with radiographic suspicion of pneumonia and less so with results of the RVP. Positivity for viruses other than influenza virus was not correlated with significantly different outcomes. Conclusions Physicians respond to results of testing for influenza virus when managing hospitalized adult patients but respond less to test results for other viruses. These data can inform the design of stewardship interventions and the selection of viral testing panels for hospitalized patients.

Background Numerous studies have identified comorbidities that are associated with Clostridioides difficile infection (CDI), but current CDC and CMS models for risk adjusting hospital CDI rates do not include patient comorbid conditions. Incorporating patient-level data could improve CDI risk adjustment, but comorbidities would need to be easily electronically available for widescale implementation. Ideally, they would also be causally related to CDI — i.e., true risk factors, not confounders — to facilitate more unbiased inter-hospital comparisons. The current study aimed to determine which comorbid conditions are causally related to CDI based upon expert consensus. Methods We used Delphi methodology to administer an iterative, two-round survey with an intervening teleconference, to eight infectious disease experts. Experts evaluated 40 comorbid conditions included in Charlson and Elixhauser comorbidity indices (and thus validated for electronic capture through administrative data), as well as other comorbidities commonly associated with CDI. Experts rated comorbid conditions from 1 (not at all related) to 5 (strongly related), based upon perceived relatedness with CDI. To assign causal relatedness, the following criteria had to be met at the end of round two: 1) majority (> 50%) of experts rating the condition at 3 (somewhat related) or higher; 2) inter-quartile range (IQR) < = 1; and 3) standard deviation (SD) < = 1. Results 8/40 (20%) comorbid conditions were ranked as causally related to CDI, including patient age, three malignancy comorbidities, two transplant-related comorbidities, HIV/AIDS, and inflammatory bowel disease. A further 18/40 (45%) qualified as indeterminately related, and 14/40 (35%) were ranked as not causally related to CDI (Table). Three of the eight causally related factors were not components of Elixhauser or Charlson indices. Table Conclusion We identified comorbid conditions that may be appropriate candidates to consider for inclusion in patient-level risk adjustment models. Some causal factors did not originate from established comorbidity indices. Thus, future work to validate electronic capture of these conditions could further reduce barriers to risk-adjustment implementation. Disclosures All Authors: No reported disclosures

Background Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006 - 2007 at six Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results Five hundred and fifty-four isolates were sequenced successfully, 353 from colonized and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide variants to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusion Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to detection and isolation of 15 (13%) C. difficile asymptomatic carriers. Carriage prevalence varied between outbreaks, from 0% to 29% (P = .004). Isolating carriers was not associated with significantly shorter outbreak durations, compared with historical controls.

SUMMARY Clostridium difficile is the main causative agent of antibiotic-associated and health care-associated infective diarrhea. Recently, there has been growing interest in alternative sources of C. difficile other than patients with Clostridium difficile infection (CDI) and the hospital environment. Notably, the role of C. difficile -colonized patients as a possible source of transmission has received attention. In this review, we present a comprehensive overview of the current understanding of C. difficile colonization. Findings from gut microbiota studies yield more insights into determinants that are important for acquiring or resisting colonization and progression to CDI. In discussions on the prevalence of C. difficile colonization among populations and its associated risk factors, colonized patients at hospital admission merit more attention, as findings from the literature have pointed to their role in both health care-associated transmission of C. difficile and a higher risk of progression to CDI once admitted. C. difficile colonization among patients at admission may have clinical implications, although further research is needed to identify if interventions are beneficial for preventing transmission or overcoming progression to CDI.

Background Clostridium difficile (CD) is the leading cause of health care–associated diarrhea and can result in asymptomatic carriage. Rates of asymptomatic CD colonization on hospital admission range from 1.4%-21%. The objective of this study was to evaluate host and bacterial factors associated with colonization on admission. Methods The Consortium de recherche quebecois sur le Clostridium difficile study provided data for analysis, including demographic information, known risk factors, and potential confounding factors, prospectively collected for 5,232 patients from 6 hospitals in Quebec and Ontario over 15 months from 2006-2007. Stool or rectal swabs were obtained for culture on admission. Pulsed-field gel electrophoresis was performed on the isolates. The presence of antibody against CD toxins A and B was measured. Results There were 212 (4.05%) patients colonized with CD on admission, and 5,020 patients were not colonized with CD. Multivariate logistic regression analysis showed that hospitalization within the last 12 months, use of corticosteroids, prior CD infection, and presence of antibody against toxin B were associated with colonization on admission. Of patients colonized on admission, 79.4% had non-NAP1, non-NAP2 strains. Conclusion There are identifiable risk factors among asymptomatic CD carriers that could serve in their detection and provide a basis for targeted screening.

The control of Clostridium difficile infection is paramount. C difficile spores are difficult to eradicate and can survive on surfaces for prolonged periods of time. Hand washing with either plain or antimicrobial soap is effective in removing C difficile spores from hands. Patients should be placed in private rooms and under contact precautions to prevent transmission to other patients. Regular hospital germicides are not sporicidal and hypochlorite solutions are required for surface disinfection. In outbreak situations, a multifaceted approach is required.

Hantaviruspulmonary syndrome (HPS) is a rare illness in eastern Canada. We present three cases of HPS among military personnel in Quebec. The three cases shared a common exposure to mouse excreta while engaged in military training in Alberta, a western province of Canada.

Background Patients who are colonized with C. difficile are at risk of developing C. difficile infections (CDI), but factors associated with disease onset are poorly understood. The objectives of this study were to identify predictors of hospital-onset CDI (HO-CDI) among asymptomatic C. difficile colonized patients and explore the potential benefit of primary prophylaxis to prevent CDI. Methods We performed a retrospective cross-sectional study of C. difficile colonized patients admitted to a tertiary academic institution in Quebec City between November 2013 and January 2017. Colonization status was determined upon hospital admission through a systematic screening program by detecting the TcdB gene by PCR on a rectal swab. Primary prophylaxis was defined as the preventive use of ≥1 dose of oral vancomycin or metronidazole in a patient without diarrhea. The choice and dosing of prophylaxis were left to the discretion of the treating physician. Univariate and multivariate logistic regression analyses were used to determine independent predictors of HO-CDI. Results Of 513 C. difficile colonized patients, 39 (7.6%) developed a HO-CDI, with a 30-day attributable mortality of 18%. We found that an increased length of hospital stay (adjusted odds ratio [aOR] per day, 1.03; P = 0.006), exposure to multiple classes of systemic antibiotics (aOR per class of antibiotic, 1.45; P = 0.03), the use of opioid analgesics (aOR, 2.70; P = 0.01) and cirrhosis (aOR, 5.57; P = 0.007), were independently associated with an increased risk of HO-CDI in multivariate analysis, whereas the use of laxatives was associated with a lower risk of CDI (aOR, 0.36; P = 0.01). Among the antimicrobials, B-lactam with B-lactamase inhibitors (OR, 3.65; P < 0.001), first-generation cephalosporins (OR, 2.38; P = 0.03), and carbapenems (OR, 2.44; P = 0.03) correlated with the greatest risk of HO-CDI. In contrast, patient age, exposure to proton pump inhibitors, and the use of prophylaxis were not significantly associated with occurrence of HO-CDI in this specific population. Conclusion This study identifies several variables that are specifically associated with the development of CDI among C. difficile colonized patients. Whether modifying these risk factors could help prevent CDI should be further investigated. Disclosures S. Trottier, CIHR: Grant Investigator, Research grant. V. Loo, Merck: Consultant and Scientific Advisor, Consulting fee. Y. Longtin, Merck: Grant Investigator, Research grant. Becton Dickinson: Grant Investigator, Grant recipient.

Since publication of the Society for Healthcare Epidemiology of America position paper onClostridium difficileinfection in 1995, significant changes have occurred in the epidemiology and treatment of this infection.C. difficileremains the most important cause of healthcare-associated diarrhea and is increasingly important as a community pathogen. A more virulent strain ofC. difficilehas been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.

Desde la publicacion del documento de posicion de la Sociedad de Salud Epidemiologica de Norteamerica sobre la infeccion por Clostridium difficile en 1995, han habido importantes cambios en la epidemiologia y tratamiento de esta infeccion. El C. difficile continua siendo la causa mas importante de diarrea asociada con el tratamiento medico y es cada vez mas importante como patogeno en la comunidad. Se ha identificado una cepa mas virulenta de C. difficile y ha sido responsable de casos mas graves de la enfermedad en todo el mundo. Se han publicado datos que informan sobre la disminucion de la eficacia de metronidazol en el tratamiento de la enfermedad severa por C. difficile. A pesar del aumento de cantidad de datos disponibles, aun existen areas de controversia hoy en dia. Esta guia actualiza las recomendaciones referentes a la epidemiologia, el diagnostico, el tratamiento, el control de la infeccion y el manejo ambiental.

Objective.To evaluate common hand hygiene methods for efficacy in removingClostridium difficik.Design.Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C.difficile.Methods.Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no Intervention. All interventions were evaluated for mean reduction in colony-forming units (CFUs) under 2 contamination protocols: “whole hand” and “palmar surface.” Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations.Results.Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log10CFU/mL [95% credible interval (Cri), 1.74-2.54 log10CFU/mL]), cold water with plain soap (1.88 log10CFU/mL [95% Cri, 1.48-2.28 log10CFU/mL), and warm water with antibacterial soap (1.51 log10CFU/mL [95% Cri, 1.12-1.91 logu, CFU/mL]), followed by antiseptic hand wipes (0.57 log10CFU/mL [95% Cri, 0.17-0.96 log10CFU/mL]). Alcohol-based handrub (0.06 log10CFU/mL [95% CrI, -0.34 to 0.45 log10CFU/mL]) was equivalent to no Intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% Cri, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% Cri, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing.Conclusions.Handwashing with soap and water showed the greatest efficacy in removingC. difficileand should be performed preferentially over the use of alcohol-based handrubs when contact withC. difficileis suspected or likely.

Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is a growing concern in many countries. This report describes patient demographics, antimicrobial susceptibilities and molecular characteristics of A. baumannii cases identified through the Canadian Ward Surveillance Study (CANWARD). In addition, clinical cases involving MDR carbapenem-resistant A. baumannii are also detailed in this report. Methods: From January to December 2007,12 hospital centres across Canada submitted pathogens from clinics, emergency rooms, intensive care units and medical/surgical wards as part of the CANWARD study. MICs were determined using microbroth dilution (CLSI). PCR and sequence analysis identified OXA genes among carbapenem-resistant isolates. PFGE was used to determine genetic relatedness and compare representatives of the Midlands 2 strain, OXA-23 clone 1 or 2, T strains and isolates collected from military sources. Results: This study identified A. baumannii in 0.33% (n=26) of infections. The majority of isolates remained susceptible to the antimicrobials tested, however, 7.7% (n= 2 ) displayed an MDR phenotype, including resistance to carbapenems. In one isolate bla oxA-58 was found to be the likely cause of carbapenem resistance while the other isolate had an insertion sequence element upstream of its intrinsic bla oxA-51 . The clinical data of these two isolates suggest that one is travel-related while the source of the other remains unknown. Conclusions: A. baumannii infections from Canadian hospitals were relatively low. Carbapenem-resistant MDR A. baumannii were also rare and unrelated to previously observed isolates from military sources. Continued surveillance in Canada is suggested in order to determine if such organisms will become a problem.

Antimicrobial therapy plays a central role in the pathogenesis of Clostridium difficile infection (CDI), presumably through disruption of indigenous intestinal microflora, thereby allowing C. difficile to grow and produce toxin. Investigations involving animal models and studies performed in vitro suggest that inhibitory activity against C. difficile and differences in the propensity to stimulate toxin production may also influence the likelihood that particular drugs may cause CDI. Although nearly all antimicrobial classes have been associated with CDI, clindamycin, third-generation cephalosporins, and penicillins have traditionally been considered to harbor the greatest risk. Recent studies have also implicated fluoroquinolones as high-risk agents, a finding that is most likely to be related in part to increasing fluoroquinolone resistance among epidemic strains (i.e., restriction-endonuclease analysis group BI/North American PFGE type 1 strains) and some nonepidemic strains of C. difficile. Restrictions in the use of clindamycin and third-generation cephalosporins have been associated with reductions in CDI. Because use of any antimicrobial has the potential to induce the onset of CDI and disease caused by other health care-associated pathogens, antimicrobial stewardship programs that promote judicious use of antimicrobials are encouraged in concert with environmental and infection control-related efforts.

Background. An increase in the incidence and severity of Clostridium difficile-associated disease in Quebec and the United States has been associated with a hypervirulent strain referred to as North American pulsed-field type 1 (NAP1)/027. Methods. In 2005, a prospective study was conducted in 88 Quebec hospitals, and 478 consecutive nosocomial isolates of C. difficile were obtained. The isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing, antimicrobial susceptibility testing, and detection of binary toxin genes and tcdC gene deletion. Data on patient age and occurrence of complications were collected. Results. PFGE typing of 478 isolates of C. difficile yielded 61 PFGE profiles. Pulsovars A (57%), B (10%), and B1 (8%) were predominant. The PFGE profile of pulsovar A was identical to that of strain NAP1. It showed 67% relatedness with 15 other PFGE patterns, among which 11 had both binary toxin genes and a partial tcdC deletion but different antibiotic susceptibility profiles. Pulsovars B and B1 were identical to strain NAP2/ribotype 001. In hospitals showing a predominant clonal A or B-B1 PFGE pattern, incidence of C. difficile-associated disease was 2 and 1.3 times higher, respectively, than in hospitals without any predominant clonal PFGE pattern. Severe disease was twice as frequent among patients with strains possessing binary toxin genes and tcdC deletion than among patients with strains lacking these virulence factors. Conclusions. This study helped to quantify the impact of strain NAP1 on the incidence and severity of C. difficile-associated disease in Quebec in 2005. The identification of the geographic dissemination of this predominant strain may help to focus regional infection-control efforts. Several studies conducted in Quebec and the United States reported a recent increase in the incidence of Clostridium difficile-associated diarrhea (CDAD), with an accompanying increase in the proportion of patients having severe complications and experiencing frequent relapses (1-4). These outbreaks were associated with a predominant strain referred to as North American

Objective:To evaluate the airborne viable bacterial concentrations generated during sputum induction and their reduction with exhaust ventilation, ultraviolet germicidal irradiation (UVGI), or both.Methods:Exhaust ventilation, upper air UVGI lights, and a portable UVGI unit were operated independently or in combination while and after sputum induction was performed for 58 patients suspected of having active tuberculosis. Viable airborne bacteria were sampled with volumetric air samplers, grown on blood agar, and identified with standard techniques.Results:During and immediately after sputum induction, concentrations of airborne bacteria, particularly respiratory tract or oropharyngeal organisms, increased rapidly, regardless of environmental conditions. The subsequent rate of reduction of airborne bacteria was most rapid with the portable UVGI unit, followed by upper air UVGI with air mixing. Exhaust ventilation achieved high air changes per hour, but efficacy in reducing airborne bacterial concentrations was low. However, the continuous entrainment of bacteria-laden air from the hallway outside may have resulted in underestimation. The efficacy of a wall-mounted upper air UVGI fixture was significantly less if there was no air mixing. The irradiation from this fixture was of adequate germicidal intensity only in a narrow horizontal plane 2.5 m above the floor.Conclusion:Sputum induction was associated with a rapid and substantial increase in airborne bacteria despite the use of exhaust ventilation providing more than 30 air changes per hour, and the adjunct use of UVGI. This emphasizes that health-care workers involved in similar cough-inducing procedures performed for patients with suspected tuberculosis must wear appropriate personal respirators (Infect Control Hosp Epidemiol2003;24:483-489)

We compared the performance of 8 Clostridium difficile enzyme immunoassays to cell cytotoxicity neutralization assay and toxigenic culture. The effect of strain type on assay performance was also examined. There were a total of 71 (14.4%) samples in which C. difficile was recovered; 58 (81.7%) of 71 were toxigenic. Compared to a composite reference standard of either C. difficile cytotoxin assay positive or toxigenic C. difficile culture positive, the sensitivities of these assays varied from 31.7% to 55.2%, while the specificities were excellent, ranging from 98.1% to 100%. Among the 57 C. difficile isolates, 30 (51.7%) were of the NAP1 genotype. Stool samples positive for the C. difficile NAP1 strain had a higher positivity rate for the toxin assays.

Background: Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) occurs primarily through the contaminated hands of health care workers who do not follow appropriate precautionary measures. This study investigates various factors associated with compliance with MRSA precautions during routine patient care. Methods: This observational study took place at a teaching hospital in Montreal, Canada. Nurses (184), physicians (41), occupational therapists and physical therapists (19), orderlies (102), housekeeping personnel (28), other health care workers (65), and visitors (49) were anonymously observed. Compliance with MRSA precautions was measured according to appropriate use of gowns and gloves as well as hand hygiene. Results: In 488 observations, the average compliance was 28%. In multivariate analysis, in comparison with nurses, compliance was lower among physicians (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.14 to 0.86), orderlies (OR, 0.37; CI, 0.2-0.69), visitors (OR, 0.2; CI, 0.08-0.49), housekeeping personnel (OR, 0.06; CI, 0.01-0.47), and other types of health care workers (OR, 0.39; CI, 0.18-0.85), but was higher among occupational and physical therapists (OR, 11.7; CI, 2.55-53.8). Conclusions: Compliance with MRSA precautions is low. The only significant predictor of MRSA compliance was the professional category of the health care worker. (Am J Infect Control 2002;30:430-3.)

Background Patients with symptomatic Clostridium difficile infection (CDI) are thought to be responsible for most transmission events, but whole genome sequencing (WGS) studies have raised interest in asymptomatic carriers’ role in transmission. Methods Patients with CDI and colonization were identified using weekly screening in a study conducted during 2006–2007 at six Canadian hospitals. Isolates were typed using pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and WGS. Toxigenic status was determined using cytotoxin testing and tcdB PCR. Incident CDI cases, not included in the initial study, were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space on the same ward within predefined limits (infectious period Results A total of 554 samples were sequenced successfully, 348 from colonized, 201 from infected, and 5 from patients with unknown status. The NAP1/027/ST1 strain was most common among infected and colonized patients. Colonized patients predominantly carried toxigenic strains. Comparing samples from infected patients with all prior samples, a donor with a plausible ward link was found for 115 (57.2%) cases using PFGE, 127 (63.2%) using MLST, and 81 (40.3%) using WGS with a threshold of ≤2 single-nucleotide variants to determine relatedness. Examining data from the two hospitals with most complete data, across all typing methods, more cases could be linked to infected patients rather than to colonized patients. Using WGS, 26 (21.9%) cases were genetically linked to infected patients only, whereas 4 (3.4%) to colonized patients only, and 30 (25.2%) to both. Of those with a genetic link to an infected patient, 21 (17.7%) had a ward link, whereas this was found for only 1 (0.8%) case linked to a colonized patient. Conclusion Asymptomatic carriers contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of NAP1/027/ST1 strain. Disclosures M. Wilcox, Merck & Co., Inc.: Consultant, Consulting fee. Cubist: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. Alere, Actelion Pharma, Astellas, Optimer, Sanofi pasteur, Summit Pharma, bioMerieux, Da Volterra, Qiagen, Cerexa, Abbott, AstraZeneca, Pfizer, Durata Therapeutics, Seres Therapeutics, Valneva, Nabriva Therapeutics, Roche, The Medicines Company, Basilea P: Consultant, Consulting fee. Alere, Actelion Pharmaceuticals, Pharmaceuticals, Astellas, Optimer Pharmaceuticals, Sanofi pasteur, Summit Pharmaceuticals, bioMerieux, Da Volterra, Qiagen, Cerexa, and Abbott: Grant Investigator, Grant recipient.

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing theirClostridium difficileinfection (CDI) prevention efforts. This document updates “Strategies to PreventClostridium difficileInfections in Acute Care Hospitals,” published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.

An outbreak of Serratia marcescens infections occurred in a university tertiary-care hospital. Alcohol-free chlorhexidine solutions were contaminated with S marcescens. The majority of patient and chlorhexidine strains had similar pulsed field-gel electrophoresis banding patterns. Chlorhexidine was recalled, and the rate of S marcescens isolation returned to baseline. Chlorhexidine without alcohol should not be used as an antiseptic.

Clostridium difficile isolates from a 2004 outbreak in Québec, Canada, were all found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and moxifloxacin. The predominant NAP1 isolates were susceptible to clindamycin, while the NAP2 isolates were resistant.

Background. Gold standard methods of detection of Helicobacter pylori are expensive, difficult to perform, or not widely available. The purpose of this study was to assess hematoxylin and eosin staining of antral tissue, a relatively inexpensive and widely available method of H. pylori detection. Materials and Methods. The hematoxylin and eosin stain was assessed as a method of H. pylori detection, with 2 × 2 table analysis using culture as the gold standard in 133 gastric biopsy specimens obtained from patients both before and following attempted eradication. Results. Performance of the stain was good among untreated patients as well as among patients having previously undergone an eradication treatment, with an overall accuracy of 92% (95% confidence intervals: 86–96), sensitivity of 93% (87–97), and specificity of 87% (69–96). Conclusion. The hematoxylin and eosin stain is an inexpensive method of H. pylori detection but with test performance characteristics inferior to Giemsa, Genta, or silver stains.

Objective: To determine the incidence of aspergillosis in patients with leukemia or bone marrow transplants during a construction-associated outbreak, and the effect of an environmental control program for Aspergillus.Design: Clinical, microbiological, and pathological records were reviewed retrospectively once the outbreak was appreciated, and prospectively thereafter, to determine the presence or absence of aspergillosis and duration of neutropenia.Setting: A university tertiary-care center with a single designated hematology-oncology unit.Patients: From January 1988 to September 1993, there were 141 patients with leukemia or bone marrow transplants identified as being neutropenic during 231 admissions to this specialized unit.Interventions: Installation of wall-mounted portable high-efficiency particulate air (HEPA)-filter air purifiers, application of copper-8-quinolinolate–formulated paint, replacement of perforated ceiling tiles with nonperforated type, sealing of all windows, replacement of horizontal, dust-accumulating blinds with vinyl, opaque, roller shades, and systematic and regular cleaning of surfaces.Results: Thirty-six cases of nosocomial aspergillosis were diagnosed during this period. The incidence density (ID) in the preconstruction period was 3.18 per 1,000 days at risk. During construction activity—before the implementation of a control strategy—the ID increased dramatically to 9.88 per 1,000 days at risk. With infection control measures implemented and continued construction work, the ID decreased to 2.91 per 1,000 days at risk, comparable to the preconstruction baseline rate.Conclusions: An environmental control strategy incorporating widely available technology may have played an important role in controlling this outbreak of construction-associated invasive aspergillosis.

Organisms expressing Klebsiella pneumoniae carbapenemase (KPC) are found in several regions worldwide but are rarely detected in Canada. The first outbreak of KPC-expressing strains of Enterobacteriaceae clinical isolates in a university-affiliated hospital intensive care unit (ICU) in Canada is described.Enterobacteriaceae isolates that were flagged by the Vitek 2 (bioMérieux, France) system as possible carbapenemase producers were subjected to the modified Hodge test. Modified Hodge test-positive organisms were analyzed by pulsed-field gel electrophoresis, tested for KPC and other beta-lactamase genes by polymerase chain reaction analysis and underwent subsequent nucleic acid sequencing. Antimicrobial susceptibility profiles were determined by Vitek 2 and Etest (bioMérieux, France). A chart review was conducted to establish epidemiological links.During the study period, 10 unique Enterobacteriaceae isolates expressing KPC were detected from nine ICU patients. Five patients had infections (three pneumonias, one surgical site infection, one urinary tract infection). Isolates included Escherichia coli (5), Klebsiella oxytoca (2), Serratia marcescens (2) and Citrobacter freundii (1). Polymerase chain reaction analysis and sequencing confirmed the presence of KPC-3 in all isolates; four also carried TEM, two CTX-M and one CMY-2. The imipenem minimum inhibitory concentrations as determined by Etest ranged from 0.75 μg/mL to ≥32 μg/mL. Pulsed field gel electrophoresis clonal patterns and patient location in the ICU revealed presumptive horizontal transmission events.In the present study, Enterobacteriaceae isolates with KPC are emerging and can result in serious infections. The KPC gene can spread via plasmids to different genera of the Enterobacteriaceae family. The dissemination of KPC in Enterobacteriaceae and the consequences for treatment and infection control measures warrant a high degree of vigilance among clinicians and microbiologists.On trouve des organismes producteurs de carbapénèmases de typeLes chercheurs ont soumis au test de Hodge modifié les isolats d’entérobactéries que le système Vitek 2 (bioMérieux, France) signalait comme de possibles producteurs de carbapénèmases. Les chercheurs ont analysé les organismes positifs au test de Hodge par électrophorèse sur gel en champ pulsé, ont vérifié la présence de KPC et d’autres gènes de bêta-lactamase par analyse de la réaction en chaîne de la polymérase et ont ensuite effectué un séquençage de l’acide nucléique. Ils ont déterminé les profils de susceptibilité antimicrobienne par le système Vitek 2 et le test E (bioMérieux, France), puis procédé à une analyse des dossiers pour établir des liens épidémiologiques.Pendant la période de l’étude, les chercheurs ont décelé dix isolats uniques d’entérobactéries productrices de KPC chez neuf patients de l’USI. Cinq patients avaient une infection (trois pneumonies, une infection au foyer d’une opération, une infection urinaire). Les isolats incluaient l’Dans la présente étude, les isolats d’entérobactéries productrices de KPC sont émergents et peuvent donner lieu à de graves infections. Le gène de KPC peut se propager par les plasmides à divers genres de la famille des entérobactéries. La dissémination du KPC dans les entérobactéries et les conséquences pour les traitements et les mesures de contrôle des infections justifient un degré élevé de vigilance chez les cliniciens et les microbiologistes.

This study investigated the relationship between hospital exposures, intestinal microbiota, and subsequent risk of Clostridium difficile-associated disease (CDAD), with use of a nested case-control design. The study included 599 patients, hospitalized from September 2006 through May 2007 in Montreal, Quebec, from whom fecal samples were obtained within 72 h after admission; 25 developed CDAD, and 50 matched controls were selected for analysis. Nonsteroidal anti-inflammatory drugs and antibiotic use were associated with CDAD. Fecal specimens were evaluated by 16S ribosomal RNA microarray to characterize bacteria in the intestinal microbiota during the at-risk period. Probe intensities were higher for Firmicutes, Proteobacteria, and Actinobacteria in the patients with CDAD, compared with controls, whereas probe intensities for Bacteroidetes were lower. After epidemiologic factors were controlled for, only Bacteroidetes and Firmicutes remained significantly and independently associated with development of CDAD. Hospital exposures were associated with changes in the intestinal microbiota and risk of CDAD, and these changes were not driven exclusively by antimicrobial use. -¬ 2010 by the Infectious Diseases Society of America. All rights reserved

A total of 66 (0.35% of overall isolates) Acinetobacter baumannii and 102 (0.55%) meropenem-resistant Pseudomonas aeruginosa were identified among 18 538 isolates collected from medical centers across Canada during the 2007-2009 period. A. baumannii was most frequently recovered from patients in intensive care units (ICUs; 42.4%) and was isolated mostly from blood cultures (53.0%) and respiratory tract specimens (33.3%). Colistin, meropenem, and amikacin were the most active agents against A. baumannii strains (≥ 92.4% coverage). Gentamicin, levofloxacin, and tigecycline were also active against this bacterial species (MIC(50) 1, 0.12, and 0.5 μg/mL, respectively). Multidrug resistance (MDR; resistance to ≥ 3 antimicrobial classes) was noted in only 4 strains (6.1%), and molecular typing revealed 6 clusters of 2 isolates per cluster that displayed >85% similarity on the dendrogram. Meropenem-resistant P. aeruginosa isolates were primarily obtained from patients in ICUs (40.2%) and the most prevalent specimen types were those collected from the respiratory tract (63.7%), followed by blood cultures (18.6%). Most of the meropenem-resistant P. aeruginosa were resistant to all antimicrobial agents tested, and low susceptibility rates were observed for levofloxacin (8.8%) and gentamicin (28.4%). Amikacin and colistin were active against 67.7% and 88.2% of the isolates, respectively. A total of 68.6% (n = 70) of meropenem-resistant P. aeruginosa were MDR. Pulsed-field gel electrophoresis analysis revealed 94 unique isolates and 2 small clusters (6 and 4 isolates, 1 hospital each). In summary, MDR A. baumannii are rare in Canada and, conversely, meropenem-resistant P. aeruginosa were mostly MDR; however, there was minimal clonal spread among these nonfermentative bacilli.

The in-vitro activities of omeprazole and three antimicrobial agents against 89 clinical isolates of Helicobacter pylori from a population with duodenal ulcer disease were determined by an agar dilution method. Resistance rates were 20% for metronidazole (MIC > 8 mg/L), 1% for clarithromycin (MIC > 2 mg/L) and zero for ampicillin (MIC > 8 mg/L). Omeprazole was relatively active against H. pylori in vitro (MIC < or = 8 mg/L).

Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website ( www.Helicobactercanada.org ). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log 2 dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log 2 dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

We describe ten cases of aortitis due to Salmonella that were treated at the University of Toronto-affiliated Hospitals between 1978 and 1997. Predisposing conditions included hypertension, diabetes mellitus, and myelodysplastic syndrome. Main presenting symptoms were fever and abdominal and back pain. The most frequent site involved was the abdominal aorta, followed by the thoracic aorta. All but one patient were treated with intravenous bactericidal antibiotics; seven also underwent surgery, four with axillobifemoral grafts and three with in situ grafts. Four of seven patients died within 1 month of the surgical procedure (three patients with in situ grafts and one patient with axillobifemoral graft). We also reviewed the pathogenesis, clinical and laboratory characteristics, and treatment of 140 cases of aortitis due to Salmonella reported in the literature since 1948. The use of bactericidal antibiotics, together with early surgical intervention and long-term suppressive antibiotic therapy, has led to improved survival.

Helicobacter pylori has an unusual pattern of genetic variation, which complicates research on this organism. To gain a better understanding of the forces behind this phenomenon, the extent to which recombination and single point mutations affect genetic variability in H. pylori was quantified and the influence of both geographical distance and clinical background were assessed. Site-directed restriction-endonuclease digestion of 2 gene fragments was performed on 168 isolates from Montreal and Berlin. Allelic diversity was found to be much higher for H. pylori than for other bacterial species. This finding is consistent with those of previous studies on H. pylori that were conducted using other techniques. However, nucleotide diversity was within the range reported for other bacterial species. Phylogenetic analysis found no grouping of strains with clinical background or geographical origin. Recombination at a rate that resulted in linkage equilibrium within genes can explain these observations.

We describe an unusual case of Mycoplasma pneumoniae infection that presented as a lobar pneumonia and pleural effusion. Mycoplasma pneumoniae was isolated from the pleural fluid of this patient.

Host hypoferremic responses occur during infection with Trypanosoma cruzi, presumably through the transfer of iron to the sites of intracellular parasite replication. Depletion of host intracellular iron stores reduces parasite pathogenicity. It has therefore been hypothesized that T. cruzi requires iron for optimal growth in host cells and that, unlike extracellular pathogens, T. cruzi may benefit from host hypoferremic responses. These hypotheses were examined by the in vitro infection of peritoneal macrophages with T. cruzi. Various doses of desferrioxamine or referrated desferrioxamine were added to the culture medium, and parasite growth was monitored. The influence of treatment on uninfected macrophage morphology, function, and iron content was also verified. Desferrioxamine reduced the rate of amastigote replication in a dose-dependent fashion, whereas referrated desferrioxamine did not. The iron content of desferrioxamine-treated macrophages was decreased by 55% without provoking significant morphological or functional changes. Thus, amastigotes used host cell iron stores for optimal growth, and desferrioxamine reduced growth by depleting host cell iron. Hence, it was suggested that depletion of host intracellular iron stores may protect against T. cruzi and, furthermore, that host responses which transfer iron to the intracellular sites of T. cruzi replication may enhance parasite pathogenicity.

The in vitro activities of omeprazole and eight antimicrobial agents against 18 clinical strains of Helicobacter pylori isolated from a pediatric population were determined by an agar dilution method. Ampicillin and erythromycin were the most active agents in vitro. All strains were susceptible to azithromycin, ciprofloxacin, doxycycline, metronidazole, and tinidazole. One isolate demonstrated resistance to cefixime (MIC, greater than or equal to 4 micrograms/ml). H. pylori was inhibited by the proton pump inhibitor omeprazole.