Changing Results to Change Results: Nudging Antimicrobial Prescribing for Clostridium difficile.

BACKGROUND: Patients who test positive for Clostridium difficile by polymerase chain reaction (PCR), with a negative toxin enzyme immunoassay (EIA), are commonly colonized and do not require treatment. However, clinicians often treat based on a positive PCR result regardless of the toxin EIA result. We evaluated the clinical impact of a microbiology reporting nudge, changing from a report that included both assay results along with treatment recommendations to one that suggested clinicians consider C difficile colonization or early infection. METHODS: We conducted a retrospective cohort study of all adult patients admitted to a large multisite community hospital with a positive C difficile PCR result and negative toxin EIA from January 1, 2016 to June 30, 2018. We examined total days of therapy (DOT) and impacts on clinical outcomes. RESULTS: One hundred ninety-nine episodes occurred preintervention and 165 episodes occurred postintervention. The mean DOTs per episode decreased from 13.6 to 7.9 days (difference -5.8 days; 95% confidence interval, -3.9 to -7.6) postintervention, with statistical process control charts suggesting special cause variation. Patients receiving no treatment increased from 6.5% to 23.6% postintervention (P < .0001). No significant changes in subsequent toxin positive disease (9.0% vs 6.7%), colectomy (0% vs 0.6%), mortality (7.5% vs 12.1%), or length of stay (18.5 vs 16 days) were observed. CONCLUSIONS: Microbiology reporting nudges raising the possibility of C difficile colonization were associated with altered prescribing, reinforcing a postanalytic strategy for invoking change. Decreases in antimicrobial prescribing occurred without increasing subsequent disease or other adverse outcomes, suggesting a safe strategy for decreasing unnecessary treatment of C difficile colonization.

Household Transmission of Carbapenemase-producing Enterobacterales in Ontario, Canada.

BACKGROUND: Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. METHODS: We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. RESULTS: Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40). CONCLUSIONS: Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.

Dissemination of Verona Integron-encoded Metallo-ß-lactamase among clinical and environmental Enterobacteriaceae isolates in Ontario, Canada.

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-ß-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental blaVIM-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010-2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); blaVIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with blaVIM-1-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two blaVIM-1-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of blaVIM-1-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.

Identification and characterization of invasive multi-drug-resistant (MDR) Bacteroides genomospecies in Canada.

We identified and characterized a genome of the multi-drug-resistant Bacteroides genomospecies recovered from an invasive specimen from a hospitalized patient in Canada. The strain was resistant to penicillin, pipercillin-tazobactam, meropenem, clindaymycin and metronidazole. The strain harboured a plasmid containing the nimE gene, which has been shown to be associated with metronidazole resistance. The study highlights the importance of being vigilant in suspecting antimicrobial drug resistance when a patient is not improving on therapy.

Emergence of Carbapenemase-Producing Enterobacteriaceae, South-Central Ontario, Canada1.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007-2015 in south-central Ontario, Canada. We reviewed patients' medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-ß-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-ß-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-ß-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST): A Pilot Randomized Trial.

INTRODUCTION: We developed the Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST) to permit hemodialysis (HD) patients with central venous catheters (catheters) to shower without additional infection risk. Our primary objective was to determine the feasibility of conducting a parallel randomized controlled trial (RCT) to evaluate the impact of HIPPO-ST on catheter-related bacteremia (CRB) in adult HD patients. METHODS: Adult HD patients using catheters were recruited from 11 HD units. Patients were randomized to receive HIPPO-ST or standard care and were followed up for 6 months. Only CRB-outcome assessors were blinded. For the study to be considered feasible, 4 of 5 feasibility outcomes, each with its own statistical threshold for success, must have been achieved. RESULTS: A total of 68 patients were randomized (33 HIPPO-ST and 35 control) and were followed up to 6 months. Of 5 measures of feasibility, 4 were achieved: (1) accurate CRB rate documented (threshold: κ level >0.80); (2) 97.8% (279/285) of satellite HD patients with catheters were screened (threshold: >95%); (3) 88% (23/26) in the HIPPO-ST arm were successfully educated by 6 months (threshold: >80%); and (4) 0% (0/29) patients in the control arm were "contaminated," that is, using HIPPO-ST (threshold: <5%). However, only 44.2% (72/163) of eligible patients consented to participate (threshold: >80%). The rate of CRB was similarly low in HIPPO-ST and control groups (0.68 vs. 0.88/1000 catheter days). DISCUSSION: This HIPPO-ST pilot study demonstrated the feasibility of the larger HIPPO-ST study, especially given the high levels of education success with the HIPPO-ST arm and the low levels of contamination in the control arm.

Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011.

BACKGROUND: In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). METHODS: From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada. RESULTS: 6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children <5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F. CONCLUSIONS: While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults.

Escherichia coli O104:H4 infections and international travel.

We analyzed travel-associated clinical isolates of Escherichia coli O104:H4, including 1 from the 2011 German outbreak and 1 from a patient who returned from the Philippines in 2010, by genome sequencing and optical mapping. Despite extensive genomic similarity between these strains, key differences included the distribution of toxin and antimicrobial drug-resistance determinants.

Multidrug-resistant pandemic (H1N1) 2009 infection in immunocompetent child.

Recent case reports describe multidrug-resistant influenza A pandemic (H1N1) 2009 virus infection in immunocompromised patients exposed to neuraminidase inhibitors because of an I223R neuraminidase mutation. We report a case of multidrug-resistant pandemic (H1N1) 2009 bearing the I223R mutation in an ambulatory child with no previous exposure to neuraminidase inhibitors.

When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto.

INTRODUCTION: There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection. METHODS: Six Toronto acute care hospitals participated in active surveillance for laboratory-confirmed influenza requiring ICU admission during periods of influenza activity from 2007 to 2009. Nasopharyngeal swabs were obtained from patients who presented to our hospitals with acute respiratory or cardiac illness or febrile illness without a clear nonrespiratory aetiology. Predictors of influenza were assessed by multivariable logistic regression analysis and the likelihood of influenza in different populations was calculated. RESULTS: In 5,482 patients, 126 (2.3%) were found to have influenza. Admission temperature ≥38°C (odds ratio (OR) 4.7 for pH1N1, 2.3 for seasonal influenza) and admission diagnosis of pneumonia or respiratory infection (OR 7.3 for pH1N1, 4.2 for seasonal influenza) were independent predictors for influenza. During the peak weeks of influenza seasons, 17% of afebrile patients and 27% of febrile patients with pneumonia or respiratory infection had influenza. During the second wave of the 2009 pandemic, 26% of afebrile patients and 70% of febrile patients with pneumonia or respiratory infection had influenza. CONCLUSIONS: The findings of our study may assist clinicians in decision making regarding optimal management of adult patients admitted to ICUs during future influenza seasons. Influenza testing, empiric antiviral therapy and empiric infection control precautions should be considered in those patients who are admitted during influenza season with a diagnosis of pneumonia or respiratory infection and are either febrile or admitted during weeks of peak influenza activity.

Neuraminidase-inhibitor resistance testing for pandemic influenza A (H1N1) 2009 in Ontario, Canada.

BACKGROUND: Oseltamivir resistance-associated H275Y mutation in the neuraminidase (NA) gene of pandemic influenza A (H1N1) 2009 was occasionally reported worldwide during the 2009-2010 influenza season. A significant proportion of those were found in immunocompromised or severely ill persons. This phenomenon remains infrequent and clear recommendations for resistance testing are lacking. OBJECTIVES: Present the suggested clinical selection criteria for antiviral susceptibility testing for influenza in Canada and to describe the Ontarian experience during the 2009-2010 influenza season. STUDY DESIGN: Using a defined algorithm, we prospectively screened for OsR with pyrosequencing and phenotypic testing during the 2009-2010 influenza season. Zanamivir resistance was screened using phenotypic and sequencing technique on selected occasions. Clinical data was gathered for the resistant cases. RESULTS: A total of 804 clinical H1N1 (2009) positive samples from Ontario were screened for oseltamivir resistance between June 2009 and March 2010. We identified oseltamivir resistance in 5 (0.6%) distinct patients aged 9-62 years. All the resistant strains bore the H275Y mutation. Susceptibility to zanamivir was maintained in all of them. Three patients harboring oseltamivir resistant strain were intensive care unit patients and four were immunocompromised. All were tested for susceptibility because of a repeat positive result for influenza A PCR. CONCLUSION: Oseltamivir resistance was not frequent during the 2009-2010 influenza season but was identified with a systematic and prospective approach to resistance testing. In order to be as sensitive as possible in the detection of those few cases, we report the suggested indications for antiviral susceptibility testing in Canada.

Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial.

CONTEXT: Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse. Given the likelihood that N95 respirators will be in short supply during a pandemic and not available in many countries, knowing the effectiveness of the surgical mask is of public health importance. OBJECTIVE: To compare the surgical mask with the N95 respirator in protecting health care workers against influenza. DESIGN, SETTING, AND PARTICIPANTS: Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals. INTERVENTION: Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season. MAIN OUTCOME MEASURES: The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than -9%. RESULTS: Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, -0.73%; 95% CI, -8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of -9%. CONCLUSION: Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00756574

Community-associated methicillin-resistant Staphylococcus aureus: prevalence in skin and soft tissue infections at emergency departments in the Greater Toronto Area and associated risk factors.

OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which is caused primarily by the Canadian methicillin-resistant Staphylococcus aureus-10 (CMRSA-10) strain (also known as the USA300 strain) has emerged rapidly in the United States and is now emerging in Canada. We assessed the prevalence, risk factors, microbiological characteristics and outcomes of CA-MRSA in patients with purulent skin and soft tissue infections (SSTIs) presenting to emergency departments (EDs) in the Greater Toronto Area. METHODS: Patients with Staphylococcus aureus SSTIs who presented to 7 EDs between Mar. 1 and Jun. 30, 2007, were eligible for inclusion in this study. Antimicrobial susceptibilities and molecular characteristics of MRSA strains were identified. Demographic, risk factor and clinical data were collected through telephone interviews. RESULTS: MRSA was isolated from 58 (19%) of 299 eligible patients. CMRSA-10 was identified at 6 of the 7 study sites and accounted for 29 (50%) of all cases of MRSA. Telephone interviews were completed for 161 of the eligible patients. Individuals with CMRSA-10 were younger (median 34 v. 63 yr, p = 0.002), less likely to report recent antibiotic use (22% v. 67%, p = 0.046) or health care-related risk factors (33% v. 72%, p = 0.097) and more likely to report community-related risk factors (56% v. 6%, p = 0.008) than patients with other MRSA strains. CMRSA-10 SSTIs were treated with incision and drainage (1 patient), antibiotic therapy (3 patients) or both (5 patients), and all resolved. CMRSA-10 isolates were susceptible to clindamycin, tetracycline and trimethoprim-sulfamethoxazole. CONCLUSION: CA-MRSA is a significant cause of SSTIs in the Greater Toronto Area, and can affect patients without known community-related risk factors. The changing epidemiology of CA-MRSA necessitates further surveillance to inform prevention strategies and empiric treatment guidelines.

Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen.

Cerebral blastomycosis is a rarely reported disease. We report three cases of cerebral blastomycosis previously treated with standard antifungal therapy, which were subsequently successfully treated with voriconazole. The first is a 29-year-old man who initially presented with concomitant cutaneous and osseous blastomycosis; the second is a 50-year-old man who initially presented with prostatic, pulmonary and cutaneous lesions. The third patient was a 63-year-old man who presented with hemiplegia and multiple intra-cerebral blastomycomas. This report represents the first two documented relapses, in Canada, of CNS blastomycosis following treatment with itraconazole and, to our knowledge, among the first three worldwide human cases of cerebral blastomycosis treated successfully with voriconazole.

Use of the Vitek-1 and Vitek-2 systems for detection of constitutive and inducible macrolide resistance in group B streptococci.

A prospective study of erythromycin and clindamycin resistance was performed with 304 consecutive group B streptococci (GBS) isolates. According to two automated susceptibility testing systems, Vitek-1 and Vitek-2, and double-disk agar diffusion, 79.9% were susceptible to both erythromycin and clindamycin. However, for macrolide-lincosamide-streptogramin B-inducible isolates, the accuracies of the Vitek-1 and Vitek-2 systems were 5.6 and 94.4%. In light of these results, we recommend that GBS be routinely tested using the double-disk diffusion method.

Emergence of macrolide resistance in throat culture isolates of group a streptococci in Ontario, Canada, in 2001.

Of 500 group A streptococci isolated from pharyngeal swabs, 72 (14.4%) were macrolide resistant, compared to 2.1% in 1997. Of these, 66 (92%) were of the M phenotype and 6 (8.3%) were of the MLS phenotype. Pulsed-field gel electrophoresis found that two clones, with patterns identical to those of serotypes M1 and M4, accounted for 19.4 and 68.1% of the macrolide-resistant isolates, respectively.