Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

The economic burden of cardiac implantable electronic device infections in Alberta, Canada: a population-based study using validated administrative data.

BACKGROUND: Cardiac implantable electronic devices (CIED) are being inserted with increasing frequency. Severe surgical site infections (SSI) that occur after device implantation substantially impact patient morbidity and mortality and can result in multiple hospital admissions and repeat surgeries. It is important to understand the costs associated with these infections as well as healthcare utilization. Therefore, we conducted a population-based study in the province of Alberta, Canada to understand the economic burden of these infections. METHODS: A cohort of adult patients in Alberta who had CIEDs inserted or generators replaced between January 1, 2011 and December 31, 2019 was used. A validated algorithm of International Classification of Diseases (ICD) codes to identify complex (deep/organ space) SSIs that occurred within the subsequent year was applied to the cohort. The overall mean 12-month inpatient and outpatient costs for the infection and non-infection groups were assessed. In order to control for variables that may influence costs, propensity score matching was completed and incremental costs between those with and without infection were calculated. As secondary outcomes, number of outpatient visits, hospitalizations and length of stay were assessed. RESULTS: There were 26,049 procedures performed during our study period, of which 320 (1.23%) resulted in SSIs. In both unadjusted costs and propensity score matched costs the infection group was associated with increased costs. Overall mean cost was $145,312 in the infection group versus $34,264 in the non-infection group. The incremental difference in those with infection versus those without in the propensity score match was $90,620 (Standard deviation $190,185). Approximately 70% of costs were driven by inpatient hospitalizations. Inpatients hospitalizations, length of stay and outpatient visits were all increased in the infection group. CONCLUSIONS: CIED infections are associated with increased costs and are a burden to the healthcare system. This highlights a need to recognize increasing SSI rates and implement measures to minimize infection risk. Further studies should endeavor to apply this work to full economic evaluations to better understand and identify cost-effective infection mitigation strategies.

Validating administrative data to identify complex surgical site infections following cardiac implantable electronic device implantation: a comparison of traditional methods and machine learning.

BACKGROUND: Cardiac implantable electronic device (CIED) surgical site infections (SSIs) have been outpacing the increases in implantation of these devices. While traditional surveillance of these SSIs by infection prevention and control would likely be the most accurate, this is not practical in many centers where resources are constrained. Therefore, we explored the validity of administrative data at identifying these SSIs. METHODS: We used a cohort of all patients with CIED implantation in Calgary, Alberta where traditional surveillance was done for infections from Jan 1, 2013 to December 31, 2019. We used this infection subgroup as our "gold standard" and then utilized various combinations of administrative data to determine which best optimized the sensitivity and specificity at identifying infection. We evaluated six approaches to identifying CIED infection using administrative data, which included four algorithms using International Classification of Diseases codes and/or Canadian Classification of Health Intervention codes, and two machine learning models. A secondary objective of our study was to assess if machine learning techniques with training of logistic regression models would outperform our pre-selected codes. RESULTS: We determined that all of the pre-selected algorithms performed well at identifying CIED infections but the machine learning model was able to produce the optimal method of identification with an area under the receiver operating characteristic curve (AUC) of 96.8%. The best performing pre-selected algorithm yielded an AUC of 94.6%. CONCLUSIONS: Our findings suggest that administrative data can be used to effectively identify CIED infections. While machine learning performed the most optimally, in centers with limited analytic capabilities a simpler algorithm of pre-selected codes also has excellent yield. This can be valuable for centers without traditional surveillance to follow trends in SSIs over time and identify when rates of infection are increasing. This can lead to enhanced interventions for prevention of SSIs.

Atypical presentation of right-sided native valve infective endocarditis.

A previously healthy 55-year-old man presented to hospital with 10 days of progressive dyspnea with fever, night sweats, and a productive cough and no history of recreational drug use or occupational or animal exposures. His wife had developed similar symptoms 2 weeks earlier but had since recovered. Physical exam revealed a new systolic murmur best heard at the left lower sternal border. Transesophageal echocardiogram demonstrated severe tricuspid regurgitation with a small vegetation. Blood cultures were positive for non-typeable Haemophilus influenzae. This case illustrates the necessity of both timely and proficient diagnosis of H. influenzae infection and the unique challenges associated with detecting H. influenzae-related pathology. Clinicians should be aware of the variable presentations of Haemophilus infection, including respiratory infection, neurological infection, and infective endocarditis. Given the fastidious nature of H. influenzae and variability between subtype pathogenicity, microbiology laboratories require tools to culture and differentiate Haemophilus species.

Un homme de 55 ans auparavant en santé s'est présenté à l'hôpital parce que depuis dix jours, il ressentait une dyspnée progressive accompagnée de fièvre, de sueurs nocturnes, de toux productive et aucuns antécédents de consommation de drogues récréatives ou d'expositions en milieu de travail ou à des animaux. Sa femme avait souffert de symptômes semblables deux semaines auparavant, mais s'était rétablie. L'examen physique a révélé un nouveau murmure systolique mieux perçu au niveau du bord inférieur gauche du sternum. L'échocardiographie transoesophagienne a révélé une régurgitation tricuspidienne marquée et de petites végétations. Les hémocultures ont donné des résultats positifs à l'Haemophilus influenzae non typable. Ce cas démontre la nécessité de poser un diagnostic rapide et compétent de l'infection à H. influenzae et les difficultés propres au dépistage des pathologies liées à l'H. influenzae. Les cliniciens devraient connaître les diverses manifestations de l'infection à Haemophilus, y compris l'infection respiratoire, l'infection neurologique et l'endocardite infectieuse. Étant donné le caractère exigeant de l'H. influenzae et la variabilité de la pathogénicité de ses sous-types, les laboratoires de microbiologie ont besoin d'outils pour mettre en culture et différencier les espèces d'Haemophilus.

Latent Class Analysis for the Diagnosis of Clostridioides difficile Infection.

BACKGROUND: Clostridioides difficile infection (CDI) is an opportunistic disease that lacks a gold-standard test. Nucleic acid amplification tests such as real-time polymerase chain reaction (PCR) demonstrate an excellent limit of detection (LOD), whereas antigenic methods are able to detect protein toxin. Latent class analysis (LCA) provides an unbiased statistical approach to resolving true disease. METHODS: A cross-sectional study was conducted in patients with suspected CDI (N = 96). Four commercial real-time PCR tests, toxin antigen detection by enzyme immunoassay (EIA), toxigenic culture, and fecal calprotectin were performed. CDI clinical diagnosis was determined by consensus majority of 3 experts. LCA was performed using laboratory and clinical variables independent of any gold standard. RESULTS: Six LCA models were generated to determine CDI probability using 4 variables including toxin EIA, toxigenic culture, clinical diagnosis, and fecal calprotectin levels. Three defined zones as a function of real-time PCR cycle threshold (Ct) were identified using LCA: CDI likely (>90% probability), CDI equivocal (<90% and >10%), CDI unlikely (<10%). A single model comprising toxigenic culture, clinical diagnosis, and toxin EIA showed the best fitness. The following Ct cutoffs for 4 commercial test platforms were obtained using this model to delineate 3 CDI probability zones: GeneXpert®: 24.00, 33.61; Simplexa®: 28.97, 36.85; Elite MGB®: 30.18, 37.43; and BD Max™: 27.60, 34.26. CONCLUSIONS: The clinical implication of applying LCA to CDI is to report Ct values assigned to probability zones based on the commercial real-time PCR platform. A broad range of equivocation suggests clinical judgment is essential to the confirmation of CDI.

A case of tick-borne relapsing fever in pregnancy.

Tick-borne relapsing fever (TBRF) is an infection caused by Borrelia spirochetes. In North America, Borrelia hermsii is the most common cause for TBRF. This vector-borne disease is transmitted by Ornithodoros hermsi, a soft-bodied tick found in high altitudes in northwestern United States and southwestern Canada. Once bitten by the tick and infected by B. hermsii, episodes of fever alternating with afebrile periods can occur. A case of TBRF in a pregnant host was complicated by Jarisch-Herxheimer reaction requiring critical care. This case emphasizes the importance of maintaining a high index of suspicion in TBRF. Clinician recognition, diagnosis and treatment of TBRF as well as public awareness of strategies to prevent tick bites should be strengthened.

Prevalence of antibiotic-resistant organisms in Canadian Hospitals. Comparison of point-prevalence survey results from 2010, 2012, and 2016.

OBJECTIVE: Point-prevalence surveys for infection or colonization with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CREs), and for Clostridium difficile infection (CDI) were conducted in Canadian hospitals in 2010 and 2012 to better understanding changes in the epidemiology of antimicrobial-resistant organisms (AROs), which is crucial for public health and care management. METHODS: A third survey of the same AROs in adult inpatients in Canadian hospitals with ≥50 beds was performed in February 2016. Data on participating hospitals and patient cases were obtained using standard criteria and case definitions. Associations between ARO prevalence and institutional characteristics were assessed using logistic regression models. RESULTS: In total, 160 hospitals from 9 of the 10 provinces with 35,018 adult inpatients participated in the survey. Median prevalence per 100 inpatients was 4.1 for MRSA, 0.8 for VRE, 1.1 for CDI, 0.8 for ESBLs, and 0 for CREs. No significant change occurred compared to 2012. CREs were reported from 24 hospitals (15%) in 2016 compared to 10 hospitals (7%) in 2012. Routine universal or targeted admission screening for VRE decreased from 94% in 2010 to 74% in 2016. Targeted screening for MRSA on admission was associated with a lower prevalence of MRSA infection. Large hospitals (>500 beds) had higher prevalences of CDI. CONCLUSION: This survey provides national prevalence rates for AROs in Canadian hospitals. Changes in infection control and prevention policies might lead to changes in the epidemiology of AROs and our capacity to detect them.

Real-world treatment of hepatitis C with second-generation direct-acting antivirals: initial results from a multicentre Canadian retrospective cohort of diverse patients.

BACKGROUND: High hepatitis C cure rates have been observed in registration trials with second-generation direct-acting antivirals. Real-world data also indicate high sustained viral response (SVR) rates. Our objective was to determine real-world SVR rates for patients infected with hepatitis C virus (HCV) who were treated with second-generation direct-acting antivirals in the first 18 months of their availability in Canada. METHODS: Four centres in Calgary contributed their treatment data for a diverse patient population including those who had or had not undergone liver transplantation, those coinfected with HIV and vulnerable populations. We included all patients documented to have started hepatitis C treatment with direct-acting antivirals between October 2014 and April 2016, with follow-up through October 2016. We used multivariate analysis to determine independent predictors of treatment failure. RESULTS: Outcome data were available for 351 patients, of whom 326 (92.9%) achieved an SVR (193/206 [93.7%], 57/59 [96.6%] and 44/51 [86.3%] for genotypes 1a, 1b and 3, respectively, p = 0.2). Independent predictors of not achieving SVR were older age (adjusted odds ratio [OR] 0.95 [95% confidence interval (CI) 0.90-1.00]), male sex (adjusted OR 0.30 [95% CI 0.10-0.89]) and, in patients with genotype 1a infection, history of hepatocellular carcinoma (adjusted OR 0.13 [95% CI 0.03-0.53]). In the entire cohort, the presence of cirrhosis, genotype and hepatocellular carcinoma were not associated with a lower SVR rate. There were no differences in SVR rate according to treatment centre, HIV coinfection or liver transplantation. Among patients with genotype 3 infection, a significantly lower SVR rate was observed for those treated outside of standard of care than for those treated within standard of care (33.3% v. 89.6%, p = 0.04). De novo hepatocellular carcinoma developed in 12 patients (3.4%) despite successful direct-acting antiviral therapy. INTERPRETATION: We report high SVR rates in a real-world diverse cohort of HCV-infected patients treated with second-generation direct-acting antivirals. The results highlight the importance of conducting real-world analyses to elucidate clinical factors associated with poorer outcomes that may not be identified in registration trials.

Genetic polymorphisms and drug susceptibility in four isolates of Leishmania tropica obtained from Canadian soldiers returning from Afghanistan.

BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by the presence of one or more lesions on the skin that usually heal spontaneously after a few months. Most cases of CL worldwide occur in Southwest Asia, Africa and South America, and a number of cases have been reported among troops deployed to Afghanistan. No vaccines are available against this disease, and its treatment relies on chemotherapy. The aim of this study was to characterize parasites isolated from Canadian soldiers at the molecular level and to determine their susceptibility profile against a panel of antileishmanials to identify appropriate therapies. METHODOLOGY/PRINCIPAL FINDINGS: Parasites were isolated from skin lesions and characterized as Leishmania tropica based on their pulsed field gel electrophoresis profiles and pteridine reductase 1 (PTR1) sequences. Unusually high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. The drug susceptibility profile of intracellular amastigote parasites was determined using an established macrophage assay. All isolates were sensitive to miltefosine, amphotericin B, sodium stibogluconate (Pentostam) and paromomycin, but were not susceptible to fluconazole. Variable levels of susceptibility were observed for the antimalarial agent atovaquone/proguanil (Malarone). Three Canadian soldiers from this study were successfully treated with miltefosine. CONCLUSIONS/SIGNIFICANCE: This study shows high heterogeneity between the two L. tropica allelic versions of a gene but despite this, L. tropica isolated from Afghanistan are susceptible to several of the antileishmanial drugs available.

Self-collected mid-turbinate swabs for the detection of respiratory viruses in adults with acute respiratory illnesses.

BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and followed up for symptoms of influenza. They were asked to have NP and MT swabs taken as soon as possible after the onset of a fever or two or more respiratory symptoms with an acute onset. The swabs were tested for viral respiratory infections using Seeplex® RV12 multiplex PCR detection kit. Seventy six pairs of simultaneous NP and MT swabs were collected from 38 symptomatic subjects. Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both. Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS: Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses. Given the ease of MT collection and similar results between the two swabs, it is likely that MT swabs should be the preferred method of respiratory cell collection for outpatient studies. In light of this data, larger studies should be performed to ensure that this still holds true and data should also be collected on the patient preference of collection methods.

First report of Actinobaculum schaalii urinary tract infection in North America.

A recurrent urinary tract infection with Actinobaculum schaalii, a fastidious, facultative anaerobic, and emerging pathogen, is described. Diagnosis was delayed when routine urine cultures were initially performed yielding recurrently negative results. Resolution of symptoms occurred after anaerobic cultures were done to allow organism isolation, identification, and appropriate antimicrobial treatment.

Use of oral miltefosine for cutaneous leishmaniasis in Canadian soldiers returning from Afghanistan.

Old world cutaneous leishmaniasis (CL) is caused by Leishmania major and Leishmania tropica, and is endemic to several Asian and Middle-Eastern countries where the rates of infection can be substantial. CL is one of the most common vector-transmitted parasitic infections in Afghanistan. Six cases of CL in Canadian soldiers returning from Afghanistan are reported in the present study. Their lesions did not improve with fluconazole therapy, and the organism demonstrated in vitro resistance. Oral miltefosine seemed effective.