Chronic Diarrhea Caused by a Klebsiella oxytoca Toxin Producer Strain Following Antibiotic-Associated Hemorrhagic Colitis: Successful Treatment by Fecal Microbiota Transplant.

Klebsiella oxytoca is a gram-negative bacterium found in fecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin-producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant.

Adverse Events Following Immunization With mRNA and Viral Vector Vaccines in Individuals With Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection From the Canadian National Vaccine Safety Network.

BACKGROUND: Adults previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop short-term immunity and may have increased reactogenicity to coronavirus disease 2019 (COVID-19) vaccines. This prospective, multicenter, active-surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2. METHODS: Canadian adults vaccinated between 22 December 2020 and 27 November 2021 were sent an electronic questionnaire 7 days post-dose 1, dose 2, and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism, or required a medical consultation, including hospitalization. RESULTS: Among 684 998 vaccinated individuals, 2.6% (18 127/684 998) reported a prior history of SARS-CoV-2 infection a median of 4 (interquartile range: 2-6) months previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA-1273, or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation (adjusted odds ratio [95% confidence interval]: 3.96 [3.67-4.28] for BNT162b2, 5.01 [4.57-5.50] for mRNA-1273, and 1.84 [1.54-2.20] for ChAdox1-S compared with no infection). Following dose 2 and 3, the greater risk associated with previous infection was also present but was attenuated compared with dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection. CONCLUSIONS: Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine dose.

Impact of a hospital-wide computerised approach to optimise the quality of antimicrobial prescriptions in patients with severe obesity: a quasi-experimental study.

BACKGROUND: Rates of adherence to available recommendations for dose adjustments in patients with severe obesity are generally low. Hence, antimicrobials are often underdosed in these patients. Antimicrobial stewardship programmes can improve the use of antimicrobials in hospitalised patients. The aim of the study was to analyse the impact of an antimicrobial stewardship programme based on a computerised clinical decision support system for optimal dosing and antimicrobial use in inpatients with severe obesity. METHODS: This quasi-experimental retrospective study using interrupted time series was conducted in an academic centre in Canada from August 2008 to June 2018. The Antimicrobial Prescription Surveillance System was implemented in August 2010 (intervention 1) and specific rules targeting patients with class III obesity (body mass index ≥ 40 kg/m2) were added in June 2014 (intervention 2). Data were collected from all hospitalised adults receiving antimicrobials which required dose adjustment for severe obesity and were stratified by body mass index. Segmented regression analysis of interrupted time series was used to evaluate the impact of the Antimicrobial Prescription Surveillance System on the proportion of inappropriate days of therapy according to posology and on antimicrobial consumption. RESULTS: Overall, 65 205 antimicrobial prescriptions (68% non-obese, 25% class I-II obesity, and 7% class III obesity) were analysed. In patients with class III obesity, the intervention was associated with a decrease in the proportion of inappropriate days of therapy (trend after the first intervention, -0.8% per 2-month period [95% CI -1.1 to -0.5], p < 0.001; intercept, 11.3% [95% CI 8.2 to 14.5], p < 0.001), which led to a reduction of 35% over an eight-year period (from pre-intervention level of 19.1%). Intervention 1 resulted in a downward trend in antimicrobial consumption, followed by an increasing trend after intervention 2. In these patients, the most frequent interventions made by pharmacists targeted posology (46%). CONCLUSIONS: Antimicrobial Prescription Surveillance System had a positive impact on dosing optimisation and antimicrobial consumption in patients with class III obesity. Improving antimicrobial prescriptions in these patients is important because suboptimal dosing could be associated with unfavourable outcomes.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case-control study.

BACKGROUND: Anosmia and dysgeusia have been reported as potential symptoms of coronavirus disease 2019. This study aimed to confirm whether anosmia and dysgeusia are specific symptoms among those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted an age-matched case-control study in the Eastern Townships region of Quebec between Mar. 10 and Mar. 23, 2020. We included adults (age ≥ 18 yr) who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction. Cases were matched (1:1) according to 5-year age groups with control patents selected randomly from among all patients who tested negative for SARS-CoV-2 during the same period. Demographic and laboratory information was collected from medical records. Clinical symptoms and comorbidities associated with anosmia and dysgeusia were obtained by telephone interview with a standardized questionnaire. RESULTS: Among 2883 people tested for SARS-CoV-2, we identified 134 positive cases (70 women [52.2%] and 64 men [47.8%]; median age 57.1 [interquartile range 41.2-64.5] yr). The symptoms independently associated with SARS-CoV-2 positivity in conditional logistic regression were anosmia or dysgeusia or both (adjusted odds ratio [OR] 62.9, 95% confidence interval [CI] 11.0-359.7), presence of myalgia (adjusted OR 7.6, 95% CI 1.9-29.9), blurred vision (adjusted OR 0.1, 95% CI 0.0-0.8) and chest pain (adjusted OR 0.1, 95% CI 0.0-0.6). INTERPRETATION: We found a strong association between olfactory and gustatory symptoms and SARS-CoV-2 positivity. These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative.

2017/18 and 2018/19 seasonal influenza vaccine safety surveillance, Canadian National Vaccine Safety (CANVAS) Network.

BackgroundThe Canadian National Vaccine Safety (CANVAS) network monitors the safety of seasonal influenza vaccines in Canada.AimTo provide enhanced surveillance for seasonal influenza and pandemic influenza vaccines.MethodsIn 2017/18 and 2018/19 influenza seasons, adults (≥ 15 years of age) and parents of children vaccinated with the seasonal influenza vaccine participated in an observational study using web-based active surveillance. Participants completed an online survey for health events occurring in the first 7 days after vaccination. Participants who received the influenza vaccine in the previous season, but had not yet been vaccinated for the current season, were unvaccinated controls.ResultsIn 2017/18, 43,751 participants and in 2018/19, 47,798 completed the online safety survey. In total, 957 of 30,173 participants vaccinated in 2017/18 (3.2%; 95% confidence interval (CI): 3.0-3.4) and 857 of 25,799 participants vaccinated in 2018/19 (3.3%; 95% CI: 3.1-3.5) reported a health problem of sufficient intensity to prevent their normal daily activities and/or cause them to seek medical care (including hospitalisation). This compared to 323 of 13,578 (2.4%; 95% CI: 2.1-2.6) and 544 of 21,999 (2.5%; 95% CI: 2.3-2.7) controls in each respective season. The event rate in vaccinated adults and children was higher than the background rate and was associated with specific influenza vaccines. The higher rate of events was associated with systemic symptoms and migraines/headaches.ConclusionIn 2017/18 and 2018/19, higher rates of events were reported following seasonal influenza vaccination than in the pre-vaccination period. This signal was associated with several seasonal influenza vaccine products.

Multilocus Variable-Number Tandem-Repeat Analysis of Clostridioides difficile Clusters in Ribotype 027 Isolates and Lack of Association with Clinical Outcomes.

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could be associated with unfavorable outcomes. We applied high-resolution multilocus variable-number tandem-repeat analysis (MLVA) to characterize C. difficile R027 isolates collected from confirmed CDI patients recruited across 10 Canadian hospitals from 2005 to 2008. PCR ribotyping was performed first to select R027 isolates that were then analyzed by MLVA (n = 450). Complicated CDI (cCDI) was defined by the occurrence of any of admission to an intensive care unit, colonic perforation, toxic megacolon, colectomy, and if CDI was the cause or contributed to death within 30 days after enrollment. Three major MLVA clusters were identified, MC-1, MC-3, and MC-10. MC-1 and MC-3 were exclusive to Quebec centers, while MC-10 was found only in Ontario. Fewer cases infected with MC-1 developed cCDI (4%) than those infected with MC-3 and MC-10 (15% and 16%, respectively), but a statistically significant difference was not reached. Our data did not identify a clear association between subpopulations of R027 and different clinical outcomes; however, the data confirmed the utility of MLVA's higher discrimination potential to better characterize CDI populations in an epidemiological analysis. For a patient with CDI, the progression toward an unfavorable outcome is a complex process that probably includes several interrelated strain and host characteristics.

A postpartum vaccination promotion intervention using motivational interviewing techniques improves short-term vaccine coverage: PromoVac study.

BACKGROUND: Due to the increasing number of vaccine-hesitant parents, new effective immunization promotion strategies need to be developed to improve the vaccine coverage (VC) of infants. This study aimed to assess the impact of an educational strategy of vaccination promotion based on motivational interviewing (MI) techniques targeting parents and delivered at the maternity ward, for the VC of infants at 3, 5, and 7 months of age. METHODS: An individual educational information session, administered using MI techniques, regarding immunization of infants aged 2, 4, and 6 months was (experimental group) or was not (control group) proposed to parents during the postpartum stay at the maternity ward. Immunization data were obtained through the Eastern Townships Public Health registry for infants at 3, 5, and 7 months of age. Absolute VC increases at 3, 5, and 7 months in the experimental group were calculated and the relative risks with the respective 95% confidence intervals were computed using univariate logistic regression with the generalized estimating equations (GEE) procedure. Multivariate regression using GEE was used to adjust for confounding variables. RESULTS: In the experimental and control groups, 1140 and 1249 newborns were included, respectively. A significant increase in VC of 3.2, 4.9, and 7.3% was observed at 3, 5, and 7 months of age (P < 0.05), respectively. The adjusted relative risk of the intervention's impact on vaccination status at 7 months of age was 1.08 (95% confidence interval: 1.03-1.14) (P = 0.002). CONCLUSIONS: An educational strategy using MI techniques delivered at the maternity ward may be effective in increasing VC of infants at ages 3, 5, and 7 months. MI could be an effective tool to overcome vaccine hesitancy.

The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Sustained impact of a computer-assisted antimicrobial stewardship intervention on antimicrobial use and length of stay.

Objectives: : Prospective audit and feedback interventions are the core components of an antimicrobial stewardship programme. Herein, we describe the sustained impact of an antimicrobial stewardship programme, based on a novel clinical decision-support system (Antimicrobial Prescription Surveillance System; APSS), on antimicrobial use and costs, hospital length of stay (LOS) in days and the proportion of inappropriate antimicrobial prescriptions. Methods: A quasi-experimental, retrospective study was conducted using interrupted time series between 2008 and 2013. Data on all hospitalized adults receiving antimicrobials were extracted from the data warehouse of a 677 bed academic centre. The intervention started in August 2010. Prospective audit and feedback interventions, led by a pharmacist, were triggered by APSS based on deviations from published and local guidelines. Changes in outcomes before and after the intervention were compared using segmented regression analysis. Results: APSS reviewed 40 605 hospitalizations for 35 778 patients who received antimicrobials. The intervention was associated with a decrease in the average LOS (level change -0.92, P < 0.01; trend -0.08, P < 0.01; intercept 11.4 days), antimicrobial consumption in DDDs/1000 inpatient days (level change -32.4, P < 0.01; trend -1.12, P < 0.02; intercept 243 DDDs per 1000 days of hospitalization), antimicrobial spending in Canadian dollars (level change -19 649, P = 0.01; trend -1881, P < 0.01; intercept $74 683) and proportion of non-concordance with local guidelines for prescribing antimicrobials (level change -2.3, P = 0.04; intercept 41%). Conclusions: The implementation of the APSS-initiated strategy was associated with a positive impact on antimicrobial use and spending, LOS and inappropriate prescriptions. The high rate of accepted interventions may have contributed to these results.

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

BACKGROUND: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. METHODS: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. RESULTS: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). CONCLUSIONS: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

Accuracy and generalizability of using automated methods for identifying adverse events from electronic health record data: a validation study protocol.

BACKGROUND: Adverse events (AEs) in acute care hospitals are frequent and associated with significant morbidity, mortality, and costs. Measuring AEs is necessary for quality improvement and benchmarking purposes, but current detection methods lack in accuracy, efficiency, and generalizability. The growing availability of electronic health records (EHR) and the development of natural language processing techniques for encoding narrative data offer an opportunity to develop potentially better methods. The purpose of this study is to determine the accuracy and generalizability of using automated methods for detecting three high-incidence and high-impact AEs from EHR data: a) hospital-acquired pneumonia, b) ventilator-associated event and, c) central line-associated bloodstream infection. METHODS: This validation study will be conducted among medical, surgical and ICU patients admitted between 2013 and 2016 to the Centre hospitalier universitaire de Sherbrooke (CHUS) and the McGill University Health Centre (MUHC), which has both French and English sites. A random 60% sample of CHUS patients will be used for model development purposes (cohort 1, development set). Using a random sample of these patients, a reference standard assessment of their medical chart will be performed. Multivariate logistic regression and the area under the curve (AUC) will be employed to iteratively develop and optimize three automated AE detection models (i.e., one per AE of interest) using EHR data from the CHUS. These models will then be validated on a random sample of the remaining 40% of CHUS patients (cohort 1, internal validation set) using chart review to assess accuracy. The most accurate models developed and validated at the CHUS will then be applied to EHR data from a random sample of patients admitted to the MUHC French site (cohort 2) and English site (cohort 3)-a critical requirement given the use of narrative data -, and accuracy will be assessed using chart review. Generalizability will be determined by comparing AUCs from cohorts 2 and 3 to those from cohort 1. DISCUSSION: This study will likely produce more accurate and efficient measures of AEs. These measures could be used to assess the incidence rates of AEs, evaluate the success of preventive interventions, or benchmark performance across hospitals.

Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. METHODS: This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. RESULTS: We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. CONCLUSIONS: This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management.

Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections.

OBJECTIVES: Patients with Clostridium difficile infection (CDI) who are re-exposed to antibiotics have a high likelihood of recurrence. We aimed to determine whether oral vancomycin as secondary prophylaxis reduces the risk of recurrence in patients recently diagnosed with CDI who undergo subsequent antibiotic exposure (CDI-AE). METHODS: We conducted a retrospective cohort study of patients diagnosed with CDI (initial episode or recurrence) between 2003 and 2011 in two tertiary care centers in Quebec, Canada and who received antibiotics not targeted against CDI within 90 days after their CDI diagnosis. Risk factors for subsequent recurrence after this exposure to antibiotics were assessed through Cox regression analyses. RESULTS: We included 551 episodes of CDI-AE (379 initial episodes, 172 recurrences). Recurrence occurred after exposure to antibiotics in 181 episodes (32.9%). Recurrence was more likely in older patients (for each additional year of age: adjusted hazard ratio (AHR), 1.01; 95% confidence interval (CI), 1.00-1.03; P=0.02) and among cases where the CDI-AE episode was itself a first (AHR, 3.59; 95% CI, 2.52-5.13; P<0.0001) or a second recurrence (AHR, 4.88; 95% CI, 3.38-7.06; P<0.0001). Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose CDI-AE itself was a recurrence (AHR, 0.47; 95% CI, 0.32-0.69; P<0.0001) but not in those whose CDI-AE was an initial episode (AHR, 0.91; 95% CI, 0.57-1.45; P=0.68). CONCLUSIONS: Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

Delusional Infestation.

Although the practice of infectious diseases involves a broad range of surgical and medical disciplines, interactions with psychiatry are infrequent. Delusional infestation is a condition where an individual has a firmly fixed false belief that they have an infection. Delusional infestation challenges the infectious diseases specialist who must diligently rule out the presence of a true infection. However, perhaps, more importantly, we may need to initiate therapy with neuroleptic medications for which we may have little specific knowledge and experience. In this note we review the diagnosis and management of patients with delusional infestation.

Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes.

Background. This analysis examined the efficacy of fidaxomicin versus vancomycin in 406 Canadian patients with Clostridium difficile infection (CDI), based on data from 2 randomized, clinical trials. Methods. Patients received fidaxomicin or vancomycin 1. Patients were assessed for clinical response recurrence of infection and sustained clinical response for 28 days after treatment completion. Patients at increased risk of recurrence were subjected to subgroup analyses. Results. Clinical response rates for fidaxomicin (90.0%) were noninferior to those with vancomycin (92.2%; 95% confidence interval for difference: -7.7, 3.5). However, fidaxomicin-treated patients had lower recurrence (14.4% versus 28.0%, p = 0.001) and higher sustained clinical response (77.1% versus 66.3%, p = 0.016). Compared with vancomycin, fidaxomicin was associated with lower recurrence rates in all subgroups, reaching statistical significance in patients with age ≥ 65 years (16.0% versus 30.9%, p = 0.026), concomitant antibiotic use (16.2% versus 38.7%, p = 0.036), and non-BI strains (11.8% versus 28.3%, p = 0.004). Higher sustained clinical response rates were observed for fidaxomicin compared with vancomycin in all subgroups; this was statistically significant in the non-BI subgroup (82.8% versus 69.1%, p = 0.021). Conclusions. In Canadian patients, fidaxomicin was superior to vancomycin in sustaining clinical response and reducing CDI recurrence.

Factors Associated With Complications of Clostridium difficile Infection in a Multicenter Prospective Cohort.

BACKGROUND: Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI). METHODS: Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression. RESULTS: A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age ≥ 80 years, heart rate >90/minute, respiratory rate >20/minute, white cell count <4 × 10(9)/L or ≥ 20 × 10(9)/L, albumin <25 g/L, blood urea nitrogen >7 mmol/L, and C-reactive protein ≥ 150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis. CONCLUSIONS: CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy.

Anosmie et dysgueusie associées à l'infection au SRAS-CoV-2: étude cas­témoins appariée selon l'âge.

CONTEXTE: On a signalé l'anosmie et la dysgueusie comme symptômes potentiels de la maladie à coronavirus 2019. Cette étude visait à confirmer si ces symptômes sont caractéristiques chez les personnes ayant eu un résultat positif au dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). MÉTHODES: Nous avons réalisé une étude cas­témoins appariée selon l'âge dans la région des Cantons-de-l'Est, au Québec, entre le 10 et le 23 mars 2020. Nous avons inclus les adultes (18 ans et plus) ayant obtenu un résultat positif au dépistage du SRAS-CoV-2 par test d'amplification en chaîne par polymérase couplée à une transcription inverse. Les cas ont été appariés (1:1) par tranche d'âge de 5 ans avec des témoins sélectionnés aléatoirement parmi tous les patients ayant eu un résultat négatif au dépistage pendant la même période. Les données démographiques et de laboratoire ont été récupérées dans les dossiers médicaux. Les symptômes cliniques et les comorbidités associés à l'anosmie et à la dysgueusie ont été notés lors d'entrevues téléphoniques faites au moyen d'un questionnaire standardisé. RÉSULTATS: Parmi les 2883 personnes soumises au dépistage du SRAS-CoV-2, nous avons recensé 134 cas positifs (70 femmes [52,2 %] et 64 hommes [47,8 %]; âge médian 57,1 ans [intervalle interquartile 41,2­64,5 ans]). Les symptômes indépendamment associés à l'infection confirmée au SRAS-CoV-2 dans une analyse de régression logistique conditionnelle étaient les suivants : anosmie et/ou dysgueusie (rapport de cotes [RC] ajusté 62,9; intervalle de confiance [IC] de 95 % 11,0­359,7), myalgie (RC ajusté 7,6; IC de 95 % 1,9­29,9), vision trouble (RC ajusté 0,1; IC de 95 % 0,0­0,8) et douleur thoracique (RC ajusté 0,1; IC de 95 % 0,0­0,6). INTERPRÉTATION: Nous avons observé un lien étroit entre les symptômes olfactifs et gustatifs et la positivité au SRAS-CoV-2. Ces symptômes devraient être considérés comme une caractéristique fréquente et distinctive de l'infection au SRAS-CoV-2 et devraient servir d'indication de dépistage, et même de répétition du dépistage chez les personnes dont le résultat initial est négatif.

Prevention of Clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam.

BACKGROUND: Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro. METHODS: The reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic. RESULTS: All strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates. CONCLUSIONS: The capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.

The Strain and the Clinical Outcome of Clostridioides difficile Infection: A Meta-analysis.

Background: The association between bacterial strains and clinical outcomes in Clostridioides difficile infection (CDI) has yielded conflicting results across studies. We conducted a systematic review and meta-analyses to assess the impact of these strains. Methods: Five electronic databases were used to identify studies reporting CDI severity, complications, recurrence, or mortality according to strain type from inception to June 2022. Random effect meta-analyses were conducted to assess outcome proportions and risk ratios (RRs). Results: A total of 93 studies were included: 44 reported recurrences, 50 reported severity or complications, and 55 reported deaths. Pooled proportions of complications were statistically comparable between NAP1/BI/R027 and R001, R078, and R106. Pooled attributable mortality was 4.8% with a gradation in patients infected with R014/20 (1.7%), R001 (3.8%), R078 (5.3%), and R027 (10.2%). Higher 30-day all-cause mortality was observed in patients infected with R001, R002, R027, and R106 (range, 20%-25%).NAP1/BI/R027 was associated with several unfavorable outcomes: recurrence 30 days after the end of treatment (pooled RR, 1.98; 95% CI, 1.02-3.84); admission to intensive care, colectomy, or CDI-associated death (1.88; 1.09-3.25); and 30-day attributable mortality (1.96; 1.23-3.13). The association between harboring the binary toxin gene and 30-day all-cause mortality did not reach significance (RR, 1.6 [0.9-2.9]; 7 studies). Conclusions: Numerous studies were excluded due to discrepancies in the definition of the outcomes and the lack of reporting of important covariates. NAP1/BI/R027, the most frequently reported and assessed strain, was associated with unfavorable outcomes. However, there were not sufficient data to reach significant conclusions on other strains.