Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Incidence, susceptibility and outcomes of candidemia in adults living in Calgary, Alberta, Canada (2010-2018).

BACKGROUND: Candidemia is increasing in frequency and is associated with high mortality. We sought to determine the burden of illness, the population it affects and its resistance profile in our region. METHODS: The Calgary Zone (CZ) provides all care for residents of Calgary and surrounding communities (~ 1.69 million) via five tertiary hospitals each served by a common single laboratory for acute care microbiology. All adult patients in the CZ with at least one Candida spp.-positive blood culture between January 1, 2010, and December 31, 2018, were identified using microbiological data from Calgary Lab Services, the laboratory that processes > 95% of all blood culture samples in the CZ, were reviewed for the study. RESULTS: The overall annual incidence of candidemia among individuals living in the CZ was 3.8 per 100,000 persons (Median age 61 years (IQR 48-72) and 221/455 (47.4%) were female). C. albicans was the most common species (50.6%), followed by C. glabrata, (24.0%). No other species accounted for more than 7% of cases. Overall mortality at 30, 90, and 365 days was 32.2, 40.1, and 48.1% respectively. Mortality rate did not differ by Candida species. Of individuals who developed candidemia, more than 50% died within the next year. No new resistance pattern has emerged in the most common Candida species in Calgary, Alberta. CONCLUSIONS: In Calgary, Alberta, the incidence of candidemia has not increased in the last decade. C. albicans was the most common species and it remains susceptible to fluconazole.

Rapid LC-MS assay for targeted metabolite quantification by serial injection into isocratic gradients.

Liquid chromatography mass spectrometry (LC-MS) has emerged as a mainstream strategy for metabolomics analyses. One advantage of LC-MS is that it can serve both as a biomarker discovery tool and as a platform for clinical diagnostics. Consequently, it offers an exciting opportunity to potentially transition research studies into real-world clinical tools. One important distinction between research versus diagnostics-based applications of LC-MS is throughput. Clinical LC-MS must enable quantitative analyses of target molecules in hundreds or thousands of samples each day. Currently, the throughput of these clinical applications is limited by the chromatographic gradient lengths, which-when analyzing complex metabolomics samples-are difficult to conduct in under ~ 3 min per sample without introducing serious quantitative analysis problems. To address this shortcoming, we developed sequential quantification using isotope dilution (SQUID), an analytical strategy that combines serial sample injections into a continuous isocratic mobile phase to maximize throughput. SQUID uses internal isotope-labelled standards to correct for changes in LC-MS response factors over time. We show that SQUID can detect microbial polyamines in human urine specimens (lower limit of quantification; LLOQ = 106 nM) with less than 0.019 normalized root mean square error. Moreover, we show that samples can be analyzed in as little as 57 s. We propose SQUID as a new, high-throughput LC-MS tool for quantifying small sets of target biomarkers across large cohorts.

STOP Signs: A Population-based Interrupted Time Series Analysis of Antibiotic Duration for Complicated Intraabdominal Infection Before and After the Publication of a Landmark RCT.

OBJECTIVE: To determine if the STOP-IT randomized controlled trial changed antibiotic prescribing in patients with Complicated Intraabdominal Infection (CIAI). SUMMARY OF BACKGROUND DATA: CIAI is common and causes significant morbidity. In May 2015, the STOP-IT randomized controlled trial showed equivalent outcomes between four-day and clinically determined antibiotic duration. METHODS: This was a population-based retrospective cohort study using interrupted time series methods. The STOP-IT publication date was the exposure. Median duration of inpatient antibiotic prescription was the outcome. All adult patients admitted to four hospitals in Calgary, Canada between July 2012 and December 2018 with CIAI who survived at least four days following source control were included. Analysis was stratified by infectious source as appendix or biliary tract (group A) versus other (group B). RESULTS: Among 4384 included patients, clinical and demographic attributes were similar before vs after publication. In Group A, median inpatient antibiotic duration was 3 days and unchanged from the beginning to the end of the study period [adjusted median difference -0.00 days, 95% confidence interval (CI) -0.37 - 0.37 days]. In Group B, antibiotic duration was shorter at the end of the study period (7.87 vs 6.73 days; -1.14 days, CI-2.37 - 0.09 days), however there was no change in trend following publication (-0.03 days, CI -0.16 - 0.09). CONCLUSIONS: For appendiceal or biliary sources of CIAI, antibiotic duration was commensurate with the experimental arm of STOP-IT. For other sources, antibiotic duration was long and did not change in response to trial publication. Additional implementation science is needed to improve antibiotic stewardship.

Methods for Quantifying the Metabolic Boundary Fluxes of Cell Cultures in Large Cohorts by High-Resolution Hydrophilic Liquid Chromatography Mass Spectrometry.

Metabolomics is a mainstream approach for investigating the metabolic underpinnings of complex biological phenomena and is increasingly being applied to large-scale studies involving hundreds or thousands of samples. Although metabolomics methods are robust in smaller-scale studies, they can be challenging to apply to larger cohorts due to the inherent variability of liquid chromatography mass spectrometry (LC-MS). Much of this difficulty results from the time-dependent changes in the LC-MS system, which affects both the qualitative and quantitative performances of the instrument. Herein, we introduce an analytical strategy for addressing this problem in large-scale microbial studies. Our approach quantifies microbial boundary fluxes using two zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) columns that are plumbed to enable offline column equilibration. Using this strategy, we show that over 397 common metabolites can be resolved in 4.5 min per sample and that metabolites can be quantified with a median coefficient of variation of 0.127 across 1100 technical replicates. We illustrate the utility of this strategy via an analysis of 960 strains of Staphylococcus aureus isolated from bloodstream infections. These data capture the diversity of metabolic phenotypes observed in clinical isolates and provide an example of how large-scale investigations can leverage our novel analytical strategy.

Staphylococcus aureus in Non-Cystic Fibrosis Bronchiectasis: Prevalence and Genomic Basis of High Inoculum ß-Lactam Resistance.

Rationale: The pathobiology of Staphylococcus aureus in non-cystic fibrosis bronchiectasis (nCFB) is poorly defined. When present at high density or "inoculum," some methicillin-sensitive S. aureus (MSSA) can inefficiently degrade antistaphylococcal ß-lactam antibiotics via BlaZ penicillinases (termed the "inoculum effect" [IE]). Given the high burden of organisms in bronchiectatic airways, this is particularly relevant. Objectives: Drawing from a prospectively collected biobank, we sought to understand the prevalence, natural history, potential for transmission, and antibiotic resistance profiles among nCFB-derived MSSA isolates. Methods: All individuals attending a regional consultancy nCFB clinic with sputum collected between 1981 and 2017 were considered, and those with one or more S. aureus-positive cultures composed the cohort. Each individual's most recent biobank isolate was subjected to whole-genome sequencing (including the blaZ gene), antibacterial susceptibility testing, and comparative ß-lactam testing at standard (5 × 105 colony-forming unit [cfu]/ml) and high (5 × 107 cfu/ml) inocula to assess for the IE and pronounced IE. Results: Seventy-four (35.4%) of 209 individuals had one or more sputum samples with S. aureus (68 MSSA, 6 methicillin-resistant S. aureus). Those with S. aureus infection were more likely to be female. Among 60 of 74 MSSA isolates subjected to whole-genome sequencing, no evidence of transmission was identified, although specific multilocus sequence typing types were prevalent, including ST-1, ST-15, ST-30, and ST-45. Antibiotic resistance was uncommon, except for macrolides (∼20%). Among the 60 MSSA samples, the prevalence of IE and pronounced IE was observed to be drug specific: meropenem (0% and 0%, respectively), cefepime (3% and 5%, respectively), ceftazidime (8% and 0%, respectively), cloxacillin (12% and 0%, respectively), cefazolin (23% and 0%, respectively), and piperacillin-tazobactam (37% and 17%, respectively). The cefazolin IE was associated with blaZ type A (P < 0.01) and ST-30 (P < 0.01), whereas the piperacillin-tazobactam IE was associated with type C blaZ (P < 0.001) and ST-15 (P < 0.05). Conclusions:S. aureus infection was common, although no evidence of transmission was apparent in our nCFB cohort. Although routine susceptibility testing did not identify significant resistance, inoculum-related resistance was found to be relevant for commonly used nCFB antibiotics, including cefazolin and piperacillin-tazobactam. Given previous associations between IEs and negative patient outcomes, further work is warranted to understand how this phenotype impacts nCFB disease progression.

Epidemiology of ticks submitted from human hosts in Alberta, Canada (2000-2019).

ABSTRACTThe geographic range and occurrence of tick species is dynamic. This has important public health implications due to important tick species that can transmit pathogens. This study presents a retrospective review of tick genera recovered from humans and submitted for identification in Alberta, Canada, over a 19-year period. The total number of ticks and proportion of genera were analyzed over time. Molecular testing for a number of pathogens associated with Ixodes scapularis and I. pacificus was conducted. A total of 2,358 ticks were submitted between 2000 and 2019, with 98.6% being acquired in Alberta. The number of ticks submitted increased significantly over time (p < 0.0001). Dermacentor ticks were the most abundant genus, followed by Ixodes and Amblyomma. There was a significant decrease in the proportion of Dermacentor ticks between 2013 and 2019 (p = 0.02), with a corresponding increase in the proportion of Ixodes ticks over the same time (p = 0.04). No statistically significant change in seasonality was identified. Borrelia burgdorferi was detected in 8/76 (10.5%; 95% CI 5.4-19.4%) of all I. scapularis and I. pacificus ticks submitted. This translated to a B. burgdorferi positivity of 0.35% (95% CI 0.15-0.68%) among all ticks received. Dermacentor species (especially D. andersoni) remains the most common tick feeding on humans in Alberta. Small numbers of vector species (including I. scapularis/pacificus) are encountered annually over widely separated geographic areas in the province. The risk of exposure to tick-borne pathogens (e.g. Lyme disease) in Alberta remains low.

Mathematical model of the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel molecular rapid diagnostic test compared with conventional methods for identification of Escherichia coli bloodstream infections.

BACKGROUND: Gram-negative pathogens, such as Escherichia coli, are common causes of bloodstream infections (BSIs) and increasingly demonstrate antimicrobial resistance. Molecular rapid diagnostic tests (mRDTs) offer faster pathogen identification and susceptibility results, but higher costs compared with conventional methods. We determined the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel, as a type of mRDT, compared with conventional methods in the identification of E. coli BSIs. METHODS: We constructed a decision analytic model comparing BCID with conventional methods in the identification and susceptibility testing of hospitalized patients with E. coli BSIs from the perspective of the public healthcare payer. Model inputs were obtained from published literature. Cost-effectiveness was calculated by determining the per-patient admission cost, the QALYs garnered and the incremental cost-effectiveness ratios (ICERs) where applicable. Monte Carlo probabilistic sensitivity analyses and one-way sensitivity analyses were conducted to assess the robustness of the model. All costs reflect 2019 Canadian dollars. RESULTS: The Monte Carlo probabilistic analyses resulted in cost savings ($27 070.83 versus $35 649.81) and improved QALYs (8.65 versus 7.10) in favour of BCID. At a willingness to pay up to $100 000, BCID had a 72.6%-83.8% chance of being cost-effective. One-way sensitivity analyses revealed length of stay and cost per day of hospitalization to have the most substantial impact on costs and QALYs. CONCLUSIONS: BCID was found to be cost-saving when used to diagnose E. coli BSI compared with conventional testing. Cost savings were most influenced by length of stay and cost per day of hospitalization.

Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

Epidemiology and risk factors for pyogenic liver abscess in the Calgary Health Zone revisited: a population-based study.

BACKGROUND: Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone. METHODS: All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999-2003 data, also collected in the CHZ. RESULTS: There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999-2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin. CONCLUSIONS: Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study.

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.

Forgoing transesophageal echocardiogram in selected patients with complicated Staphylococcus aureus bacteremia.

Infective endocarditis (IE) has been increasingly recognized as an important complication of Staphylococcus aureus bacteremia (SAB), leading to a low threshold for echocardiography and extended treatment with anti-staphylococcal agents. However, outside of IE, many indications for prolonged anti-staphylococcal therapy courses are present. We sought to determine the frequency in which findings from a transesophageal echocardiogram (TEE) changed clinical SAB management in a large Canadian health region. Residents (> 18 years) with SAB from 2012 to 2014 who underwent transthoracic echocardiogram (TTE) and TEE were assessed. Patients potentially benefiting from an extended course of anti-staphylococcal agents were defined a priori. Patient demographics, treatment (including surgical), and clinical outcomes were extracted and evaluated. Of the 705 episodes of SAB that underwent a screening echocardiogram, 203 episodes underwent both a TTE and TEE, of which 92.1% (187/203) contained an a priori indication for extended anti-staphylococcal therapy. Regardless of TEE results, actual duration of therapy did not differ in SAB episodes that had ≥ 1 extended anti-staphylococcal therapy criteria (36.7 days, IQR 23.4-48.6 vs. 43.8 days, IQR 33.3-49.5, p = 0.17). Additionally, there were no cases in which TEE was utilized as the sole reason to shorten duration of therapy or proceed to surgery for those with SAB. Routine performance of TEE may be unnecessary in all SAB as many patients have pre-existing indications for extended anti-staphylococcal therapy independent of TEE findings. An algorithm to selectively identify cases of SAB that would benefit from TEE can reduce resource and equipment expenditure and patient risks associated with TEE.

Rapid detection of carbapenemase-producing organisms directly from blood cultures positive for Gram-negative bacilli.

INTRODUCTION: The rapid detection of carbapenemase-producing organisms (CPOs) directly from blood cultures (BCs) positive for Gram-negative bacilli (GNB) may accelerate the appropriate treatment of at-risk patients. OBJECTIVE: To evaluate the performance of two commercial assays in the rapid detection of CPOs directly from BC positive for GNB. METHODS: BC positive for GNB were tested for the presence of CPOs with ß CARBA® and NG-Test® CARBA 5. A subset of sterile BC samples was seeded with multidrug-resistant (MDR) GNB. Positive BCs from clinical and seeded samples were tested directly with ß CARBA and CARBA 5 from BC pellets. RESULTS: Sixty-five samples were tested (30 clinical, 35 seeded). ß CARBA had a sensitivity, specificity, NPV, and PPV of 100%, 65.7%, 100%, and 71.4%, respectively. CARBA 5 had a sensitivity, specificity, NPV, and PPV of 90.0%, 100%, 92.1%, and 100%. False negatives for CARBA 5 occurred with 1 GES, 1 VIM-1, and 1 IMP-14. CONCLUSIONS: This study demonstrates that the detection of CPOs directly from positive BC can be accurately achieved. ß CARBA had excellent sensitivity but suffered from poor specificity. CARBA 5 had good sensitivity and specificity but is unable to detect certain CPOs.

High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.

BACKGROUND: International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis. METHODS: We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis. RESULTS: The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine. DISCUSSION: In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

Epidemiology and Outcome Determinants of Staphylococcus aureus Bacteremia Revisited: A Population-Based Study.

PURPOSE: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to re-define the burden, epidemiology and mortality-associated risk factors of SAB in a large Canadian health region. METHODS: Residents (> 18 years) experiencing SAB from 2012 to 2014 were assessed. Incidence rates were calculated using civic census results. Factors associated with 30-day mortality were determined through multivariate logistic regression. Incidence and risk factors for SAB were compared to 2000-2006 data. RESULTS: 780 residents experienced 840 episodes of SAB (MRSA; 20%). Incidence rates increased from 23.5 to 32.0 cases/100,000 from 2012 to 2014; [IRR 1.15 (95% CI 1.07-1.23); p < 0.001]. Compared to a decade ago, incidence of SAB has increased [IRR 1.28 (95% CI 1.21-1.36); p < 0.001] despite minimal change in nosocomial SAB. MRSA proportion did not change through the study (p = 0.3), but did increase relative to a decade ago (20.0% vs 11.0%, p < 0.001). Thirty-day mortality rates were 30.6% and 21.3% for MRSA and MSSA, respectively (p = 0.01), similar to rates from 2000 to 2006. Several clinical, demographic, and biochemical factors were independently associated with SAB mortality. CONCLUSIONS: SAB is common within our population resulting in significant mortality. Incidence rates of SAB are increasing in our health region; however, 30-day mortality rates remain stable.

Incidence and Outcomes of Staphylococcus aureus Bacteriuria: A Population-based Study.

BACKGROUND: Staphylococcus aureus bacteriuria (SABU) may represent multiple processes ranging from asymptomatic colonization to a marker of S. aureus bacteremia (SAB). Our objective was to describe SABU at a population-based level and determine patient characteristics associated with SAB. METHODS: A retrospective study was performed using electronic databases. All urine cultures positive for S. aureus between 2010 and 2013 within the Calgary Health Zone were included. Patient characteristics were compared among patients with and without SAB and risk factors identified using multiple logistic regression modeling. RESULTS: A total of 2540 urine cultures positive for S. aureus from 2054 patients were analyzed. The incidence of SABU was greatest among geriatric males with multiple comorbidities. SAB occurred in 175 (6.9%) of SABU patients. Those with SAB were more likely to be hospitalized, male, have a recent urinary procedure, have pure S. aureus culture in urine, and have laboratory findings suggesting systemic infection. Patients with isolated SABU were more likely to be ≥65 years, have dementia, and have abnormal urinalyses with pyuria and urine nitrites. In-hospital mortality in patients with SABU and SABU+SAB was 9.2% and 17.5%, respectively. Patients with SABU detected ≥48 hours before SAB had the highest risk of death. CONCLUSIONS: Less than 7% of patients with SABU have or will develop SAB. Characteristics associated with SABU were identified that established higher risk for systemic infection. Investigating SABU patients with these characteristics for systemic infection is warranted because a delay in diagnosis is associated with increased mortality.

Infectious diseases consultation improves key performance metrics in the management of Staphylococcus aureus bacteremia: A multicentre cohort study.

Background: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes. Methods: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis. Results: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography. Conclusions: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes.

Historique: La bactériémie à Staphylococcus aureus (BSA) provoque une morbidité et une mortalité marquées. Les auteurs ont cherché à déterminer les facteurs associés aux consultations en infectiologie (CeI) et à comprendre le lien entre ces consultations et la prise en charge et le pronostic des patients atteints d'une BSA. Méthodologie: Entre 2012 et 2014, les auteurs ont réalisé une étude rétrospective multicentrique dans une grande zone de santé canadienne afin de déterminer les facteurs associés aux CeI et l'exécution des principaux déterminants de la qualité des soins dans la prise en charge et les résultats cliniques de la BSA. Au moyen d'une analyse multivariée, ils ont établi a priori les facteurs soumis aux déterminants de la qualité des soins et les ont étudiés pour les associer aux CeI et à la mortalité toutes causes confondues au bout de 30 jours. Résultats: Sur les 961 épisodes de BSA qu'ont vécus 892 patients adultes, 605 ont donné lieu à une CeI. Les patients dirigés vers une telle consultation étaient plus susceptibles d'avoir reçu des valvules et des articulations artificielles et de souffrir d'une BSA d'origine communautaire ou d'une autre source connue, mais ces consultations diminuaient avec le vieillissement. Les CeI étaient le meilleur prédicteur indépendant de mesures démontrant la qualité des soins, y compris des hémocultures et des échocardiographies répétées. La mortalité au bout de 30 jours s'élevait à 20 % dans la cohorte, et les facteurs protecteurs incluaient les CeI, la réalisation du contrôle des sources, un traitement ciblé dans les 48 heures et des hémocultures de suivi, mais pas des échocardiographies. Conclusions: Les auteurs ont constaté un écart important entre les traitements et les explorations que les patients ont subis en raison de leur BSA et ce qui est considéré comme une prise en charge optimale de leur maladie. La CeI s'associe à une meilleure réalisation des déterminants de la qualité des soins ciblés et d'un taux de mortalité réduit pour la BSA. D'après leurs constatations, les auteurs proposent que la CeI soit obligatoire en cas de BSA, afin d'améliorer la prise en charge et le pronostic des patients.

Evaluation of Simplexa Group A Strep Direct Kit Compared to Hologic Group A Streptococcal Direct Assay for Detection of Group A Streptococcus in Throat Swabs.

Diagnosis of bacterial pharyngitis is confirmed by detection of group A Streptococcus (GAS) in patient throat samples. Testing of throat samples has historically relied on culture, but new molecular methods allow much faster test turnaround time (i.e., same day versus 48 to 72 h for culture). Our laboratory uses the Hologic GAS Direct (GASD) assay for screening more than 125,000 throat samples per year. Simplexa GAS Direct is a new real-time quantitative PCR (qPCR) assay that does not require initial DNA extraction. Performance of Simplexa qPCR was compared to GASD. A total of 289 throat swabs were collected from patients attending ambulatory clinics in Calgary, Alberta, Canada. A total of 60 (20.8%) of the samples were initially GAS positive by either method: 54 by both methods, 4 by Simplex qPCR alone, and 2 by GASD alone. An in-house PCR using a unique GAS primer set was used to resolve the 6 discrepant results. Overall, GASD compared to Simplexa qPCR had a sensitivity, specificity, positive predictive value, and negative predictive value of 93.1% versus 100%, 100% versus 100%, 100% versus 100%, and 98.31% versus 100%, respectively. Implementation of Simplexa qPCR in our laboratory setting would cost more but allow the high sample volume to be reported in half the time and save 0.62 medical laboratory technician (MLT) full-time equivalent (FTE). In comparison to culture, the implementation of Simplexa qPCR would save 2.79 medical laboratory assistant (MLA) FTE plus 0.94 MLT FTE. Simplexa qPCR has improved performance and diagnostic efficiency in a high-volume laboratory compared to GASD for GAS detection in throat swabs.

Rates of colonization with extended-spectrum ß-lactamase-producing Escherichia coli in Canadian travellers returning from South Asia: a cross-sectional assessment.

BACKGROUND: A previous study in Calgary showed that travel to India was associated with high risk of community-onset infections with extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. We performed a follow-up study to determine the rate of rectal acquisition of ESBL-producing E. coli among travellers to South Asia and to identify the behaviours putting such travellers at high risk for acquiring ESBL-producing E. coli. METHODS: The study was performed at a travel clinic in Calgary. Travellers 18 years or older who were planning to visit South Asia for a period of at least 5 days were included. Three rectal swabs were obtained, and 2 questionaires were administered (before and after travel). RESULTS: A total of 149 travellers participated between January 2012 and July 2014; of these, 116 (78%) provided rectal swabs upon return to Calgary and completed both pre- and post-travel questionaires. Of the 109 travellers without colonization with ESBL-producing E. coli upon enrollment, 70 (64%) acquired ESBL-producing E. coli during travel. Of the 90 participants who visited India, 66 (73%) were positive for ESBL-producing E. coli upon their return to Calgary. Most ESBL-producing E. coli specimens were identified as producing the enzyme CTX-M-15. Behaviours associated with a statistically significant risk of acquiring ESBL-producing E. coli included visiting India (odds ratio [OR] 19.9, 95% confidence interval [CI] 4.5-88.8), consuming meals with the local population (OR 6.9, 95% CI 1.2-39.6), taking any type of antibiotic during travel (OR 4.3, 95% CI 1.3-14.3) and travelling for any purpose other than business (OR 12.4, 95% CI 2.8-55.2). INTERPRETATION: In this study, travel to India was associated with the highest risk of acquiring ESBL-producing E. coli relative to travel to other countries in South Asia. Nonbusiness travel, consuming foods with the local population and the use of antibiotics while travelling were associated with an increased risk of acquiring these antibiotic-resistant organisms while in India. Trial registration: ClinicalTrials.gov, no. NCT01296165.

The epidemiology of Staphylococcus aureus carriage in patients attending inner city sexually transmitted infections and community clinics in Calgary, Canada.

BACKGROUND: Although the nares represent the most common carriage site for traditional hospital-associated strains of Staphylococcus aureus (SA), the predominant site of carriage of SA in the community is less certain. METHODS: We conducted a cross-sectional study in 285 patients attending sexually transmitted diseases and inner-city clinics to evaluate the prevalence, body site colonisation and risk factors associated with carriage of methicillin susceptible SA (MSSA). All isolates were characterized by pulsed field gel electrophoresis, staphylococcal cassette chromosome mec, staphylococcal protein A and multilocus sequence typing. RESULTS: The prevalence of colonisation with SA was 57.5% (164/285); 162 (56.8%) participants were colonized with MSSA, and 4 (1.4%) with methicillin-resistant SA (MRSA), 2 of them were co-colonised with both MRSA and MSSA. The most common sites of colonisation were the throat (73.1%), nares (65.2%) and interdigital web spaces of the hand (21.3%). Three out of 4 MRSA isolates were USA300-MRSA strains. Twelve MSSA isolates were closely related to the USA300 CA-MRSA. We identified sexual behaviours such as having more than 6 heterosexual sexual partners in the last 6 months and trimming pubic hair to be independently associated with MSSA colonisation, and more specifically practicing oral sex as a risk factor for throat colonisation. CONCLUSION: There is a high prevalence of MSSA carriage in this population, with a low prevalence of MRSA. The throat was the most common site of carriage and sexual behaviours were found to be risk factors for MSSA colonisation. Close strain relatedness of MSSA and USA300-MRSA isolates suggests either gain or loss of the SCCmec element, respectively.