Plasmid genomic epidemiology of blaKPC carbapenemase-producing Enterobacterales in Canada, 2010-2021.

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. Klebsiella pneumoniae carbapenemase (blaKPC) is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn4401 transposon. This means that alongside clonal expansion, blaKPC can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 blaKPC carbapenemase-producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short-read and long-read sequencing, we obtained 202 complete and circular blaKPC-encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian blaKPC-encoding plasmids. We further estimated the genomic location of incomplete blaKPC-encoding contigs and predicted a plasmid cluster for 95% (603/635) of these. We identified different patterns of carbapenemase mobilization across Canada related to different plasmid clusters, including clonal transmission of IncF-type plasmids (108/829, 13%) in K. pneumoniae clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in Enterobacter hormaechei ST316, and horizontal transmission of IncL/M (142/829, 17%) and IncN-type plasmids (149/829, 18%) across multiple genera. Our findings highlight the diversity of blaKPC genomic loci and indicate that multiple, distinct plasmid clusters have contributed to blaKPC spread and persistence in Canada.

Effectiveness of prophylactic intranasal photodynamic disinfection therapy and chlorhexidine gluconate body wipes for surgical site infection prophylaxis in adult spine surgery.

BACKGROUND: Current measures to prevent spinal surgical site infection (SSI) lack compliance and lead to antimicrobial resistance. We aimed to examine the effectiveness of bundled preoperative intranasal photodynamic disinfection therapy (nPDT) and chlorhexidine gluconate (CHG) body wipes in the prophylaxis of spine SSIs in adults, as well as determine our institutional savings attributable to the use of this strategy and identify adverse events reported with nPDT-CHG. METHODS: We performed a 14-year prospective observational interrupted time-series study in adult (age > 18 yr) patients undergoing emergent or elective spine surgery with 3 time-specific cohorts: before rollout of our institution's nPDT-CHG program (2006-2010), during rollout (2011-2014) and after rollout (2015-2019). We used unadjusted bivariate analysis to test for temporal changes across patient and surgical variables, and segmented regression to estimate the effect of nPDT-CHG on the annual SSI incidence rates per period. We used 2 models to estimate the cost of nPDT-CHG to prevent 1 additional SSI per year and the annual cumulative cost savings through SSI prevention. RESULTS: Over the study period, 13 493 patients (mean 964 per year) underwent elective or emergent spine surgery. From 2006 to 2019, the mean age, mean Charlson Comorbidity Index (CCI) score and mean Spine Surgical Invasiveness Index (SSII) score increased from 48.4 to 58.1 years, from 1.7 to 2.6, and from 15.4 to 20.5, respectively (p < 0.001). Unadjusted analysis confirmed a significant decrease in the annual number (74.6 to 26.8) and incidence (7.98% to 2.67%) of SSIs with nPDT-CHG (p < 0.001). After adjustment for mean age, mean CCI score and mean SSII score, segmented regression showed an absolute reduction in the annual SSI incidence rate of 3.36% per year (p < 0.001). The estimated annual cost to prevent 1 additional SSI per year was about $1350-$1650, and the estimated annual cumulative cost savings were $2 484 856-$2 495 016. No adverse events were reported with nPDT-CHG. CONCLUSION: Preoperative nPDT-CHG administration is an effective prophylactic strategy for spinal SSIs, with significant cost savings. Given its rapid action, minimal risk of antimicrobial resistance, broad-spectrum activity and high compliance rate, preoperative nPDT-CHG decolonization should be the standard of care for all patients undergoing emergent or elective spine surgery.

Surface and Air Contamination With Severe Acute Respiratory Syndrome Coronavirus 2 From Hospitalized Coronavirus Disease 2019 Patients in Toronto, Canada, March-May 2020.

BACKGROUND: We determined the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in air and on surfaces in rooms of patients hospitalized with coronavirus disease 2019 (COVID-19) and investigated patient characteristics associated with SARS-CoV-2 environmental contamination. METHODS: Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at 6 acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 ribonucleic acid (RNA), cultured to determine potential infectivity, and whole viral genomes were sequenced. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated. RESULTS: Severe acute respiratory syndrome coronavirus 2 RNA was detected from surfaces (125 of 474 samples; 42 of 78 patients) and air (3 of 146 samples; 3 of 45 patients); 17% (6 of 36) of surface samples from 3 patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, polymerase chain reaction-positive nasopharyngeal swab (cycle threshold of ≤30) on or after surface sampling date, higher Charlson comorbidity score, and shorter time from onset of illness to sampling date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. CONCLUSIONS: The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited.

AMPlify: attentive deep learning model for discovery of novel antimicrobial peptides effective against WHO priority pathogens.

BACKGROUND: Antibiotic resistance is a growing global health concern prompting researchers to seek alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) are attracting attention again as therapeutic agents with promising utility in this domain, and using in silico methods to discover novel AMPs is a strategy that is gaining interest. Such methods can sift through large volumes of candidate sequences and reduce lab screening costs. RESULTS: Here we introduce AMPlify, an attentive deep learning model for AMP prediction, and demonstrate its utility in prioritizing peptide sequences derived from the Rana [Lithobates] catesbeiana (bullfrog) genome. We tested the bioactivity of our predicted peptides against a panel of bacterial species, including representatives from the World Health Organization's priority pathogens list. Four of our novel AMPs were active against multiple species of bacteria, including a multi-drug resistant isolate of carbapenemase-producing Escherichia coli. CONCLUSIONS: We demonstrate the utility of deep learning based tools like AMPlify in our fight against antibiotic resistance. We expect such tools to play a significant role in discovering novel candidates of peptide-based alternatives to classical antibiotics.

Editorial Expression of Concern: Comparative effectiveness of ß-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

An amendment to this paper has been published and can be accessed via the original article.

Comparison of outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who are treated with ß-lactam vs vancomycin empiric therapy: a retrospective cohort study.

BACKGROUND: Prior studies suggested that vancomycin may be inferior to ß-lactams for the empiric treatment of methicillin-susceptible S. aureus (MSSA) bacteremia. We assessed whether empiric therapy with ß-lactams compared to vancomycin was associated with differences in clinical outcomes in patients with MSSA bacteremia. METHODS: We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric ß-lactam or vancomycin therapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, recurrent infection at 6 months, duration of bacteremia and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression. RESULTS: Of 814 patients identified, 400 met inclusion criteria (ß-lactam = 200, vancomycin = 200). Overall 28-day mortality was 8.5 % (n=34). There were more cases of infective endocarditis in the ß-lactam than in the vancomycin group [45 (22.5 %) vs 23 (11.5 %), p < 0.01]. Adjusted mortality at 28 days was similar between the two groups (OR: 1.14; 95 % CI: 0.49-2.64). No differences in secondary outcomes were observed. Transition to cloxacillin or cefazolin occurred within a median of 67.8 h in the vancomycin group. CONCLUSIONS: Empiric therapy with ß-lactams was not associated with differences in all-cause mortality, recurrent infection, microbiological cure or hospital length-of-stay compared to vancomycin. Vancomycin monotherapy may be appropriate for the empiric treatment of MSSA bacteremia if definitive therapy with cloxacillin or cefazolin can be initiated within 3 days.

Comparative effectiveness of ß-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

BACKGROUND: Vancomycin may be inferior to ß-lactams for the empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We compared empiric ß-lactams to vancomycin to assess clinical outcomes in patients with MSSA bacteremia. METHODS: We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric ß-lactam with or without vancomycin or vancomycin monotherapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, duration of bacteremia, and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression. RESULTS: Of 669 patients identified, 255 met inclusion criteria (ß-lactam = 131, vancomycin = 124). Overall 28-day mortality was 7.06 % (n = 18). There were more cases of infective endocarditis in the ß-lactam than in the vancomycin group [24 (18.3 %) vs 12 (9.7 %), p = 0.05]. Adjusted mortality at 28 days was similar between the two groups (OR 0.85; 95 % CI 0.27-2.67). The duration of bacteremia was longer in the vancomycin group (97.1 vs 70.7 h, p = 0.007). Transition to cloxacillin or cefazolin occurred within a median of 68.3 h in the vancomycin group. CONCLUSIONS: Empiric ß-lactams was associated with earlier clearance of bacteremia by a median of 1 day compared to vancomycin. Future prospective studies are needed to confirm our findings.

Comparison of clinical and epidemiological features of Shiga toxin-producing Escherichia coli O157 and non-O157 infections in British Columbia, 2009 to 2011.

INTRODUCTION: Shiga toxin-producing Escherichia coli (STEC) are major foodborne agents that have the potential to cause severe enteric illnesses and large outbreaks worldwide. Several studies found non-O157 infections to be clinically milder than O157 STEC infections. OBJECTIVE: To compare the clinical and epidemiological profiles of O157 and non-O157 STEC human infections in British Columbia (BC). METHODS: All STEC cases reported in BC from 2009 to 2011 by four local health authorities were included in the study. Cases were classified according to STEC serotype based on laboratory information. Information was gathered via case interview forms. Data analysis included the χ(2) test and Mann-Whitney test; P<0.05 was considered to be statistically significant. RESULTS: A total of 260 STEC cases were reported, including 154 (59.2%) O157 cases, 63 (24.2%) non-O157 cases and 43 (16.5%) STEC cases with no serotype identified. Hospitalization rate was higher and duration of hospitalization was significantly longer for O157 cases compared with non-O157 cases, but other clinical features were not significantly different. Patients with non-O157 infections were significantly more likely to have travelled outside Canada, less likely to report food exposure at social gatherings and more likely to consume bagged greens and cheese. DISCUSSION: O157 is the predominant O serotype in BC and appeared to be more clinically severe than non-O157 STEC infections. However, the true incidence and severity of non-O157 remain unknown due to our current inability to detect all non-O157 cases. The present study and the literature suggest the need to identify more predictive virulence factors because serotype does not consistently predict disease severity.

INTRODUCTION: Les Escherichia coli producteurs de Shigatoxine (ECST) sont d'importants agents de toxi-infection alimentaire qui ont le potentiel de provoquer de graves maladies entériques et de vastes éclosions dans le monde. Selon plusieurs études, les infections à ECST non O157 sont plus modérées sur le plan clinique que celles à ECST O157. OBJECTIF: Comparer les profils cliniques et épidémiologiques des infections humaines à ECST O157 et non O157 en Colombie-Britannique (CB). MÉTHODOLOGIE: Les chercheurs ont inclus dans l'étude tous les cas d'ECST déclarés en CB entre 2009 et 2011 par quatre régies de la santé locales. Ils ont classé les cas selon le sérotype d'ECST tiré de données de laboratoire et ont obtenu de l'information au moyen de formulaires d'entrevue des cas. L'analyse des données incluait le test χ2 et le test de Mann-Whitney, et le P<0,05 était considéré comme statistiquement significatif. RÉSULTATS: Au total, 260 cas d'ECST ont été signalés, dont 154 cas O157 (59,2 %), 63 cas non O157 (24,2%) et 43 cas sans sérotype défini (16,5 %). Le taux d'hospitalisation était plus élevé et la durée d'hospitalisation considérablement plus longue dans les cas O157 que dans les cas non O157, mais d'autres caractéristiques cliniques n'étaient pas très différentes. Les patients atteints d'une infection non O157 étaient beaucoup plus susceptibles d'avoir voyagé à l'extérieur du Canada, moins susceptibles de déclarer avoir été exposés à des aliments lors de rencontres sociales et plus susceptibles d'avoir consommé des légumes verts emballés et du fromage. EXPOSÉ: Le sérotype O157 est le sérotype O prédominant en CB et semblait être plus grave sur le plan clinique que les infections à ECST non O157. Cependant, on ne connaît toujours pas la véritable incidence et la véritable gravité des infections non O157 en raison de notre incapacité à déceler tous les cas non O157. D'après la présente étude et les publications, il faudra déterminer des facteurs de virulence plus prédictifs, parce que le sérotype ne permet pas de prédire systématiquement la gravité de la maladie.

Abbott ID NOW™ COVID-19 assay: do not discard the swab.

We compared the performance of ID NOW™ COVID-19 assay nasal swabs with RT-PCR of nasopharyngeal swabs for SARS-CoV-2 in an outbreak setting, determining whether addition of RT-PCR of residual nasal swabs (rNS) (post ID NOW™ elution) would increase overall analytic sensitivity. Devices were placed at 2 long term and 1 acute care sites and 51 participants were recruited. Prospective paired nasopharyngeal and nasal samples were collected for RT-PCR and ID NOW™.  ID NOW™ had a positive and negative categorical agreement of 86% and 93% compared to RT-PCR of nasopharyngeal swabs. Sensitivity and specificity of the ID NOW™ was 86% and 100%, positive and negative predictive value was 100% and 95% (COVID-19 positivity rate: 8%). Addition of rNS RT-PCR increased the positive and negative categorical agreement to 93% and 97%. Based on these results, we propose an alternative workflow which includes complementary testing of rNS on a secondary assay.

Prediction of pediatric outcome after prenatal diagnosis and expectant antenatal management of congenital cystic adenomatoid malformation.

OBJECTIVE: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and antenatal expectant management in a provincial tertiary referral center that does not offer fetal surgery. METHODS: Retrospective cohort of 71 consecutive cases of prenatally diagnosed CCAM meeting study criteria (1996-2004). CVR was calculated on the initial ultrasound at the referral center, and associated with hydrops (Fisher's exact test) and a composite adverse postnatal outcome consisting of death, intubation for respiratory distress, extracorporeal membrane oxygenation, non-elective surgery for symptomatology, or respiratory infection requiring hospital admission (Mann-Whitney test). RESULTS: A CVR > 1.6 was significantly associated with hydrops (p = 0.003). In addition, the CVR was significantly associated with the composite adverse postnatal outcome (p = 0.004) at a mean age of follow-up of 41 months (range < 1-117 months). For CVR and postnatal outcome, the area-under-the-curve receiver operating characteristic was 0.81 (95% CI 0.69-0.93, p = 0.006), and choosing a CVR cut-off of < 0.56, the negative predictive value was 100% (95% CI 0.85-1.00). CONCLUSION: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR < 0.56 predictive of good prognosis after birth.

Pattern of acquisition of hospital-associated pathogens in the ICU of an academic tertiary care hospital.

BACKGROUND: Among hospitalized patients, a 48-hour window from time of hospitalization defines nosocomial infections and guides empiric antibiotic selection. This time frame may lead to overuse of broad-spectrum antibiotics. Our primary objective was to determine the earliest and median time since hospital admission to acquire antibiotic-resistant pathogens among patients admitted to the intensive care unit (ICU) of an academic, tertiary care hospital. METHODS: Retrospective chart review was conducted for adult patients admitted to the ICU from home or another hospital within the same health authority in 2018, to identify the time to acquisition of hospital-associated pathogens: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, non-ESBL ceftriaxone-resistant Enterobacterales, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Patients transferred from hospitals outside the health authority, admitted to ICU after 14 days of hospitalization, who were solid organ or bone marrow transplant recipients, or who were otherwise immunocompromised were excluded. RESULTS: In 2018, 1,343 patients were admitted to this ICU; 820 met the inclusion criteria. Of these, 121 (14.76%) acquired a hospital-associated pathogen in the ICU. The probability of isolating a hospital-associated pathogen by 48 hours of hospital admission was 3%. The earliest time to isolate any of these pathogens was 29 hours, and the median was 9 days (interquartile range [IQR] 3.8-15.6 days). CONCLUSIONS: Most patients (85.3%) in this ICU never acquired a hospital-associated pathogen. The median time to acquire a hospital-associated pathogen among the remaining patients suggests that initiating empiric broad-spectrum antibiotics on the basis of a 48-hour threshold may be premature.

HISTORIQUE : Chez les patients hospitalisés, une fenêtre de 48 heures après le moment de l'hospitalisation définit les infections nosocomiales et oriente la sélection d'antibiotiques empiriques. Cette période peut favoriser la surutilisation d'antibiotiques à large spectre. L'objectif primaire de l'étude visait à déterminer la période la plus courte et la période médiane à compter de l'admission pour que les patients admis en soins intensifs à partir d'un hôpital universitaire de soins tertiaires contractent des agents pathogènes antibiorésistants. MÉTHODOLOGIE: Les chercheurs ont procédé à un examen rétrospectif des dossiers des patients adultes admis en soins intensifs à partir de la maison ou d'un autre hôpital de la même autorité sanitaire en 2018, afin de déterminer la période avant de contracter des agents pathogènes associés au milieu hospitalier : Staphylococcus aureus résistant à la méthicilline, entérocoque résistant à la vancomycine, Enterobacterales producteurs de bêta-lactamases à spectre élargi (BLSE), Enterobacterales résistant à la ceftriaxine non producteurs de BLSE, Pseudomonas aeruginosa et Stenotrophomonas maltophilia. Ont été exclus les patients transférés d'un hôpital hors de l'autorité sanitaire, admis en soins intensifs plus de 14 jours après l'hospitalisation, receveurs d'un organe plein ou de moelle osseuse ou autrement immunodéprimés. RÉSULTATS: En 2018, 1 343 patients ont été admis en soins intensifs, dont 820 respectaient les critères d'inclusion. De ce nombre, 121 (14,67 %) ont contracté un agent pathogène en soins intensifs. La probabilité d'isoler un tel agent dans les 48 heures suivant l'admission en milieu hospitalier s'élevait à 3 %. Ces agents pathogènes ont été isolés au plus tôt 29 heures après l'hospitalisation, et au bout d'une période médiane de neuf jours (plage interquartile [PIQ] 3,8 à 15,6 jours). CONCLUSIONS: La plupart des patients (85,3%) de cette unité de soins intensifs n'ont jamais contracté d'agent pathogène associé au milieu hospitalier. Selon la période médiane avant d'acquérir un tel agent pathogène chez les autres patients, il serait prématuré d'entreprendre une antibiothérapie à large spectre au seuil de 48 heures.

Antimicrobial efficacy and durability of copper formulations over one year of hospital use.

OBJECTIVE: To evaluate 3 formulations of copper (Cu)-based self-sanitizing surfaces for antimicrobial efficacy and durability over 1 year in inpatient clinical areas and laboratories. DESIGN: Randomized control trial. SETTING: We assessed 3 copper formulations: (1) solid alloy 80% Cu-20% Ni (integral copper), (2) spray-on 80% Cu-20% Ni (spray-on) and (3) 16% composite copper-impregnated surface (CIS). In total, 480 coupons (1 cm2) of the 3 products and control surgical grade (AISI 316) stainless steel were inserted into gaskets and affixed to clinical carts used in patient care areas (including emergency and maternity units) and on microbiology laboratory bench work spaces (n = 240). The microbial burden and assessment of resistance to wear, corrosion, and material compatibility were determined every 3 months. Participants included 3 tertiary-care Canadian adult hospital and 1 pediatric-maternity hospital. RESULTS: Copper formulations used on inpatient units statistically significantly reduced bacterial bioburden compared to stainless steel at months 3 and 6. Only the integral copper product had significantly less bacteria than stainless steel at month 12. No statistically significant differences were detected in microbial burden between copper formulations and stainless-steel coupons on microbiology laboratory benches where bacterial counts were low overall. All mass changes and corrosion rates of the formulations were acceptable by engineering standards. CONCLUSIONS: Copper surfaces vary in their antimicrobial efficacy after 1 year of hospital use. Frequency of cleaning and disinfection influence the impact of copper; the greatest reduction in microbial bioburden occurred in clinical areas compared to the microbiology laboratory where cleaning and disinfection were performed multiple times daily.

qSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

BACKGROUND: Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. METHODS: We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. RESULTS: Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. CONCLUSIONS: Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

HISTORIQUE: Les infections sanguines peuvent rester non diagnostiquées chez les patients septiques avant l'obtention des cultures sanguines, en raison d'une antibiothérapie antérieure. Les chercheurs ont puisé dans l'étude de cohorte FABLED pour déterminer si le score rapide de l'évaluation séquentielle d'insuffisance des organes (Sequential Organ Failure Assessment, qSOFA) pourrait dépister les patients à plus haut risque de bactériémie avec fiabilité, malgré la possibilité de cultures sanguines faussement négatives en raison d'une antibiothérapie antérieure. MÉTHODOLOGIE: Les chercheurs ont réalisé une étude diagnostique multicentrique chez des patients adultes ayant de graves manifestations de sepsis. Les patients ont été inscrits dans l'un des sept centres participants entre novembre 2013 et septembre 2018. Tous les patients de l'étude de cohorte FABLED avaient subi deux séries de cultures sanguines avant de recevoir une thérapie antimicrobienne, de même qu'une autre série de cultures sanguines dans les quatre heures suivant le début du traitement. Les participants ont été classés en fonction de leur score de qSOFA, un score d'au moins 2 étant considéré comme positif. RÉSULTATS: Chez les 325 patients ayant de graves manifestations de sepsis, un score de qSOFA positif (défini comme un score d'au moins 2) à l'admission était sensible à 58 % (IC à 95 %, 48 % à 67 %) et spécifique à 41 % (IC à 95 %, 34 % à 48 %) pour prédire la bactériémie. Chez les patients dont les cultures sanguines étaient négatives après la prise d'antimicrobiens, un score de qSOFA positif était sensible à 57 % (IC à 95 %, 42 % à 70 %) et spécifique à 42 % (IC à 95 %, 35 % à 49 %) pour dépister les patients atteints d'une bactériémie avant le début du traitement. CONCLUSIONS: Selon les résultats, le score de qSOFA ne peut pas être utilisé pour dépister les patients à risque de bactériémie occulte à cause de l'administration d'antibiotiques avant la culture sanguine.

First reported outbreak of the emerging pathogen Candida auris in Canada.

BACKGROUND: Candida auris was first described in Japan in 2009 and has since been detected in over 40 countries. The yeast is concerning for multiple reasons, primarily: (1) challenges with accurate identification; (2) reported multidrug resistance; (3) published mortality rates of 30%-60%; and (4) persistence in the environment associated with human transmission. We report the emergence of a healthcare-associated cluster in the Greater Vancouver area in 2018 and describe the measures implemented to contain its transmission. METHODS: Cases were identified through passive and ring surveillance of affected wards. Positive isolates were sent to provincial and national reference laboratories for confirmation and genomic characterization. Extensive infection control measures were implemented immediately after the initial case was identified. RESULTS: Four cases were identified during the outbreak. In a 4-month period, over 700 swabs were collected in order to screen 180 contacts. Whole genome sequencing concluded that all isolates clustered together and belonged to the South Asian clade. No isolates harbored FKS gene mutations associated with resistance to echinocandins. Infection control measures, including surveillance, education, cleaning and/or disinfection, patient cohorting, isolation, and hand hygiene, effectively contained the outbreak; it was declared over within 2 months. CONCLUSIONS: The spread of C auris in healthcare facilities has not spared Canadian institutions. Our experience demonstrates that strict infection control measures combined with microbiological screening can effectively halt transmission in healthcare centers. The necessity of active prospective screening remains unclear.

Infection control, occupational and public health measures including mRNA-based vaccination against SARS-CoV-2 infections to protect healthcare workers from variants of concern: A 14-month observational study using surveillance data.

BACKGROUND: We evaluated measures to protect healthcare workers (HCWs) in Vancouver, Canada, where variants of concern (VOC) went from <1% VOC in February 2021 to >92% in mid-May. Canada has amongst the longest periods between vaccine doses worldwide, despite Vancouver having the highest P.1 variant rate outside Brazil. METHODS: With surveillance data since the pandemic began, we tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in all 25,558 HCWs in Vancouver Coastal Health, by occupation and subsector, and compared to the general population. Cox regression modelling adjusted for age and calendar-time calculated vaccine effectiveness (VE) against SARS-CoV-2 in fully vaccinated (≥ 7 days post-second dose), partially vaccinated infection (after 14 days) and unvaccinated HCWs; we also compared with unvaccinated community members of the same age-range. FINDINGS: Only 3.3% of our HCWs became infected, mirroring community rates, with peak positivity of 9.1%, compared to 11.8% in the community. As vaccine coverage increased, SARS-CoV-2 infections declined significantly in HCWs, despite a surge with predominantly VOC; unvaccinated HCWs had an infection rate of 1.3/10,000 person-days compared to 0.89 for HCWs post first dose, and 0.30 for fully vaccinated HCWs. VE compared to unvaccinated HCWs was 37.2% (95% CI: 16.6-52.7%) 14 days post-first dose, 79.2% (CI: 64.6-87.8%) 7 days post-second dose; one dose provided significant protection against infection until at least day 42. Compared with community infection rates, VE after one dose was 54.7% (CI: 44.8-62.9%); and 84.8% (CI: 75.2-90.7%) when fully vaccinated. INTERPRETATION: Rigorous droplet-contact precautions with N95s for aerosol-generating procedures are effective in preventing occupational infection in HCWs, with one dose of mRNA vaccination further reducing infection risk despite VOC and transmissibility concerns. Delaying second doses to allow more widespread vaccination against severe disease, with strict public health, occupational health and infection control measures, has been effective in protecting the healthcare workforce.

Neither Blood Culture Positivity nor Time to Positivity Is Associated With Mortality Among Patients Presenting With Severe Manifestations of Sepsis: The FABLED Cohort Study.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and health care costs worldwide. METHODS: We conducted a multicenter, prospective cohort study evaluating the yield of blood cultures drawn before and after empiric antimicrobial administration among adults presenting to the emergency department with severe manifestations of sepsis. Enrolled patients who had the requisite blood cultures drawn were followed for 90 days. We explored the independent association between blood culture positivity and its time to positivity in relation to 90-day mortality. RESULTS: Three hundred twenty-five participants were enrolled; 90-day mortality among the 315 subjects followed up was 25.4% (80/315). Mortality was associated with age (mean age [standard deviation] in those who died was 72.5 [15.8] compared with 62.9 [17.7] years among survivors; P < .0001), greater Charlson Comorbidity Index (2 [interquartile range {IQR}, 1-3] vs 1 [IQR, 0-3]; P = .008), dementia (13/80 [16.2%] vs 18/235 [7.7%]; P = .03), cancer (27/80 [33.8%] vs 47/235 [20.0%]; P = .015), positive quick Sequential Organ Failure Assessment score (57/80 [71.2%] vs 129/235 [54.9%]; P = .009), and normal white blood cell count (25/80 [31.2%] vs 42/235 [17.9%]; P = .02). The presence of bacteremia, persistent bacteremia after antimicrobial infusion, and shorter time to blood culture positivity were not associated with mortality. Neither the source of infection nor pathogen affected mortality. CONCLUSIONS: Although severe sepsis is an inflammatory condition triggered by infection, its 90-day survival is not influenced by blood culture positivity nor its time to positivity. CLINICAL TRIALS REGISTRATION: NCT01867905.

Candida Keratitis: Epidemiology, Management, and Clinical Outcomes.

PURPOSE: To examine the epidemiological characteristics, trends, risk factors, management strategies, and clinical outcomes of Candida albicans and non-albicans keratitis over a 15-year period in a tertiary Canadian eye center. METHODS: In a retrospective observational case series of Candida keratitis from 2003 to 2017, demographics, risk factors, corrected distance visual acuity (CDVA) at initial and final consultations, medical and surgical management, and follow-up duration were recorded. RESULTS: Twenty-one cases of Candida keratitis were identified (62.5% of total fungal keratitis; 10 C. albicans and 11 non-albicans). The most commonly associated risk factors were topical steroid use (16 patients, 76%), ocular surface disease (15 patients, 71%), contact lens use (11 patients, 52%), and previous corneal surgery (8 patients, 38%); all patients had 2 or more combined risk factors. The number of patients with a visual acuity of 20/200 or better remained the same before and after the treatment (5/21, 24%). The mean duration of the antifungal treatment was 98 ± 126 days. Sixteen patients ultimately required surgical management (76%; 12 therapeutic keratoplasties, 3 enucleation, and 1 optical keratoplasty). When comparing C. albicans with non-albicans keratitis, we found no difference in presenting visual acuity, final visual acuity, or requirement for surgical management. CONCLUSIONS: Candida keratitis accounts for the most identified fungal keratitis cases in this temperate climate area. An exposure to multiple risk factors appears necessary. A surgical intervention is required for the resolution of most cases. Different subspecies of Candida ultimately resulted in similar clinical outcomes.

In vitro evaluation of antimicrobial efficacy and durability of three copper surfaces used in healthcare.

Antimicrobial properties of solid copper (Cu) surfaces against various microorganisms have been demonstrated, but little is known about the durability and relative antimicrobial efficacy of different Cu formulations currently used in healthcare. The aim of this study was to assess whether three different formulations of copper-bearing alloys (integral, spray-on and Cu-impregnated surfaces) and a stainless steel control differed in their antimicrobial efficacy, durability, and compatibility with hospital-grade cleaner/disinfectants. The U.S. Environmental Protection Agency draft protocol for the evaluation of bactericidal activity of Cu containing alloys was modified to more accurately reflect cleaning methods in healthcare. The three different Cu alloys were evaluated using 25 × 25 × 3 mm disks subjected to one year of simulated cleaning and disinfection using the Wiperator™ with microfiber cloths presoaked in three common hospital disinfectants: accelerated hydrogen peroxide, quaternary ammonium, or sodium hypochlorite solutions. Bactericidal activity was evaluated using Staphylococcus aureus and Pseudomonas aeruginosa. While all Cu formulations exhibited some antimicrobial activity, integral and spray-on Cu alloys showed the greatest efficacy. Assessments of durability included documentation of changes in mass, morphological changes by scanning electron microscopy, chemical composition alteration by energy-dispersive x-ray spectroscopy, and surface roughness alteration using profilometry over one year of simulated use. The integral Cu alloy had the least mass loss (0.20% and 0.19%) and abrasion-corrosion rate (6.28 and 6.09 µm/yr) compared to stainless steel. The integral product also showed the highest durability. Exposure to disinfectants affected both the antimicrobial efficacy and durability of the various copper products.

Potential influence of rapid diagnostics on timeliness of management decisions for patients with positive blood cultures.

Background: The Accelerate Pheno system (AXDX) provides rapid identification (ID; 90 minutes) and antimicrobial susceptibility testing (AST; approximately 7 hours) from positive blood culture (BC) bottles. We assessed the potential of AXDX results to influence more timely antibiotic interventions with a convenience sample of 158 positive BCs. Methods: BCs with a mono-microbial Gram stain likely to be on the AXDX panel were run in parallel with the standard of care (SOC). Using results from the SOC, the medical microbiologist on call (MMOC) noted interventions made at the time of BC Gram stain and when ID and AST results were available. The timing of MMOC intervention was noted and compared with fastest potential SOC time and AXDX time. Results: Of 158 specimens selected for analysis, 144 were evaluable. ID was available 11.9 hours and AST 27.7 hours faster than SOC. Correct ID was provided for 85.2% of specimens and AST for 59.0% of specimens, with 97.5% essential agreement compared with the SOC. One hundred and thirteen clinical interventions were made on 100 specimens: 54.9% were narrowing; 33.6%, escalation; 6.2%, consultation with ID; and 3.5%, further investigation. If AXDX data had been used immediately once available, interventions would have been possible 24 hours earlier for ID interventions and 39 hours earlier for AST results. Conclusions: Results from rapid diagnostic panels such as AXDX have the potential to support timely antimicrobial de-escalation and other decisions to benefit patients, especially if paired with stewardship interventions.

Historique: Le système Accelerate Pheno (AXDX) permet de procéder à une identification rapide (ID; 90 minutes) et à des tests de susceptibilité antimicrobienne (AST; environ sept heures) à partir de bouteilles d'hémoculture (BH) positives. À l'aide d'un échantillon de commodité de 158 BH positives, les auteurs ont évalué le potentiel de résultats du système AXDX pour favoriser des interventions antibiotiques plus opportunes. Méthodologie: Les auteurs ont comparé les BH présentant une coloration de Gram monomicrobienne susceptible de se trouver sur le panel AXDX avec la norme de soins (NdS). À l'aide des résultats de la NdS, le microbiologiste médical sur appel (MMSA) a consigné les interventions effectuées au moment de la coloration de Gram de la BH et lorsque les résultats de l'ID et de l'AST étaient disponibles. Le moment de l'intervention du MMSA était consigné et comparé avec la durée de la NdS au potentiel le plus rapide et la durée de l'AXDX. Résultats: Des 158 échantillons sélectionnés en vue d'être analysés, 144 étaient évaluables. L'ID était disponible 11,9 heures et l'AST, 27,7 heures plus rapidement que la NdS. L'ID exacte était fournie pour 85,2 % des échantillons et l'AST exacte, pour 59,0 % des échantillons, selon une entente essentielle de 97,5 % par rapport à la NdS. Cent treize interventions ont été effectuées sur 100 échantillons : 54,9 % visaient à réduire le spectre, 33,6 %, à accroître la médication, 6,2 %, à demander une consultation avec l'ID et 3,5 %, à obtenir des explorations plus approfondies. Si les données de l'AXDX avaient été utilisées dès l'obtention des résultats, il aurait été possible d'agir 24 heures plus rapidement pour les interventions d'ID et 39 heures plus rapidement pour les résultats de l'AST. Conclusions: Les résultats des panels diagnostiques rapides comme l'AXDX ont le potentiel de favoriser une désescalade antimicrobienne et d'autres décisions au profit des patients, surtout s'ils s'associent à des interventions de gestion.

Real-world Time to Positivity of 2 Widely Used Commercial Blood Culture Systems in Patients With Severe Manifestations of Sepsis: An Analysis of the FABLED Study.

BACKGROUND: Of all microbiological tests performed, blood cultures have the most impact on patient care. Timely results are essential, especially in the management of sepsis. While there are multiple available blood culture systems on the market, they have never been compared in a prospective study in a critically ill population. METHODS: We performed an analysis of the FABLED study cohort to compare culture results and time to positivity (TTP) of 2 widely used blood culture systems: BacT/Alert and BACTEC. In this multisite prospective study, patients with severe manifestations of sepsis had cultures drawn before antibiotics using systematic enrollment criteria and blood drawing methodology allowing for minimization of pre-analytical biases. RESULTS: We enrolled 315 patients; 144 had blood cultures (47 positive) with BacT/Alert and 171 with BACTEC (53 positive). Patients whose blood cultures were processed using the BacT/Alert system were younger (median, 64 vs 70 years; P = .003), had a higher proportion of HIV (9.03% vs 1.75%; P = .008) and a lower qSOFA (P = .003). There were no statistically significant differences in the most commonly identified bacterial species. TTP was shorter for BACTEC (median [interquartile range {IQR}], 12.5 [10-14] hours) compared with BacT/Alert (median [IQR], 17 [14-21] hours; P < .0001). CONCLUSIONS: In this large prospective multi-centre study comparing the two blood culture systems among patients with severe manifestations of sepsis, and using a rigorous pre-analytical methodology, the BACTEC system yielded positive culture results 4.5 hours earlier than BacT/Alert. These results apply to commonly isolated bacteria. However, our study design did not allow direct comparison of TTP for unusual pathogens nor of clinical sensitivity between systems. More research is needed to determine the clinical implications of this finding.