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.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

High-dose cephalexin for cellulitis: a pilot randomized controlled trial.

BACKGROUND: Up to 3% of all Emergency Department (ED) visits are due to skin and soft tissue infections such as non-purulent cellulitis. The current treatment failure rate is approximately 20%. Evidence is lacking regarding the optimal outpatient management of cellulitis. OBJECTIVES: To evaluate the feasibility of a randomized trial comparing high-dose (1000 mg) to standard-dose (500 mg) cephalexin to treat ED patients with cellulitis. METHODS: A parallel arm double-blind randomized controlled pilot trial conducted at two EDs in Canada. Eligible participants were adults (age ≥ 18 years) presenting to the ED with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient management with oral antibiotics. Participants were randomized to high-dose or standard-dose cephalexin four times daily for 7 days. The primary feasibility outcome was participant recruitment rate (target ≥ 35%). The preliminary primary effectiveness outcome was oral antibiotic treatment failure. RESULTS: Of 134 eligible participants approached for trial participation, 69 (51.5%, 95% CI 43.1 to 59.8%) were recruited and randomized. After excluding three randomized participants due to an alternate diagnosis, 33 participants were included in each arm. Nineteen eligible cases (14.2%) were missed. Loss to follow-up was 6.1%. Treatment failure occurred in four patients (12.9%) in the standard-dose arm versus one patient (3.2%) in the high-dose arm. A greater proportion had minor adverse events in the high-dose arm. No patients had an unplanned hospitalization within 14 days. CONCLUSION: This pilot randomized controlled trial comparing high-dose to standard-dose cephalexin for ED patients with cellulitis demonstrated a high participant recruitment rate and that a full-scale trial is feasible. High-dose cephalexin had fewer treatment failures but with a higher proportion of minor adverse effects. The findings of this pilot will be used to inform the design of a future large trial. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04471246).

RéSUMé: CONTEXTE: Jusqu'à 3% de toutes les visites aux urgences sont dues à des infections de la peau et des tissus mous, comme la cellulite non purulente. Le taux actuel d'échec du traitement est d'environ 20%. Il manque des données probantes sur la gestion optimale de la cellulite en consultation externe. OBJECTIFS: Évaluer la faisabilité d'un essai randomisé comparant la céfalexine à dose élevée (1000 mg) à la céfalexine à dose normale (500 mg) pour traiter les patients des urgences atteints de cellulite. MéTHODES: Un essai pilote contrôlé randomisé en double aveugle à bras parallèles mené dans deux services d'urgence au Canada. Les participants éligibles étaient des adultes (âge ≥ 18 ans) se présentant aux urgences avec une cellulite non purulente et déterminés par l'urgentiste traitant comme pouvant bénéficier d'une prise en charge ambulatoire par antibiotiques oraux. Les participants ont été randomisés entre la céfalexine à dose élevée et la céfalexine à dose normale, quatre fois par jour pendant 7 jours. Le résultat primaire de faisabilité était le taux de recrutement des participants (objectif ≥ 35%). Le résultat primaire préliminaire d'efficacité était l'échec du traitement antibiotique oral. RéSULTATS: Sur les 134 participants éligibles sollicités pour participer à l'essai, 69 (51,5%, IC à 95% 43,1% à 59,8%) ont été recrutés et randomisés. Après avoir exclu trois participants randomisés en raison d'un autre diagnostic, 33 participants au total ont été inclus dans chaque bras. Au total, 19 cas éligibles (14,2%) ont été manqués. Le taux de perte au suivi était de 6,1%. L'échec du traitement est survenu chez quatre patients (12,9%) dans le groupe à dose standard contre un patient (3,2%) dans le groupe à dose élevée. Une plus grande proportion de patients ont eu des effets indésirables mineurs dans le groupe à forte dose. Aucun patient n'a été hospitalisé de façon imprévue dans les 14 jours. CONCLUSION: Cet essai pilote randomisé et contrôlé comparant la céphalexine à dose élevée à la céfalexine à dose normale pour les patients des urgences atteints de cellulite a démontré un taux élevé de recrutement de participants et la faisabilité d'un essai à grande échelle. La céfalexine à forte dose a entraîné moins d'échecs thérapeutiques, mais avec une proportion plus élevée d'effets indésirables mineurs. Les résultats de ce projet pilote serviront de base à la conception d'un futur essai à grande échelle. INSCRIPTION à L'ESSAI: Cet essai a été enregistré sur ClinicalTrials.gov (NCT04471246).

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Outpatient parenteral antibiotic therapy (OPAT) and inpatient treatment strategies for emergency department patients with cellulitis: a cost analysis.

OBJECTIVES: Emergency department (ED) patients with cellulitis requiring intravenous antibiotics may be treated via outpatient parenteral antibiotic therapy (OPAT) as opposed to hospitalization. The primary objective was to compare healthcare costs for the following strategies: community intravenous antibiotics with referral to an OPAT clinic operated by infectious disease specialists ('OPAT clinic' strategy); community intravenous antibiotics with return to ED if necessary ('return to ED' strategy); and hospital admission. METHODS: Using a hospital administrative database, we conducted a cost analysis using patient-level data of adult cellulitis patients presenting to two tertiary care EDs and were treated with intravenous antibiotics in one of three ways: OPAT clinic strategy; return to ED strategy; and hospital admission. Costs were estimated from Canada's publicly funded health system perspective. The primary outcome was the mean total cost (2015 CAD) per patient for each treatment strategy. A generalized linear model was performed to adjust for baseline characteristics, including age, sex and comorbidities. RESULTS: A total of 808 patients met inclusion criteria: OPAT clinic strategy (N = 341); return to ED strategy (N = 228) and hospital admission (N = 239). The mean total cost of care for the treatment strategies were: OPAT clinic: $2170 (95% CI $1905-$2436); return to ED: $1493 (95 %CI $1264-$1722); and hospital admission: $10,145 (95% CI $8668-$11,622). Results from the regression analysis suggested that the OPAT clinic strategy was associated with a cost-saving of $7394 (95% CI $6154-$8633, p < 0.001) compared to hospital admission and an increased cost of $651 (95% CI $367-$935, p < 0.001) when compared to the return to ED approach. CONCLUSIONS: This is the first Canadian study that compares the cost of different OPAT strategies for cellulitis patients. While both OPAT strategies are safe and far less costly than hospital admission, our findings suggest that a dedicated OPAT clinic for patients with cellulitis is more expensive than the return to ED strategy.

RéSUMé: OBJECTIFS: Les patients des services d'urgence atteints de cellulite nécessitant des antibiotiques intraveineux peuvent être traités par une antibiothérapie parentérale ambulatoire (OPAT) plutôt que par une hospitalisation. L'objectif principal était de comparer les coûts des soins de santé pour les stratégies suivantes : antibiotiques intraveineux communautaires avec orientation vers une clinique OPAT gérée par des spécialistes des maladies infectieuses (stratégie "clinique OPAT") ; antibiotiques intraveineux communautaires avec retour aux urgences si nécessaire (stratégie de "retour aux urgences") ; et admission à l'hôpital. MéTHODES: À l'aide d'une base de données administratives hospitalières, nous avons effectué une analyse des coûts en utilisant les données relatives aux patients adultes atteints de cellulite se présentant à deux urgences de soins tertiaires et traités par antibiotiques intraveineux de l'une des trois manières suivantes : Stratégie de la clinique OPAT ; stratégie de retour aux urgences; et admission à l'hôpital. Les coûts ont été estimés du point de vue du système de santé public du Canada. Le principal résultat était le coût total moyen (2015 CAD) par patient pour chaque stratégie de traitement. Un modèle linéaire généralisé a été réalisé pour ajuster les caractéristiques de base, y compris l'âge, le sexe et les comorbidités. RéSULTATS : Au total, 808 patients répondaient aux critères d'inclusion : stratégie clinique OPAT (N = 341) ; stratégie de retour aux urgences (N = 228) et admission à l'hôpital (N = 239). Le coût total moyen des soins pour les stratégies de traitement était le suivant : Clinique OPAT: 2 170 $ (IC 95 %: 1 905 $­2 436 $) ; retour aux urgences : 1 493 $ (IC à 95 %: 1 264 $­1 722 $) ; et hospitalisation : 10 145 $ (IC à 95 %: 8 668 $­11 622 $). Les résultats de l'analyse de régression suggèrent que la stratégie de la clinique OPAT est associée à une économie de 7 394 $ (IC à 95 %: 6 154 $­8 633 $, p < 0,001) par rapport à l'admission à l'hôpital et à une augmentation des coûts de 651 $ (IC à 95 %: 367 $­935 $, p < 0,001) par rapport à l'approche du retour aux urgences. CONCLUSIONS : Il s'agit de la première étude canadienne qui compare le coût de différentes stratégies d'OPAT pour les patients atteints de cellulite. Si les deux stratégies OPAT sont sûres et bien moins coûteuses que l'admission à l'hôpital, nos résultats suggèrent qu'une clinique OPAT dédiée aux patients atteints de cellulite est plus coûteuse que la stratégie de retour aux urgences.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Antimicrobial use in Canadian acute-care hospitals: Findings from three national point-prevalence surveys between 2002 and 2017.

OBJECTIVES: The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use. METHODS: Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%. RESULTS: In each survey, 28-47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%-37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%-41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%-40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60). CONCLUSIONS: The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.

The impact of an outpatient parenteral antibiotic therapy (OPAT) clinic for adults with cellulitis: an interrupted time series study.

Emergency department (ED) patients with cellulitis requiring intravenous antibiotics may be eligible for outpatient parenteral antibiotic therapy (OPAT). The primary objective was to determine whether implementation of an OPAT clinic results in decreased hospitalizations and return ED visits for patients receiving OPAT. We conducted an interrupted time series study involving adults with cellulitis presenting to two EDs and treated with intravenous antibiotics. The intervention was the OPAT clinic, which involved follow up at 48-96 h with an infectious disease physician to determine the need for ongoing intravenous antibiotics (implemented January 1, 2014). The primary outcomes were hospital admission and return ED visits within 14 days. Secondary outcomes were treatment failure (admission after initiating OPAT) and adverse peripheral line or antibiotic events. We used an interrupted time series design with segmented regression analysis over one-year pre-intervention and one-year post-intervention. 1666 patients were included. At the end of the study period, there was a non-significant 12% absolute increase in hospital admissions (95% CI - 1.6 to 25.5%; p = 0.084) relative to what would have been expected in the absence of the intervention, but a significant 40.7% absolute reduction in return ED visits (95% CI 25.6-55.9%; p < 0.001). Treatment failure rates were < 2% and adverse events were < 6% in both groups. Implementation of an OPAT clinic significantly reduced return ED visits for cellulitis, but did not reduce hospital admission rates. An ED-to-OPAT clinic model is safe, and has a low rate of treatment failures.

Polymicrobial Clostridioides difficile lung empyema.

Clostridioides (Clostridium) difficile is a well-known cause of enteritis and antibiotic-associated diarrhea. Extraintestinal C. difficile infection is uncommon, with most extraintestinal infections involving the intra-abdominal cavity and anatomic structures adjacent to the colon. Empyema secondary to C. difficile is especially rare, with only a handful of cases reported in the medical literature. A standard antibiotic treatment regimen for C. difficile empyema does not currently exist, and data chronicling successful treatment is limited. We present the case of an 80-year-old woman with a polymicrobial C. difficile empyema who was successfully treated with multiple chest tube insertions and intravenous vancomycin.

Le Clostridioides (Clostridium) difficile est une cause bien connue d'entérite et de diarrhée associée aux antibiotiques. L'infection à C. difficile extra-intestinale est peu courante, et la plupart des infections extra-intestinales touchent la cavité intra-abdominale et les structures adjacentes au colon. L'empyème secondaire au C. difficile est particulièrement rare, et seulement une poignée de cas sont signalés dans les publications médicales. Il n'y a pas d'antibiothérapie standard de l'empyème à C. difficile, et les données sur les traitements réussis sont limitées. Les auteurs présentent le cas d'une femme de 80 ans atteinte d'un empyème polymicrobien à C. difficile qui a été traitée avec succès par l'insertion de multiples drains thoraciques et par de la vancomycine par voie intraveineuse.

Antimicrobial use among adult inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program: 2009 to 2016.

BACKGROUND: Antimicrobial resistance is a growing threat to the world's ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. METHODS: In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014-2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). RESULTS: Between 2009 and 2016, 16-18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. CONCLUSIONS: This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

A behavioural approach to specifying interventions: what insights can be gained for the reporting and implementation of interventions to reduce antibiotic use in hospitals?

BACKGROUND: Reducing unnecessary antibiotic exposure is a key strategy in reducing the development and selection of antibiotic-resistant bacteria. Hospital antimicrobial stewardship (AMS) interventions are inherently complex, often requiring multiple healthcare professionals to change multiple behaviours at multiple timepoints along the care pathway. Inaction can arise when roles and responsibilities are unclear. A behavioural perspective can offer insights to maximize the chances of successful implementation. OBJECTIVES: To apply a behavioural framework [the Target Action Context Timing Actors (TACTA) framework] to existing evidence about hospital AMS interventions to specify which key behavioural aspects of interventions are detailed. METHODS: Randomized controlled trials (RCTs) and interrupted time series (ITS) studies with a focus on reducing unnecessary exposure to antibiotics were identified from the most recent Cochrane review of interventions to improve hospital AMS. The TACTA framework was applied to published intervention reports to assess the extent to which key details were reported about what behaviour should be performed, who is responsible for doing it and when, where, how often and with whom it should be performed. RESULTS: The included studies (n = 45; 31 RCTs and 14 ITS studies with 49 outcome measures) reported what should be done, where and to whom. However, key details were missing about who should act (45%) and when (22%). Specification of who should act was missing in 79% of 15 interventions to reduce duration of treatment in continuing-care wards. CONCLUSIONS: The lack of precise specification within AMS interventions limits the generalizability and reproducibility of evidence, hampering efforts to implement AMS interventions in practice.

Barriers and Facilitators to Implementation of Antibiotic Stewardship Programmes in Hospitals in Developed Countries: Insights From Transnational Studies.

Objectives: To identify perceived influences on implementation of antibiotic stewardship programmes (ASPs) in hospitals, across healthcare systems, and to exemplify the use of a behavioral framework to conceptualize those influences. Methods: EMBASE and MEDLINE databases were searched from 01/2001 to 07/2017 and reference lists were screened for transnational studies that reported barriers and/or facilitators to implementing actual or hypothetical ASPs or ASP-supporting strategies. Extracted data were synthesized using content analysis with the Theoretical Domains Framework as an organizing framework. Commonly reported influences were quantified. Results: From 3,196 abstracts 75 full-text articles were screened for inclusion. Eight studies met the eligibility criteria. The number of countries involved in each study ranged from 2 to 36. These studies included a total of 1849 participants. North America, Europe and Australasia had the strongest representation. Participants were members of special interest groups, designated hospital representatives or clinical experts. Ten of the 14 theoretical domains in the framework were present in the results reported in the included studies. The most commonly reported (≥4 out of 8 studies) influences on ASP implementation were coded in the domain "environmental context and resources" (e.g., problems with data and information systems; lack of key personnel; inadequate financial resources) and "goals" (other higher priorities). Conclusions: Despite an extensive transnational research effort, there is evidence from international studies of substantial barriers to implementing ASPs in hospitals, even in developed countries. Large-scale efforts to implement hospital antibiotic stewardship in those countries will need to overcome issues around inadequacy of information systems, unavailability of key personnel and funding, and the competition from other priority initiatives. We have enhanced the evidence base to inform guidance by taking a behavioral approach to identify influences on ASP uptake. Systematic review registration: PROSPERO registration number CRD42017076425.

Treatment failure definitions for non-purulent skin and soft tissue infections: a systematic review.

OBJECTIVE: There is currently no uniform definition for antimicrobial treatment failure for adults with non-purulent skin and soft tissue infections (SSTIs). The objective of this systematic review was to identify treatment failure definitions and their common components in the literature. METHODS: Five electronic databases were searched from inception to March 2019. Two independent reviewers identified studies involving adults (age ≥ 18 years) with non-purulent SSTIs in which antimicrobial treatment failure was a defined outcome. There were no language restrictions. Only randomized trials or observational studies were included. RESULTS: After screening 4953 abstracts, 26 studies (N = 6629 patients) met full inclusion criteria. Reported treatment failure ranged from 0 to 29.5%. The most common definition components were hospital admission (78.9%), change in antibiotics (65.4%), and persistent or worsening signs and symptoms of infection (34.6%). Only one study listed specific criteria for persistent or worsening signs and symptoms of infection. CONCLUSIONS: For studies involving non-purulent SSTIs, the outcome of treatment failure is inconsistently defined and reported failure rates are highly variable. This systematic review has highlighted the need for more robust treatment failure definitions for non-purulent SSTIs. Research should focus on the development of a uniform treatment failure definition that should be used in future studies.

Trends in health care-associated infections in acute care hospitals in Canada: an analysis of repeated point-prevalence surveys.

BACKGROUND: Health care-associated infections are a common cause of patient morbidity and mortality. We sought to describe the trends in these infections in acute care hospitals, using data from 3 national point-prevalence surveys. METHODS: The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted descriptive point-prevalence surveys to assess the burden of health care-associated infections on a single day in February of 2002, 2009 and 2017. Surveyed infections included urinary tract infection, pneumonia, Clostridioides difficile infection, infection at surgical sites and bloodstream infections. We compared the prevalence of infection across the survey years and considered the contribution of antimicrobial-resistant organisms as a cause of these infections. RESULTS: We surveyed 28 of 33 (response rate 84.8%) CNISP hospitals (6747 patients) in 2002, 39 of 55 (response rate 71.0%) hospitals (8902 patients) in 2009 and 47 of 66 (response rate 71.2%) hospitals (9929 patients) in 2017. The prevalence of patients with at least 1 health care-associated infection increased from 9.9% in 2002 (95% confidence interval [CI] 8.4%-11.5%) to 11.3% in 2009 (95% CI 9.4%-13.5%), and then declined to 7.9% in 2017 (95% CI 6.8%-9.0%). In 2017, device-associated infections accounted for 35.6% of all health care-associated infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 3.9% of all organisms identified from 2002 to 2017; other antibiotic-resistant organisms were uncommon causes of infection for all survey years. INTERPRETATION: In CNISP hospitals, there was a decline in the prevalence of health care-associated infection in 2017 compared with previous surveys. However, strategies to prevent infections associated with medical devices should be developed. Apart from MRSA, few infections were caused by antibiotic-resistant organisms.

Diagnosis and Management of Non-Purulent Cellulitis in the Emergency Department.

A 47-year-old homeless male presents to the emergency department (ED) with right lower extremity swelling, erythema and pain. He has diabetes mellitus, and had one prior episode of cellulitis three months ago affecting the same leg. He has a history of medication noncompliance. At triage, his temperature is 38.3°C but the remaining vital signs are unremarkable. On examination of the affected leg, there is an approximately 10 × 10 cm area of erythema, induration and increased warmth. There is mild tenderness to palpation and you wonder if there is a small degree of fluctuance. There is no lymphangitis, crepitus, necrosis or pain out of proportion to clinical findings.

Evaluation of an emergency department to outpatient parenteral antibiotic therapy program for cellulitis.

OBJECTIVE: Emergency department (ED) patients with non-purulent skin and soft tissue infections (SSTIs) requiring intravenous antibiotics may be managed via outpatient parenteral antibiotic therapy (OPAT). Prospective studies describing the performance of an ED-to-OPAT clinic program are lacking. The primary objective was to determine the OPAT treatment failure rate for ED patients with non-purulent SSTIs. METHODS: We conducted a prospective observational cohort study of adults with non-purulent SSTIs managed via an ED-to-OPAT clinic program. OPAT treatment failure was defined as hospitalization after a minimum of 48 h of OPAT for: worsening infection; intravenous line complications; or adverse antibiotic effects. Secondary outcomes were to describe OPAT clinic processes, patient satisfaction, and physician rationale for selecting intravenous antibiotics. RESULTS: We enrolled a consecutive sample of 153 patients [mean age 60.5 years, 82 male (53.6%)]; 137 patients (89.5%) attended their clinic appointment. OPAT treatment failure was 4.4%. None of the adverse intravenous line (10.9%) and adverse antibiotic (8.0%) events required hospitalization. Patients reported high satisfaction with timeliness of referral (median score 9 out of 10) and overall care received (median score of 10). The top five reasons given by physicians for selecting intravenous therapy were: clinical impression (52.9%); failed oral therapy (41.8%); diabetes (17.6%); severe pain (7.8%); and peripheral vascular disease (7.8%). CONCLUSIONS: This prospective study demonstrates that an ED-to-OPAT clinic program for non-purulent SSTIs is safe, has a low rate of treatment failures and results in high patient satisfaction. The rationale for selecting intravenous antibiotics showed significant variability among ED physicians.

Predictors of Oral Antibiotic Treatment Failure for Nonpurulent Skin and Soft Tissue Infections in the Emergency Department.

BACKGROUND: Current guideline recommendations for optimal management of nonpurulent skin and soft tissue infections (SSTIs) are based on expert consensus. There is a lack of evidence to guide emergency physicians regarding selection of patients for oral versus intravenous antibiotic therapy. The primary objective was to identify predictors associated with oral antibiotic treatment failure. METHODS: We performed a health records review of adults (age ≥ 18 years) with nonpurulent SSTIs treated at two tertiary care emergency departments (EDs). Oral antibiotic treatment failure was defined as any of the following after a minimum of 48 hours of oral therapy due to worsening infection: 1) hospitalization, 2) change in class of oral antibiotic, or 3) switch to intravenous therapy. Multivariable logistic regression was used to identify predictors independently associated with oral antibiotic treatment failure. RESULTS: We identified 500 patients (mean ± SD age = 64 ± 19 years, 279 male [55.8%], and 126 [25.2%] with diabetes). Of 288 patients who had received a minimum of 48 hours of oral antibiotics, there were 85 oral antibiotic treatment failures (29.5%). Tachypnea at triage (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 1.80 to 22.08), chronic ulcers (OR = 4.90, 95% CI = 1.68-14.27), history of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection (OR = 4.83, 95% CI = 1.51 to 15.44), and cellulitis in the past 12 months (OR = 2.23, 95% CI = 1.01 to 4.96) were independently associated with oral antibiotic treatment failure CONCLUSION: This is the first study to evaluate predictors of oral antibiotic treatment failure for nonpurulent SSTIs treated in the ED. Tachypnea at triage, chronic ulcers, history of MRSA colonization or infection, and cellulitis within the past year were independently associated with oral antibiotic treatment failure. Emergency physicians should consider these risk factors when deciding on oral versus intravenous antimicrobial therapy for outpatient management of nonpurulent SSTIs.