Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. RESULTS: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression.

BACKGROUND: The prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use. OBJECTIVE: To identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19. DATA SOURCES: We searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021. STUDY ELIGIBILITY CRITERIA: Studies including at least 50 patients with COVID-19 in any healthcare setting. METHODS: We used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication. RESULTS: Out of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6-7.1%) and secondary infection was 13.1% (95% CI 9.8-17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5-54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55-0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80-1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species. CONCLUSIONS: While the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.

Pharmacokinetic/Pharmacodynamic Considerations of Alternate Dosing Strategies of Tocilizumab in COVID-19.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters that likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the US FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, although weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/pharmacodynamic insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required.

Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis.

BACKGROUND: The proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance. OBJECTIVE: The aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19. DATA SOURCES: We searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing. PARTICIPANTS: The study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult). METHODS: The main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis. RESULTS: We screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3-80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03-0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18-1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15-1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7-15.2%) from 31 studies. CONCLUSIONS: Three-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.

Using a behavioural framework to optimize antibiotic prescribing by family medicine residents.

This article was migrated. The article was marked as recommended. Background and objectives:Overprescribing of antibiotics in primary care is a prominent concern in the context of increasing antimicrobial resistance worldwide. Medical trainees are a key group to deliver thoughtful antimicrobial stewardship training. This study examined the factors influencing antibiotic prescribing for upper respiratory tract infections (URTI) by family medicine residents in order to identify educational interventions. Methods: Using purposive sampling of family medicine residents, semi-structured interviews were conducted until thematic saturation was reached. Interviews were coded into the domains of the Theoretical Domains Framework (TDF). Belief statements were created to characterize each domain and categorized as enablers or barriers to appropriate prescribing. Domains were plotted on the Behaviour Change Wheel (BCW) and intervention functions identified. Results:Twelve participants were interviewed. Nine domains of the TDF were relevant to antibiotic prescribing. Social influence was a prominent theme with the preceptor and patient being key influences on resident prescribing. Learning goals were also a key theme including the desire to strengthen independent clinical decision-making skills and improve antibiotic knowledge. Residents' beliefs about capabilities were challenged when faced with diagnostic uncertainty. Additional domains included: professional role; environmental context and resources; intentions; beliefs about consequences and capabilities, and knowledge. Using the BCW, nine intervention functions were identified to change antibiotic prescribing behaviour. Conclusion: This study found nine domains of the TDF were relevant to family medicine resident antibiotic prescribing for URTI. Nine intervention functions could be used to guide intervention design.

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis.

BACKGROUND: Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood. AIMS: To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19. SOURCES: We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection. CONTENT: Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%). IMPLICATIONS: Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.

Nurse Prompting for Prescriber-Led Review of Antimicrobial Use in the Critical Care Unit.

BACKGROUND: Developing a sustainable strategy for prescriber-led review of antimicrobial use in a critical care unit may improve antimicrobial use without the need for additional resources. METHODS: Using a quality improvement framework, the researchers created a prompt for prescriber-led review of antimicrobial use. The outcome measure was antimicrobial use (days of therapy per 1000 patient days). The process measure was the proportion of relevant cases for which an antimicrobial prompt was provided. Balancing measures included mortality rate, length of stay, 48-hour readmission rates, and multiple organ dysfunction score. Interrupted time series with segmented regression analysis was used for the outcome measure. RESULTS: Process analysis identified critical care unit nurses for antimicrobial use prompting. A standard script was developed to incorporate a days of therapy prompt into nurse rounds, with primed prescriber responses. Before the intervention, monthly antimicrobial use was 804 days of therapy per 1000 patient days, with a positive trend (7.3 days of therapy per 1000 patient days, P < .05). After the intervention, there was an immediate reduction of 217 days of therapy per 1000 patient days (P < .05), with a nonsignificant negative trend, representing a 20% (95% CI, -15% to -25%) reduction. No significant change was noted in use of the control class of medications. The proportion of relevant cases for which an antimicrobial prompt was provided increased from 21% to 48% during the intervention period. Balancing measures were comparable before and after the intervention. CONCLUSIONS: Nurse prompting can lead to significant reductions in antimicrobial use, providing a sustainable mechanism for independent antimicrobial reassessment.

Implementation of a Clinical Decision Support Tool to Improve Antibiotic IV-to-Oral Conversion Rates at a Community Academic Hospital.

BACKGROUND: Antibiotic IV-to-oral (IV-PO) conversion is a key initiative of antimicrobial stewardship programs. Guidelines and education are commonly described interventions to promote IV-PO conversion; however, technological interventions may be more effective in changing practice. OBJECTIVE: To determine the impact of a clinical decision support (CDS) tool on the adoption and sustainability of an antibiotic IV-PO conversion program at a community academic hospital. METHODS: A quasi-experimental study consisting of 3 phases was conducted. During phase 1, the pre-intervention antibiotic IV-PO conversion rate was determined. During phase 2, the IV-PO conversion policy was updated, education was provided to pharmacists and physicians, and a post-intervention evaluation was conducted. During phase 3, a CDS tool was developed to generate real-time electronic alerts prompting pharmacists to assess antibiotic therapy, and post-intervention audits were performed 1 month, 3 months, and 15 months after implementation of the tool. Pantoprazole IV-PO conversion was assessed during each phase as a non-equivalent dependent variable. The primary outcome was the proportion of patients eligible for IV-PO conversion who were switched to oral therapy. RESULTS: Of 332 patients receiving targeted IV antibiotic therapy during the overall study period, 122 (37%) met the criteria for IV-PO conversion. The phase 2 IV-PO conversion rate of 35% (9/26) was comparable to the pre-intervention rate of 29% (10/35) (p = 0.61). Implementation of the CDS tool significantly increased the conversion rate to 78% (14/18), an increase that was sustained at 3 months (71% [17/24]) and 15 months (74% [14/19]) after implementation (p < 0.05 for all comparisons with phases 1 and 2). Pantoprazole conversion rates were similar across all phases. CONCLUSIONS: Implementation of the CDS tool was effective in improving and sustaining antibiotic IV-PO conversion rates and enhancing policy compliance beyond the effects of policy revision and education. Refinement of both the policy and the tool is warranted to maximize adoption of the IV-PO conversion program.

CONTEXTE: Le passage de l'antibiothérapie par voie intraveineuse (IV) à la voie orale (PO) (IV-PO) est une initiative clé des programmes de gestion des antimicrobiens. On a communément recours à des formations et à des lignes directrices pour encourager le passage d'une voie à l'autre; cependant, les interventions technologiques sont parfois plus efficaces pour favoriser le changement de pratique. OBJECTIF: Déterminer l'impact d'un outil d'aide à la décision clinique (ADC) sur l'adoption et la viabilité d'un programme de conversion IV-PO dans un hôpital universitaire. MÉTHODES: Une étude quasi expérimentale en trois phases a été menée. La première phase a permis la détermination du taux de conversion IV-PO avant l'intervention. La deuxième phase concernait l'actualisation de la politique de conversion IV-PO, la formation des pharmaciens et médecins et la conduite d'une évaluation après l'intervention. La troisième phase a vu le développement d'un outil ADC qui génère des alertes électroniques en temps réel pour inciter les pharmaciens à évaluer l'antibiothérapie. Des évaluations ont en outre été effectuées 1 mois, 3 mois et 15 mois après la mise en place de l'outil. Le passage de l'administration du pantoprazole par voie intraveineuse (IV) à voie orale (PO) a été évalué au cours de chaque phase comme une variable dépendante non équivalente. Le résultat principal fut la proportion de patients admissibles à la conversion IV­PO qui ont été orientés vers un traitement par voie orale. RÉSULTATS: Des 332 patients recevant une antibiothérapie ciblée par voie intraveineuse (IV) pendant l'étude, 122 (37 %) répondaient au critère de la conversion IV­PO. Le taux de conversion IV­PO de 35 % (9/26) de la phase 2 était comparable au taux avant l'intervention de 29 % (10/35) (p = 0,61). La mise en place de l'outil ADC a grandement augmenté le taux de conversion, qui est passé à 78 % (14/18): une augmentation maintenue trois mois (71 % [17/24]) et 15 mois (74 % [14/19]) après la mise en place (p < 0,05 par rapport aux phases 1 et 2). Les taux de conversion du pantoprazole étaient similaires durant toutes les phases. CONCLUSIONS: La mise en place de l'outil ADC a permis d'améliorer et de maintenir les taux de conversion IV­PO et de renforcer le respect des politiques au-delà des effets de la révision des politiques et de la formation à celles-ci. Le perfectionnement de la politique et de l'outil se justifie pour maximiser l'adoption du programme de conversion IV­PO.

Potential Negative Effects of Antimicrobial Allergy Labelling on Patient Care: A Systematic Review.

BACKGROUND: Antimicrobial allergy labels, either self-reported or placed in a patient's medical record, are common, but in many cases they are not associated with a true immunoglobulin E-mediated allergic response. OBJECTIVE: To assess the impact of antimicrobial allergy labels on antimicrobial prescribing, resource utilization, and clinical outcomes. DATA SOURCES: The MEDLINE, Embase, CINAHL, and Scopus electronic databases were searched for the period 1990 to January 2016. STUDY SELECTION: Controlled studies with the objective of assessing antimicrobial prescribing, resource utilization, and/or clinical outcomes associated with antimicrobial allergy labels were included. RESULTS: The search identified 560 unique citations, of which 7 articles met the inclusion criteria. One additional article identified by an expert in the field was also included. Four of the identified papers were limited to penicillin or other ß-lactam allergies. Six studies noted differences in antibiotic selection between patients with allergy labels and those without such labels. Broader-spectrum or second-line agents (e.g., vancomycin, clindamycin, and fluoroquinolones) were more commonly prescribed for patients with penicillin allergy labels. Antibiotic therapy costs were significantly higher for patients with allergy labels than for those without. The impact of allergy labels on clinical outcomes was mixed. One study indicated a longer length of hospital stay, 2 studies reported higher readmission rates, and 1 study reported a higher rate of antibiotic-resistant organisms for patients with allergy labels. CONCLUSIONS: Most of the available literature is limited to penicillin or ß-lactam allergy. The growing body of knowledge supports the concept that ß-lactam allergy labels are not benign and that labelling in the absence of a true allergy has a negative effect on patient care. Allergy labelling appears to be associated with suboptimal antibiotic selection, greater treatment costs, prolonged length of stay, greater readmission rates, and higher prevalence of antibiotic-resistant organisms. There is an opportunity for antimicrobial stewardship programs to implement systematic allergy verification to optimize antimicrobial therapy and improve patient care.

CONTEXTE: Les mentions d'allergies aux antimicrobiens, soit autodéclarées soit consignées dans un dossier médical, sont fréquentes, mais dans bien des cas elles ne signalent pas une véritable réaction allergique à médiation par l'immunoglobuline E. OBJECTIF: Évaluer l'effet des mentions d'allergie aux antimicrobiens sur les habitudes de prescription d'antimicrobiens, l'utilisation des ressources et les résultats cliniques. SOURCES DES DONNÉES: Les bases de données numériques MEDLINE, Embase, CINAHL et Scopus ont été interrogées pour la période allant de 1990 à janvier 2016. SÉLECTION DES ÉTUDES: Les essais cliniques comparatifs dont l'objectif était d'évaluer les habitudes de prescription d'antimicrobiens, l'utilisation des ressources ou les résultats cliniques associés aux mentions d'allergie aux antimicrobiens ont été inclus. RÉSULTATS: La recherche a permis de trouver 560 citations distinctes et ainsi de repérer sept articles qui répondaient aux critères d'inclusion. Un article supplémentaire signalé par un expert du domaine a été inclus à l'analyse. Quatre de ces articles se limitaient aux allergies à la pénicilline ou à d'autres ß-lactamines. Six études ont noté des différences dans le choix des antibiotiques entre les patients ayant une mention d'allergie à leur dossier et ceux n'en ayant pas. Des antibiotiques à plus large spectre ou des médicaments de deuxième intention (comme la vancomycine, la clindamycine et les fluoroquinolones) étaient plus souvent prescrits pour les patients ayant une mention d'allergie à la pénicilline. Les coûts des antibiothérapies étaient significativement plus élevés pour les patients ayant une mention d'allergie que pour ceux n'en ayant pas à leur dossier. L'effet des mentions d'allergie sur les résultats cliniques était inégal. Une étude indiquait un séjour plus long à l'hôpital, deux études indiquaient des taux de réadmission plus élevés et une étude indiquait un taux plus élevé d'organismes résistants aux antibiotiques pour les patients ayant une mention d'allergie comparativement à ceux n'en ayant pas. CONCLUSIONS: La majeure partie des articles disponibles se limitent aux allergies à la pénicilline ou à d'autres ß-lactamines. De plus en plus, le savoir vient appuyer le concept voulant que les mentions d'allergies aux ß-lactamines ne soient pas bénignes et que leur emploi en l'absence d'une allergie réelle ait un effet négatif sur les soins aux patients. Les mentions d'allergie semblent être associées à un choix sous-optimal d'antibiotiques, des coûts de traitement plus élevés, des séjours plus longs, des taux de réadmission plus élevés et une plus grande prévalence d'organismes résistants aux antibiotiques. Or, les programmes de gérance des antimicrobiens pourraient permettre de mettre en œuvre des procédures de vérification systématique des allergies afin d'optimiser l'antibiothérapie et d'améliorer les soins aux patients.

Point-of-Care ß-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

Background: ß-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is an important infection. Methicillin-resistant S aureus (MRSA) screening is performed on hospitalized patients for infection control purposes. OBJECTIVE: To assess the usefulness of past MRSA screening for guiding empirical antibiotic therapy for SAB. METHODS: A retrospective cohort study examined consecutive patients with confirmed SAB and previous MRSA screening swab from six academic and community hospitals between 2007 and 2010. Diagnostic test properties were calculated for MRSA screening swab for predicting methicillin resistance of SAB. RESULTS: A total of 799 patients underwent MRSA screening swabs before SAB. Of the 799 patients, 95 (12%) had a positive and 704 (88%) had a negative previous MRSA screening swab. There were 150 (19%) patients with MRSA bacteremia. Overall, previous MRSA screening swabs had a positive likelihood ratio of 33 (95% CI 18 to 60) and a negative likelihood ratio of 0.45 (95% CI 0.37 to 0.54). Diagnostic accuracy differed depending on mode of acquisition (ie, community-acquired, nosocomial or health care-associated infection) (P<0.0001) and hospital (P=0.0002). At best, for health care-associated infection, prior MRSA screening swab had a positive likelihood ratio of 16 (95% CI 9 to 28) and a negative likelihood ratio of 0.27 (95% CI 0.17 to 0.41). CONCLUSIONS: A negative prior MRSA screening swab cannot reliably rule out MRSA bacteremia and should not be used to guide empirical antibiotic therapy for SAB. A positive prior MRSA screening swab greatly increases likelihood of MRSA, necessitating MRSA coverage in empirical antibiotic therapy for SAB.

HISTORIQUE: La bactériémie à Staphylococcus aureus (BSA) est une infection grave. Les patients hospitalisés subissent un dépistage du S. aureus résistant à la méthicilline (SARM) afin de prévenir les infections. OBJECTIF: Évaluer l'utilité d'un dépistage antérieur du SARM pour orienter l'antibiothérapie empirique de la BSA. MÉTHODOLOGIE: Les chercheurs ont effectué une étude de cohorte rétrospective dans six hôpitaux universitaires et hôpitaux généraux entre 2007 et 2010 auprès de patients consécutifs atteints d'une BSA confirmée ayant déjà subi un prélèvement de dépistage du SARM. Ils ont calculé les propriétés des tests diagnostiques par prélèvement pour diagnostiquer le SARM et prédire la résistance de la BSA à la méthicilline. RÉSULTATS: Au total, 799 patients avaient déjà subi des prélèvements pour dépister le SARM avant une BSA. De ce nombre, 95 (12 %) ont présenté un résultat positif et 704 (88 %) avaient déjà subi un prélèvement pour dépister le SARM. Cent cinquante patients (19 %) avaient une bactériémie à SARM. Dans l'ensemble, les prélèvements antérieurs pour dépister le SARM avaient un ratio de probabilité positif de 33 (95 % IC 18 à 60) et négatif de 0,45 (95 % IC 0,37 à 0,54). La précision diagnostique différait en fonction du mode d'acquisition (origine non nosocomiale, origine nosocomiale ou association aux soins de santé) (P<0,0001) et de l'hôpital (P=0,0002). Dans le meilleur des cas, en présence d'une infection associée aux soins de santé, un prélèvement antérieur pour dépister un SARM s'associait à un ratio de probabilité positif de 16 (95 % IC 9 à 28) et négatif de 0,27 (95 % IC 0,17 à 0,41). CONCLUSIONS: Un prélèvement antérieur négatif au SARM ne permet pas d'écarter une bactériémie par le SARM avec fiabilité et ne devrait pas orienter l'antibiothérapie empirique de la BSA. Un prélèvement antérieur positif au SARM accroît considérablement la probabilité de SARM, ce qui oblige à en tenir compte pour l'antibiothérapie empirique de la BSA.

Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia: Results From a Retrospective Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to develop a prediction model to identify patients with low-risk Staphylococcus aureus bacteremia (SAB), in whom infective endocarditis (IE) can be ruled out based on transthoracic echocardiogram (TTE). BACKGROUND: S. aureus is a major cause of bacteremia and often leads to IE. Current guidelines recommend performing transesophageal echocardiography on all patients or treating all patients empirically with prolonged intravenous antibiotics; however, this approach is resource intensive, many physicians do not adhere to guidelines, and recent studies suggest that low-risk patients may not require transesophageal echocardiography. METHODS: We conducted a retrospective cohort study of 833 consecutive hospitalized patients with SAB from 7 academic and community hospitals in Toronto, Canada, over a 3-year period (2007 to 2010). Patients who received a TTE within 28 days of bacteremia (n = 536) were randomly divided into derivation and validation cohorts. Multivariable logistic regression analysis was used to determine high-risk criteria for IE in the derivation cohort, and criteria were then applied to the validation cohort to determine diagnostic properties. RESULTS: Four high-risk criteria predicted IE: indeterminate or positive TTE (p < 0.001), community-acquired bacteremia (p = 0.034), intravenous drug use (p < 0.001), and high-risk cardiac condition (p < 0.004). In the validation cohort, the presence of any 1 of the high-risk criteria had 97% sensitivity (95% confidence interval [CI]: 87% to 100%) and 99% negative predictive value (95% CI: 96% to 100%) for IE. The negative likelihood ratio was 0.05 (95% CI: 0.007 to 0.35). CONCLUSIONS: A normal TTE ruled out IE in patients without community-acquired SAB, high-risk cardiac conditions, and intravenous drug use. This study provides evidence that clinical risk stratification combined with a normal TTE may be adequate to rule out IE in most patients with SAB.

Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study.

BACKGROUND: We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge. RESULTS: Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2-4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52-.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06-1.56; P = .0109) for being discharged alive. CONCLUSIONS: ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.

Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study.

OBJECTIVES: We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse. METHODS: A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study. Ninety-day mortality was compared between the two groups matched by propensity scores. RESULTS: Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31-1.08, P = 0.0846) for 90 day mortality. CONCLUSIONS: There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.

Examining the safety and efficacy of a chemotherapy dosing method in Allogeneic Stem Cell Transplant patients of extreme body size.

BACKGROUND: There is no consensus on a universal dosing method for calculating high-dose chemotherapy in allogeneic Stem Cell Transplant (SCT) patients. The Metropolitan Life (Met-Life) Insurance Company's weight-height tables have been used to determine body weight for chemotherapy dosing for SCT, however no formal study has been done to determine if the Met-Life weight- height tables can be used for chemotherapy dosing in SCT. We retrospectively studied the use of Met-Life weight-height tables for chemotherapy dosing in SCT. Our goal is to determine if patients with extremes of body size who had undergone an SCT and were dosed according to the Met-Life weight- height tables had an increase of Treatment Related Morbidity (TRM) or mortality or relapse. PATIENTS AND METHODS: Patients were grouped into three different treatment regimens, cyclophosphamide/TBI, busulphan/cyclophosphamide, and AraC/cyclophosphamide/TBI. Patients in each treatment regimen were further divided into five equal groups based on weight. Treatment related morbidity and mortality was evaluated by comparing the lowest and highest quintiles to the middle quintiles within each treatment regimen. RESULT: Data from 262 patients was evaluated in this study. Overall, there was not an increase in TRM or mortality or in relapse in patients with extremes of body size. CONCLUSION: The Met-Life weight-height tables could be used to dose patients undergoing allogeneic SCTs. Additional prospective studies would need to be done comparing other chemotherapy dosing methods with the Met-Life weight-height tables to further validate this conclusion.

Documenting drug-related problems with personal digital assistants in a multisite health system.

PURPOSE: A scalable, multiuser, personal digital assistant (PDA)-based documentation tool for pharmacist collection of data on drug-related problems (DRPs) is described. SUMMARY: A PDA-based tool for documenting DRPs and pharmacist interventions was developed with database software. Data fields were based on the pharmaceutical care model. PDA synchronization stations were configured to transmit encrypted data from three hospital sites to a central server. Pharmacists in a multisite health care organization were trained to use the documentation tool. Data were analyzed with commercially available software. Users' opinions about the tool were solicited in a survey. Twenty-eight PDAs containing a 15-field database were issued to 39 pharmacists in 31 service areas. Data were successfully transmitted from all hospital sites over the existing corporate local area network. During a two-month period, 5084 DRPs were documented; 90% of them were resolved at the time of data entry. The most frequent types of DRPs were the need to add a drug (31%) and the ordering of an unnecessary drug (15%). Most pharmacists reported that the tool was easy to use, was well integrated with the workflow, and required less than 30 minutes per day for documenting DRPs. CONCLUSION: A PDA-based documentation tool was successfully used in a multisite health care organization to collect data on DRPs and document pharmacist interventions.