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.

Clinical findings and patient outcomes following surgical treatment of chronic gastrointestinal foreign body obstructions in dogs and cats: 72 cases (2010-2020).

The objective of this study was to characterize clinicopathologic factors and outcomes for dogs and cats with chronic small intestinal foreign body obstructions (CFBO). Medical records of 72 dogs and cats diagnosed with CFBO between 2010 to 2020 were reviewed for duration of clinical signs, pre-surgical and intraoperative findings, complications, and outcomes. A chronic foreign body was defined as clinical signs, or the observation of foreign material ingestion, at least 7 days prior to presentation. Twenty-two (31%) patients had a small intestinal resection and anastomosis (SIRA) and were more likely to have longer duration of clinical signs (P = 0.01). Eleven (15%) patients developed major post-operative complications. Sixty-eight (94%) patients survived to follow-up. Although all patients that did not survive (n = 4, 100%) had a SIRA, patients with CFBO had a high survival rate. Therefore, clients should not be deterred from pursuing surgical intervention.

L'objectif de cette étude était de caractériser les facteurs clinico-pathologiques et les résultats pour les chiens et les chats atteints d'obstructions chroniques par corps étrangers de l'intestin grêle (CFBO). Les dossiers médicaux de 72 chiens et chats diagnostiqués avec CFBO entre 2010 et 2020 ont été examinés pour la durée des signes cliniques, les résultats pré-chirurgicaux et peropératoires, les complications et les résultats. Un corps étranger chronique était défini comme des signes cliniques ou l'observation d'une ingestion de corps étrangers au moins 7 jours avant la présentation. Vingt-deux (31 %) patients ont subi une résection et anastomose de l'intestin grêle (SIRA) et étaient plus susceptibles d'avoir des signes cliniques de plus longue durée (P = 0,01). Onze (15 %) patients ont développé des complications postopératoires majeures. Soixante-huit (94 %) patients ont survécu jusqu'au suivi. Bien que tous les patients qui n'ont pas survécu (n = 4, 100 %) aient eu un SIRA, les patients avec CFBO avaient un taux de survie élevé. Par conséquent, les clients ne doivent pas être dissuadés de poursuivre une intervention chirurgicale.(Traduit par Docteur Serge Messier).

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.

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.

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.

E0771 and 4T1 murine breast cancer cells and interleukin 6 alter gene expression patterns but do not induce browning in cultured white adipocytes.

Breast cancer remains a substantial clinical problem worldwide, and cancer-associated cachexia is a condition associated with poor prognosis in this and other malignancies. Adipose tissue is involved in the development and progression of cancer-associated cachexia, but its various roles and mechanisms of action are not completely defined, especially as it relates to breast cancer. Interleukin 6 has been implicated in several mechanisms contributing to increased breast cancer tumorigenesis, as well as a net-negative energy balance and cancer-associated cachexia via adipose tissue remodeling in other models of cancer; however, its potential role in breast cancer-associated white adipose browning has not been explored. In this study, we demonstrate localized white adipose tissue browning in a spontaneous model of murine mammary cancer. We then used an in vitro murine adipocyte culture system with the E0771 and 4T1 cell lines as models of breast cancer. We demonstrate that while the E0771 and 4T1 secretomes and cross-talk with white adipocytes alter white adipocyte mRNA expression, they do not directly induce white adipocyte browning. Additionally, we show that neither exogenous administration of interleukin 6 alone or with its soluble receptor directly induce white adipocyte browning. Together, these results demonstrate that neither the E0771 or 4T1 murine breast cancer cell lines, nor interleukin 6, directly cause browning of cultured white adipocytes. This suggests that their roles in adipose tissue remodeling are more complex and indirect in nature.

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.