Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments.

INTRODUCTION: Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. METHODS: This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. RESULTS: A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7-7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. CONCLUSIONS: AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

Supply-chain factors and antimicrobial stewardship.

Efficient and secure supply chains are vital for effective health services worldwide. In low- and middle-income countries, the accessibility, affordability and availability of essential medicines, including antimicrobials, remain challenging. Ineffective supply chains often cause antimicrobial shortages, leading to inappropriate use of alternative agents and increasing the risk of antimicrobial resistance. Shortages, coupled with insecure supply chains, also encourage the infiltration of substandard and falsified medicines, leading to suboptimal treatment and further promoting antimicrobial resistance. Addressing antimicrobial supply-chain issues should be considered a key component of antimicrobial stewardship programmes. We have explored the link between medicine supply chains and antimicrobial use in seven focus countries: Kenya, Malawi, Nigeria, Sierra Leone, Uganda, United Republic of Tanzania and Zambia. We explored country medicine supply-system structures, national medicine supply-chain policy documents and global study reports. Our aim was to develop evidence-based strategies to enhance the effectiveness and efficiency of the medicine supply chains in supporting antimicrobial stewardship efforts. Better management of medical supply chains involves rational selection, quantification, forecasting, procurement, storage, distribution, use and stock management of antimicrobials. Important supply-chain considerations include pooled procurement networks to ensure consistent pricing of quality-assured antimicrobials, and improved resource utilization and information exchange among relevant stakeholders. We propose adaptable recommendations for integrating medicine supply chains as an essential part of antimicrobial stewardship programmes, with a call for action at the local, regional and national levels in low- and middle-income countries.

Partout dans le monde, les performances des services de santé dépendent de l'efficacité et de la sécurité des chaînes d'approvisionnement. Mais dans les pays à revenu faible et intermédiaire, l'accessibilité et la disponibilité des médicaments à prix abordable, y compris des antimicrobiens, représentent toujours un défi. L'inefficacité des chaînes d'approvisionnement entraîne souvent des pénuries d'antimicrobiens et, par conséquent, un recours à des alternatives inappropriées et une augmentation du risque de résistance aux antimicrobiens. Ces pénuries, alliées à des chaînes d'approvisionnement peu fiables, favorisent également l'introduction de médicaments falsifiés et de qualité inférieure, altérant l'efficacité du traitement et renforçant encore davantage la résistance aux antimicrobiens. Résoudre les problèmes liés aux chaînes d'approvisionnement en antimicrobiens devrait donc figurer parmi les priorités des programmes de gestion des antimicrobiens. Le présent document s'intéresse au lien entre les chaînes d'approvisionnement en médicaments et l'utilisation d'antimicrobiens dans sept pays cibles: le Kenya, le Malawi, le Nigeria, l'Ouganda, la République-Unie de Tanzanie, la Sierra Leone et la Zambie. Pour chacun de ces pays, nous avons examiné les structures du système d'approvisionnement en médicaments, les documents relatifs à la politique d'approvisionnement national et les rapports d'études globaux. Notre objectif consistait à développer des stratégies fondées sur des données factuelles, afin d'améliorer le fonctionnement et l'efficacité des chaînes d'approvisionnement en médicaments et de contribuer ainsi aux efforts de gestion des antimicrobiens. Une meilleure logistique requiert une certaine rationalité dans la sélection, la quantification, la planification, l'approvisionnement, le stockage, la distribution, l'utilisation et la gestion des stocks d'antimicrobiens. Dans ce contexte, plusieurs éléments sont importants tels que les réseaux d'achats groupés, qui assurent la stabilité des prix pour des antimicrobiens de qualité garantie, ou encore l'optimisation des ressources et l'échange d'informations entre les acteurs concernés. Nous formulons des recommandations ajustables en vue de rendre les chaînes d'approvisionnement en médicaments incontournables dans les programmes de gestion des antimicrobiens, avec un appel à agir à l'échelle locale, régionale et nationale dans les pays à revenu faible et intermédiaire.

Unas cadenas de suministro eficientes y seguras son vitales para la eficacia de los servicios sanitarios en todo el mundo. En los países de ingresos bajos y medios, la accesibilidad, asequibilidad y disponibilidad de los medicamentos esenciales, incluidos los antimicrobianos, sigue siendo un reto. Con frecuencia, las cadenas de suministro ineficaces provocan escasez de antimicrobianos, lo que conlleva un uso inadecuado de agentes alternativos y aumenta el riesgo de resistencia a los antimicrobianos. La escasez, sumada a la inseguridad de las cadenas de suministro, también favorece la infiltración de medicamentos de calidad inferior y adulterados, lo que conduce a un tratamiento subóptimo y fomenta aún más la resistencia a los antimicrobianos. Abordar los problemas de la cadena de suministro de antimicrobianos se debería considerar un componente clave de los programas de administración de antimicrobianos. Hemos explorado la relación entre las cadenas de suministro de medicamentos y el uso de antimicrobianos en siete países seleccionados: Kenia, Malawi, Nigeria, Sierra Leona, Uganda, República Unida de Tanzania y Zambia. Exploramos las estructuras de los sistemas de suministro de medicamentos de los países, los documentos de política nacional sobre la cadena de suministro de medicamentos y los informes de estudios globales. Nuestro objetivo era desarrollar estrategias basadas en evidencias para mejorar la eficacia y la eficiencia de las cadenas de suministro de medicamentos en apoyo de los esfuerzos de administración antimicrobiana. Una mejor gestión de las cadenas de suministro de medicamentos implica la selección racional, la cuantificación, la previsión, la adquisición, el almacenamiento, la distribución, el uso y la gestión de las existencias de antimicrobianos. Entre las consideraciones importantes sobre la cadena de suministro se incluyen las redes de adquisición mancomunada para garantizar precios coherentes de antimicrobianos de calidad garantizada y una mejor utilización de los recursos e intercambio de información entre las partes interesadas pertinentes. Proponemos recomendaciones adaptables para integrar las cadenas de suministro de medicamentos como parte esencial de los programas de administración de antimicrobianos, con una llamada a la acción a nivel local, regional y nacional en los países de ingresos bajos y medios.

Antimicrobial stewardship in the era of the COVID-19 pandemic: A systematic review protocol on the opportunities and challenges for Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) remains one of the leading threats to global public health and this may increase following COVID-19 pandemic. This is particularly the case in Africa where regulations on antimicrobial usage are weak. This protocol outlines the steps to undertake a systematic review to synthesize evidence on drivers of AMR and evaluate existing approaches to strengthening antimicrobial stewardship (AMS) programs in Sub-Saharan Africa (SSA). On the basis of the evidence generated from the evidence synthesis, the overarching goal of this work is to provide recommendations to support best practices in AMS implementation in SSA. METHODS: A systematic search will be conducted using the following databases: Global Health Library, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Google Scholar, Global Health, Embase, African Journals Online Library, Web of Science, antimicrobial databases (WHO COVID-19, TrACSS, NDARO, and JPIAMR), and the Cochrane databases for systematic reviews. Studies will be included if they assess AMR and AMS in SSA from January 2000 to January 31, 2023. RESULTS: The primary outcomes will include the drivers of AMR and approaches to AMS implementation in SSA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses will guide the reporting of this systematic review. CONCLUSIONS: The findings are expected to provide evidence on best practices and resource sharing for policy consideration to healthcare providers and other stakeholders both at the local and international levels. Additionally, the study seeks to establish drivers specific to AMR during the COVID-19 era in the SSA, for example, with the observed increasing trend of antimicrobial misuse during the first or second year of the pandemic may provide valuable insights for policy recommendation in preparedness and response measures to future pandemics. PROSPERO REGISTRATION NUMBER: CRD42022368853.

Pharmacist-driven antimicrobial stewardship interventions in patients with COVID-19: a scoping review.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a highly infectious disease that can be treated with antivirals in addition to other antimicrobials in cases of secondary or concomitant infections. This creates potential for antimicrobials misuse, which increases antimicrobial resistance (AMR). Pharmacists are known to undertake prominent roles in combatting AMR. AIM: The aim of this review was to characterize pharmacist-driven interventions that have been performed in patients with COVID-19 globally and describe their impact on antimicrobial use. METHOD: We followed the Joanna Briggs Institutes manual framework for scoping reviews in our study. Studies that reported antimicrobial stewardship (AMS) interventions performed by pharmacists in COVID-19 patients were included. Articles that did not report outcomes or did not mention pharmacists in the intervention were excluded. Restrictions included English-only articles from inception date until June 2022. Articles were searched from four databases. RESULTS: Eleven publications were included in the review. The most common AMS intervention was pharmacist-driven interventions reported in 63.2% of all studies, followed by guideline development and application (26.3%), and medication supply coordination (10.5%), respectively. The outcomes of the interventions were difficult to compare but showed a reduction in antimicrobial use and prevention of adverse drug reactions with a relatively high acceptance rate from physicians. CONCLUSION: Pharmacists played an important role in performing AMS-related interventions in COVID-19 patients and helped in the fight against the worsening of AMR during the pandemic. The impact of pharmacist-driven AMS interventions in patients with COVID-19 seemed to be positive and improved outcomes related to antimicrobial use.

Nurses' knowledge and implementation of antimicrobial stewardship and infection prevention strategies in acute paediatric settings.

BACKGROUND: Nurses are the first point of contact for patients and are responsible for monitoring and reporting signs of infection. The COVID-19 pandemic cemented nurses' leadership role in infection prevention. Despite this, nurses' contribution to antimicrobial stewardship initiatives remains under-recognized. AIM: To determine how paediatric nurses understood their role and contribution to antimicrobial stewardship and infection prevention and control practices in three different acute paediatric wards. METHODS: Forty-three nurses were recruited from an adolescent ward, an oncology ward, and a surgical ward in a metropolitan tertiary children's hospital for a qualitative exploratory descriptive study. FINDINGS: Thematic and content analysis derived three themes from the data: understanding of preventable infections; embracing evidence-based guidelines to protect the patient; and roles in preventing and controlling infections and antimicrobial stewardship. Associated subthemes were: desensitized to COVID-19; understanding infection prevention and control precautions; correct use of hospital policy and guidelines; restrictions associated with the use of electronic medical records; understanding of sepsis management and the importance of timely microbiological testing; ambivalence on antimicrobial stewardship roles; and high priority placed on consumer education. CONCLUSION: Nurses' understanding of their role focused on practices such as performing hand hygiene, standard precautions, and reporting the use of high-risk antimicrobials. A lack of understanding of paediatric COVID-19 transmission and presentations was also reported. Education on best practice in infection prevention and AMS was recognized as crucial for both nurses and parents.

Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.

OBJECTIVE: To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention. DESIGN: Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period. SETTING: 38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021. PARTICIPANTS: 1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period. INTERVENTION: Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual. MAIN OUTCOME MEASURES: The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality. RESULTS: The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26). CONCLUSIONS: Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03970356.

The multi-drug resistant organisms infections decrease during the antimicrobial stewardship era in cirrhotic patients: An Italian cohort study.

BACKGROUND AND PURPOSE: Bacterial infections represent a major cause of morbidity and mortality in cirrhotic patients. Our aim was to assess the incidence of bacterial infections, in particular due to multidrug-resistant organisms (MDROs) before and after the introduction of the antimicrobial stewardship program, "Stewardship Antimicrobial in VErona" (SAVE). In addition, we also analysed the liver complications and the crude mortality during the whole follow up. METHODS: We analysed 229 cirrhotic subjects without previous hospitalization for infections enrolled at the University Verona Hospital from 2017 to 2019 and followed up until December 2021 (mean follow-up 42.7 months). RESULTS: 101 infections were recorded and 31.7% were recurrent. The most frequent were sepsis (24.7%), pneumonia (19.8%), spontaneous bacterial peritonitis (17.8%). 14.9% of infections were sustained by MDROs. Liver complications occurred more frequently in infected patients, and in case of MDROs infections with a significantly higher MELD and Child-Pugh score. In Cox regression analysis, mortality was associated with age, diabetes and bacterial infections episodes (OR 3.30, CI 95%: (1.63-6.70). Despite an increase in total infections over the past three years, a decrease in the incidence rate in MDROs infections was documented concurrently with the introduction of SAVE (IRD 28.6; 95% CI: 4.6-52.5, p = 0.02). CONCLUSIONS: Our study confirms the burden of bacterial infections in cirrhotic patients, especially MDROs, and the strong interconnection with liver complications. The introduction of SAVE decreased MDROs infections. Cirrhotic patients require a closer clinical surveillance to identify colonized patients and avoid the horizontal spread of MDROs in this setting.

Infection prevention and antibiotic stewardship program needs and practices in 2021: A survey of the Society for Healthcare Epidemiology of America Research Network.

In total, 50 healthcare facilities completed a survey in 2021 to characterize changes in infection prevention and control and antibiotic stewardship practices. Notable findings include sustained surveillance for multidrug-resistant organisms but decreased use of human resource-intensive interventions compared to previous surveys in 2013 and 2018 conducted prior to the COVID-19 pandemic.

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria.

BACKGROUND: Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems. OBJECTIVES: To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic. METHODS: A quasi-experimental, before-after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented. RESULTS: A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (-1.8%; P < 0.001). A decrease of -4.9 DDD/100 patient-days (PD) (95% CI -7.3 to -2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0-3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30-0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18-0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59-3.77). CONCLUSIONS: Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic.

Antimicrobial stewardship in solid organ transplant-Opportunities in the National Health Service.

BACKGROUND: Antimicrobial stewardship (AMS) is an intervention, which ensures the appropriateness of antimicrobial use to avoid in part the rising problem of antimicrobial resistance and negative effects of inappropriate antimicrobial use. In the solid organ transplant (SOT) population, which is prone to a particularly high risk of infection resulting from immunosuppression and anatomical issues with each type of SOT, the need for good stewardship has never been more important. This article looks at current AMS practice in SOT units in the United Kingdom and how things could be improved in the future. METHODS: The current practice of AMS alongside national antimicrobial resistance rates were reviewed using national mandatory reporting data. The background to the current practice and policies in place in the National Health Service (NHS) were also reviewed and possibilities for future approaches explored. RESULTS: AMS is a requirement within all NHS hospitals in the United Kingdom as per government policy. Mandatory reporting of specific bloodstream infections (BSIs) and antimicrobial consumption alongside financial incentives has been the approach nationwide. Gram-negative resistance rates in BSIs have been increasing prior to the COVID-19 pandemic. Little SOT-specific data on antimicrobial resistance exists, and the general approach to AMS in SOT units has generally modeled the national approach. CONCLUSION: Although there is a good, standardized approach to AMS in the NHS, there is a need for SOT-specific AMS approaches to be developed in the United Kingdom. More data is required on antimicrobial resistance rates, and studies are needed to investigate optimal antimicrobial prophylaxis regimens for each solid organ group. Tools to aid AMS efforts and novel treatment options for complex multiresistant infection must also be explored amongst transplant centers.

Antimicrobial stewardship implementation before and during the COVID-19 pandemic in the acute care settings: a systematic review.

INTRODUCTION: Antibiotics are widely administered for various indications, leading to increased antimicrobial resistance (AMR) in acute care hospitals. Since the onset of the COVID-19 pandemic, Antimicrobial Stewardship (AMS) effective strategies should be used to maintain the rational use of antibiotics and decrease the threat of Antimicrobial Resistance (AMR). AIM: This systematic literature review aims to investigate the AMS intervention Before-the-pandemic (BP) and During-the-pandemic (DP) from the literature. DESIGN AND SETTING: Systematic literature review of primary studies on AMS implementation in acute care settings. METHODS: Relevant studies published between 2000 and March 2021 were obtained from Medline (via PubMed), OVID, CINAHL, International Pharmaceutical Abstracts, Psych Info, Scopus, Web of Science, Cochrane Library, OpenGrey, and Google Scholar, using a comprehensive list of search terms. Public Health England (PHE) toolkit was agreed upon as a gold standard for the AMS implementation. RESULTS: There were 8763 articles retrieved from the databases. Out of these, 13 full-text articles met the inclusion criteria for the review. The AMS implementation was identified in the included studies into AMS strategies (Core strategies & Supplemental strategies), and AMS measures BP and DP. CONCLUSION: This Systematic literature review summarises AMS implementation strategies and measures all over the previous 20 years of research. There are many lessons learnt from COVID-19 pandemic. The proper selection of the AMS implementation strategies and measures appeared to be effective in maintaining the appropriate use of antibiotics and decreasing the AMR threat, especially during the COVID-19 pandemic. Further studies are required to provide empirical data to evaluate the AMS implementation and identify which of these strategies and measures were effective BP and DP. In order to be prepared for any emergency/crisis or future pandemics.

Evaluating Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening as a Tool for Antimicrobial Stewardship.

INTRODUCTION: Initiation of broad-spectrum empiric antibiotics is common when infection is suspected in hospitalized adults. The benefits of early utilization of effective antibiotics are well documented. However, the negative effects of inappropriate antibiotic use have led to antimicrobial stewardship mandates. Recent data demonstrate the utility of methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal screening to steward anti-MRSA empiric antibiotics in pneumonia. We hypothesize that MRSA PCR nasal swabs would also be effective to rule out other MRSA infection to effectively limit unnecessary antibiotics for any infectious source. METHODS: We performed a single-center retrospective chart review of all adult patient encounters from October 2019-July 2021 with MRSA PCR nasal testing. We then reviewed all charts to evaluate for the presence of infections based on source cultures results, as the gold standard. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated from 2 × 2 contingency tables. RESULTS: Among all patients with MRSA nasal screening, 1189 patients had any infection. Prevalence of MRSA nasal carriage among patients screened was 12%. Prevalence of MRSA infection among all infections was 7.5%. MRSA nasal swabs demonstrated a negative predictive value of 100% for MRSA urinary tract infection, 97.9% for MRSA bacteremia, 97.8% for MRSA pneumonia, 92.1% for MRSA wound infection, and 96.6% for other MRSA infections. Overall, MRSA PCR nasal swabs had a sensitivity of 68.5%, specificity of 90.1%, positive predictive value of 23.7%, and negative predictive value of 98.5% for any infections. CONCLUSIONS: MRSA PCR nasal swabs have a high negative predictive value for all infections. Our data support the use of MRSA PCR nasal swabs to rule out MRSA infection and thereby allow early de-escalation of MRSA coverage in hospitalized patients requiring empiric antibiotics. Implementation of MRSA screening could decrease antibiotic-associated morbidity, resistance, and costs. More studies should be conducted to validate these results and support these findings.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalised with COVID-19 (COVASP): a pragmatic, cluster-randomised, non-inferiority trial.

BACKGROUND: The COVID-19 pandemic has been associated with increased antimicrobial use despite low rates of bacterial co-infection. Prospective audit and feedback is recommended to optimise antibiotic prescribing, but high-quality evidence supporting its use for COVID-19 is absent. We aimed to study the efficacy and safety of prospective audit and feedback in patients admitted to hospital for the treatment of COVID-19. METHODS: COVASP was a prospective, pragmatic, non-inferiority, small-unit, cluster-randomised trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, AB, Canada, with COVID-19 pneumonia. All patients aged at least 18 years who were admitted from the community to a designated study bed with microbiologically confirmed SARS-CoV-2 infection in the preceding 14 days were included if they had an oxygen saturation of 94% or lower on room air, required supplemental oxygen, or had chest-imaging findings compatible with COVID-19 pneumonia. Patients were excluded if they were transferred in from another acute care centre, enrolled in another clinical trial that involved antibiotic therapy, expected to progress to palliative care or death within 48 h of hospital admission, or managed by any member of the research team within 30 days of enrolment. COVID-19 unit and critical care unit beds were stratified and randomly assigned (1:1) to the prospective audit and feedback plus standard of care group or the standard of care group. Patients were masked to their bed assignment but the attending physician and study team were not. The primary outcome was clinical status on postadmission day 15, measured using a seven-point ordinal scale. We used a non-inferiority margin of 0·5. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT04896866, and is now closed. FINDINGS: Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0-5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0-3·0] vs 2·0 [IQR 2·0-4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. INTERPRETATION: This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population. FUNDING: None.

Antibiotic spectrum index as an antimicrobial stewardship tool in paediatric intensive care settings.

OBJECTIVES: Antibiotic spectrum index (ASI) is a recently developed antimicrobial stewardship (AMS) tool that aims to classify antibiotics based on activity against clinically relevant bacterial pathogens. METHODS: We utilised ASI in a 2-year retrospective study between April 2019 and April 2021 in four paediatric intensive care units of a specialist UK children's hospital to quantify antibiotic use based on age, presence of immunosuppression and AMS input. We then compared ASI to days of therapy (DOT) to determine the utility of this AMS metric. We have made changes to Gerber's original ASI list and score of antibiotics to align with prescribing and resistance patterns in the UK. RESULTS: Median ASI/antibiotic days increased with age: for infants under 1 year of age 4.1 (IQR 4.0-4.3), for children 1-5 years 4.4 (IQR 4.0-4.6) and for children over 5 years 4.5 (IQR 4.1-4.6). Immunocompromised patients received much broader-spectrum antibiotics than immunocompetent patients throughout the whole study period. Patients who had AMS input had a higher ASI compared with those who did not throughout the whole period, likely due to more complex patients being discussed on such rounds. CONCLUSIONS: Our results show a complex picture of changing antibiotic consumption and prescribing in a large specialist paediatric hospital in the UK with a long-standing AMS programme before and throughout the COVID-19 pandemic. ASI shows less variability than DOT and can potentially be used to identify patient groups and time periods where broader-spectrum antibiotics are used to help guide further AMS efforts.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use. OBJECTIVE: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria. METHODS: Systematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. RESULTS: We retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics. CONCLUSION: There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

First publication of endemic channels as part of a pediatric Antimicrobial Stewardship Program: when to turn on the alarms? Recommendations of a pediatric ASP program.

BACKGROUND: Pediatric Antimicrobial Stewardship Programs (ASP) consider DOT a fundamental measure to quantify the impact of ASP. Novel strategies have been described, but no endemic channels (EC) have been reported to compare antibiotic use within historical patterns. This report describes the process of constructing an EC and analyzing its interpretation. METHODS: This was a descriptive study of the construction, implementation, and analysis of EC. The median and quartile method, as well as the geometric mean (GM) and confidence interval (CI) methods using DOT for the last 4 years were used. ECs have also been elaborated on in critical services (PICU). RESULTS: GM and CI method seem to be more sensitive in identifying changes in antimicrobial use. Ceftriaxone increased its use starting in December 2021, reaching the warning zone in March 2022 in relation to increased cases of bacterial and complicated pneumonia. Piperacillin-tazobactam showed an important increase in PICU during the first 8 months of 2021, reaching the alert zone until August 2021; thereafter, its use decreased, and this variation was related to a modification in the presentation of complicated appendicitis during the COVID 19 pandemic restrictions. The use of ampicillin-sulbactam has increased since January 2022 because of a change in local guidelines regarding its use in appendicitis and peritonitis. The changes identified in each EC allowed ASP to take different conducts. CONCLUSION: EC allowed us to construct a new tool to measure ASP impact, internal comparison of antibiotic use facilitated taking timely interventions. EC could be useful for all pediatric and adult ASP.

Procalcitonin for antimicrobial stewardship among cancer patients admitted with COVID-19.

Background: Procalcitonin (PCT) has been used to guide antibiotic therapy in bacterial infections. We aimed to determine the role of PCT in decreasing the duration of empiric antibiotic therapy among cancer patients admitted with COVID-19. Methods: This retrospective study included cancer patients admitted to our institution for COVID-19 between March 1, 2020, and June 28, 2021, with a PCT test done within 72 hr after admission. Patients were divided into two groups: PCT <0.25 ng/ml and PCT ≥0.25 ng/ml. We assessed pertinent cultures, antibacterial use, and duration of empiric antibacterial therapy. Results: The study included 530 patients (median age, 62 years [range, 13-91]). All the patients had ≥1 culture test within 7 days following admission. Patients with PCT <0.25 ng/ml were less likely to have a positive culture than were those with PCT ≥0.25 ng/ml (6% [20/358] vs. 17% [30/172]; p<0.0001). PCT <0.25 ng/ml had a high negative predictive value for bacteremia and 30 day mortality. Patients with PCT <0.25 ng/ml were less likely to receive intravenous (IV) antibiotics for >72 hr than were patients with PCT ≥0.25 ng/ml (45% [162/358] vs. 69% [119/172]; p<0.0001). Among patients with PCT <0.25 ng/ml and negative cultures, 30 day mortality was similar between those who received IV antibiotics for ≥72 hr and those who received IV antibiotics for shorter durations (2% [2/111] vs. 3% [5/176], p=0.71). Conclusions: Among cancer patients with COVID-19, PCT level <0.25 ng/ml is associated with lower likelihood of bacterial co-infection and greater likelihood of a shorter antibiotic course. In patients with PCT level <0.25 ng/ml and negative cultures, an antibiotic course of >72 hr may not be necessary. PCT could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19. Funding: This research was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports MD Anderson Cancer Center's Clinical Trials Office.

Optimization of antimicrobial prescription in the hospital.

Internal Medicine wards are an appropriate focus of antibiotic stewardship, along with emergency departments and intensive care units, because a large proportion of patients are with parenteral broad-spectrum antibiotics. Given the unmet clinical need of antibiotic optimization in the hospital and the importance of front-line practitioners for antibiotic stewardship, the barriers and tactics to overcome them were discussed in a round table at the European Congress of Internal Medicine. Better rapid diagnostic tests should help to increase appropriate early antibiotic rates, favoring diversity in antibiotic choices adapted to the awareness of local resistance patterns. Providing such is a greater challenge in low-resource settings. Prescriptions should be personalized, adjusting dosage and source control to specific patients' conditions. Shorter antibiotic duration and de-escalation are major drivers to reduce adverse events, with mortality and recurrence rates being independent of antimicrobial duration. Appropriate diagnostic tests with quick turnaround times decrease excessive antibiotic use. Antimicrobial optimization requires a multidisciplinary approach and it should be a core competence of training specialists, improving opportunities to provide safer patient care.