Prevention of Infection in Kidney Patients

Renal patients are particularly vulnerable to infection in part because they are relatively, or significantly, immunocompromised, undergo numerous invasive procedures and typically have frequent contact with healthcare institutions putting them at much higher risk of nosocomial infections. In addition, they are typically exposed to multiple antibiotics, which may select out resistant organisms or damage protective microbiomes. The Covid-19 pandemic has brought the life and death importance of infection control to every renal unit and forced a, perhaps overdue, appreciation of the issues and responsibilities associated with nosocomial infections. In addition, our patients are disproportionately impacted by the growing emergence of antimicrobial resistance. This chapter reviews the key aspects of nosocomial infections in renal patients and the important elements of infection control and antibiotic stewardship that can protect our patients. © Springer Nature Switzerland AG 2014, 2022.

A new strategy to integrate silver nanowires with waterborne coating to improve their antimicrobial and antiviral properties

PurposeThis study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own.Design/methodology/approachPrepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated.FindingsThe obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses.Originality/valueThe new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

Effect of E-Learning on Appropriate Antibiotic Prescribing by Medical Students: A Quasi-Experimental Study during COVID-19 Pandemic

Aims: This study aimed to determine the effect of E-learning on the understanding of appropriate antibiotic prescribing (AAP) by medical students and to assess their satisfaction with this method. Materials and Methods: This quasi-experimental study was conducted among the physiopathology students of Kashan University of Medical Sciences in the first and second semesters of 2020-2021. Students were divided into E-learning education as an intervention group (IG) and face-to-face education as a control group (CG). After the final examination, the mean scores of students in both groups were compared. In addition, the level of students' satisfaction in the IG with E-learning method was assessed using a standard questionnaire. Data were analyzed using SPSS 22. Results: We included 85 and 47 students in the CG and IG. The mean and standard deviation (SD) of the understanding score about antibiotics in the E-learning group and the face-to-face education group were 18.8 +/- 1.26 and 17.16 +/- 1.93 out of 19, respectively, which were statistically significantly different (P = 0.004). The mean and SD of the overall score of satisfaction of the students in the IG was 85.48 +/- 23.08 out of 130 points (medium level). Furthermore, the level of satisfaction of male students was significantly higher than female students (P = 0.009). Conclusion: E-learning was effective in improving the process of educating students to the AAP. This education method can be used as an alternative or complementary of face-to-face education, especially in critical conditions such as the pandemic of diseases including COVID-19.

Fabrication of noble metal–based antimicrobial nanosystems

Recently, the outbreak of diverse infectious diseases mainly caused by microbes led to increase in the human mortality rate. Microbes being small cell structures are more powerful to fight with human cells for their proliferation as well as subsequent growth. At times, it pioneers the world with its contagiousness (for example, swine flu, SARS-CoV-2, dengue virus, etc.) causing greater impact to public health. Numerous efforts are in progress to design and develop efficient antimicrobial systems. Antimicrobial systems include self-disinfecting surfaces, wall coatings, paints, sanitizers, etc., to improve their microbial resistance to surfaces as well as killing of pathogens. Noble metal–based antimicrobial systems are pioneers of the field right from history. Under the broad category of noble metal nanostructures, silver (Ag), gold (Au), platinum (Pt), palladium (Pd), and copper (Cu) prove its excellence as high-ranked antimicrobial markers. Yet, there exist some challenges to uplift its efficacy, henceforth fabrication process with its associated theory for building competent antimicrobial nanosystems with noble metals should be paid attention. The crucial factor is the fabrication step within which their properties would be tuned greatly. By proper design of fabrication process, noble metals could possibly function rapidly to destroy the microbial colonization by breaking the respiratory chains of pathogens of concern. Development of hydrophobic surfaces for noble metal nanomaterial–based antimicrobial systems is increasing in recent era, since it can act as shield against bio film formation by the microbial adherence to surfaces. This chapter entitles the diverse fabrication procedures with their mechanisms, pairing process of noble metals, surface modifications, tuning parameters at synthetic stages for engineering the noble metal–based antimicrobial nanosystems to enrich the higher biocidal resistance. © 2023 Elsevier Inc. All rights reserved.

Antimicrobial Effect of Silver Nanoparticle-Based Thin Films

The global pandemic of disease COVID-19 caused by the pathogenic SARS-Cov-2 virus brought more interest in the public health community for known silver with its potential antimicrobial properties to fight infection. One of the ways to stop virus to protect community transmission is the application of nanotechnology of silver nanoparticles on the exposed surfaces of daily used materials in public, e.g., transportation, community spaces, hospitals, and everywhere where the potential infection load is increased. Published technology to coat AgNPs on surfaces differs in the preparation of nanocomposites and substrates, which results in different mechanical and antimicrobial properties. In our study, we focused on the properties of AgNPs prepared by HiTUS and PVD technology with a challenge to test the antimicrobial effect towards the model of gram-negative bacteria (Escherichia coli), fungi (Trichoderma harzianum) and related enteroviruses (Poliovirus and Coxsackie). All tested materials showed 59% or more growth inhibition of E. coli. Growth of T. harzianum was inhibited by 16% in the presence of AgTiB2 50W, and other materials caused 37% to 68% inhibition. Enteroviruses infection was completely inhibited after 1 hour of AgNPs treatment. Only Coxsackie A7 retained infection capability after 30 minutes of treatment with AgNPs. Moreover, the ICP-OES-measured amounts of silver released in cultivation media are lower than most published studies of silver nanoparticles with a comparable antimicrobial effect. Keeping silver concentration at the lowest possible limit is one of the most critical factors for producing environmentally safe antimicrobial materials for everyday use.

A comprehensive review on technological advances in alternate drug discovery process:Drug repurposing

The traditional de novo drug discovery is time consuming, costly and in some instances the drugs will fail to treat the disease which result in a huge loss to the organization. Drug repurposing is an alternative drug discovery process to overcome the limitations of the De novo drug discovery process. Ithelps for the identification of drugs to the rare diseases as well as in the pandemic situationwithin short span of time in a cost-effective way. The underlying principle of drug repurposing is that most of the drugs identified on a primary purpose have shown to treat other diseases also. One such example is Tocilizumab is primarily used for rheumatoid arthritis and it is repurposed to treat cancer and COVID-19. At present, nearly30% of the FDA approved drugs to treat various diseases are repurposed drugs. The drug repurposing is either drug-centric or disease centric and can be studied by using both experimental and in silico studies. The in silico repurpose drug discovery process is more efficient as it screens thousands of compounds from the diverse libraries within few days by various computational methods like Virtual screening, Docking, MD simulations,Machine Learning, Artificial Intelligence, Genome Wide Association Studies (GWAS), etc. with certain limitations.These limitationscan be addressed by effective integration of advanced technologies to identify a novel multi-purpose drug.Copyright © 2023, Association of Biotechnology and Pharmacy. All rights reserved.

The European Union's New Pharmaceutical Strategy for Europe

[...]on 25 Nov. 2020, the European Commission (EC) announced the new Pharmaceutical Strategy for Europe, which is likely to result in significant changes to the European Union (EU) regulatory framework and will have a substantial impact on both the marketing of medicinal products and the strategic business planning of pharmaceutical companies (2). (2021), the priority areas are as follows: * The performance and adequacy of the current legislation * Unmet medical needs-with a definition or set of principles for "unmet medical needs" under discussion * Incentives for innovation, including the area of unmet needs and a reflexion on regulatory data and market exclusivity * Antimicrobial resistance that includes measures to support innovation of antibiotic development * Future-proofing the regulatory framework for novel products * Improved patient access to, and affordability of, medicines in the EU * Competitiveness of the European markets to ensure affordable medicines, including considering measures to support patients' access to affordable medicines * Encouraging the repurposing of off patent medicines * Ensuring security of supply of medicinal products in the EU * Ensuring high-quality manufacture and distribution in the EU including consideration of the need to strengthen or adapt good manufacturing practice (GMP) to reflect new manufacturing methodologies * Environmental challenges (4). Availability, accessibility, and affordability of medicinal products The section on 'Prioritising unmet medical needs' in the strategy reflects the belief within EU Bianca Piachaud-Moustakis is lead writer at PharmaVision, Pharmavision.co.uk. institutions that "current incentive models neither provide an adequate solution for unmet medical needs nor appropriately incentivise investments in innovation" (2).

Nanoparticles as an exotic antibacterial, antifungal, and antiviral agents

Globally, concerns regarding the COVID-19 pandemic its prevention have become important. Because of COVID-19 and other microbial diseases, enhance research work has emerged revealing new antimicrobial and antiviral materials and techniques. Tremendous growth in nanotechnology has opened up the door to fabricating numerous nanomaterials. These nanomaterials are employed as antimicrobial and antiviral agents for various applications with 99.99% effectiveness compared with conventional techniques. Nanoparticles possess unique physicochemical characteristics for multiple applications. This chapter details the use of nanoparticles for antifungal, antimicrobial, and antiviral applications. It describes various kinds of nanoparticles, such as nanometals, metal oxides, polymeric nanomaterials, and carbon-based nanomaterials. © 2023 Elsevier Inc. All rights reserved.

Cytokine elimination in suspected COVID-19 perymyocarditis

Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.

Not a waste: Wastewater surveillance to enhance public health

Domestic wastewater, when collected and evaluated appropriately, can provide valuable health-related information for a community. As a relatively unbiased and non-invasive approach, wastewater surveillance may complement current practices towards mitigating risks and protecting population health. Spurred by the COVID-19 pandemic, wastewater programs are now widely implemented to monitor viral infection trends in sewersheds and inform public health decision-making. This review summarizes recent developments in wastewater-based epidemiology for detecting and monitoring communicable infectious diseases, dissemination of antimicrobial resistance, and illicit drug consumption. Wastewater surveillance, a quickly advancing Frontier in environmental science, is becoming a new tool to enhance public health, improve disease prevention, and respond to future epidemics and pandemics.

INVESTIGATION OF THE ANTIBIOTIC RESISTANCE PROFILE OF KLEBSIELLA PNEUMONIAE ISOLATES ISOLATED FROM DIFFERENT CLINICAL SPECIMENS: ONE-YEAR DATA DURING THE COVID-19 PANDEMIC PROCESS.

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material(s) and Method(s): In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially.Copyright © 2023 University of Ankara. All rights reserved.

Prospect of nanomaterials as antimicrobial and antiviral regimen

Abatract: In recent years studies of nanomaterials have been explored in the field of microbiology due to the increasing evidence of antibiotic resistance. Nanomaterials could be inorganic or organic, and they may be synthesized from natural products from plant or animal origin. The therapeutic applications of nano-materials are wide, from diagnosis of disease to targeted delivery of drugs. Broad-spectrum antiviral and antimicrobial activities of nanoparticles are also well evident. The ratio of nanoparticles surface area to their volume is high and that allows them to be an advantageous vehicle of drugs in many respects. Effective uses of various materials for the synthesis of nanoparticles impart much specificity in them to meet the requirements of specific therapeutic strategies. The potential therapeutic use of nanoparticles and their mechanisms of action against infections from bacteria, fungi and viruses were the focus of this review. Further, their potential advantages, drawbacks, limitations and side effects are also included here. Researchers are characterizing the exposure pathways of nano-medicines that may cause serious toxicity to the subjects or the environment. Indeed, societal ethical issues in using nano-medicines pose a serious question to scientists beyond anything.

Vulnerability and antimicrobial resistance

It is now well-recognised that antimicrobial resistance (AMR), or the ability of organisms to resist currently available antibiotics and other antimicrobial drugs, represents one of the greatest dangers to human health in the 21st Century. As of 2022, AMR is a top-10 global public health threat. Various national and transnational initiatives have been implemented to address accelerating AMR, and the pressure to find local and global solutions is increasing. Despite this urgency, surprisingly limited progress is being made in rolling back or even slowing resistance. A multitude of perspectives exist regarding why this is the case. Key concerns include an enduring dependency on market-driven drug development, the lacklustre governance and habitual over-prescribing of remaining antimicrobial resources, and rampant short-termism across societies. While rarely presented in such terms, these disparate issues all speak to the social production of vulnerability. Yet vulnerability is rarely discussed in the AMR literature, except in terms of 'disproportionate effects' of AMR. In this paper, we offer a reconceptualisation of vulnerability as manifest in the AMR scene, showing that vulnerability is both a predictable consequence of AMR and, critically, productive of AMR to begin with. We underline why comprehending vulnerability as embodied, assembled, multivalent and reproduced through surveillance matters for international efforts to combat resistance.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India

Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists

Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Taking hospital pathogen surveillance to the next level.

High-throughput bacterial genomic sequencing and subsequent analyses can produce large volumes of high-quality data rapidly. Advances in sequencing technology, with commensurate developments in bioinformatics, have increased the speed and efficiency with which it is possible to apply genomics to outbreak analysis and broader public health surveillance. This approach has been focused on targeted pathogenic taxa, such as Mycobacteria, and diseases corresponding to different modes of transmission, including food-and-water-borne diseases (FWDs) and sexually transmitted infections (STIs). In addition, major healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and carbapenemase-producing Klebsiella pneumoniae are the focus of research projects and initiatives to understand transmission dynamics and temporal trends on both local and global scales. Here, we discuss current and future public health priorities relating to genome-based surveillance of major healthcare-associated pathogens. We highlight the specific challenges for the surveillance of healthcare-associated infections (HAIs), and how recent technical advances might be deployed most effectively to mitigate the increasing public health burden they cause.

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.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study.

INTRODUCTION: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study. METHODS: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up. RESULTS: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age. CONCLUSION: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up. TRIAL REGISTRATION: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832. PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Impact of COVID-19 on healthcare-associated infections: Antimicrobial consumption does not follow antimicrobial resistance.

BACKGROUND: This study aimed to analyze the Healthcare-Associated Infections (HAI) rates and antimicrobial consumption in Intensive Care Units (ICU) in São Paulo city during the COVID-19 pandemic and compare them with the pre-pandemic period. METHODS: This cohort included all hospitals that reported HAI rates (Central-Line-Associated Bloodstream Infection ‒ CLABSI and Ventilator-Associated Pneumonia ‒ VAP), the proportion of microorganisms that caused CLABSI, the proportion of resistant microorganisms, and antimicrobial consumption from January 2017 ‒ December 2020. Hospitals were stratified by the number of beds, Central Venous Catheter (CVC) utilization rate, Mechanical-Ventilation (MV) utilization rate, and type of funding. Statistical analyses were based on time-series plots and regression models. RESULTS: 220 ICUs were included. The authors observed an abrupt increase in CLABSI rates after the pandemic onset. High CLABSI rates during the pandemic were associated with hospital size, funding (public and non-profit private), and low CVC use (≤ 50%). An increase in VAP rates was associated with public hospitals, and high MV use (> 35%). The susceptibility profile of microorganisms did not differ from that of the pre-pandemic period. polymyxin, glycopeptides, and antifungal use increased, especially in COVID-19 ICUs. CONCLUSIONS: HAI increased during COVID-19. The microorganisms' susceptibility profile did not change with the pandemic, but the authors observed a disproportionate increase in large-spectrum antimicrobial drug use.