Recurrent urinary tract infections and prophylactic antibiotic use in women: cross-sectional study.

BACKGROUND: Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics. AIM: To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care. DESIGN AND SETTING: Retrospective cross-sectional study in Welsh General Practice using the SAIL Databank. METHOD: We describe the characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010-2020, and associated urine culture results from 2015 - 2020. RESULTS: 6.0% of women (n=92,213) had rUTIs, and 1.7% (n=26,862) were prescribed prophylactic antibiotics. Only 49% of prophylactic antibiotic users met the definition of rUTIs before initiation. 81% of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. 64% of women taking prophylactic antibiotics had a urine culture result before initiation, and 18% (n=320) of women prescribed trimethoprim had resistance to it on the antecedent sample. CONCLUSION: A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64% of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.

Metal copper and silver revealed potent antimicrobial activity for treating Caenorhabditis elegans infected with carbapenemase-producing Klebsiella pneumonia.

OBJECTIVES: The increasing issue of bacterial resistance, coupled with inadequate progress in developing new antibiotics, necessitates exploring alternative treatments. Antibacterial biomaterials, such as silver and copper, possess advantageous properties such as heat resistance, durability, continuity, and safety. Particularly, they can effectively eliminate pathogenic bacteria while preserving cellular integrity, emphasizing the necessity of identifying optimal metal ion concentrations for practical application. Caenorhabditis elegans (C. elegans) can serve as a noteworthy model in this context. This study employed a C. elegans infection model to assess the efficacy of antibacterial metal ions. METHODS: Hematoxylin-eosin (HE) staining and inductively coupled plasma mass spectrometry (ICP-MS) assay were utilized to determine the toxic levels of metal ions in mice. Additionally, RNA sequencing (RNA-seq) and assessment of reactive oxygen species (ROS) production in the C. elegans model were conducted to elucidate the mechanisms underlying metal ion toxicity. RESULTS: Silver ion concentrations ranging from 10-6 to 10-7 M and copper ion concentrations ranging from 10-4 to 10-5 M exhibited antimicrobial properties without eliciting cytotoxic effects. Analysis of the transcriptome data derived from mRNA isolated from C. elegans indicated that CRKP infection activated the FoxO signaling pathway, potentially leading to ROS accumulation and C. elegans demise. CONCLUSIONS: In conclusion, C. elegans serves as a comprehensive infection model for assessing antibacterial metal ions.

Advances in hepatitis delta research: emerging insights and future directions.

OBJECTIVES: Hepatitis delta virus (HDV) is a defective virus needing the envelope provided by hepatitis B virus (HBV) in order to enter liver cells and propagate. Chronic HDV infection is considered the most severe viral hepatitis, resulting in accelerated fibrosis progression until cirrhosis and its complications (hepatocellular carcinoma, liver decompensation) compared with HBV mono-infected patients. Off-label treatment with interferon has represented the only treatment option in the last 40 years, resulting in suboptimal virological response rates and being limited by safety issues especially in patients with advanced cirrhosis. Recently, the first HBV-HDV entry inhibitor Bulevirtide (BLV) has been approved by the European Medicines Agency (EMA) for treatment of chronic compensated HDV. METHODS: This review summarises most recent updates on HDV epidemiology, diagnosis and treatment, with a special focus both on clinical trials and real-life studies about BLV. An overview on new HDV compounds under development is also provided. RESULTS: BLV, the HBV-HDV entry inhibitor, has shown promising safety and efficacy data in clinical trials and in real-life studies, also in patients with advanced cirrhosis and portal hypertension. However, according to EMA label treatment is currently intended long-term until clinical benefit and predictors of responses are still undefined. The potential combination with PegIFNα seems to increase virological and clinical responses. New compounds are under development or in pipeline for treatment of HDV. CONCLUSION: After more than 40 years since HDV discovery, new treatment options are currently available to provide efficient strategies for chronic hepatitis Delta.

Quantitative and qualitative evaluation of antimicrobial usage: the first step for antimicrobial stewardship.

The identification of antimicrobial use patterns is essential for determining key targets for antimicrobial stewardship interventions and evaluating the effectiveness thereof. Accurately identifying antimicrobial use patterns requires quantitative evaluation, which focuses on measuring the quantity and frequency of antimicrobial use, and qualitative evaluation, which assesses the appropriateness, effectiveness, and potential side effects of antimicrobial prescriptions. This paper summarizes the quantitative and qualitative methods used to evaluate antimicrobials, drawing insights from overseas and domestic cases.

Inverted amino acids reduce the adhesion and biofilm biomass of early oral colonizers.

BACKGROUND: Early colonizers adhere to the dental surface and facilitate the initial adhesion of secondary colonizers to form oral biofilms, which may cause oral infections. OBJECTIVES: This study aimed to determine the antimicrobial, anti-adhesion and antibiofilm potency of inverted amino acids on early colonizer streptococci and their mixed species. MATERIAL AND METHODS: The following test strains were used: Streptococcus gordonii (American Type Culture Collection (ATCC) 35105); Streptococcus mitis (ATCC 49456); Streptococcus oralis (ATCC 10557); Streptococcus salivarius (ATCC 7073); and Streptococcus sanguinis (ATCC BAA-1455). The concentration-dependent antimicrobial potency of d-alanine (d-ala), d-arginine (d-arg), d-leucine (d-leu), d-methionine (d-met), and d-tryptophan (d-try) was determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method with AlamarBlue modification. The adhesion of primary colonizers in the presence of 25-mM d-amino acids (dAAs) was assessed using the colony forming unit (CFU) assay. The CFU assay was conducted on 24-h flow cell bacterial biofilm models after exposure to 25-mM inverted dAAs. RESULTS: No minimum inhibitory concentration (MIC) point was detected at any concentration tested. The minimum bactericidal concentration (MBC) point was not observed. The adhesion of S. mitis, S. oralis and mixed species was reduced by all tested dAAs. No adverse effects were observed on S. gordonii with any of the tested dAAs. The biofilm biomass of test strains under flow conditions was significantly reduced after a 5-min exposure to all tested dAAs at 25-mM concentration. CONCLUSIONS: D-amino acids did not inhibit bacterial growth and did not show bactericidal or bacteriostatic effects on test strains at any concentration tested (ranging from 6.25 mM to 100 mM). However, dAAs effectively inhibit the adhesion of early colonizers, thereby preventing the formation of oral biofilm.

Long-term Oral Suppressive Antimicrobial Therapy in Infective Endocarditis (SATIE Study): An Observational Study.

Background: The role of suppressive antimicrobial therapy (SAT) in infective endocarditis (IE) management has yet to be defined. The objective of this study was to describe the use of SAT in an IE referral center and the patients' outcomes. Methods: We conducted a retrospective observational study in a French IE referral center (Paris). All patients with IE who received SAT between 2016 and 2022 were included. Results: Forty-two patients were included (36 male [86%]; median age [interquartile range {IQR}], 73 [61-82] years). The median Charlson Comorbidity Index score (IQR) was 3 (1-4). Forty patients (95%) had an intracardiac device. The most frequent microorganisms were Enterococcus faecalis (15/42, 36%) and Staphylococcus aureus (12/42, 29%). SAT indications were absence of surgery despite clinical indication (28/42, 67%), incomplete removal of prosthetic material (6/42, 14%), uncontrolled infection source (4/42, 10%), persistent abnormal uptake on nuclear imaging (1/42, 2%), or a combination of the previous indications (3/42, 7%). Antimicrobials were mainly doxycycline (19/42, 45%) and amoxicillin (19/42, 45%). The median follow-up time (IQR) was 398 (194-663) days. Five patients (12%) experienced drug adverse events. Five patients (12%) presented with a second IE episode during follow-up, including 2 reinfections (different bacterial species) and 3 possible relapses (same bacterial species). Fourteen patients (33%) in our cohort died during follow-up. Overall, the 1-year survival rate was 84.3% (73.5%-96.7%), and the 1-year survival rate without recurrence was 74.1% (61.4%-89.4%). Conclusions: SAT was mainly prescribed to patients with cardiac devices because of the absence of surgery despite clinical indication. Five (12%) breakthrough second IE episodes were reported. Prospective comparative studies are required to guide this empirical practice.

Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias / Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG / Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study

Introducción: Los programas de optimización de antimicrobianos (PROA) son herramientas clave en la adecuación de estos fármacos. La información disponible sobre la aplicación e indicadores para monitorizar estos programas en urgencias es limitada. El objetivo del estudio es conocer el grado de implantación de programas PROA en los servicios de urgencias, así como el uso de antimicrobianos en estas unidades. Material y métodos. Estudio multicéntrico retrospectivo. Se envió una invitación a todos los participantes del grupo de trabajo de farmacéuticos de urgencias REDFASTER-SEFH. Se utilizó un cuestionario de 21 ítems, contestado por un equipo formado por especialistas en los servicios de farmacia hospitalaria, urgencias, enfermedades infecciosas y microbiología. Resultados. 18 hospitales completaron la encuesta. Catorce (77,8%) disponían de un responsable PROA en la unidad. El valor de DDD por 1000 ingresos osciló entre 36,5 y 400,5 (mediana 100,4 [RIQ:57,2-157,3]). El grupo de carbapenémicos y macrólidos presentó una amplia variabilidad. Únicamente seis (33,3%) hospitales disponían de informe anual de resistencias específico para urocultivos y hemocultivos en urgencias. El porcentaje de multirresistentes en urocultivos fue del 12,5% y en hemocultivos del 12,2%. El porcentaje de adecuación en bacteremia de acuerdo con el resultado del hemocultivo fue del 81,0% (RIQ:74,6-85,0%), y en infección urinaria del 78,0% (RIQ:71,5-88,0%). Conclusiones. Pese a la existencia de responsables PROA, actividades formativas y guías de tratamiento en urgencias, la información sobre el uso de antimicrobianos y el perfil de resistencias en estas unidades es limitado. Futuras actividades han de ir encaminadas a mejorar la información sobre los resultados PROA propios para estas unidades. (AU)

Introduction: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know theextent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. Material and methods. Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. Results. Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). Conclusions: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units. (AU)

Antibacterial and anti-coronavirus investigation of selected Senegalese plant species according to an ethnobotanical survey.

ETHNOPHARMACOLOGICAL RELEVANCE: In Senegal, upper and lower respiratory tract infections constitute a real health problem. To manage these disorders, most people rely on the use of local medicinal plants. This is particularly the case for species belonging to the botanical families, Combretaceae, Fabaceae, Myrtaceae and Rubiaceae, which are widely used to treat various respiratory problems such as colds, flu, rhinitis, sinusitis, otitis, angina, bronchitis, bronchiolitis and also pneumonia. AIM OF THE STUDY: The aim of this study was to identify medicinal plants traditionally used for the management of infectious diseases, in particular those of the respiratory tract. On the basis of these ethnopharmacological uses, this study made it possible to highlight the antibacterial, antiviral and cytotoxic activities of selected plant species. MATERIALS AND METHODS: An ethnobotanical survey was conducted in Senegal among informants, including herbalists, traditional healers, and households, using medicinal plants in the management of infectious diseases, with a focus on respiratory tract infections. The most cited plant species were evaluated in vitro on a panel of 18 human pathogenic bacteria may be involved in respiratory infections and against the human coronavirus HCoV-229E in Huh-7 cells. The antiviral activity of the most active extracts against HCoV-229E was also evaluated on COVID-19 causing agent, SARS-CoV-2 in Vero-81 cells. In parallel, cytotoxic activities were evaluated on Huh-7 cells. RESULTS: A total of 127 informants, including 100 men (78.74%) and 27 women (21.26%) participated in this study. The ethnobotanical survey led to the inventory of 41 plant species belonging to 19 botanical families used by herbalists and/or traditional healers and some households to treat infectious diseases, with a specific focus on upper respiratory tract disorders. Among the 41 plant species, the most frequently mentioned in the survey were Guiera senegalensis J.F. Gmel. (95.2%), Combretum glutinosum Perr. Ex DC. (93.9%) and Eucalyptus spp. (82.8%). Combretaceae (30.2%) represented the most cited botanical family with six species, followed by Fabaceae (29.3%, 12 species). A total of 33 crude methanolic extracts of the 24 plant species selected for their number of citations were evaluated in vitro for their antimicrobial and cytotoxic activities. Guiera senegalensis, Combretum glutinosum, Vachellia nilotica subsp. tomentosa (Benth.) Kyal. & Boatwr, Eucalyptus camaldulensis Dehnh., and Terminalia avicennioides Guill. & Perr., showed antibacterial activities. The most active plants against HCoV-229E were: Ficus sycomorus L., Mitragyna inermis (Willd.) Kuntze, Pterocarpus erinaceus Poir., and Spermacoce verticillata L. One of these plants, Mitragyna inermis, was also active against SARS-CoV-2. CONCLUSION: This work confirmed the anti-infective properties of plant species traditionally used in Senegal. Overall, the most frequently cited plant species showed the best antibacterial activities. Moreover, some of the selected plant species could be considered as a potential source for the management of coronavirus infections. This new scientific data justified the use of these plants in the management of some infectious pathologies, especially those of the respiratory tract.

Comparison of Cefazolin and Ceftriaxone Enterobacterales Susceptibilities for Inpatient Treatment of Urinary Tract Infections and Risk of Hospital-Onset Clostridioides difficile Infection.

PURPOSE: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost, and perceived safety. However, third-generation cephalosporins increase the risk of health care facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States is limited. This analysis assessed the comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empirical agent to manage inpatient UTI and limit ceftriaxone collateral damage. METHODS: This was a retrospective single-center observational study. Microbiologic susceptibility data were analyzed for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis urinary specimens taken from adult inpatients admitted from January 1, 2022, to December 31, 2022. Primary outcome was incidence of E coli, K pneumoniae, and P mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC <16 µg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. FINDINGS: A total of 1150 urine samples were identified as E coli, K pneumoniae, and P mirabilis in 2022. Susceptibility to cefazolin was observed in 1064 (92.5%) of 1150 isolates using the MIC breakpoint for uncomplicated UTI and to ceftriaxone in 1115 (97.0%) of 1150 isolates (P < 0.001). From 2016 to 2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions, with HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure, and 11 cases (0.15%) developed in cefazolin-exposed admissions (adjusted odds ratio, 2.44; 95% CI, 1.25-4.76; P < 0.001). IMPLICATIONS: Cefazolin exhibits high susceptibility for uropathogens commonly implicated in cases of uncomplicated UTI, the most common UTI diagnosis among inpatients. Although ceftriaxone shows a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared with cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage such as HOCDI, use of cefazolin for uncomplicated UTI may be evaluated by using local susceptibility data.

Uso de antimicrobianos en la unidad de cuidados intensivos de un hospital público de Loreto / Use of antimicrobials in the intensive care unit of a Loreto public hospital

RESUMEN Introducción. El uso inapropiado de antimicrobianos en las unidades de cuidados intensivos (UCI) contribuye a la resistencia bacteriana. Objetivo. El propósito del presente estudio fue medir el uso y tipo de antimicrobianos en los pacientes hospitalizados en la Unidad de Cuidados Intensivos del Hospital Regional de Loreto (HRL). Métodos. Estudio de tipo descriptivo. Revisamos 120 historias clínicas en pacientes de UCI-HRL desde enero a junio 2023. Resultados. La mayoría de los pacientes usaron antimicrobianos (74,2%), indicados por shock séptico (42,7%), de 1 a 3 antimicrobianos (93,2%), con terapia de 1 a 3 días (45%). Del total de antimicrobianos usados, la mayor proporción fueron bactericidas 89 (90,4%), de la familia de cefalosporinas (33,1%) y carbapenémicos (23,5%); los fármacos más empleados fueron ceftriaxona (26,5%) y meropenem (21,1%) por vía intravenosa (90,4%). Conclusión. La mayor proporción de pacientes hospitalizados usan antimicrobianos de la familia de cefalosporinas y carbapenémicos.

ABSTRACT Introduction. Inappropriate use of antimicrobials in the Intensive Care Unit (ICU) contributes to bacterial resistance. Objective. The purpose of the present study was to measure the use and type of antimicrobials in patients hospitalized in the Intensive Care Unit of the Loreto Regional Hospital (HRL). Methods. Descriptive study. We reviewed 120 medical records in ICU-HRL patients from January to June 2023. Results. Most patients used antimicrobials (74.2%), indicated for septic shock (42.7%), 1 to 3 antimicrobials (93.2%), with therapy of 1 to 3 days (45%). Of the total number of antimicrobials used, the greatest proportion were bactericides 89 (90.4%), from the cephalosporin family (33.1%) and carbapenemics (23.5%); the most commonly used drugs were ceftriaxone (26.5%) and meropenem (21.1%) by the intravenous route (90.4%). Conclusion. The highest proportion of hospitalized patients use antimicrobials of the cephalosporin and carbapenemics family.

[Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study]. / Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG.

OBJECTIVE: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know the extent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. METHODS: Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. RESULTS: Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). CONCLUSIONS: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units.

Exploring determinants of antimicrobial prescribing behaviour using the Theoretical Domains Framework.

BACKGROUND: Few theoretically-based, qualitative studies have explored determinants of antimicrobial prescribing behaviour in hospitals. Understanding these can promote successful development and implementation of behaviour change interventions (BCIs). OBJECTIVE: (s): To use the Theoretical Domains Framework (TDF) to explore determinants of clinicians' antimicrobial prescribing behaviour, identifying barriers (i.e., impediments) and facilitators to appropriate antimicrobial practice. METHODS: Semi-structured interviews with purposively-sampled doctors and pharmacists with a wide range of specialties and expertise in Hamad Medical Corporation hospitals in Qatar. Interviews based on previous quantitative research and the TDF were audio-recorded, transcribed and independently analysed by two researchers using the TDF as an initial coding framework. RESULTS: Data saturation was achieved after interviewing eight doctors and eight pharmacists. Inter-related determinants of antimicrobial prescribing behaviour linked to ten TDF domains were identified as barriers and facilitators that may contribute to inappropriate or appropriate antimicrobial prescribing. The main barriers identified were around hospital guidelines and electronic system deficiencies (environmental context and resources); knowledge gaps relating to guidelines and appropriate prescribing (knowledge); restricted roles/responsibilities of microbiologists and pharmacists (professional role and identity); challenging antimicrobial prescribing decisions (memory, attention and decision processes); and professional hierarchies and poor multidisciplinary teamworking (social influences). Key facilitators included guidelines compliance (goals and intentions), and participants' beliefs about the consequences of appropriate or inappropriate prescribing. Further education and training, and some changes to guidelines including their accessibility were also considered essential. CONCLUSIONS: Antimicrobial prescribing behaviour in hospitals is a complex process influenced by a broad range of determinants including specific barriers and facilitators. The in-depth understanding of this complexity provided by this work may support the development of an effective BCI to promote appropriate antimicrobial stewardship.

Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

Objectives: We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods: This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. Results: There were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. Conclusion: Third-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. RESULTS: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. DISCUSSION/CONCLUSION: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

Association of Papacarie Duo® and low-level laser in antimicrobial photodynamic therapy (aPDT).

Dental caries is a multifactorial, non-communicable disease. Effective treatment options for minimally invasive removal of carious tissue include Papacarie Duo® gel and antimicrobial photodynamic therapy (aPDT). aPDT involves a combination of a light source and photosensitizer. Given that Papacarie Duo® contains a percentage of blue dye, this study aims to explore the antimicrobial potential of Papacarie Duo® when associated with a light source against Streptococcus mutans strains. The chosen light source was a low-power diode laser (λ = 660 nm, E = 3 J, P = 100 mW, t = 30 s). To assess antimicrobial capacity, planktonic suspensions of Streptococcus mutans were plated on Brain Heart Infusion Agar (BHI) to observe the formation of inhibition halos. The studied groups included methylene blue (0.005%), Papacarie Duo®, distilled water (negative control), 2% chlorhexidine (positive control), Papacarie Duo® + laser, and methylene blue (0.005%) + laser. Following distribution onto plates, each group was incubated at 37 °C for 48 h under microaerophilic conditions. Inhibition halos were subsequently measured using a digital caliper. The results showed that chlorhexidine had the greatest antimicrobial effect followed by the group of irradiated methylene blue and irradiated Papacarie Duo®. All experimental groups demonstrated antimicrobial potential, excluding the negative control group. The study concludes that Papacarie Duo® exhibits antimicrobial properties when associated with a low-power diode laser.

Impact of Antibiotic-Loaded PMMA Spacers on the Osteogenic Potential of hMSCs.

Antibiotic-loaded PMMA bone cement is frequently used in modern trauma and orthopedic surgery. Although many of the antibiotics routinely applied are described to have cytotoxic effects in the literature, clinical experience shows no adverse effects for bone healing. To determine the effects of antibiotic-loaded PMMA spacers on osteogenesis in vitro, we cultivated human bone marrow mesenchymal stem cells (BM-hMSCs) in the presence of PMMA spacers containing Gentamicin, Vancomycin, Gentamicin + Clindamycin as well as Gentamicin + Vancomycin in addition to a blank control (agarose) and PMMA containing no antibiotics. The cell number was assessed with DAPI staining, and the osteogenic potential was evaluated by directly measuring the amount of hydroxyapatite synthesized using radioactive 99mTc-HDP labelling as well as measuring the concentration of calcium and phosphate in the cell culture medium supernatant. The results showed that Gentamicin and Vancomycin as well as their combination show a certain amount of cytotoxicity but no negative effect on osteogenic potential. The combination of Gentamicin and Clindamycin, on the other hand, led to a drastic reduction in both the cell count and the osteogenic potential.