Nanocomposites used in the treatment of skin lesions: a scoping review.

OBJECTIVE: To map the nanocomposites used in the treatment of skin lesions. METHOD: A scoping review, according to the Joanna Briggs Institute methodology, carried out on eight databases, a list of references and Google Scholar to answer the question: "Which nanocomposites are used as a cover for the treatment of skin lesions?". Two independent reviewers selected the final sample using inclusion/exclusion criteria using the EndNote® and Rayyan programs. Data was extracted using an adapted form and reported using the PRISMA checklist extension, and the protocol was registered in the Open Science Framework (OSF). RESULTS: 21 articles were selected, with nanofibers, nanogels and nanomembranes as the nanocomposites described in wound healing, alone or in association with other therapies: negative pressure and elastic. Silver nanomaterials stand out in accelerating healing due to their antimicrobial and anti-inflammatory action, but caution should be exercised due to the risk of cytotoxicity and microbial resistance. CONCLUSION: Nanocomposites used in wound treatment are effective in accelerating healing and reducing costs, and the addition of bioactives to nanomaterials has added extra properties that contribute to healing.

Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Exploring patients' perspectives: a mixed methods study on Outpatient Parenteral Antimicrobial Therapy (OPAT) experiences.

BACKGROUND: Outpatient Parenteral Antimicrobial Therapy (OPAT), an alternative to inpatient intravenous antibiotic therapy, has shown benefits in international studies such as increased patient satisfaction. Because OPAT has been used only sporadically in Germany so far, no structured results on patients' experiences and concerns regarding OPAT have yet been available. This study therefore aims to explore the experiences of OPAT patients in a pilot region in Germany. METHODS: This is an observational study in a German pilot region, including a survey of 58 patients on their experiences with OPAT, and in-depth interviews with 12 patients (explanatory-sequential mixed-methods design). RESULTS: Patients reported that they were satisfied with OPAT. That a hospital discharge was possible and anti-infective therapy could be continued in the home environment was rated as being particularly positive. In the beginning, many patients in the interviews were unsure about being able to administer the antibiotic therapy at home on their own. However, healthcare providers (doctors and pharmacy service provider staff) were able to allay these concerns. Patients appreciated regular contact with care providers. There were suggestions for improvement, particularly concerning the organization of the weekly check-up appointments and the provision of information about OPAT. CONCLUSIONS: Patients were generally satisfied with OPAT. However, the treatment structures in Germany still need to be expanded to ensure comprehensive and high-quality OPAT care. TRIAL REGISTRATION: NCT04002453, https://www. CLINICALTRIALS: gov/ , (registration date: 2019-06-21).

[A randomized controlled trial on the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing in the treatment of deep partial-thickness burn wounds in children].

Objective: To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children. Methods: This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar. Results: When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group (Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group (Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group (t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group (Z=-3.05, P<0.05). Conclusions: Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.

What to Know about Antimicrobial Coatings in Arthroplasty: A Narrative Review.

Periprosthetic joint infections (PJIs) are one of the most worrying complications orthopedic surgeons could face; thus, methods to prevent them are evolving. Apart from systemic antibiotics, targeted strategies such as local antimicrobial coatings applied to prosthetics have been introduced. This narrative review aims to provide an overview of the main antimicrobial coatings available in arthroplasty orthopedic surgery practice. The search was performed on the PubMed, Web of Science, SCOPUS, and EMBASE databases, focusing on antimicrobial-coated devices used in clinical practice in the arthroplasty world. While silver technology has been widely adopted in the prosthetic oncological field with favorable outcomes, recently, silver associated with hydroxyapatite for cementless fixation, antibiotic-loaded hydrogel coatings, and iodine coatings have all been employed with promising protective results against PJIs. However, challenges persist, with each material having strengths and weaknesses under investigation. Therefore, this narrative review emphasizes that further clinical studies are needed to understand whether antimicrobial coatings can truly revolutionize the field of PJIs.

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)

Updated antimicrobial dosing recommendations for obese patients.

The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.

Barriers and facilitators for the implementation and expansion of outpatient parenteral antimicrobial therapy: a systematic review.

Outpatient parenteral antimicrobial therapy (OPAT) has been expanding in recent years and serves as a viable solution in reducing the shortage of hospital beds. However, the wider implementation of OPAT faces numerous challenges. This review aimed to assess implementation barriers and facilitators of OPAT services. Studies describing barriers and facilitators of the OPAT service were retrieved from PubMed, Scopus, MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science Proceedings, International Pharmaceutical Abstracts and PsycINFO. All types of study designs published in the English language were included. Studies that did not mention any barrier or facilitator, did not differentiate OPAT and inpatient, focused on specific antimicrobials or diseases, and made no distinction between parenteral and other treatments were excluded. Qualitative analysis was performed using the 'best-fit' framework approach and the Consolidated Framework for Implementation Research (CFIR). The review was PROSPERO registered (CRD42023441083). A total of 8761 studies were screened for eligibility and 147 studies were included. Problems in patient selection, lack of awareness, poor communication and co-ordination, lack of support, lack of structured service and inappropriate prescriptions were identified. OPAT provides safe, effective and efficient treatment while maintaining patients' privacy and comfort, resulting in less daily life disruption, and reducing the risk of infection. Satisfaction and preference for OPAT were very high. Initiatives in strengthening OPAT such as antimicrobial stewardship and telemedicine are beneficial. Challenges to and facilitators of OPAT were identified among patients, health professionals, OPAT service providers and healthcare administrators. Understanding them is crucial to designing targeted initiatives for successful OPAT service implementation.

In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal / Actividad in vitro de cefiderocol y otros antimicrobianos recientemente aprobados frente a gramnegativos multirresistentes aislados en unidades de cuidados intensivos en España y Portugal

Introduction. The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. Material and methods. A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. Results. Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. Conclusions. Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria. (AU)

Introducción. La resistencia a los antimicrobianos constituye una importante amenaza para la salud pública, especialmente en el caso de las infecciones relacionadas con la asistencia sanitaria causadas por patógenos gramnegativos resistentes a los carbapenémicos, las cuales están aumentando en todo el mundo. El objetivo de este estudio fue proporcionar datos sobre la actividad antimicrobiana in vitro de cefiderocol y la de antibióticos comparadores disponibles en el arsenal terapéutico frente a una colección definida de microorganismos multirresistentes (MDR) obtenidos de muestras clínicas, incluidas bacterias gramnegativas resistentes a carbapenemas procedentes de diferentes regiones de España y Portugal. Material y métodos. Se recogieron un total de 477 aislados clínicos de Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii y Stenotrophomonas maltophilia de forma prospectiva (n=265) y retrospectiva (n=212) (2016-2019). El estudio de sensibilidad se realizó por microdilución standard y los resultados se analizaron empleando criterios del CLSI de 2021 y de EUCAST de 2021. Resultados. En general, cefiderocol demostró una buena actividad frente a aislados de Enterobacterales, siendo 99,5% sensible según criterios del CLSI y 94,5% según los de EUCAST. Cefiderocol demostró una excelente actividad frente a aislados de P. aeruginosa y S. maltophilia, siendo todos ellos sensibles a este compuesto considerando los puntos de corte del CLSI. En relación a A. baumannii (n=64), sólo un aislado fue resistente a cefiderocol. Conclusiones. Nuestros resultados concuerdan con los de otros estudios realizados fuera de España y Portugal en los que se destaca la excelente actividad de cefiderocol frente a bacterias gramnegativas MDR. Cefiderocol constituye una alternativa terapéutica a las disponibles en el tratamiento de las infecciones causadas por estos microorganismos. (AU)

Audit of antimicrobial stewardship in medical inpatients in Waikato, New Zealand 2021.

AIMS: Given the threat of rising antimicrobial resistance (AMR), 10 audit standards were selected to audit antimicrobial stewardship (AMS) in secondary care to assess guideline adherence and establish quality improvement initiatives in antimicrobial prescribing. METHODS: Patients were included if they received intravenous (IV) antibiotics across seven medical wards in Waikato or Thames hospitals, New Zealand, in November 2021. Audit standards were defined from the regional antimicrobial prescribing policy and adult antimicrobial guidelines. RESULTS: In total, 205 patients were audited. Microbiological sampling standards were met in 87 of 126 occasions (69.0%). Antimicrobial choices adhered to guidelines in 89 of 163 patients (54.6%), where guidelines were available. Documentation of antimicrobial indications in the medical notes and antimicrobial review at 48 to 72 hours met the standards at over 90%. Only 2 of 13 patients (15.4%) receiving piperacillin/tazobactam or a carbapenem were discussed with Infectious Diseases (ID). Documentation of indications and durations on paper-based medication charts was infrequent, around 12%. Evaluating for health equity, similar results were observed for Maori and non-Maori. CONCLUSIONS: Our audit identified specific areas for AMS quality improvement initiatives. Regular audit should become an essential element of the New Zealand AMS strategy. We believe increased AMS resources are required.

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. Results: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Outpatient parenteral antimicrobial therapy with continuous infusion of meropenem: A retrospective analysis of three years of clinical experience / Tratamiento antimicrobiano domiciliario endovenoso con infusión continua de meropenem: un análisis restrospectivo de tres años de experiencia clínica

Introduction: Data regarding outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion of meropenem (CIM) remain scarce and controversial. We aimed to analyze its outcomes. Methods: We conducted a retrospective analysis of a cohort of patients who received OPAT with CIM during a three-year period at a single center in northwest Spain. Demographics, clinical data and OPAT outcomes were recorded. Results: Since January 2017–December 2019, 34 patients received 35 OPAT episodes with CIM. The median age was 75 years, and 18 (51.4%) had a Charlson comorbidity index>2. Twelve (34.3%) had respiratory infection, 11 (31.4%) urinary tract infection, and 12 (34.3%) other infections. Twenty-one (60%) received a dose of 6g/day, and 27 (77.1%) received combined antibiotic therapy. The duration of OPAT with CIM was 10 median days. Pseudomonas aeruginosa was the most frequently (34.3%) isolated microorganism and 10 (28.6%) infections were polymicrobial. During OPAT and hospital at home unit admission, 4 (11.4%) patients had any adverse reaction that required CIM withdrawal, 2 (5.7%) were readmitted, and 3 (8.8%) died (2 infection-related deaths). After 30 days from discharge 6 (18.8%) of 32 not-censored patients had unplanned readmissions (2 infection-related), 6 (18.8%) developed recurrence (3 relapses, 3 reinfections) and 1 (3.1%) died (none-infection-related death). Twenty-three (71.9%) of these 32 patients did not experience unplanned readmission, recurrence or death. Conclusion: CIM can be an option to be administrated in OPAT programs in selected patients. Further studies are warranted to increase evidence regarding its use, and to externally validate our findings.(AU)

Introducción: Los datos sobre el tratamiento antimicrobiano domiciliario endovenoso (TADE) con infusión continua de meropenem (ICM) son escasos y controvertidos. Nuestro objetivo fue analizar sus resultados. Métodos: Realizamos un análisis retrospectivo de una cohorte de pacientes que recibieron TADE con ICM durante tres años en un centro del noroeste de España. Se registraron datos demográficos, clínicos y resultados. Resultados: Desde enero de 2017 a diciembre de 2019, 34 pacientes recibieron 35 episodios de TADE con ICM. La mediana de edad fue de 75 años y 18 (51,4%) tenían un índice de comorbilidad de Charlson>2. Doce (34,3%) tenían infección respiratoria, 11 (31,4%) urinaria y 12 (34,3%) otras infecciones. Veintiuno (60%) recibieron una dosis de 6g/día y 27 (77,1%) antibioterapia combinada. La duración mediana del TADE con ICM fue de 10 días. Pseudomonas aeruginosa fue el microorganismo aislado más frecuentemente (34,3%) y 10 (28,6%) infecciones fueron polimicrobianas. Durante el TADE, 4 (11,4%) pacientes presentaron alguna reacción adversa que requirió retirada de ICM, 2 (5,7%) reingresaron y 3 (8,8%) fallecieron (2 muertes relacionadas con infección). Tras 30 días desde el alta, 6 (18,8%) de 32 pacientes tuvieron reingresos no programados (2 relacionados con infección), 6 (18,8%) desarrollaron recurrencia (3 recidivas, 3 reinfecciones) y 1 (3,1%) falleció (sin relación con infección). Veintitrés (71,9%) de 32 pacientes no experimentaron reingreso no programado, recidiva o muerte. Conclusión: La ICM puede ser una opción para ser administrada en programas de TADE en pacientes seleccionados. Se necesitan más estudios para aumentar la evidencia sobre su uso y validar externamente nuestros hallazgos.(AU)