Macrophage membrane-coated nanoparticles for the treatment of infectious diseases.

Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented.

Phytochemical and ethnomedicinal evidences of the use of Alternanthera brasiliana (L.) Kuntze against infectious diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Popularly known as "penicilina" and "terramicina", Alternanthera brasiliana (L.) Kuntze belongs to the Amaranthaceae family and stands out for its ethnomedicinal uses in the treatment of infections caused by pathogenic microorganisms in some countries. AIM OF THE STUDY: The present study aimed to carry out a literature review and analyze whether the scientific evidence really validates the numerous indications for the use of A. brasiliana in traditional medicine for the treatment of infectious diseases. Phytochemical and toxicological studies related to this species were also analyzed. MATERIAL AND METHODS: Scientific documents were retrieved from Google Scholar, PubMed®, ScienceDirect®, SciELO, SpringerLink®, Scopus®, and Web of Science™ databases. The literature was reviewed from the first report on the antimicrobial activity of A. brasiliana in 1994 until April 2024. RESULTS: According to the scientific documents analyzed, it was observed that A. brasiliana is widely used as a natural antibiotic for the treatment of infectious diseases in Brazil, mainly in the states of Rio Grande do Sul, Mato Grosso, and Minas Gerais. Its ethnomedicinal uses have also been reported in other countries such as Colombia and India. The leaves (78%) of A. brasiliana are the main parts used in the preparation of herbal medicines by traditional communities. Several A. brasiliana extracts showed low activity when evaluated against pathogens, including gram-positive bacteria, gram-negative bacteria, parasitic protozoa, and fungi. Only two studies reported that extracts from this plant showed high activity against the herpes simplex virus, Mycobacterium smegmatis, and Candida albicans. Phytochemicals belonging to the classes of phenolic compounds and flavonoid (52%), saturated and unsaturated fatty acids (33%), steroids and phytosterols (8%), terpenoids (5%), and fatty alcohol esters (2%) were identified in A. brasiliana. Toxicity (in vivo) and cytotoxicity (in vitro) studies of polar and non-polar extracts obtained from A. brasiliana leaves indicated that this plant is biologically safe. CONCLUSION: Despite being widely used as a natural antibiotic by traditional communities, scientific investigations related to the antimicrobial potential of A. brasiliana extracts have indicated inactivity against several pathogens.

How New Regulation of Laboratory-Developed Antimicrobial Susceptibility Tests Will Affect Infectious Diseases Clinical Practice.

Antimicrobial resistance (AMR) affects 2.8 million Americans annually. AMR is identified through antimicrobial susceptibility testing (AST), but current and proposed regulatory policies from the United States Food and Drug Administration (FDA) jeopardize the future availability of AST for many microorganisms. Devices that perform AST must be cleared by the FDA using their susceptibility test interpretive criteria, also known as breakpoints. The FDA list of breakpoints is relatively short. Today, laboratories supplement FDA breakpoints using breakpoints published by the Clinical and Laboratory Standards Institute, using legacy devices and laboratory-developed tests (LDTs). FDA proposes to regulate LDTs, and with no FDA breakpoints for many drug-bug combinations, the risk is loss of AST for key clinical indications and stifling innovation in technology development. Effective solutions require collaboration between manufacturers, infectious diseases clinicians, pharmacists, laboratories, and the FDA.

Infectious Diseases: What You May Have Missed in 2023.

In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin-tazobactam, ceftobiprole for the treatment of complicated Staphylococcus aureus bacteremia, and early switch from intravenous to oral antibiotics in patients with gram-negative bacteremia. Another article examines differences in all-cause mortality in patients with Clostridioides difficile infection who receive different treatments. Additional articles provide evidence about the treatment of patients with HIV infection: the utility of preexposure prophylaxis to prevent HIV infection, the efficacy of pitavastatin in reducing cardiovascular disease, and the efficacy of dexamethasone for the treatment of tuberculous meningitis in persons with HIV.

Diagnóstico por amplificación isotérmica de ácidos nucleicos. Oportunidad para la farmacia comunitaria / Diagnosis by isothermal amplification of nucleic acids. Opportunity for community pharmacy

Esta revisión se centra en describir nuevos sistemas de diagnóstico molecular de tipo POC disponibles en el mercado que pueden implementarse fácilmente en farmacias comunitarias y tienen el potencial de ampliar la cartera de servicios farmacéuticos y hacer una contribución significativa a la mejora de la salud pública.El conocimiento de nuevas técnicas de diagnóstico molecular distintas de la PCR es relativamente desconocido. Sin embargo, las opciones disponibles son diversas y han alcanzado suficiente madurez tecnológica para su uso a gran escala. La pandemia de SARS-CoV-2 ha sacado al mercado pruebas de diagnóstico que, en algunos casos, se han utilizado exclusivamente en investigación durante décadas.La tecnología isotérmica de amplificación de ácidos nucleicos sigue evolucionando y es probable que en los próximos años seamos testigos de un aumento exponencial de su uso, así como del desarrollo de nuevas mejoras que simplifiquen y reduzcan aún más el coste de cada ensayo.Igualmente, no podemos obviar el hecho de que durante la pandemia de COVID-19, el público se ha habituado a autodiagnosticarse a través de canales de distribución masiva como las farmacias comunitarias, lo que puede abrir el sector a otras enfermedades —como las de transmisión sexual o salud animal—, el control de alimentos, la contaminación del agua y del aire (hongos) o la presencia de alérgenos.El conocimiento de estas nuevas tecnologías es esencial estrategia de vigilancia tecnológica e inteligencia competitiva del sector farmacéutico.(AU)

Optimizing Antimicrobial Stewardship in the Emergency Department.

Antibiotic stewardship is a core component of emergency department (ED) practice and impacts patient safety, clinical outcomes, and public health. The unique characteristics of ED practice, including crowding, time pressure, and diagnostic uncertainty, need to be considered when implementing antibiotic stewardship interventions in this setting. Rapid advances in pathogen detection and host response biomarkers promise to revolutionize the diagnosis of infectious diseases in the ED, but such tests are not yet considered standard of care. Presently, clinical decision support embedded in the electronic health record and pharmacist-led interventions are the most effective ways to improve antibiotic prescribing in the ED.

Uncovering the secrets of resistance: An introduction to computational methods in infectious disease research.

Antimicrobial resistance (AMR) is a growing global concern with significant implications for infectious disease control and therapeutics development. This chapter presents a comprehensive overview of computational methods in the study of AMR. We explore the prevalence and statistics of AMR, underscoring its alarming impact on public health. The role of AMR in infectious disease outbreaks and its impact on therapeutics development are discussed, emphasizing the need for novel strategies. Resistance mutations are pivotal in AMR, enabling pathogens to evade antimicrobial treatments. We delve into their importance and contribution to the spread of AMR. Experimental methods for quantitatively evaluating resistance mutations are described, along with their limitations. To address these challenges, computational methods provide promising solutions. We highlight the advantages of computational approaches, including rapid analysis of large datasets and prediction of resistance profiles. A comprehensive overview of computational methods for studying AMR is presented, encompassing genomics, proteomics, structural bioinformatics, network analysis, and machine learning algorithms. The strengths and limitations of each method are briefly outlined. Additionally, we introduce ResScan-design, our own computational method, which employs a protein (re)design protocol to identify potential resistance mutations and adaptation signatures in pathogens. Case studies are discussed to showcase the application of ResScan in elucidating hotspot residues, understanding underlying mechanisms, and guiding the design of effective therapies. In conclusion, we emphasize the value of computational methods in understanding and combating AMR. Integration of experimental and computational approaches can expedite the discovery of innovative antimicrobial treatments and mitigate the threat posed by AMR.

Microbiological Rapid On-Site Evaluation for Pulmonary Infectious Diseases.

The prompt initiation of empirical anti-infective therapy is crucial in patients presenting with unexplained pulmonary infection. Although imaging acquisition is relatively straightforward in clinical practice, its lack of specificity often necessitates additional time-consuming tests such as sputum culture, bronchoalveolar-lavage fluid culture, or genetic sequencing to identify the underlying etiology of the disease accurately. Moreover, the limited efficacy of empirical anti-infective treatment may contribute to antibiotic misuse. Recent advancements in interpreting microbial background on rapid on-site evaluation (ROSE) slides have enabled clinicians to promptly obtain samples through bronchoscopy (e.g., alveolar lavage, mucosal brushing, tissue clamp), facilitating bedside staining and interpretation that provides essential microbial background information. Consequently, this establishes a foundation for developing targeted anti-infection treatment and individualized drug therapy plans. With a better understanding of which pathogens are causing infections in real-time, physicians can avoid unnecessary broad-spectrum antibiotics contributing to antibiotic resistance. Establishing a rapid and standardized M-ROSE workflow within respiratory medicine departments or intensive care units will greatly assist physicians in formulating accurate treatment strategies for patients, which holds significant clinical implications.

Finding value in novel antibiotics: How can infectious diseases adopt incremental cost-effectiveness to improve new antibiotic utilization?

Research and development of innovative antimicrobials is paramount to addressing the antimicrobial resistance threat. Although antimicrobial discovery and development has increased, difficulties have emerged in the pharmaceutical industry after market approval. In this minireview, we summarize clinical trial data on recently approved antibiotics, calculate incremental cost-effectiveness ratio (ICER) values, and explore ways to adapt ICER calculations to the limitations of antimicrobial clinical trial design. We provide a systematic review and analysis of randomized, controlled studies of antibiotics approved from 2014 - 2022 and extracted the relevant clinical data. Adapted-ICER (aICER) calculations were conducted using the primary condition-specific outcome that was reported in each study (percent mortality or percent cure rate). The literature search identified 18 studies for the 8 total antibiotics which met inclusion criteria and contained data required for aICER calculation. aICER values ranged from -$17,374 to $4,966 per percent mortality and -$43,931 to $2,529 per percent cure rate. With regards to mortality, ceftolozane/tazobactam and imipenem/cilastatin/relebactam proved cost efficacious, with aICER values of $4,965 per percent mortality and $1,955 per percent mortality respectively. Finding value in novel antibiotic agents is imperative to further justifying their development, and aICER values are the most common method of determining value in healthcare. The current outcomes of clinical trials are difficult to translate to aICER, which most effectively use Quality-Adjusted Life Years (QALY) as the quality standard in other fields such as oncology. Future antimicrobial trials should consider introducing methods of assessing measures of health gain such as QALY to better translate the value of novel antimicrobials in healthcare.

Combating Antimicrobial Resistance by Employing Antimicrobial Peptides: Immunomodulators and Therapeutic Agents against Infectious Diseases.

The rising prevalence of multiple-drug-resistant pathogens poses a formidable challenge to conventional antimicrobial treatments. The inability of potent antibiotics to combat these "superbugs" underscores the pressing need for alternative therapeutic agents. Antimicrobial peptides (AMPs) represent an alternative class of antibiotics. AMPs are essential immunomodulatory molecules that are found in various organisms. They play a pivotal role in managing microbial ecosystems and bolstering innate immunity by targeting and eliminating invading microorganisms. AMPs also have applications in the agriculture sector by combating animal as well as plant pathogens. AMPs can be exploited for the targeted therapy of various diseases and can also be used in drug-delivery systems. They can be used in synergy with current treatments like antibiotics and can potentially lead to a lower required dosage. AMPs also have huge potential in wound healing and regenerative medicine. Developing AMP-based strategies with improved safety, specificity, and efficacy is crucial in the battle against alarming global microbial resistance. This review will explore AMPs' increasing applicability, their mode of antimicrobial activity, and various delivery systems enhancing their stability and efficacy.

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.

Assessing Environmental Risks during the Drug Development Process for Parasitic Vector-Borne Diseases: A Critical Reflection.

Parasitic vector-borne diseases (VBDs) represent nearly 20% of the global burden of infectious diseases. Moreover, the spread of VBDs is enhanced by global travel, urbanization, and climate change. Treatment of VBDs faces challenges due to limitations of existing drugs, as the potential for side effects in nontarget species raises significant environmental concerns. Consequently, considering environmental risks early in drug development processes is critically important. Here, we examine the environmental risk assessment process for veterinary medicinal products in the European Union and identify major gaps in the ecotoxicity data of these drugs. By highlighting the scarcity of ecotoxicological data for commonly used antiparasitic drugs, we stress the urgent need for considering the One Health concept. We advocate for employing predictive tools and nonanimal methodologies such as New Approach Methodologies at early stages of antiparasitic drug research and development. Furthermore, adopting progressive approaches to mitigate ecological risks requires the integration of nonstandard tests that account for real-world complexities and use environmentally relevant exposure scenarios. Such a strategy is vital for a sustainable drug development process as it adheres to the principles of One Health, ultimately contributing to a healthier and more sustainable world.

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection.

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.

Resolution pharmacology and the treatment of infectious diseases.

Inflammation is elicited by the host in response to microbes, and is believed to be essential for protection against infection. However, we have previously hypothesized that excessive or misplaced inflammation may be a major contributor to tissue dysfunction and death associated with viral and bacterial infections. The resolutive phase of inflammation is a necessary condition to achieve homeostasis after acute inflammation. It is possible that targeting inflammation resolution may be beneficial for the host during infection. In this review, we summarize the evidence demonstrating the expression, roles and effects of the best described pro-resolving molecules in the context of bacterial and viral infections. Pro-resolving molecules play a pivotal role in modulating a spectrum of pathways associated with tissue inflammation and damage during both viral and bacterial infections. These molecules offer a blend of anti-inflammatory, pro-resolving and sometimes anti-infective benefits, all the while circumventing the undesired and immune-suppressive unwanted effects associated with glucocorticoids. Whether these beneficial effects will translate into benefits to patients clearly deserve further investigation.

Nanotechnology's frontier in combatting infectious and inflammatory diseases: prevention and treatment.

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

Resumen ejecutivo del documento de consenso sobre el manejo compartido del paciente con infección por VIH entre Atención Primaria y Hospitalaria / Executive summary of the consensus document on the shared care of patients with HIV infection between Primary and Hospital Care

La realidad actual del diagnóstico y tratamiento de la infección por virus de la inmunodeficiencia humana (VIH) justifica un abordaje multidisciplinar y coordinado entre Atención Primaria y Atención Hospitalaria, contemplando la bidireccionalidad y la comunicación entre los dos escenarios asistenciales. El presente documento de consenso, coordinado entre el Grupo de Estudio del SIDA de la Sociedad Española de Enfermedades Infecciosas (SEIMC-GeSIDA) y la Sociedad Española de Medicina de Familia y Comunitaria (semFYC), nace de esta necesidad. Aquí se resumen las recomendaciones de los cuatro bloques que lo componen: el primero trata aspectos de prevención y diagnóstico de la infección por el VIH; en el segundo se contempla la atención y el manejo clínico de las personas que viven con VIH; el tercero trata aspectos sociales, incluyendo temas legales y de confidencialidad, la calidad de vida y el papel de las ONG; por último, el cuarto bloque aborda la formación/docencia y la investigación bidireccional y compartida.(AU)

The current reality of the diagnosis and treatment of HIV infection justifies a multidisciplinary and coordinated approach between primary care and hospital care. This entails a two-way relationship and communication between the two care settings. This consensus document, coordinated by the AIDS Study Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC-GeSIDA) and the Spanish Society of Family and Community Medicine (semFYC), arose because of this need. Here, the recommendations of the four blocks that comprise it are summarized: the first tackles aspects of prevention and diagnosis of HIV infection; the second contemplates the clinical care and management of people living with HIV; the third deals with social aspects, including legal and confidentiality issues, quality of life, and the role of NGOs; finally, the fourth block addresses two-way and shared training/teaching and research.(AU)