Treatment Of Infectious Diseases Research Articles

An adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A, as a novel therapeutic approach to inflammatory diseases.

Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs. To test this hypothesis, we developed AdV.C3-Tat/HIV-Box A, an inflammation-inducible cassette that remains innocuous in the absence of inflammation but releases HMGB1 Box A, an antagonist of high mobility group box 1 (HMGB1), in response to inflammatory stimuli such as lipopolysaccharide (LPS) or influenza virus infection. We report here that this novel inflammation-inducible HMGB1 Box A construct in a non-replicative adenovirus (AdV) vector mitigates lung and systemic inflammation therapeutically in response to influenza infection. We anticipate that this strategy will apply to the treatment of multiple diseases in which HMGB1-mediated signaling is a central driver of inflammation.IMPORTANCEMany inflammatory diseases are mediated by the action of a host-derived protein, HMGB1, on Toll-like receptor 4 (TLR4) to elicit an inflammatory response. We have engineered a non-replicative AdV vector that produces HMGB1 Box A, an antagonist of HMGB1-induced inflammation, under the control of an endogenous complement component C3 (C3) promoter sequence, that is inducible by LPS and influenza in vitro and ex vivo in macrophages (Mϕ) and protects mice and cotton rats therapeutically against infection with mouse-adapted and human non-adapted influenza strains, respectively, in vivo. We anticipate that this novel strategy will apply to the treatment of multiple infectious and non-infectious diseases in which HMGB1-mediated TLR4 signaling is a central driver of inflammation.

Evaluating the capacity of tertiary general hospitals in Beijing to prevent and treat respiratory infectious diseases: a delphi study

BackgroundThe capacity of tertiary general hospitals to prevent and treat respiratory infectious diseases plays a key role in effectively containing the spread of major epidemics within hospitals and ensuring early treatment for patients. This, in turn, helps control the transmission of diseases at the societal level and safeguard public health. However, there is a lack of detailed indicators for assessing hospitals’ capacity in this area, which makes it difficult to evaluate and manage practices. Therefore, this study aimed to develop a comprehensive evaluation index system to assess the capabilities of tertiary general hospitals in preventing and treating respiratory infectious diseases.MethodsThis study utilizes a three-dimensional evaluation model, “Structure-Process-Outcome” as the theoretical basis and first-level index of the indicator system for evaluating the abilities of tertiary general hospitals in preventing and treating respiratory infectious disease. A combination of literature review, semi-structured interviews, and Delphi expert consultation was employed to ensure comprehensive and reliable indicators. The hierarchical analysis method (AHP) was used to determine the weights of the indicators.ResultsThe effective response rates for the two rounds of the Delphi survey were 95.2% and 100%, respectively. The expert authority coefficients were 0.905 and 0.923, respectively. Kendall’s W for the importance of all the indicators increased from 0.274 to 0.327 (P < 0.001), and for feasibility, it increased from 0.198 to 0.240 (P < 0.001). After two rounds of expert consultation, a final evaluation indicator system was established, including 3 first-level indicators, 12 s-level indicators, and 41 third-level indicators, with assigned weights.ConclusionThis study establishes a comprehensive evaluation index system, providing a scientific basis for evaluating the capacity of tertiary general hospitals to prevent and treat respiratory infectious diseases. The system provides valuable reference for improving hospital preparedness and response strategies, and for evaluating the infectious disease prevention and treatment system in Beijing, China.

Introduction about Global infectious disease and use of nanotechnology

Infectious diseases, including COVID-19, malaria, tuberculosis, and sexually transmitted diseases (STDs), pose significant threats to global health. Nanotechnology has emerged as a promising tool in the diagnosis, treatment, and prevention of these diseases. This review highlights the applications of nanotechnology in combating infectious diseases. Nanoparticles, such as metallic nanoparticles, liposomes, and quantum dots, have been employed in the detection and treatment of infectious diseases. Nanotechnology-based drug delivery systems have improved the efficacy and reduced the toxicity of antiviral and antibacterial drugs. Additionally, nanotechnology has enabled the development of point-of-care diagnostics and vaccines for infectious diseases. This review provides an overview of the current state of nanotechnology in infectious disease management and highlights its potential to revolutionize the field. By leveraging the unique properties of nanoparticles, nanotechnology can provide innovative solutions for the diagnosis, treatment, and prevention of infectious diseases, ultimately improving global health outcomes. Keywords: Nanotechnology, Infectious diseases, COVID-19, Malaria, Tuberculosis, HIV/AIDS

High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation

High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation

Miniaturized electrophoresis: An integrated microfluidic cartridge with functionalized hydrogel-assisted LAMP for sample-to-answer analysis of nucleic acid.

Accurate detection of pathogenic nucleic acids is crucial for early diagnosis, effective treatment, and containment of infectious diseases. It facilitates the timely identification of pathogens, aids in monitoring disease outbreaks, and helps prevent the spread of infections within healthcare settings and communities. We developed a multi-layered, paper-based microfluidic and miniaturized electrophoresis system for rapid nucleic acid extraction, separation, amplification, and detection, designed for resource-limited settings. Constructed from acrylic, transparency film, pressure-sensitive adhesion, and Whatman paper using a CO2 laser, the setup simplifies traditional methods and eliminates the need for complex equipment. DNA extraction and purification are achieved using Zweifach-Fung bifurcation and Fahraeus effect principles, with detection via a hydrogel-assisted colorimetric isothermal reverse transcriptase-loop-mediated isothermal amplification technique. The system accurately identified the SARS-CoV-2 N-gene and β-actin human gene, validated by a compact electrophoresis setup. In clinical validation with 12 patient specimens, the system demonstrated a positive predictive agreement of 83.0% and a negative predictive agreement of 100%. The system achieves a limit of detection of 1 copy/μl and can potentially transform nucleic acid detection assays in healthcare settings. This study addresses key challenges in nucleic acid detection, such as ensuring sample quality and quantity, reducing reliance on sophisticated equipment, preventing contamination, simplifying procedures, and providing rapid and accurate diagnostics for emerging pathogens.

Emerging Nanobiotechnology Solutions for Diagnosis and Treatment of Infectious Diseases

Nanotechnology has emerged as a transformative force in combating infectious diseases, especially highlighted by its applications during the COVID - 19 pandemic. This review discusses the multifaceted roles of nanotechnology in enhancing diagnostic accuracy, therapeutic efficacy and vaccine development. It emphasizes the critical importance of rapid, sensitive diagnostics for early infection identification, utilizing fluorescent nanoparticles and nanosensors that enable detection at unprecedentedly low and light concentrations. Additionally, the review explores the development of nanoparticle - based drug delivery systems for targeted therapy and immune response modulation, which promise to improve the outcomes of infectious disease treatment. The potential of point - of - care POC diagnostics leveraging nanotechnology for real - time cost - effective and portable disease monitoring, particularlyin resource - limited settings, is thoroughly examined. Through detailed examples including graphene - based biosensors and nanoparticles enhanced immunotherapeutics, the paper illustrates how nanotechnology is reshaping the landscape of infectious disease management, offering novel solutions to the age - old problems of diagnosis, treatment and prevention, challenges such as cost, regulatory approval and the need for global collaboration are acknowledged. Alongside the optimistic outlook for nanotechnology role is advancing public health and global infectious disease.

Development of a topical formulation of a thiadiazole derivative

Introduction. Development of broad-spectrum antibacterial medicines for treatment of bacterial and fungal infections of animal skin is an urgent task of pharmaceutical industry, medicine and agricultural industry. The most promising dosage form for the treatment of superficial infectious diseases is gel. The most important advantages are the absence of side effects associated with ingestion, as well as the formation of a protective film that prevents re-infection of the animal.Aim. To develop the composition of topical form in the form of gel on the basis of active pharmaceutical substance with a wide spectrum of antimicrobial action for therapy of infectious diseases of animal skin.Materials and methods. The object of the study was an original substance – thiadiazole derivative, obtained by the organic synthesis department of the Department of Organic Chemistry of the Federal State Budgetary Educational Institution of Higher Professional Education SPHFU of the Ministry of Health of Russia. Gel formers (sodium alginate and carbomer), propylene glycol, surfactants (surfactants), etc. were used in the work. The obtained thiadiazole gels were studied in terms of pH, appearance, thermostability, colloidal stability, film formation, in addition, the rheological properties of the gels were determined.Results and discussion. It was found that gels in which sodium alginate and carbomer acted simultaneously as gel formers had thixotropic properties providing the best stability of the structure. The gels in which glycerin was added formed an elastic film preventing damage and drying of the animal skin.Conclusion. As a result of this study, a topical formulation in the form of a gel containing a new thiadiazole derivative was developed for the treatment of infectious diseases of animal skin.

Multidrug-resistant ESBL-producing Klebsiella pneumoniae complex in Czech hospitals, wastewaters and surface waters

BackgroundMultidrug-resistant (MDR) bacteria pose a significant challenge to the treatment of infectious diseases. Of particular concern are members of the Klebsiella pneumoniae species complex (KpSC), which are frequently associated with hospital-acquired infections and have the potential to spread outside hospitals via wastewaters. In this study, we aimed to investigate the occurrence and phylogenetic relatedness of MDR KpSC from patients with urinary tract infections (UTIs), hospital sewage, municipal wastewater treatment plants (mWWTPs) and surface waters and to evaluate the clinical relevance of the KpSC subspecies.MethodsA total of 372 KpSC isolates resistant to third-generation cephalosporins and/or meropenem were collected from patients (n = 130), hospital sewage (n = 95), inflow (n = 54) and outflow from the mWWTPs (n = 63), river upstream (n = 13) and downstream mWWTPs (n = 17) from three cities in the Czech Republic. The isolates were characterized by antimicrobial susceptibility testing and whole-genome sequencing (Illumina). The presence of antibiotic resistance genes, plasmid replicons and virulence-associated factors was determined. A phylogenetic tree and single nucleotide polymorphism matrix were created to reveal the relatedness between isolates.ResultsThe presence of MDR KpSC isolates (95%) was identified in all water sources and locations. Most isolates (99.7%) produced extended-spectrum beta-lactamases encoded by blaCTX−M−15. Resistance to carbapenems (5%) was observed mostly in wastewaters, but carbapenemase genes, such as blaGES−51 (n = 10), blaOXA−48 (n = 4), blaNDM−1 (n = 4) and blaKPC−3 (n = 1), were found in isolates from all tested locations and different sources except rivers. Among the 73 different sequence types (STs), phylogenetically related isolates were observed only among the ST307 lineage. Phylogenetic analysis revealed the transmission of this lineage from patients to the mWWTP and from the mWWTP to the adjacent river and the presence of the ST307 clone in the mWWTP over eight months. We confirmed the frequent abundance of K. pneumoniae (K. pneumoniae sensu stricto and K. pneumoniae subsp. ozaenae) in patients suffering from UTIs. K. variicola isolates formed only a minor proportion of UTIs, and K. quasipneumoniae was not found among UTIs isolates; however, these subspecies were frequently observed in hospital sewage communities during the first sampling period.ConclusionThis study provides evidence of the transmission and persistence of the ST307 lineage from UTIs isolates via mWWTPs to surface waters. Isolates from UTIs consisted mostly of K. pneumoniae. Other isolates of KpSC were observed in hospital wastewaters, which implies the impact of sources other than UTIs. This study highlights the influence of urban wastewaters on the spread of MDR KpSC to receiving environments.

National Survey of Factors Associated with Physician Antibiotic Prescribing Preferences.

The development of new infectious disease therapies has become a public health priority given the suboptimal efficacy and adverse effects with current drugs for some patients. Understanding the factors associated with physician antibiotic prescribing preferences can help guide policymakers seeking to incentivize the development of interventions that improve patient outcomes for the treatment and prevention of infectious diseases. To determine the factors associated with physician decision-making when prescribing antibiotics for community-acquired pneumonia (CAP), uncomplicated urinary tract infection (UTI), and cellulitis. A cross-sectional online survey in April 2023. Physicians enrolled in an online panel who reported having prescribed antibiotics within the past year. Respondents were asked to select 1 to 15 characteristics that they deemed most important. From their selected characteristics, for each type of infection, they were then asked to rank up to five on a scale with 5 points given to the top-scoring characteristic and 1 point to the bottom-scoring. The primary outcome was the mean score for each characteristic across the three types of infections weighted by the number of respondents in the sample, with higher scores indicating higher importance. Among the 130 physician participants, 106 (82%) completed the survey. Just under half (46%) were female; 89% of respondents were White, 3% Black, and 9% another race, while 15% reported Hispanic ethnicity. The highest-scored factors influencing antibiotic prescription preferences were the cure rate (treatment efficacy) (mean score: 2.87), severity of the infection (1.88), rare but major side effects (1.33), interactions with other drugs (1.33), previous experience and knowledge of the drug (1.19), and future risk of resistant infection to the patient (1.15). Out-of-pocket patient costs were prioritized lowest (mean score: 0.25). In considering which antibiotic to prescribe, physicians prioritize clinical outcomes related to drug efficacy and safety over public health- or economics-focused factors.

Antibacterial Activity of Ethanolic Extract of Cardiospermum halicacabum against Methicillin-Resistant Staphylococcus aureus

We investigated the antibacterial activity of Cardiospermum halicacabum extract against methicillin-resistant Staphylococcus aureus (MRSA) via the disk diffusion method and identified the plant’s bioactive phytochemicals. Additionally, we evaluated the synergistic effects, and primary mechanism of action of the plant extract against the S. aureus strain PB57 (MRSA). The ethanolic extract of C. halicacabum contained beneficial secondary metabolites such as the flavonoids apigenin, terpenoids and tannins. The total phenolic content, expressed as the gallic acid equivalent (g GAE/kg), was 87.66 ± 14.56 g GAE/kg at a concentration of the 1 mg/mL. The plant extract inhibited and killed the S. aureus strain PB57 with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.98 mg/mL. Electron microscopy revealed that the plant extract caused damage to the ultrastructures of the cells of the pathogens. The compounds in the extract remained below known maximum acceptable cytotoxicity thresholds for fibroblast cells, which are typically in the range of [include specific value from relevant guidelines or literature]. Further cytotoxicity assays are required to determine the precise safety margins for therapeutic use. Although the extract showed promise against MRSA, its application as a broad treatment for infectious diseases requires more specific testing on other pathogens. Based on the scope of our research, C. halicacabum could be a viable candidate for the development of treatments targeting MRSA-related infections. HIGHLIGHTS Our investigation revealed that the ethanolic extract of Cardiospermum halicacabum exhibited significant antibacterial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain PB57. The extract contained beneficial secondary metabolites, including flavonoids such as apigenin, as well as terpenoids and tannins. Moreover, the electron microscope shown that the extract disrupted the pathogen’s cell structures and, despite showing some cytotoxicity at higher doses, remained within safe limits, positioning C. halicacabum as a potential treatment for infectious diseases. GRAPHICAL ABSTRACT

A phenotypic study of the resistome in a peri-urban ecosystem

Since the discovery of antibiotics, the dispersion of resistance genes has increased exponentially, leading to the current state in which it has become increasingly difficult to achieve an effective treatment for infectious diseases. The enormous capacity for genetic exchange between microorganisms is causing resistance genes to be able to reach all environments, even those where there is no anthropogenic impact or exposure to these drugs. In this work, a phenotypic study of the resistome has been conducted in a peri-urban ecosystem (Granada, Spain), wherein the resistance to 32 antibiotics of 710 bacterial strains isolated from 70 samples from different ecological niches with varying levels of exposure to antibiotics and anthropic action has been determined. The study of resistances using phenotypic procedures constitutes a very useful and complementary alternative to genomic methods. The obtained results show a high percentage of resistance in all the subsystems analysed, stating high multi-resistance profiles. Vancomycin and erythromycin were the antibiotics to which the highest levels of resistance were observed, whereas the lowest levels were obtained in chloramphenicol. Regarding the environments studied, the highest percentages of resistance were found in wastewater, farms and food. It should be noted that in natural soil samples (not exposed to antibiotics or anthropogenic activities), worrying levels of resistance to practically all the groups of antibiotics analysed were detected. These results support the generally accepted conclusion that an appropriate control and management of wastewater and solid waste that may contain antibiotics or resistant bacteria is really important to prevent the wide propagation of the resistome in the environment.

Clinico-histopathological characteristics and management outcome of rare chronic infective granulomatous diseases: A case series study

Granulomatous skin diseases are common cutaneous dermatoses commonly encountered by practicing dermatologist. Granulomatous skin lesions are distinctive pattern of chronic inflammatory response of skin due to reaction against various organic and inorganic antigens. Granulomas are characterized by focal collection of epithelioid cells or histiocytes, admixed with variable number of leucocytes (especially mononuclear cells) and multinucleated giant cells. Granulomatous reaction is a type IV hypersensitivity reaction evoked by poorly soluble reactive substances. Incidence and prevalence of different types of granulomatous dermatitis depend on geographic location. Granulomatous skin lesions are common in the eastern parts of India. Many granulomatous skin lesions have identical histomorphology and conversely a single pathology can produce varied histological features. Some rare suppurative chronic granulomatous skin diseases include Botryomycosis, Actinomycosis, Rhinosporoidosis, Nocardiosis, and Cutaneous Tuberculosis. To describe clinical, histopathological features and treatment outcome of rare chronic infective granulomatous diseases. In this observational case series study, we retrospectively analysed six biopsy proven cases of rare chronic infective granulomatous diseases presented to our department (OPD) of Dermatology, Venereology and Leprosy (DVL) over a period of six months between June 2023 to November 2023 at Great Eastern Medical School and Hospital (GEMS), Srikakulam, Andhra Pradesh, India. The patient’s full clinical history, morphology of lesions, histopathological findings and treatment outcome were analysed. Along with histopathology, other necessary laboratory investigations were performed if required. A total of six patients were involved in the study, of whom four were males and two were females. The male to female ratio was 2:1, with a slight male majority. The most common age group was 31-40 years for both males and females. Painful raised lesion for long duration was the predominant complaint among those patients. Out of these six rare chronic granulomatous diseases, bacterial infections were common than fungal infection. All the cases showed clinical improvement after one month of starting treatment.: Most of the patients had a chronic history with improper treatment. So, it is imperative that the clinical diagnosis has to be confirmed with histopathology for the definitive diagnosis and appropriate treatment of these rare chronic infective granulomatous diseases. All these rare cases showed excellent progress after starting the right treatment.

A rapid dual-mode SERS/FL cytosensor assisted via DNA Walker-based plasmonic nanostructures

Various surface-enhanced Raman scattering (SERS) biosensors offer powerful tools for the ultrasensitive detection of circulating tumor cells (CTCs) and tumor diagnosis. Despite their efficacy, the swift and precise preparation of SERS plasmonic nanostructures poses an ongoing challenge. In this study, we introduce DNA-assisted plasmonic nanostructures capable of producing dual signals and facilitating DNA Walker signal amplification, resulting in the development of a SERS/Fluorescent (FL) dual-mode cytosensor for CTCs detection. Firstly, Au@Ag nanoparticle multimers (Au@AgNMs) featuring interparticle nano-gaps were synthesized through DNA self-assembly and in-situ deposition, which provided plasmonic nanostructures. Hence, the nano-gap distance among Au@AgNMs was meticulously regulated after optimization to achieve both SERS enhancement and fluorescence quenching. Subsequently, the aptamer (Apt) of MUC1 recognized CTCs specifically for strand displacement reaction (SDR) and further triggered the DNA Walker reaction for signal amplification. The limit of detection (LOD) of proposed cytosensor can be obtained as low as 5 cells/mL in SERS mode and 21 cells/mL in FL mode. Hence, SERS mode confers highly precise information, while FL mode allow for rapid quantitative analysis. This dual-mode cytosensor based on plasmonic nanostructures facilitates the early detection and precise treatment of cancer or infectious diseases.

Heterologous protein exposure and secretion optimization in Mycoplasma pneumoniae

The non-pathogenic Mycoplasma pneumoniae engineered chassis (Mycochassis) has demonstrated the ability to express therapeutic molecules in vitro and to be effective for treatment of lung infectious diseases in in vivo mouse models. However, the expression of heterologous molecules, whether secreted or exposed on the bacterial membrane has not been optimized to ensure sufficient secretion and/or exposure levels to exert a maximum in vivo biological effect. Here, we have improved the currently used secretion signal from MPN142 protein. We found that mutations at P1’ position of the signal peptide cleavage site do not abrogate secretion but affect it. Increasing hydrophobicity and mutations at the C-terminal of the signal peptide increases secretion. We tested different lipoprotein signal peptides as possible N-terminal protein anchoring motifs on the Mpn cell surface. Unexpectedly we found that these peptides exhibit variable retention and secretion rates of the protein, with some sequences behaving as full secretion motifs. This raises the question of the biological role of the lipobox motif traditionally thought to anchor membrane proteins without a helical transmembrane domain. These results altogether represent a step forward in chassis optimization, offering different sequences for secretion or membrane retention, which could be used to improve Mycochassis as a delivery vector, and broadening its therapeutic possibilities.

USO DA BIOLOGIA MOLECULAR NA PRODUÇÃO DE NOVOS MEDICAMENTOS

INTRODUCTION: Molecular biology, by acting in the development of biotechnological drugs, such as Zidovudine and Sofosbuvir, offers significant innovations in modern pharmacology, providing more specific and effective therapies for complex diseases. These drugs, although promising, still face challenges related to high costs and limited accessibility. The field is constantly evolving, seeking to improve the specificity and sensitivity of therapies for better prognoses. GENERAL OBJECTIVE: To explore the applications of molecular biology in the production of new drugs and its impact on the creation of personalized treatments. METHODOLOGY: This work is a qualitative, exploratory bibliographic review, which analyzes 7 articles published between 2020 and 2024 on molecular biology correlated to drug development. The research used databases such as BVS, DrugBank, PubMed and others, applying rigorous criteria for their selection. RESULTS: This study analyzes the potential of molecular biology for the development of new drugs, highlighting techniques such as PCR, DNA sequencing and CRISPR/Cas9. A review highlights the importance of these approaches in personalizing therapies and identifying molecular targets, in addition to discussing the pharmacodynamics and pharmacokinetics of drugs. Advances in molecular pharmacology offer new opportunities for more targeted and specific treatments with several drugs in complex diseases. CONCLUSION: The integrative review highlighted the importance of molecular biology techniques, such as DNA sequencing, PCR and CRISPR/Cas9, in drug development and personalized medicine, demonstrating their effectiveness in the treatment of genetic and infectious diseases. It is urgent to carry out new studies to explore the interactions of these technologies and their clinical applications, evolving towards better pharmacological treatments.

Comparative treatment of homeless persons with an infectious disease in the US emergency department setting: a retrospective approach

BackgroundResearch has long documented the increased emergency department usage by persons who are homeless compared with their housed counterparts, as well as an increased prevalence of infectious diseases. However, there...

Dual Detection of Norfloxacin and Gatifloxacin by Excitation Tuning Strategy Based on Yellow Carbon Dots.

Fluoroquinolones (FQs) are widely used in hospitals, animal husbandry and aquaculture for the treatment of infectious diseases. However, overuse of FQs poses a potential threat to the environment and human. Detection of antibiotics is of great importance in various fields. In this paper, bright yellow fluorescence carbon dots (y-CDs) with quantum yield of 32% were synthesized via a simple and rapid microwave-assisted method using o-phenylenediamine and salicylic acid as raw materials. The fluorescence properties of y-CDs varied under different excitation wavelengths. It is discovered that the excitation wavelength is a critical factor to develop a dual functional fluorescence probe. Under selected excitation wavelength (355nm), y-CDs can realize dual detection of norfloxacin (NOR) and gatifloxacin (GAT) with good selectivity and high sensitivity in a "turn-on" mode. The detection limits of NOR and GAT are 0.0881 µM and 0.0125 µM, respectively. y-CDs prove practical application in the detection of NOR and GAT in milk and egg samples.

Antibacterial Activity of N-Hexan and Ethyl Acetate Fractions of Gaharu Leaves (Aquilaria malaccensis) Against Bacteria Causing Skin Infection

Gaharu (Aquilaria malaccensis) leaves are plants that are useful in the treatment of infectious diseases. This study aims to obtain n-hexane and ethyl acetate fractions of Gaharu leaves that have antibacterial activity against skin infection bacteria by agar diffusion. The results of antibacterial activity screening of the n-hexane fraction and ethyl acetate fraction at a concentration of 0.1% is bacteriostatic. The test results of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) using concentrations of 0.1%, 0.2%, 0.4%, 0.8%, 1.6%, 3.2%, 6.4% and 12.8% obtained MIC value of n-hexane fraction at 0.2% against P. acnes, P. aeurogynes bacteria and 0.4% against S. aureus, S. epidermidis bacteria, MIC value of ethyl acetate fraction was 0.2% against P. aeuroginosa, S. aureus bacteria and 0.4% against P. acnes, S. epidermidis bacteria. MBC value of n-hexan fraction was 0.4% against P. acnes, P. aeuroginosa bacteria, 0.8% against S. aureus bacteria, 1.6% against S. epidermidis bacteria, MBC value of ethyl acetate fraction was 0.4% against P. acnes, P. aeuroginosa, S. aureus bacteria, 0.8% against S. epidermidis bacteria. The results of the antibacterial activity using concentrations of 1.56%, 3.12%, 6.25%, 12.5% and 25% obtained the largest inhibition zone diameter of the n-hexane fraction was 13,99 mm and the ethyl acetate fraction was 27,68 mm against S. epidermidis bacteria at a concentration of 25%. Based on the results, it can be concluded that the antibacterial activity of the ethyl acetate fraction against all test bacteria is stronger than the n-hexane fraction

Claims-Based Algorithm to Identify Pre-Exposure Prophylaxis Indications for Tenofovir Disoproxil Fumarate and Emtricitabine Prescriptions (2012-2014): Validation Study.

To monitor the use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and related medicines for pre-exposure prophylaxis (PrEP) as HIV prevention using commercial pharmacy data, it is necessary to determine whether TDF/FTC prescriptions are used for PrEP or for some other clinical indication. This study aimed to validate an algorithm to distinguish the use of TDF/FTC for HIV prevention or infectious disease treatment. An algorithm was developed to identify whether TDF/FTC prescriptions were for PrEP or for other indications from large-scale administrative databases. The algorithm identifies TDF/FTC prescriptions and then excludes patients with International Classification of Diseases (ICD)-9 diagnostic codes, medications, or procedures that suggest indications other than for PrEP (eg, documentation of HIV infection, chronic hepatitis B, or use of TDF/FTC for postexposure prophylaxis). For evaluation, we collected data by clinician assessment of medical records for patients with TDF/FTC prescriptions and compared the assessed indication identified by the clinician review with the assessed indication identified by the algorithm. The algorithm was then applied and evaluated in a large, urban, community-based sexual health clinic. The PrEP algorithm demonstrated high sensitivity and moderate specificity (99.6% and 49.6%) in the electronic medical record database and high sensitivity and specificity (99% and 87%) in data from the urban community health clinic. The PrEP algorithm classified the indication for PrEP in most patients treated with TDF/FTC with sufficient accuracy to be useful for surveillance purposes. The methods described can serve as a basis for developing a robust and evolving case definition for antiretroviral prescriptions for HIV prevention purposes.

Long-Circulating Nanoemulsion with Oxygen and Drug Co-Delivery for Potent Photodynamic/Antibiotic Therapy Against Multidrug-Resistant Gram-Negative Bacterial Infection.

Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES). To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against Acinetobacter baumannii (A. baumannii) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo. ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL-1 of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating A. baumannii-induced acute peritonitis, accompanied by good biocompatibility in vivo. Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.