Recent advances in anti-infective drug discovery最新文献

Onychomycosis is regarded as one of the most common and least concerned fungal problems. Although various treatment approaches have been well-established, still treatment strategies suffer from certain drawbacks, so there is a need to discuss novel therapies that could ultimately eliminate all the conventional barriers. It is a nail infection that begins in the toenail and spreads, causing significant negative impacts on patients' quality of life. The purpose of this work was to highlight the limitations of conventional treatments and shed light on novel therapies for managing onychomycosis. A comprehensive review on existing topical and systemic therapies was conducted, with a focus on their drawbacks, such as recurrence and lower efficacy. This review aimed to explore the increasing prevalence of onychomycosis, which poses a serious health issue; however, the advent of nanobased drug delivery systems offers hope for more effective management of this prevalent disease. These systems could potentially overcome the limitations of conventional treatments, thereby improving patient outcomes.

Background: Tinea infections are superficial fungal infections caused by three species of fungi (i.e. Epidermophyton, Microsporum, and Trichophyton) collectively termed dermatophytes. Dermatophytes are fungi that cause skin, nail bed, and hair infections. These infections are classified based on infection site, including tinea pedis (foot), tinea corporis (body), tinea capitis (head), and tinea cruris (groin). Dermatophytes can spread by direct contact with other people (anthropophilic organisms), animals (zoophilic organisms), and soil (geophilic organisms), as well as indirectly from fomities.

Objective: This review aims to summarize the allopathic drugs along with their mechanism of action and herbal drugs including their parts of the plant used for the treatment of tinea infections.

Methods: The literature review was performed using the following databases: PubMed (https://pubmed.ncbi.nlm.nih.gov/), and Google Scholar (https://scholar.google.com/), to identify the various drugs involved in the treatment of dermatophytosis along with their mechanisms.

Results: The following keywords were applied in the search strategy: "Tinea", "Dermatophytosis", "Ringworm infection", "Pathogenesis of tinea", "Tinea pedis", and "Tinea capitis". This article also reviews several formulations that are available in the market for treating ringworm infection.

Conclusion: The current review provides information about the classification of dermatophytosis based on infection site and environmental habitat, pathogenesis, immunopathogenesis of dermatophytes, and herbals and allopathic drugs used for their treatment.

Background: The emergence of resistance to multiple drugs has posed a multitude of difficulties that demand immediate attention and solutions. Multiple drug resistance arises from the accumulation of numerous genes within a single cell, each conferring resistance to a specific drug, and from the heightened expression of genes responsible for multidrug efflux pumps. These pumps effectively expel a diverse array of drugs from the cell.

Objective: The multi-drug-resistant organisms, including methicillin-resistant Staphylococcus aureus, are the hub of numerous diseases, from minute ailments to fatal diseases, like catheter infections. Nowadays, a combination of many antibiotics is given together as a multimodality therapy to cure MRSA infections. However, researchers are exploring novel approaches to find better solutions.

Methods: De novo designing of the peptide sequences has been done through an in silico tool. The peptides were further screened using different computational methods. Following this, the selection was conducted utilizing physicochemical properties as criteria. Molecular docking of the selected peptide sequence was carried out. Based on the highest docking score, the model complex was chosen for validation purposes by conducting studies through molecular dynamics simulations.

Results: A total of fifty-two novel antimicrobial peptides were designed and evaluated based on various parameters, targeting MRSA-specific proteins PBP2a and PVL toxin. Among these designed peptides, the peptide sequence VILRMFYHWAVKTNGP emerged as the optimal candidate, satisfying all the necessary parameters to be an effective antimicrobial peptide.

Conclusion: Molecular docking and MD simulation results showed that the designed peptide sequence could be the possible solution for MRSA treatment.

Introduction: Recent research has been concentrated on investigating the involvement of Toxoplasma gondii (T. gondii) in the progression of liver disorders. This study aims to investigate the prevalence of T. gondii infection in patients with non-alcoholic fatty liver disease (NAFLD), as well as the effects of toxoplasmosis infection on biological biomarkers such as aspirate transaminase (AST), alanine transaminase (ALT), cholesterol (Chol), and triglyceride (Tg) levels in Sistan, southeast Iran.

Methods: A case-control study was conducted between December 2021 and September 2022. The study included 225 patients diagnosed with NAFLD as the case group and 225 healthy blood donors as the control group. The controls were selected from the same region and were matched with the patients based on gender and age. We collected serum samples from all patients and utilized an enzyme-linked immunosorbent assay to analyze them for the existence of anti-T. gondii IgG antibodies. A questionnaire and medical records were utilized to gather data on the patient's demographic factors.

Results: The prevalence of anti-T. gondii IgG antibodies were 68 (30.2%) in patients with NAFLD, whereas it was 11 (4.88%) in the control group. The seroprevalence of T. gondii in NAFLD patients increased in correlation with age (P < 0.001). The prevalence of NAFLD was significantly greater in the seropositive group compared to the seronegative group (P < 0.001). In addition, the levels of the metabolic markers Chol and Tg were significantly higher in T. gondii seropositive NAFLD patients compared to T. gondii seronegative NAFLD patients.

Conclusion: The findings of this study indicate a high seroprevalence of T. gondii in patients with NAFLD. Further studies are warranted to investigate the underlying mechanisms and potential therapeutic implications of this association.

Background: Acinetobacter baumannii is an opportunistic hospital pathogen with high antibiotic resistance, and the ability to produce biofilm. This study aimed to investigate epsA, ompA, and bap genes involved in biofilm formation in MDR and XDR clinical isolates of Acinetobacter baumannii in Khorramabad, Iran.

Methods: In this study, 79 A. baumannii isolates were collected from various samples of the patients admitted to tertiary hospitals in Khorramabad city, Iran, between January and August 2019. After performing the semi-quantitative evaluation of biofilm production by microtiter plate assay, screening of isolates carrying epsA, ompA, and bap genes was done by PCR method. Finally, statistical analyses were conducted using SPSS 22.

Results: Among 79 A. baumannii isolates, 52% XDR, 40% MDR, and 16% non-XDRMDR isolates were found to be biofilm producers. All XDR and 94% MDR isolates had ompA and epsA genes, and bap genes were detected among > 80% of these isolates. Moreover, the presence of biofilm-related genes and biofilm production among non-XDRMDR isolates were less than among resistant isolates (p≤ 0.01).

Conclusion: Based on the results, biofilm production and simultaneous presence of epsA, ompA, and bap genes among MDR, and XDR A. baumannii isolates have been found to be significantly more than non-XDR-MDR isolates.

Leprosy, often known as Hansen's disease is a contagious chronic infectious disease caused by Mycobacterium leprae (M. leprae). Our methodology is easily repeatable in tertiary care settings with diagnostic accuracy resources and staff capable of building a stewardship team. Comprehensive antimicrobial policies and programmes are required to properly alleviate the initial issue.

Background: Remdesivir, a viral RNA polymerase inhibitor, has been a powerful weapon in the battle against the SARS-CoV-2 pandemic. Originally approved for use in hospitalized patients, remdesivir improves clinical outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving efficacious in hospitalized patients, its use was approved in early disease for symptomatic, non-hospitalized patients that present risk factors for progression to severe disease.

Objective: To evaluate whether administration of the antiviral medication remdesivir at an outpatient basis has an effect on hospital admissions of patients presenting with SARSCoV- 2 infection.

Methods: We conducted an observational clinical trial involving 107 non-hospitalized COVID-19 patients who attended the emergency department of a third-level greek hospital seeking care for symptoms appearing within the previous 5 days and who had at least one risk factor for progression to severe disease. After arterial blood gas evaluation, eligible patients received intravenous remdesivir at a dose of 200 mg on day 1 and 100 mg on days 2 and 3. The efficacy endpoint was set as COVID-19-related hospitalization or death in the next 14 days.

Results: A total of 107 patients (57.0% men) participated in the study, 51 (47.7%) of them fully vaccinated. Most prevalent were age ≥ 60 years old, cardiovascular/cerebrovascular disease, immunosuppression or malignancy, obesity, diabetes mellitus, and chronic lung disease. All patients enrolled completed the 3-day course, with a total of 3 out of 107 patients (2.8%) eventually having a COVID-19-related hospitalization by day 14, while no deaths were reported by day 14.

Conclusion: Among non-hospitalized patients with at least one risk factor for progression to severe COVID-19, a 3-day course of intravenous remdesivir yielded favourable results.